Publications by authors named "Wei Han"

1,610 Publications

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Hybrid micelles enhance tumour therapy by remodelling biodistribution and improving intracellular drug release.

Biomater Sci 2021 Sep 23. Epub 2021 Sep 23.

Department of Emergency Medicine, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, No. 1098 Xueyuan Avenue, Shenzhen 518000, PR China.

PEGylated micelles have been widely used for tumour therapy. Although PEGylation can prolong the blood circulation time, there is only less than 5% of administered micelles that can be transported to tumour sites and over 95% are cleared by the reticuloendothelial system (RES). Besides, the limited intracellular drug release also restricts their efficacy. To improve the therapeutic efficacy of PEGylated micelles, a safe, simple and efficient hybrid micellar system, composed of poly(aminoethyl ethylene phosphate)-poly(L-lactic acid) (PAEEP-PLLA) and poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLLA), was developed. The hybrid micelles significantly prolonged the blood circulation time by decreasing the plasma protein adsorption and reducing the clearance by the RES. The deposition of the hybrid micelles in the liver and spleen was reduced, and the tumour accumulation was greatly improved. In addition, the intracellular drug release of the hybrid micelles was obviously increased due to the easy degradation of PAEEP in the endo/lysosomes. The tumour growth inhibition efficiency of the hybrid micelles was much higher than that of the PEG-PLLA micelles (84.5% 44.5%). Furthermore, the hybrid micelles exhibited low hemolysis and reduced deposition in normal organs, which revealed their excellent bio-safety. Therefore, we established a promising hybrid micelle system for efficient anti-tumour therapy.
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http://dx.doi.org/10.1039/d1bm01158hDOI Listing
September 2021

Intraocular Pressure, Age, and Central Corneal Thickness in a Healthy Chinese Children Population: The Handan Offspring Myopia Study.

Ophthalmic Epidemiol 2021 Sep 19:1-8. Epub 2021 Sep 19.

Department ofGlaucoma, The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Purpose: To assess the distribution and factors related to intraocular pressure (IOP) in a Chinese children population in Northern China.

Methods: 1,238 offspring aged 6 to 18 years, residing in six villages, were recruited for this current study, the Handan Offspring Myopia Study. Participants underwent an interviewer-administered questionnaire and a complete ocular examination, including standardized measurement of IOP with Perkins applanation tonometry.

Results: 1,648 eyes of 828 children were included in the analysis. The mean IOP was 13.9 ± 1.6 mmHg. The mean IOP for the study population increased from 13.0 ± 1.5 mmHg for those 6 to 7 years of age to 14.2 ± 1.4 mmHg for those 15 years of age or older ( < .001). The mean central corneal thickness (CCT) was 548.7 ± 32.1 μm, and had no difference among different age groups and gender. In univariate regression analysis, age (0.12 mmHg per 1 year old), height (0.09 mmHg per 5 cm), weight (0.02 mmHg per kg), body mass index (0.07 mmHg per 1 m/kg2), systolic blood pressure (0.06 mmHg per 5 mmHg), CCT (0.06 mmHg per 5 μm), and SE (-0.11 mmHg per 1 D) were correlated with IOP. In multivariate regression analysis, higher IOP was only associated with older ages ( = .002) and thicker CCT ( = .001).

Conclusion: The mean IOP in healthy rural Chinese children aged 6-18 years is about 14 mmHg, which is lower than in adults in the same locality. The mean IOP is slightly increasing with age during childhood, which is opposite to the result among adults. Age and CCT are the major independent factors associated with IOP.
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http://dx.doi.org/10.1080/09286586.2021.1966806DOI Listing
September 2021

Effect of Glycyrrhiza uralensis against ulcerative colitis through regulating the signaling pathway of FXR/P-gp.

Am J Transl Res 2021 15;13(8):9296-9305. Epub 2021 Aug 15.

Department of Proctology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine Nanjing, Jiangsu Province, China.

Objective: Ulcerative colitis (UC) is a moderate to severe inflammatory bowel disease, with a characteristic inflammatory response. Chinese herbal medicine can play a role in UC treatment. Herein, we aimed to investigate the function of Glycyrrhiza uralensis in UC treatment and the underlying mechanism.

Methods: After establishing an animal model of UC, different agents of kuijieguanchang prescription, Glycyrrhiza uralensis, mesalazine, and GW4064 were administrated to mice. The apoptosis rate was measured by TUNEL assay, and the expression of different biomarkers was tested by western blot and qPCR.

Results: Glycyrrhiza uralensis could regulate apoptosis of intestinal mucosal cells, through regulating the expression of apoptosis-related proteins and protective proteins of intestinal mucosa. The administration of Glycyrrhiza uralensis could greatly enhance the expression of muc1, muc3, and the pro-apoptotic protein, BAX. The proteins involved in malignancy from UC, such as Bcl-2 and fgf-15, were dramatically downregulated after using the Glycyrrhiza uralensis. Moreover, it was illustrated that Glycyrrhiza uralensis acted against UC by activating the signaling of P-gp through upregualting its expression. The upregulation of FGFR4, SHP, and P-gp in liver conferred protective function in UC.

Conclusion: Glycyrrhiza uralensis could regulate apoptosis of intestinal mucosal cells, through regulating the expression of apoptosis-related proteins and protective proteins of intestinal mucosa. The results provide novel options for UC treatment, as well as a rationale for pharmacology of Chinese traditional medicine, that is favorable for use of herbal medicine.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430177PMC
August 2021

Sequential different B cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt Lymphoma.

Blood Adv 2021 Sep 14. Epub 2021 Sep 14.

Department of Hematology/Oncology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China, China.

Single antigen-targeted chimeric antigen receptor (CAR) T-cell therapy may be insufficient to induce a durable response in pediatric aggressive B-cell lymphomas. The clinical trial (ChiCTR1800014457) examined the feasibility of sequential different B cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt lymphoma. Twenty-three patients received the first CD19 CAR T-cell infusion. The patients who did not achieve an ongoing complete response sequentially underwent one or more additional infusions of CAR T-cell targeting CD22 followed by CD20 according to their disease status and CAR T-cell persistence after each infusion. The median time from the last infusion to cutoff date was 17 months (range, 15 to 23). The estimated 18-month complete response rate was 78% (95% confidence interval [CI], 54 to 91). The estimated 18-month progression-free survival rate was 78% (95% CI, 55 to 90), with 78% (95% CI, 37 to 94) in patients with bulky diseases and 60% (95% CI, 25 to 83) in patients with central nervous system (CNS) involvement. During the first CD19 CAR T-cell infusion, grade 3 or higher cytokine release syndrome (CRS) and neurotoxicity occurred in 34.8% and 21.7% of all patients, respectively. During subsequent infusions, few incidences of higher than grade 2 CRS and neurotoxicity were observed. All adverse events were reversible. The severity of neurotoxicity was not significantly different between patients with CNS and non-CNS involvement. Sequential CAR T-cell therapy may result in a durable response and is safe in pediatric refractory/relapsed Burkitt lymphoma. Patients with CNS involvement may benefit from sequential CAR T-cell therapy. This trial was registered at www.chictr.org.cn/index.aspx as ChiCTR1800014457.
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http://dx.doi.org/10.1182/bloodadvances.2021004557DOI Listing
September 2021

Late-Stage Intermolecular Allylic C-H Amination.

J Am Chem Soc 2021 Sep 13;143(37):14969-14975. Epub 2021 Sep 13.

Department of Chemistry, Roger Adams Laboratory, University of Illinois, 505 South Mathews Avenue, Urbana, Illinois 61801, United States.

Allylic amination enables late-stage functionalization of natural products where allylic C-H bonds are abundant and introduction of nitrogen may alter biological profiles. Despite advances, intermolecular allylic amination remains a challenging problem due to reactivity and selectivity issues that often mandate excess substrate, furnish product mixtures, and render important classes of olefins (for example, functionalized cyclic) not viable substrates. Here we report that a sustainable manganese perchlorophthalocyanine catalyst, [Mn(ClPc)], achieves selective, preparative intermolecular allylic C-H amination of 32 cyclic and linear compounds, including ones housing basic amines and competing sites for allylic, ethereal, and benzylic amination. Mechanistic studies support that the high selectivity of [Mn(ClPc)] may be attributed to its electrophilic, bulky nature and stepwise amination mechanism. Late-stage amination is demonstrated on five distinct classes of natural products, generally with >20:1 site-, regio-, and diastereoselectivity.
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http://dx.doi.org/10.1021/jacs.1c06335DOI Listing
September 2021

Kawasaki Disease- Management Strategies Given Symptoms Overlap to COVID-19: A Review.

JNMA J Nepal Med Assoc 2021 Apr 30;59(236):417-424. Epub 2021 Apr 30.

Children's Hospital of Shaanxi Provincial People's Hospital, 3rd Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an Shanxi, 710001, China.

Kawasaki disease is an acute, self-limiting vasculitis in children. Early treatment is necessary to prevent cardiovascular complications. The acute phase of Kawasaki disease may present with hemodynamic instability. An association between viral respiratory infections and Kawasaki disease has been reported. Studies have shown that Kawasaki and Kawasaki-like disease may be associated with and have symptoms overlapping COVID-19. Children with COVID-19 may present as Kawasaki-like disease with pediatric inflammatory multisystem syndrome, or macrophage activation syndrome. Clinicians need to be aware of the early diagnosis and management of Kawasaki disease to prevent the development of coronary artery aneurysms. The symptoms overlap of multisystem inflammatory disease seen in COVID-19 adds to the difficulties in timely diagnosis and treatment. Children with Kawasaki disease require regular follow-up plans for coronary artery aneurysms. This adds to the difficulties during the changed environment of COVID-19 for control and prevention. Missed diagnosis and early treatment of Kawasaki disease with immunoglobulin and aspirin results in the development of coronary artery aneurysm in up to 25% of cases, with grave consequences. Here, we briefly review the management of typical and atypical Kawasaki disease which has symptoms overlapping with the multisystem inflammatory disease as seen in COVID-19.
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http://dx.doi.org/10.31729/jnma.5698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369595PMC
April 2021

A prognostic model (BATAP) with external validation for patients with transplant-associated thrombotic microangiopathy.

Blood Adv 2021 Sep 10. Epub 2021 Sep 10.

Peking University People's Hospital, Peking University Institute of Hematology;National Clinical Research Center for Hematologic Disease;Beijing Key Laboratory of Hematopoietic Stem Cell Transplanta, Beijing, China.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Information on markers for early prognostication remains limited, and no predictive tools for TA-TMA are available. We attempt to develop and validate a prognostic model for TA-TMA. A total of 507 patients who developed TA-TMA following allo-HSCT were retrospectively identified and separated into a derivation cohort and a validation cohort according to the time of transplantation to perform external temporal validation. Patient age (OR 2.371, 95% CI 1.264-4.445), anemia (OR 2.836, 95% CI 1.566-5.138), severe thrombocytopenia (OR 3.871, 95% CI 2.156-6.950), elevated total bilirubin (OR 2.716, 95% CI 1.489-4.955) and proteinuria (OR 2.289, 95% CI 1.257-4.168) were identified as independent prognostic factors for the 6-month outcome of TA-TMA. A risk score model termed BATAP (Bilirubin, Age, Thrombocytopenia, Anemia, Proteinuria) was then constructed according to the regression coefficients. The validated c-statistics were 0.816 (95% CI 0.766-0.867) and 0.756 (95% CI 0.696-0.817) in the internal and external validation, respectively. Calibration plots indicated that the model-predicted probabilities correlated well with the actual observed frequencies. This predictive model may facilitate the prognostication of TA-TMA and contribute to the early identification of high-risk patients.
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http://dx.doi.org/10.1182/bloodadvances.2021004530DOI Listing
September 2021

Numerical Analysis on Erosion and Optimization of a Blast Furnace Main Trough.

Materials (Basel) 2021 Aug 26;14(17). Epub 2021 Aug 26.

State Key Laboratory of Advanced Special Steel, Shanghai Key Laboratory of Advanced Ferrometallurgy, Department of Materials Engineering, School of Materials Science and Engineering, Shanghai University, Shanghai 200444, China.

The main trough of a blast furnace (BF) is a main passage for hot metal and molten slag transportation from the taphole to the torpedo and the slag handling. Its appropriate working status and controlled erosion ensure a safe, stable, high-efficiency and low-cost continuous production of hot metal. In this work, the tapping process of a main trough of a BF in the east of China was numerically studied with the help of a CFD library written in C++, called OpenFOAM, based on the use of the Finite Volume Method (FVM). The results show that turbulence intensity downstream of the hot metal impact position becomes weaker and the turbulence area becomes larger in the main trough. During the tapping, thermal stress of wall refractory reaches the maximum value of 1.7 × 107 Pa at the 4 m position in the main trough. Furthermore, baffles in the main trough placed between 5.8 m and 6.2 m were found to control and reduce the impact of the turbulence on the refractory life. The metal flowrate upstream of the baffles can be decreased by 6%, and the flow velocity on the upper sidewall and bottom wall decrease by 9% and 7%, respectively, compared with the base model. By using baffles, the minimum fatigue life of the refractory in the main trough increases by 15 tappings compared with the base model, so the period between the maintenance stops can be prolonged by about 2 days.
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http://dx.doi.org/10.3390/ma14174851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432703PMC
August 2021

Pretransplant HLA mistyping in diagnostic sample of a T-ALL patient due to loss of heterozygosity in the major histocompatibility complex.

Transpl Immunol 2021 Sep 4;69:101463. Epub 2021 Sep 4.

Department of Hematology, The First Hospital of Jilin University, Changchun, China. Electronic address:

Purpose: The degree of HLA compatibility between donor and recipient in hematopoietic stem cell transplantation is critical. In this report, we describe an acute lymphoblastic leukemia case with loss of heterozygosity (LOH) encompassing the entire HLA.

Methods: HLA molecular typing was performed on peripheral blood (PB) and buccal swabs (BS). Chromosomal microarray analysis (CMA) was performed using a whole genome platform.

Results: Typing results on PB sample collected during blast crisis demonstrated homozygosity at the-B,-C,-DR, and -DP loci. A BS sample demonstrated heterozygosity at the above loci. A subsequent PB sample drawn after count recovery confirmed heterozygosity. The CMA performed on PB samples collected during blast crisis revealed a large terminal region of copy-neutral LOH involving chromosome region 6p25.3p21.31, spanning approximately 33.32 Mb. The results of the CMA assay on sample collected after count recovery did not demonstrate LOH.

Conclusions: LOH at the HLA gene locus may significantly influence the donor search resulting in mistakenly choosing homozygous donors. We recommend confirming the HLA typing of recipients with hematological malignancies when homozygosity is detected at any locus by using BS samples, or alternatively from PB when remission is achieved.
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http://dx.doi.org/10.1016/j.trim.2021.101463DOI Listing
September 2021

Integrative Analysis of Minichromosome Maintenance Proteins and Their Prognostic Significance in Melanoma.

Front Oncol 2021 19;11:715173. Epub 2021 Aug 19.

Department of Burn and Plastic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Background: Minichromosome maintenance () is known for participating in cell cycle progression, as well as DNA replication. While the diverse expression patterns and prognostic values of s in melanoma still remained unclear.

Methods: In the present study, the transcriptional and clinical profiles of s were explored in patients with melanoma from multiple databases, including GEO, TCGA, ONCOMINE, GEPIA, UALCAN, cBioPortal, and TIMER databases.

Results: We found that the elevated expressions of and were significantly expressed in melanoma compared to normal skin. High mRNA levels of , , and were closely related to worse prognosis in patients with melanoma. GSEA showed hallmark pathways were most involved in mTORC1 signaling, G2M checkpoint, E2F targets, and mitotic spindle. Furthermore, we found potential correlations between the expression and the immune cell infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells.

Conclusion: Upregulated gene expression in melanoma probably played a crucial part in the development and progression of melanoma. The upregulated expressions could be used as potential prognostic markers to improve the poor outcome and prognostic accuracy in patients with melanoma. Our study might shed light on the selection of prognostic biomarkers as well as the underlying molecular pathogenesis of melanoma.
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http://dx.doi.org/10.3389/fonc.2021.715173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417415PMC
August 2021

Comprehensive Pan-Cancer Analysis and the Regulatory Mechanism of ASF1B, a Gene Associated With Thyroid Cancer Prognosis in the Tumor Micro-Environment.

Front Oncol 2021 20;11:711756. Epub 2021 Aug 20.

Department of Thyroid and Breast Surgery, Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

Background: The incidence of thyroid cancer, whose local recurrence and metastasis lead to death, has always been high and the pathogenesis of papillary thyroid carcinoma (PTC) has not been clearly elucidated. Therefore, the research for more accurate prognosis-related predictive biomarkers is imminent, and a key gene can often be a prognostic marker for multiple tumors.

Methods: Gene expression profiles of various cancers in the TCGA and GTEx databases were downloaded, and genes significantly associated with the prognosis of THCA were identified by combining differential analysis with survival analysis. Then, a series of bioinformatics tools and methods were used to analyze the expression of the gene in each cancer and the correlation of each expression with prognosis, tumor immune microenvironment, immune neoantigens, immune checkpoints, DNA repair genes, and methyltransferases respectively. The possible biological mechanisms were also investigated by GSEA enrichment analysis.

Results: 656 differentially expressed genes were identified from two datasets and 960 DEGs that were associated with disease-free survival in THCA patients were screened survival analysis. The former and the latter were crossed to obtain 7 key genes, and the gene with the highest risk factor, ASF1B, was selected for this study. Differential analysis of multiple databases showed that ASF1B was commonly and highly expressed in pan-cancer. Survival analysis showed that high ASF1B expression was significantly associated with poor patient prognosis in multiple cancers. In addition, ASF1B expression levels were found to be associated with tumor immune infiltration in THCA, KIRC, LGG, and LIHC, and with tumor microenvironment in BRCA, LUSC, STAD, UCEC, and KIRC. Further analysis of the relationship between ASF1B expression and immune checker gene expression suggested that ASF1B may regulate tumor immune patterns in most tumors by regulating the expression levels of specific immune checker genes. Finally, GSEA enrichment analysis showed that ASF1B high expression was mainly enriched in cell cycle, MTORC1 signaling system, E2F targets, and G2M checkpoints pathways.

Conclusions: ASF1B may be an independent prognostic marker for predicting the prognosis of THCA patients. The pan-cancer analysis suggested that ASF1B may play an important role in the tumor micro-environment and tumor immunity and it has the potential of serving as a predictive biomarker for multiple cancers.
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http://dx.doi.org/10.3389/fonc.2021.711756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417739PMC
August 2021

Welfare receipt and the risk of vitamin D deficiency in Japanese patients on maintenance hemodialysis: a cross-sectional, retrospective study.

Ren Replace Ther 2021 26;7(1):45. Epub 2021 Aug 26.

Division of Nephrology and Hypertension, Kawasaki Municipal Tama Hospital, 1-30-37, Shukugawara, Tama-ku, Kawasaki, Kanagawa 214-8525 Japan.

Background: Vitamin D deficiency is often observed in patients undergoing maintenance hemodialysis and is associated with significantly increased risk of overall mortality. Despite reports of poor nutrition/intake, vitamin D status among patients on maintenance hemodialysis receiving welfare remains unknown. This study investigated the vitamin D status in welfare recipients undergoing maintenance hemodialysis.

Methods: This cross-sectional study investigated vitamin D status among 106 outpatients undergoing maintenance hemodialysis at two medical facilities in Japan. Patients were divided into welfare and non-welfare groups based on their status as of September 2018. Patients were divided into two categories: serum vitamin D deficiency, defined as serum 25(OH)D concentrations < 12 ng/mL, or non-deficiency. Vitamin D deficiency was used as a dependent variable, while welfare receipt was used as the main predictor variable.

Results: Mean [± standard deviation] patient age, median [interquartile range] body mass index, and hemodialysis duration were 66.9 [± 10.8] years, 21.5 [19.6, 24.3] kg/m, and 7.9 [2.9, 12.3] years, respectively. Among 106 patients, 45 were women (42.5%) and 16 (15.1%) were receiving welfare. The welfare group had a higher diabetes prevalence ( = 0.003) and significantly lower median serum 25-hydroxyvitamin D concentrations (11.5 [8.7, 14.0] vs. 14.8 [11.2, 19.9] ng/mL,  = 0.005). Multiple logistic regression analysis revealed that welfare receipt was a significant risk factor for vitamin D deficiency (odds ratio [95% confidence interval], 4.41 [1.08, 18.07]).

Conclusions: Welfare recipients undergoing maintenance hemodialysis are at significantly increased risks of vitamin D deficiency compared with patients not receiving welfare.
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http://dx.doi.org/10.1186/s41100-021-00364-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390068PMC
August 2021

F-FDG texture analysis predicts the pathological Fuhrman nuclear grade of clear cell renal cell carcinoma.

Abdom Radiol (NY) 2021 Aug 28. Epub 2021 Aug 28.

Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Purpose: This article analyzes the image heterogeneity of clear cell renal cell carcinoma (ccRCC) based on positron emission tomography (PET) and positron emission tomography-computed tomography (PET/CT) texture parameters, and provides a new objective quantitative parameter for predicting pathological Fuhrman nuclear grading before surgery.

Methods: A retrospective analysis was performed on preoperative PET/CT images of 49 patients whose surgical pathology was ccRCC, 27 of whom were low grade (Fuhrman I/II) and 22 of whom were high grade (Fuhrman III/IV). Radiological parameters and standard uptake value (SUV) indicators on PET and computed tomography (CT) images were extracted by using the LIFEx software package. The discriminative ability of each texture parameter was evaluated through receiver operating curve (ROC). Binary logistic regression analysis was used to screen the texture parameters with distinguishing and diagnostic capabilities and whose area under curve (AUC) > 0.5. DeLong's test was used to compare the AUCs of PET texture parameter model and PET/CT texture parameter model with traditional maximum standardized uptake value (SUVmax) model and the ratio of tumor SUVmax to liver SUVmean (SUL)model. In addition, the models with the larger AUCs among the SUV models and texture models were prospectively internally verified.

Results: In the ROC curve analysis, the AUCs of SUVmax model, SUL model, PET texture parameter model, and PET/CT texture parameter model were 0.803, 0.819, 0.873, and 0.926, respectively. The prediction ability of PET texture parameter model or PET/CT texture parameter model was significantly better than SUVmax model (P = 0.017, P = 0.02), but it was not better than SUL model (P = 0.269, P = 0.053). In the prospective validation cohort, both the SUL model and the PET/CT texture parameter model had good predictive ability, and the AUCs of them were 0.727 and 0.792, respectively.

Conclusion: PET and PET/CT texture parameter models can improve the prediction ability of ccRCC Fuhrman nuclear grade; SUL model may be the more accurate and easiest way to predict ccRCC Fuhrman nuclear grade.
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http://dx.doi.org/10.1007/s00261-021-03246-xDOI Listing
August 2021

Predicting mortality from intracranial hemorrhage in allogeneic hematopoietic stem cell transplantation patients.

Blood Adv 2021 Aug 27. Epub 2021 Aug 27.

Peking University People's Hospital, Peking University Institute of Hematology; National Clinical Research Center for Hematologic Disease; Beijing Key Laboratory of Hematopoietic Stem Cell Transplan, Beijing, China.

Intracranial hemorrhage (ICH) is a rare but fatal central nervous system complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, factors that are predictive of early mortality in patients who develop ICH after undergoing allo-HSCT have not been systemically investigated. From January 2008 to June 2020, 70 allo-HSCT patients with ICH diagnosis formed the derivation cohort. Forty-one allo-HSCT patients with ICH diagnosis were collected from 12 other medical centers during the same period, and they comprised the external validation cohort. We used these 2 cohorts to develop and validate a grading scale that enables the prediction of 30-day mortality from ICH in all-HSCT patients. Four predictors, lactate dehydrogenase level, albumin level, white blood cell count and disease status, were retained in the multivariable logistic regression model, and a simplified grading scale, termed the LAWS score, was developed. The LAWS score was adequately calibrated (Hosmer-Lemeshow test, p>0.05) in both cohorts. It had good discrimination power in both the derivation cohort (C-statistic of 0.859, 95% CI 0.776-0.945) and the external validation cohort (C-statistic of 0.795, 95% CI 0.645-0.945). The LAWS score is the first scoring system capable of predicting the 30-day mortality from ICH in allo-HSCT patients. It showed good performance in identifying allo-HSCT patients at increased risk of early mortality after ICH diagnosis. We anticipate that it would help risk-stratify allo-HSCT patients with ICH and facilitate future studies on developing individualized and novel interventions for patients within different LAWS risk groups.
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http://dx.doi.org/10.1182/bloodadvances.2021004349DOI Listing
August 2021

A unique death pathway keeps RIPK1 D325A mutant mice in check at embryonic day 10.5.

PLoS Biol 2021 Aug 26;19(8):e3001304. Epub 2021 Aug 26.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.

Tumor necrosis factor receptor-1 (TNFR1) signaling, apart from its pleiotropic functions in inflammation, plays a role in embryogenesis as deficiency of varieties of its downstream molecules leads to embryonic lethality in mice. Caspase-8 noncleavable receptor interacting serine/threonine kinase 1 (RIPK1) mutations occur naturally in humans, and the corresponding D325A mutation in murine RIPK1 leads to death at early midgestation. It is known that both the demise of Ripk1D325A/D325A embryos and the death of Casp8-/- mice are initiated by TNFR1, but they are mediated by apoptosis and necroptosis, respectively. Here, we show that the defects in Ripk1D325A/D325A embryos occur at embryonic day 10.5 (E10.5), earlier than that caused by Casp8 knockout. By analyzing a series of genetically mutated mice, we elucidated a mechanism that leads to the lethality of Ripk1D325A/D325A embryos and compared it with that underlies Casp8 deletion-mediated lethality. We revealed that the apoptosis in Ripk1D325A/D325A embryos requires a scaffold function of RIPK3 and enzymatically active caspase-8. Unexpectedly, caspase-1 and caspase-11 are downstream of activated caspase-8, and concurrent depletion of Casp1 and Casp11 postpones the E10.5 lethality to embryonic day 13.5 (E13.5). Moreover, caspase-3 is an executioner of apoptosis at E10.5 in Ripk1D325A/D325A mice as its deletion extends life of Ripk1D325A/D325A mice to embryonic day 11.5 (E11.5). Hence, an unexpected death pathway of TNFR1 controls RIPK1 D325A mutation-induced lethality at E10.5.
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http://dx.doi.org/10.1371/journal.pbio.3001304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389420PMC
August 2021

Molecular characteristics of single patient-derived glioma stem-like cells from primary and recurrent glioblastoma.

Anticancer Drugs 2021 Aug 20. Epub 2021 Aug 20.

Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou Department of Clinical Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Glioblastoma has high recurrence, while the sensitivity of recurrent glioblastoma to chemotherapy is lower than that of primary glioblastoma. Moreover, there is no standardized treatment for recurrent glioblastoma. Unfortunately, the biological mechanism of recurrent glioblastoma is still unclear, and there are few related studies. We compared the phenotypes of clinical glioblastoma specimens, in-vitro cultured glioma stem-like cells (GSCs) and patient-derived xenograft tumor (PDX) models to explore the molecular genetic characteristics of primary and recurrent glioblastoma from the same patient. In vitro, SU5-2, GSCs derived from recurrent glioblastoma specimens, had stronger proliferative activity and self-renewal ability. Meanwhile, SU5-2 was more resistant to temozolomide and invasive than SU5-1, which derived from primary glioblastoma specimens. Further analysis of the expression of costimulatory molecules showed that the expression of B7-H1, B7-H2 and B7-H3 of SU5-2 were upregulated. In vivo, Kaplan-Meier survival curve analysis showed that the median survival of the recurrent PDX group was worse. The results of gene detection in vitro, PDX model and clinical samples were consistent. Our results showed that the GSCs based on glioblastoma specimens and the PDX models could replicate the main molecular genetic characteristics of original tumors, which provided a reliable experimental platform for both tumor translation kinds of research and screening of molecular therapeutic targets.
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http://dx.doi.org/10.1097/CAD.0000000000001217DOI Listing
August 2021

Tear dynamics testing and quantitative proteomics analysis in patients with chronic renal failure.

J Proteomics 2021 Sep 17;248:104351. Epub 2021 Aug 17.

Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, China. Electronic address:

Ocular surface changes may develop in patients with chronic renal failure (CRF) undergoing hemodialysis. In recent years, an association of CRF with dry eye syndrome has been emphasized. However, tear proteomics of CRF patients has not been analyzed. Here, we performed systematic profiling of the tear film proteins in CRF patients through use of isobaric tags for relative and absolute quantitative (iTRAQ) MS/MS, aiming to identify associations between dry eye symptoms and expression of tear proteomic changes in patients with CRF undergoing hemodialysis. Twenty CRF patients and ten healthy subjects underwent a series of ophthalmic examinations. Tear samples from the participants were analyzed by iTRAQ approach. A total of 1139 tear proteins were screened, and 212 differentially expressed proteins were identified. The pattern changes included 77 whose expression levels were upregulated (fold increase >1.2) whereas 135 others that were downregulated (fold decrease <1/1.2). Bioinformatics analysis showed that these proteins were significantly enriched in lipid metabolism, inflammatory, and immune response pathways. Furthermore, APOA1, APOA4, APOB, APOE, S100A8, S100A9, S100A4, HSP90B and other molecules were significantly changed. Our study elucidated the characteristics of tear dynamics and protein markers in CRF patients undergoing hemodialysis. Significance: Despite the association of chronic renal failure (CRF) with dry eye disease, there are no reports describing potentially important differentially expressed tear proteins in CRF patients undergoing hemodialysis. It is still a challenge to obtain a comprehensive description of the pathogenesis of dry eye in CRF patients which hinders establishing a patient specific therapeutic scheme. Our study is the first iTRAQ proteomics analysis of the tears of patients with CRF, which reveals the changes in the protein expression profile in CRF patients afflicted with dry eye disease. The identity was verified of some relevant differentially expressed proteins, and they may be candidate diagnostic markers of dry eye disease in patients with CRF. These tear film protein constituents found in hemodialysis patients can be of important clinical significance in treating this condition. SIGNIFICANCE: Despite the association of chronic renal failure (CRF) with dry eye disease, there are no reports describing potentially important differentially expressed tear proteins in CRF patients undergoing hemodialysis. It is still a challenge to obtain a comprehensive description of the pathogenesis of dry eye in CRF patients which hinders establishing a patient specific therapeutic scheme. Our study is the first iTRAQ proteomics analysis of the tears of patients with CRF, which reveals the changes in the protein expression profile in CRF patients afflicted with dry eye disease. The identity was verified of some relevant differentially expressed proteins, and they may be candidate diagnostic markers of dry eye disease in patients with CRF. These tear film protein constituents found in hemodialysis patients can be of important clinical significance in treating this condition.
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http://dx.doi.org/10.1016/j.jprot.2021.104351DOI Listing
September 2021

Evaluation of autofluorescence visualization system in the delineation of oral squamous cell carcinoma surgical margins.

Photodiagnosis Photodyn Ther 2021 Aug 16;36:102487. Epub 2021 Aug 16.

Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing 210029, China; Depatment of Oral and Maxillofacial Surgery, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address:

Introduction: Delineating the margins of Oral squamous cell carcinoma (OSCC) is a critical step for optimaltumor resection. The aim of this study was to evaluate the accuracy of lesion surgical margin identification using autofluorescence visualization.

Materials And Methods: Thirty patients with OSCC were included in this study. For each lesion, the fluorescence loss boundary was determined using VELscope before ablative surgical resection (with a 1.5-2cm safety margin) was performed. A total of 126 samples were obtained from 30 surgical specimens, each containing the tissue from the fluorescence loss boundary to surgical margin. The status of each sample was determined by oral pathologists and the staining intensities of Ki-67, E-cadherin, and Vimentin at the fluorescence loss boundary and surgical margin were evaluated by immunohistochemistry.

Results: Fluorescence loss regions were identified in all patients. Of the 126 samples collected, HE staining identified 77 normal epithelia (61.1%), 26 mild dysplasia (20.6%), 17 severe dysplasia (13.4%) and 6 carcinomas in situ (4.9%). A significant correlation was found between the differentiation grade of tumor cells and the pathological status of the surgical marginal specimens (P<0.05). Forty-two of the 126 samples were randomly selected for further immunohistochemical staining. No significant differences were seen in Ki-67, E-cadherin, or Vimentin expression at the fluorescence loss boundary or surgical margin, however, the proteins' expression level was positively correlated with the degree of dysplasia (P<0.01).

Conclusion: Autofluorescence visualization has potential as a simple surgical margin setting device for OSCC and may help delineate the superficial area of OSCC with acceptable accuracy. However, when considering the inherent limitations of this system, we suggest that the approach should only be applied under certain conditions, such as when dealing with superficial, well-differentiated lesions.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102487DOI Listing
August 2021

Spider Web-Inspired Graphene Skeleton-Based High Thermal Conductivity Phase Change Nanocomposites for Battery Thermal Management.

Nanomicro Lett 2021 Aug 18;13(1):180. Epub 2021 Aug 18.

Shanghai Key Lab of Electrical Insulation and Thermal Ageing, The State Key Laboratory of Metal Matrix Composites, Department of Polymer Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.

Phase change materials (PCMs) can be used for efficient thermal energy harvesting, which has great potential for cost-effective thermal management and energy storage. However, the low intrinsic thermal conductivity of polymeric PCMs is a bottleneck for fast and efficient heat harvesting. Simultaneously, it is also a challenge to achieve a high thermal conductivity for phase change nanocomposites at low filler loading. Although constructing a three-dimensional (3D) thermally conductive network within PCMs can address these problems, the anisotropy of the 3D framework usually leads to poor thermal conductivity in the direction perpendicular to the alignment of fillers. Inspired by the interlaced structure of spider webs in nature, this study reports a new strategy for fabricating highly thermally conductive phase change composites (sw-GS/PW) with a 3D spider web (sw)-like structured graphene skeleton (GS) by hydrothermal reaction, radial freeze-casting and vacuum impregnation in paraffin wax (PW). The results show that the sw-GS hardly affected the phase transformation behavior of PW at low loading. Especially, sw-GS/PW exhibits both high cross-plane and in-plane thermal conductivity enhancements of ~ 1260% and ~ 840%, respectively, at an ultra-low filler loading of 2.25 vol.%. The thermal infrared results also demonstrate that sw-GS/PW possessed promising applications in battery thermal management.
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http://dx.doi.org/10.1007/s40820-021-00702-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374024PMC
August 2021

Distress, Appraisal, and Coping Among the Frontline Healthcare Provider Redeployed to the Epicenter in China During COVID-19 Pandemic.

Front Psychol 2021 30;12:678369. Epub 2021 Jul 30.

Shenzhen Hospital, University of Hong Kong, Shenzhen, China.

The central issue of this research is to evaluate the extent of cognitive appraisal and coping processes within the pandemic encounter and determines their influence on frontline healthcare providers who had been dispatched to the coronavirus disease 2019 (COVID-19) epicenter (HPDE) distress symptoms. An electronic survey of the HPDE and frontline healthcare providers who worked in their original medical facility (HPOF) was conducted from March 1 to 15, 2020. Two variables, appraisal (measured with an 18-item questionnaire) and coping (measured The Brief Cope questionnaire), were used in the analysis to explain distress symptoms (Impact of Event Scale-Revised). A total of 723 eligible respondents completed the survey with a response rate of 57.3% (351 HPDE and 372 HPOF). The mean IES-R scores of HPDE respondents were 26.47 ± 11.7. Of HPDE respondents, 246 (70.09%) reported distress symptoms (score 9-88). The scores of intrusion, avoidance, and hyperarousal for HPDE were 10.28 ± 4.7, 8.97 ± 4.3, and 7.20 ± 3.2, respectively. The respondents had higher scores in overall distress and three subscales than HPOF. Appraisal and coping variables explained 77% of the distress variance. Five appraisal variables (health of self, health of family/others, virus spread, vulnerability or loss of control, and general health) were positively associated with distress symptoms. Four coping variables (active coping, positive reframing, self-distraction, and behavioral disengagement) were negatively associated with distress level, whereas self-blame was positively associated with distress symptoms. Regarding the appraisal, the scores of HPDE were significantly higher than HPOF (all -values < 0.05), whereas being isolated was not significantly different between HDPE nurses and HPOF nurses. HPDE was significantly more likely to use humor, emotional support, instrumental support, self-distractions, venting, substance use, denial, behavioral disengagement, and self-blame ( < 0.05), whereas HPOF was significantly more likely to use active coping and acceptance ( < 0.05). HPDE doctors were significantly more likely than nurses to use active coping and acceptance ( < 0.05), whereas HPDE nurses were significantly more likely to use emotional support and use self-blame ( < 0.05). Frontline healthcare providers who had been dispatched to the COVID-19 epicenter respondents had a higher distress level. Therefore, we should provide proactive psychological support based on specific appraisal and coping variables.
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http://dx.doi.org/10.3389/fpsyg.2021.678369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362893PMC
July 2021

SRC3 acetylates calmodulin in the mouse brain to regulate synaptic plasticity and fear learning.

J Biol Chem 2021 Aug 4;297(3):101044. Epub 2021 Aug 4.

Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, China. Electronic address:

Protein acetylation is a reversible posttranslational modification, which is regulated by lysine acetyltransferase (KAT) and lysine deacetyltransferase (KDAC). Although protein acetylation has been shown to regulate synaptic plasticity, this was mainly for histone protein acetylation. The function and regulation of nonhistone protein acetylation in synaptic plasticity and learning remain largely unknown. Calmodulin (CaM), a ubiquitous Ca sensor, plays critical roles in synaptic plasticity such as long-term potentiation (LTP). During LTP induction, activation of NMDA receptor triggers Ca influx, and the Ca binds with CaM and activates calcium/calmodulin-dependent protein kinase IIα (CaMKIIα). In our previous study, we demonstrated that acetylation of CaM was important for synaptic plasticity and fear learning in mice. However, the KAT responsible for CaM acetylation is currently unknown. Here, following an HEK293 cell-based screen of candidate KATs, steroid receptor coactivator 3 (SRC3) is identified as the most active KAT for CaM. We further demonstrate that SRC3 interacts with and acetylates CaM in a Ca and NMDA receptor-dependent manner. We also show that pharmacological inhibition or genetic downregulation of SRC3 impairs CaM acetylation, synaptic plasticity, and contextual fear learning in mice. Moreover, the effects of SRC3 inhibition on synaptic plasticity and fear learning could be rescued by 3KQ-CaM, a mutant form of CaM, which mimics acetylation. Together, these observations demonstrate that SRC3 acetylates CaM and regulates synaptic plasticity and learning in mice.
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http://dx.doi.org/10.1016/j.jbc.2021.101044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390517PMC
August 2021

Multifunctional Zn-Ln (Ln = Eu and Tb) heterometallic metal-organic frameworks with highly efficient I capture, dye adsorption, luminescence sensing and white-light emission.

Dalton Trans 2021 Sep 6;50(33):11619-11630. Epub 2021 Aug 6.

College of Chemistry and Materials Science, Key Laboratory of Green and Precise Synthetic Chemistry and Applications, Ministry of Education Huaibei Normal University, Anhui 235000, China.

A new family of isostructural 3d-4f heterometallic metal-organic frameworks (HMOFs), [ZnEuTb(TZI)(DMA)(HO)]·4DMA [x = 0 (1), 0.3 (2), 0.6 (3), 0.9 (4), 1 (5), 1.2 (6), 1.5 (7), 1.8 (8), 2 (9)], has been synthesized using the 5-(4-(tetrazol-5-yl) phenyl)isophthalic acid (HTZI) ligand, Ln ions and Zn ions under solvothermal conditions. All HMOFs exhibit a (3,3,4,5,5)-connected 6·6(4·6·8)(4·6·8)(4·6·8) topology, which features three different types of motifs: one is a mononuclear Zn ion and the other two motifs are binuclear [Zn(COO)Ln] clusters. The adsorption experiments indicate that ZnTb (1) could efficiently remove almost all I from cyclohexane solution after 12 h and also showed better adsorption towards neutral red (NR) dye (adsorption: only the ZnTb (1) was taken as one representative). Simultaneously, the luminescence sensing showed that ZnTb (1) and ZnEu (9) have excellent response and sensitivity towards pollutants such as Fe ions and 2,4,6-trinitrophenol (TNP) with high selectivity and a fairly low limit of detection through luminescence quenching effect. Moreover, seven trimetallic-doped HMOFs 2-8 analogues of ZnLn (single) HMOFs were designed and prepared, showing different changes of luminescent color. More interestingly, ZnEuTb (7) with white-light emission was fabricated by doping relative concentrations of Eu and Tb ions. To the best of our knowledge, ZnEuTb (7) represents a novel kind of heterometallic ZnLn HMOFs with white-light emission. It could be deduced that the excellent characteristics, namely strong typical luminescence emission of Zn and Ln ions, microporous channels, active open metal sites (tetra-coordinated Zn-metal sites), and uncoordinated carboxylate O atoms and uncoordinated tetrazolate N atoms, made the above HMOFs an ideal platform for adsorption, luminescence sensing, and white-light emission. More significantly, these HMOFs are the first reported Zn-Ln heterometallic materials with the HTZI ligand.
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http://dx.doi.org/10.1039/d1dt01968fDOI Listing
September 2021

Acetylation of calmodulin regulates synaptic plasticity and fear learning.

J Biol Chem 2021 Jul 31;297(3):101034. Epub 2021 Jul 31.

Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, China. Electronic address:

Synaptic plasticity is critical for brain function, including learning and memory. It is regulated by gene transcription and protein synthesis as well as posttranslational modifications at synapses. Although protein acetylation has been shown to be involved in the regulation of synaptic plasticity, this was mainly for histone protein acetylation. To investigate whether acetylation of nonhistone proteins is important for synaptic plasticity, we analyzed mouse brain acetylome and found that calmodulin (CaM), a ubiquitous Ca sensor, was acetylated on three lysine residues, which were conserved across species. NMDA receptor-dependent long-term potentiation (LTP) is considered the most compelling form of synaptic plasticity. During LTP induction, activation of NMDA receptor triggers Ca influx, and the Ca binds with CaM and activates calcium/calmodulin-dependent protein kinase IIα (CaMKIIα), which is essential for LTP induction. By using home-generated and site-specific antibodies against acetylated CaM, we show that CaM acetylation is upregulated by neural activities in an NMDA receptor-dependent manner. Moreover, mutation of acetyllysines in CaM1 proteins disrupts synaptic plasticity and fear learning in a mouse model. We further demonstrate that acetylation of CaM reduces the binding free energy and increases the binding affinity toward CaMKIIα, a protein kinase pivotal to synaptic plasticity and learning. Taken together, our results demonstrate importance of CaM acetylation in regulating synaptic plasticity and learning.
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http://dx.doi.org/10.1016/j.jbc.2021.101034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383114PMC
July 2021

CC16-TNF-α negative feedback loop formed between Clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation.

Aging (Albany NY) 2021 08 2;13(15):19442-19459. Epub 2021 Aug 2.

Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao 266011, China.

CC16 is almost exclusively expressed in non-ciliated epithelial Clara cells, and widely used as a Clara cell marker. Diesel exhaust particles (DEPs), the fine particulate matters produced by diesel engines, cause or exacerbate airway-related diseases. Our previous study documented that DEP inhibits the CC16 expression in the immortalized mouse Clara cell line through methylation of C/EBPα promoter. However, the molecular mechanism by which DEP regulates CC16 secretion is unclear. Here, we isolated CC16 containing Clara cells (CC16) from human distal lung, and found that DEP inhibited CC16 secretion from CC16 cells via methylation of C/EBPα and inhibition of Munc18b transcription. CC16 cell conditioned media containing different concentrations of CC16 was prepared and used for culture of airway epithelial cells BEAS-2B with no expression of CC16. A positive correlation was observed between CC16 level and DEP-induced autophagy activity, and a negative correlation between CC16 level and DEP-induced pro-inflammatory cytokine TNF-α, IL-6, and IL-8 level, suggesting that CC16 might mitigate DEP-induced inflammation via promoting autophagy in BEAS-2B cells. This result was further confirmed by adding recombinant CC16 to BEAS-2B cells exposed to DEP. Moreover, CC16 level was significantly increased when CC16 cells were cultured in BEAS-2B cell conditioned medium containing TNF-α or the normal medium supplemented with recombinant TNF-α, suggesting that TNF-α induced CC16 production and secretion from CC16 cells. Collectively, these data point that CC16 and TNF-α form a negative feedback loop, and this negative feedback loop between Clara cells and normal airway epithelial cells protects against DEP exposure-induced inflammation.
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http://dx.doi.org/10.18632/aging.203356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386526PMC
August 2021

Effect of the Re-Vitrification of Embryos at Different Stages on Embryonic Developmental Potential.

Front Endocrinol (Lausanne) 2021 14;12:653310. Epub 2021 Jul 14.

Chongqing Key Laboratory of Human Embryo Engineering, Chongqing Reproductive and Genetics Institute, Chongqing Health Center for Women and Children, Chongqing, China.

Background: Using re-vitrified human embryos for frozen-warmed embryo transfer (FET) is a valuable option when there are no other cryopreserved embryos to use, however, except for the PGT cases, no published data are available for FET with human embryos that were re-vitrified at different developmental stages.

Objective: To evaluate the effect of re-vitrification of embryos at different stages on embryonic developmental potential.

Method: This study included clinical retrospective and mouse experimental studies. For the retrospective study, a total of 25 FET cycles with re-vitrified day 3 embryos (re-vitrification group 1) and 54 FET cycles with re-vitrified day 5 blastocysts (re-vitrification group 2) between January 2015 and December 2019 were included in this study. The corresponding FET cycles with once-vitrified embryos were identified using propensity score (PS) matching according to the time of embryo transfer. For the mouse experimental study, we divided embryos into 5 groups: fresh (group 1), vitrified at the 8-cell stage (group 2), vitrified at the early blastocyst stage (group 3), vitrified at the 8-cell stage, and re-vitrified at the 8-cell (group 4) or early blastocyst stage (group 5). The fresh embryos was selected as control group. The primary outcome in this study was delivery outcomes.

Results: No significant difference in delivery rate was detected between re-vitrification group 1 (24.00%) and the corresponding control group (28.00%). However, re-vitrification group 2 (46.3%) showed a significant decrease in delivery rate compared with the two corresponding control groups (63.89% and 64.12%) ( < 0.05). Our experiment using mouse embryos also confirmed the clinical data, and showed that re-vitrification at the blastocyst stage following the first round of vitrification at the 8-cell stage reduced the delivery rate. In addition, both re-vitrified groups showed a significantly higher expression level of . However, only re-vitrification at the blastocyst stage increased the expression level of

Conclusions: Re-vitrification at the 8-cell and blastocyst stages has different effects on embryonic developmental potential, as re-vitrification at blastocyst stage following a previous vitrification at 8-cell stage reduced the delivery rate, while vitrification at the 8-cell stage twice achieved comparable pregnancy outcomes to the once-vitrified group.
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http://dx.doi.org/10.3389/fendo.2021.653310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317612PMC
July 2021

Oncogenic roles of lncRNA BLACAT1 and its related mechanisms in human cancers.

Biomed Pharmacother 2020 Oct 17;130:110632. Epub 2020 Sep 17.

Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China. Electronic address:

Long non-coding RNAs (lncRNAs) play indispensable roles in mediating regulation of epigenetics, and their dysregulation is strongly associated with the initiation and progression of human cancers. Recently, lncRNA bladder cancer-associated transcript 1 (BLACAT1) has been observed to exert oncogenic effects on cancers, including glioma, breast cancer, lung cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, ovarian cancer, cervical cancer and osteosarcoma. Additional mechanical analyses have uncovered that lncRNA BLACAT1 is positively correlated with tumor stage, lymph node metastasis and distant metastasis of primary tumors via involvement with various cellular activities, thus leading to poor overall survival and progression-free survival (PFS). In this review, we generalize the oncogenic roles of BLACAT1 in multiple human cancers through correlation with clinical implications and cellular activities. Moreover, we forecast its potential clinical application as a novel biomarker and a promising therapeutic target for cancers.
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http://dx.doi.org/10.1016/j.biopha.2020.110632DOI Listing
October 2020

IFNγ-mediated repression of system xc drives vulnerability to induced ferroptosis in hepatocellular carcinoma cells.

J Leukoc Biol 2021 08;110(2):301-314

Department of Gastroenterology, Shanghai Tenth People's Hospital Affiliated to Tongji University, Tongji University, School of Medicine, Shanghai, China.

IFNγ released from CD8 T cells or natural killer cells plays a crucial role in antitumor host immunity. Several studies have found that IFNγ is involved in regulating tumor cell proliferation and apoptosis. However, few studies have examined its role in cell ferroptosis. Here, we found that IFNγ treatment enhanced glutathione depletion, promoted cell cycle arrested in G0/G1 phase, increased lipid peroxidation, and sensitized cells to ferroptosis activators. Additionally, IFNγ down-regulated the mRNA and protein levels of SLC3A2 and SLC7A11, two subunits of the glutamate-cystine antiporter system xc via activating the JAK/STAT pathway in hepatocellular carcinoma (HCC) cell lines. Furthermore, IFNγ increased reactive oxygen species levels and decreased mitochondiral membrane potential in Bel7402 and HepG2 cells. These changes were accompanied by decreased system xc activity. Cancer cells exposed to TGFβ1 for 48 h showed sensitization to IFNγ + erastin-induced ferroptosis, with decreased system xc expression. In conclusion, IFNγ repressed system xc activation via activating JAK/STAT signaling. Additionally, enhanced lipid peroxidation was associated with altered mitochondrial function in HCC cells. Our findings identified a role for IFNγ in sensitizing HCC cells to ferroptosis, which provided new insights for applying IFNγ as a cancer treatment.
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http://dx.doi.org/10.1002/JLB.3MA1220-815RRRDOI Listing
August 2021

Effects of anthracnose on C, N and P stoichiometry in the shoot of forage oat in north Shanxi Province, China.

Ying Yong Sheng Tai Xue Bao 2021 Jul;32(7):2477-2484

Datong Qianye Pasture Science and Technology Limited Company, Tianzhen 038200, Shanxi, China.

The C, N and P stoichiometry are helpful to understand the capacity of carbon assimilation and nutrient utilization efficiency during plant growth, as well as to diagnose nutrient limitation status. There is still a knowledge gap about the effects of disease on plant stoichiometry. In this study, forage oats () suffering from anthracnose were the object of research conducted in north Shanxi Province. The C, N and P stoichiometry in the shoot of oat were examined at different degrees of disease occurrence. We analyzed the relationship of plant stoichiometry with disease duration, cultivar, and cultivation methods. The results showed that C, N and P contents decreased with the increasing degree of disease occurrence. The C, N and P contents in the plants with serious disease were significantly lower than that of healthy plants with a decreasing rate of 5.4%, 20.0% and 24.2%, respectively. C:N and C:P showed an increasing trend with the increases of the degree of disease occurrence. C:N and C:P of the plants with serious disease were significantly increased by 18.5% and 22.2%, respectively, than that of healthy plants. There was no significant difference for C content among different sampling sites, which indicated that the three varieties of forage oats might have disease tolerance capacity to ensure crop production. However, the stoichiometric values of N and P varied from place to place. The longer the disease duration was, the more reduction of N and P contents. Compared with monoculture oats, the P utilization efficiency of mixture oats was decreased by anthracnose. In summary, anthracnose had negative impacts on carbon assimilation capacity of forage oats in northern Shanxi. Anthracnose increased the restriction of N and P nutrition on the aboveground parts. However, anthracnose significantly improved N and P utilization efficiency. For the production practice, it was recommended to take necessary control measures to reduce the adverse effects of diseases on the economic benefits and ecological functions of forage oats.
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http://dx.doi.org/10.13287/j.1001-9332.202107.027DOI Listing
July 2021

[Efficacy and safety of stress ulcer prophylaxis in septic patients: a retrospective cohort study based on large database].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jun;33(6):641-647

Department of Emergency, Shenzhen University General Hospital, Shenzhen 518055, Guangdong, China.

Objective: To evaluate the effects and safety of stress ulcer prophylaxis (SUP) versus no prophylaxis in adult septic patients at risk of gastrointestinal bleeding (GIB).

Methods: A retrospective cohort study was conducted, the data was extracted from Electronic Intensive Care Unit-Collaborative Research Database (eICU-CRD). All patients who received proton pump inhibitor (PPI) or H receptor antagonist (HRA) or combined/sequential use for SUP within the first 48 hours of intensive care unit (ICU) admission were enrolled in the SUP group, those who did not received any SUP were enrolled in the non-SUP group. The differences of in-hospital mortality, length of ICU stay (LOS), the incidence of GIB and secondary infection complications between the two groups were compared. Propensity score matching (PSM) was conducted to balance the distributions of study variables between the two groups. Further subgroup analysis was performed according to whether SUP was used for more than 3 days. Multivariate Logistic regression analysis was conducted to analyze the factors influencing the outcome of GIB and secondary pneumonia.

Results: A total of 11 413 patients were included in the final analysis, with 9 799 patients in SUP group and 1 614 in non-SUP group. A 1:1 PSM created 1 600 patients in each cohort. (1) Baseline characteristics: compared with SUP group, patients in non-SUP group were older [years old: 69.0 (56.0, 80.0) vs. 67.0 (56.0, 78.0)], acute physiology and chronic health evaluation IV (APACHE IV) score and sequential organ failure assessment (SOFA) score were significantly lower [APACHE IV score: 65 (50, 73) vs. 72 (58, 87), SOFA score: 5 (4, 7) vs. 7 (5, 9)], higher rates of underlying diseases such as hypertension and diabetes [hypertension: 15.6% (252/1 614) vs. 12.2% (1 196/9 779), diabetes: 4.5% (72/1 614) vs. 3.3% (325/9 779), both P < 0.05], indicating that patients in the SUP group were more severe. (2) Comparison of clinical outcome: before PSM, SUP group had significantly higher in-hospital mortality [17.2% (1 688/9 799) vs. 10.9% (176/1 614)], longer LOS [days: 4.4 (2.9, 7.7) vs. 3.1 (2.5, 4.3)], and higher incidence of secondary pneumonia than non-SUP group [11.3% (1 112/9 799) vs. 6.8% (110/1 614)], with significant differences (all P < 0.05). There was no significant difference in the incidence of GIB and Clostridium difficile infection (CDI) between the two groups. After PSM, no significant differences were observed between the two groups with regard to in-hospital mortality, incidence of GIB and CDI. However, the SUP group had longer LOS [days: 3.9 (2.8, 6.6) vs. 3.1 (2.5, 4.3)], and higher incidence of secondary pneumonia [10.9% (174/1 600) vs. 6.8% (108/1 600)] compared with non-SUP group, the differences were statistically significant (all P < 0.05). Subgroup analysis showed that compared with SUP < 3 days group, patients in SUP ≥ 3 days group had higher disease severity score [APACHE IV score: 66 (51, 79) vs. 62 (48, 72), SOFA score: 6 (4, 8) vs. 5 (4, 7), both P < 0.05], in addition, patients in SUP ≥ 3 days group had higher in-hospital mortality, incidence of GIB and secondary pneumonia (16.4% vs. 10.7%, 6.1% vs. 1.8%, 19.0% vs. 8.6%, respectively), and longer ICU LOS [days: 6.6 (4.1, 11.8) vs. 3.5 (2.6, 5.3), all P < 0.05]. (3) Multivariate Logistic regression analysis showed that SUP ≥ 3 days group was associated with more GIB than that of non-SUP group [odds ratio (OR) = 1.84, 95% confidence interval (95%CI) was 1.07-3.08, P = 0.030], and the incidence of GIB was less in SUP < 3 days group than that of non-SUP group (OR = 0.57, 95%CI was 0.34-0.94, P = 0.020). When compared with non-SUP group, the risk of secondary pneumonia was increased both in SUP ≥ 3 days group and SUP < 3 days group (OR values were 2.95 and 1.34, 95%CI were 2.10-4.13 and 1.01-1.77, P values were < 0.001 and 0.040, respectively).

Conclusions: Among critically ill adult patients with sepsis at risk for GIB, SUP showed no effect on reducing in-hospital mortality, the rate of GIB and CDI, but was associated with increased risk of secondary pneumonia and prolonged LOS.
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http://dx.doi.org/10.3760/cma.j.cn121430-20210402-00504DOI Listing
June 2021

Ti C T MXene Conductive Layers Supported Bio-Derived Fe Se /MXene/Carbonaceous Nanoribbons for High-Performance Half/Full Sodium-Ion and Potassium-Ion Batteries.

Adv Mater 2021 Aug 19;33(34):e2101535. Epub 2021 Jul 19.

Sino-Russian International Joint Laboratory for Clean Energy and Energy Conversion Technology, College of Physics, International Center of Future Science, Jilin University, Changchun, 130012, P. R. China.

Owing to their cost-effectiveness and high energy density, sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs) are becoming the leading candidates for the next-generation energy-storage devices replacing lithium-ion batteries. In this work, a novel Fe Se heterostructure is prepared on fungus-derived carbon matrix encapsulated by 2D Ti C T MXene highly conductive layers, which exhibits high specific sodium ion (Na ) and potassium ion (K ) storage capacities of 610.9 and 449.3 mAh g at a current density of 0.1 A g , respectively, and excellent capacity retention at high charge-discharge rates. MXene acts as conductive layers to prevent the restacking and aggregation of Fe Se sheets on fungus-derived carbonaceous nanoribbons, while the natural fungus functions as natural nitrogen/carbon source to provide bionic nanofiber network structural skeleton, providing additional accessible pathways for the high-rate ion transport and satisfying surface-driven contribution ratios at high sweep rates for both Na/K ions storages. In addition, in situ synchrotron diffraction and ex situ X-ray photoelectron spectroscopy measurements are performed to reveal the mechanisms of storage and de-/alloying conversion process of Na in the Fe Se /MXene/carbonaceous nanoribbon heterostructure. As a result, the assembled Na/K full cells containing MXene-supported Fe Se @carbonaceous anodes possess stable large-ion storage capabilities.
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http://dx.doi.org/10.1002/adma.202101535DOI Listing
August 2021
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