Publications by authors named "Lu Yao"

1,116 Publications

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[Critical quality attribute assessment of big brand traditional Chinese medicine: modular identification of Tongren Niuhuang Qingxin Pills based on efficacy with chemical properties].

Zhongguo Zhong Yao Za Zhi 2021 Apr;46(7):1606-1615

School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102488, China Engineering Research Center of Chinese Medicine Production and New Drug Development, Ministry of Education Beijing 102488,China.

Identification of critical quality attribute(CQA) is crucial in quality control of Tongren Niuhuang Qingxin Pills(TRNHQXP). In this study, 661 active components in TRNHQXP were selected by liquid chromatography-mass spectrometry(LC-MS) and network pharmacology based on reported data and TCMSP, BATMAN-TCM, and TCMID databases, as well as mass spectrometry data, and 1 413 targets of the active components were obtained through SwissTargetPrediction. The 152 potential targets obtained from the intersection of predicted targets with 456 stroke targets underwent functional enrichment analysis by Metascape. The 27 Chinese medicinals in TRNHQXP were divided into four sets according to efficacies. Thirty-seven key targets in the blood-activating and stasis-resolving set and 41 in the tonifying set were screened out. On the basis of these potential key targets, 137 potential key CQA of TRNHQXP for stroke were reversely predicted. This study revealed the possible mechanism of TRNHQXP in treating stroke and established a modular identification method for the potential CQA of big brand traditional Chinese medicine(TCM) based on efficacies and chemical properties. Consequently, the CQA of TRNHQXP were identified by this method, which has provided a reference for the following experimental studies of CQA.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210218.301DOI Listing
April 2021

[Critical quality attribute assessment of big brand traditional Chinese medicine: quality control of Tongren Niuhuang Qingxin Pills in texture and sensory attributes].

Zhongguo Zhong Yao Za Zhi 2021 Apr;46(7):1598-1605

School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102488, China Engineering Research Center of Chinese Medicine Production and New Drug Development, Ministry of Education Beijing 102488, China.

Texture sensory attributes are the key items in quality control of Chinese medicinal honeyed pills. The purpose of this study is to develop a quality control method for assessing the texture sensory attributes of Chinese medicinal honeyed pills based on real-world Tongren Niuhuang Qingxin pilular masses and finished products. First, parameters of texture profile analysis(TPA) were optimized through single factor and central composite design(CCD) experiments to establish a detection method for texture sensory attri-butes of Tongren Niuhuang Qingxin Pills. The results showed that the established detection method was stable and reliable, with the optimal parameters set up as follows: deformation percentage of 70%, detection speed at 30 mm·min~(-1), and interval time of 15 s. Furthermore, 540 data points yielded form six texture sensory attributes of pills from 30 batches were subjected to multivariate statistical process control(MSPC) with Hotelling T~2 and squared prediction error(SPE) control charts to establish the quality control method of Tongren Niuhuang Qingxin Pills. This study is expected to provide a reference for improving the quality control system of Chinese medicinal honeyed pills.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210309.301DOI Listing
April 2021

[Critical quality attribute assessment of big brand traditional Chinese medicine: study on NIR field detection method of chemical properties of moisture in Tongren Niuhuang Qingxin Pills].

Zhongguo Zhong Yao Za Zhi 2021 Apr;46(7):1592-1597

School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102488, China Engineering Research Center of Chinese Medicine Production and New Drug Development, Ministry of Education Beijing 102488, China.

For the field detection problems of critical quality attribute(CQA) of moisture content in traditional Chinese medicine(TCM) manufacturing process, big brand TCM Tongren Niuhuang Qingxin Pills were used as the carrier, to establish a moisture content NIR field detection model with or without cellophane in real world production with use of near infrared(NIR) spectroscopy combined with stoichiometry. With the moisture content determined by drying method as reference value, the partial least square method(PLS) was used to analyze the correlation between the spectrum and the moisture reference value. Then the spectral pretreatment methods were screened and optimized to further improve the accuracy and stability of the model. The results showed that the best quantitative model was developed by the spectral data pretreatment of standard normal variate(SNV) with the latent variable factor number of 2 and 7 of Tongren Niuhuang Qingxin Pills with or without cellophane samples. The prediction coefficient of determination(R_(pre)~2) and standard deviation of prediction(RMSEP) of the model with cellophane samples were 0.765 7 and 0.157 2%; R_(pre)~2 and RMSEP of the model without cellophane samples were 0.772 2 and 0.207 8%. The NIR quantitative models of moisture content of Tongren Niuhuang Qingxin Pills with and without cellophane both showed good predictive performance to realize the rapid, accurate and non-destructive quantitative analysis of moisture content in such pills, and provide a method for the field quality control of the critical chemical attributes of moisture in the manufacturing of big brand TCM.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210205.305DOI Listing
April 2021

[Critical quality attribute assessment of big brand traditional Chinese medicine: visualization of blending process for rare medicines in Tongren Niuhuang Qingxin Pills based on spatial distribution uniformity].

Zhongguo Zhong Yao Za Zhi 2021 Apr;46(7):1585-1591

School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102488, China Engineering Research Center of Chinese Medicine Production and New Drug Development, Ministry of Education Beijing 102488, China.

The spatial distribution uniformity of valuable medicines is the critical quality attribute in the process control of Tongren Niuhuang Qingxin Pills. With the real world sample of the mixed end-point powder of Tongren Niuhuang Qingxin Pills as the research object, hyperspectral imaging technology was used to collect a total of 32 400 data points with a size of 180 pix×180 pix. Spectral angle matching(SAM), classical least squares and mixed tuned matched filtering(MTMF) were used to identify the spatial distribution of rare medicines. MTMF model showed higher identification accuracy, therefore the spatial distribution of the blended intermediates was identified based on the MTMF model. The histogram method was also used to evaluate the spatial distribution uniformity of rare medicines. The results showed that the standard deviation was 4.78, 6.5, 3.48, 1.96, and 3.00 respectively for artificial bezoar, artificial musk, Borneol, Antelope horn and Buffalo horn; the variance was 22.8, 42.3, 12.1, 3.82, and 9.00, and the skewness was 1.26, 1.71, 0.06,-0.86, and 1.04, respectively. The final results showed that the most even blending was achieved in concentrated powder of Borneol, Antelope horn and Buffalo horn, followed by artificial bezoar, and last artificial musk. A visualization method was established for quality attributes of distribution uniformity in blending process of Tongren Niuhuang Qingxin Pills. It could provide evidences of quality control methods in the mixing process of big brand traditional Chinese medicine.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210218.303DOI Listing
April 2021

Lactoferrin Is a Potential Activator of the Vitamin D Receptor in Its Regulation of Osteogenic Activities in C57BL/6J Mice and MC3T3-E1 Cells.

J Nutr 2021 May 12. Epub 2021 May 12.

Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China.

Background: Lactoferrin (LF) has been shown to promote bone anabolism, and the vitamin D receptor (VDR) mediates the effects of vitamin D on bone. We hypothesized that LF improves bone health by increasing VDR expression.

Objectives: We sought to determine the role of VDR activation in LF-induced osteogenic activity in vivo and in vitro and the underlying molecular mechanisms.

Methods: Sixty male C57BL/6J mice (aged 4 wk) were randomly assigned into 6 groups and fed vitamin D-deficient (VDD; 0 IU/kg) or vitamin D-normal diet (VDN; 1000 IU cholecalciferol/kg) and administered placebo or LF (100 or 1000 mg/kg body weight) by gavage for 24 wk. Trabecular bone structure was analyzed using micro-CT, and VDR expression was assessed by immunohistochemistry. In vitro, MC3T3-E1 cells were treated with 100 μg LF/mL to evaluate its effect on VDR expression. Finally, the direct recruitment of LF to the Vdr promoter was confirmed by chromatin immunoprecipitation assay. In addition, cells were transfected with pGL3-basic Vdr vector for monitoring Vdr promoter activation using luciferase assays.

Results: LF supplementation at 100 and 1000 mg/kg revealed an ∼6.5% (P < 0.05) increase in bone mineral density in mice on VDD diet and exhibited an enhanced expression of VDR in bone compared with control. This increased expression of VDR was also observed in the bone of mice on the VDN diet, but the effect was more pronounced in VDD diet. In vitro, compared with the control group, Vdr mRNA expression was 18 times greater (P < 0.05) and peaked at 2 h posttreatment of LF. By cotransfection of the pGL3-basic Vdr vector, LF induced luciferase activity by 30% (P < 0.05) in MC3T3-E1 cells.

Conclusions: In vivo and in vitro, LF, a potential activator of VDR, promotes osteogenesis. This suggests that dairy products, which are rich in LF, may serve as a functional food to improve bone health.
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http://dx.doi.org/10.1093/jn/nxab105DOI Listing
May 2021

USP36-Mediated Deubiquitination of DOCK4 Contributes to the Diabetic Renal Tubular Epithelial Cell Injury Wnt/β-Catenin Signaling Pathway.

Front Cell Dev Biol 2021 23;9:638477. Epub 2021 Apr 23.

Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease but the efficacy of current treatment remains unsatisfactory. The pathogenesis of DKD needs a more in-depth research. Ubiquitin specific proteases 36 (USP36), a member of deubiquitinating enzymes family, has aroused wide concerns for its role in deubiquitinating and stabilizing target proteins. Nevertheless, the role of USP36 in diabetes has never been reported yet. Herein, we identified an increased expression of USP36 both and in diabetic renal tubular epithelial cells (TECs), and its overexpression is related to the enhanced epithelial-to-mesenchymal transition (EMT). Further investigation into the mechanisms proved that USP36 could directly bind to and mediate the deubiquitination of dedicator of cytokinesis 4 (DOCK4), a guanine nucleotide exchange factor (GEF) that could activate Wnt/β-catenin signaling pathway and induce EMT. Our study revealed a new mechanism that USP36 participates in the pathogenesis of DKD, and provided potential intervening targets accordingly.
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http://dx.doi.org/10.3389/fcell.2021.638477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102983PMC
April 2021

Molecular identity of human limbal heterogeneity involved in corneal homeostasis and privilege.

Ocul Surf 2021 May 5. Epub 2021 May 5.

State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China; Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China; Eye Hospital of Shandong First Medical University, Jinan, China. Electronic address:

Purpose: The corneal limbus maintains the homeostasis, immune and angiogenic privilege of cornea. This study aimed to depict the landscape of human limbus tissues by single-cell RNA sequencing (scRNA-seq).

Methods: Single cells of human limbus collected from donor corneas were performed scRNA-seq using 10x Genomics platform, followed by clustering cell types through the t-distributed stochastic neighbor embedding (t-SNE) and unbiased computational informatic analysis. Immunofluorescent staining using human corneas to validate the analysis results.

Results: 47,627 cells acquired from six human limbus were performed scRNA-seq. 14 distinct clusters were identified and 8 cell types were annotated with representative markers. In-depth dissection revealed three limbal epithelial cell subtypes and refined the X-Y-Z hypothesis of corneal epithelial maintenance. We further unveiled two cell states with higher stemness (TP63 and CCL20 cells), and two other differentiated cell states (GPHA2 and KRT6B  cells) in homeostatic limbal stem/progenitor cells (LSPCs) that differ in transcriptional profiles. Cell-cell communication analysis revealed the central role of LSPCs and their bidirectional regulation with various niche cells. Moreover, comparative analysis between limbus and skin deciphered the pivotal contribution of limbal immune cells, vascular and lymphatic endothelial cells to corneal immune and angiogenic privilege.

Conclusions: The human limbus atlas provided valuable resource and foundations for understanding corneal biology, disease and potential interventions.
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http://dx.doi.org/10.1016/j.jtos.2021.04.010DOI Listing
May 2021

IL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy.

J Immunother Cancer 2021 May;9(5)

Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA

Background: Synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are ideal solid tumors for the development of adoptive cellular therapy (ACT) targeting NY-ESO-1, as a high frequency of tumors homogeneously express this cancer-testes antigen. Data from early phase clinical trials have shown antitumor activity after the adoptive transfer of NY-ESO-1-specific T cells. In these studies, persistence of NY-ESO-1 specific T cells is highly correlated with response to ACT, but patients often continue to have detectable transferred cells in their peripheral blood following progression.

Method: We performed a phase I clinical trial evaluating the safety of NY-ESO-1-specific endogenous T cells (ETC) following cyclophosphamide conditioning. Peripheral blood mononuclear cells (PBMCs) from treated patients were evaluated by flow cytometry and gene expression analysis as well as through ex vivo culture assays with and without IL-15.

Results: Four patients were treated in a cohort using ETC targeting NY-ESO-1 following cyclophosphamide conditioning. Treatment was well tolerated without significant toxicity, but all patients ultimately had disease progression. In two of four patients, we obtained post-treatment tumor tissue and in both, NY-ESO-1 antigen was retained despite clear detectable persisting NY-ESO-1-specific T cells in the peripheral blood. Despite a memory phenotype, these persisting cells lacked markers of proliferation or activation. However, in ex vivo culture assays, they could be induced to proliferate and kill tumor using IL-15. These results were also seen in PBMCs from two patients who received gene-engineered T-cell receptor-based products at other centers.

Conclusions: ETC targeting NY-ESO-1 with single-agent cyclophosphamide alone conditioning was well tolerated in patients with SS and those with MRCL. IL-15 can induce proliferation and activity in persisting NY-ESO-1-specific T cells even in patients with disease progression following ACT. These results support future work evaluating whether IL-15 could be incorporated into ACT trials post-infusion or at the time of progression.
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http://dx.doi.org/10.1136/jitc-2020-002232DOI Listing
May 2021

Ketogenic diet-mediated steroid metabolism reprogramming improves the immune microenvironment and myelin growth in spinal cord injury rats according to gene and co-expression network analyses.

Aging (Albany NY) 2021 May 6;13. Epub 2021 May 6.

Department of Rehabilitation Medicine, Peking University Third Hospital, Beijing 100191, China.

The ketogenic diet has been widely used in the treatment of various nervous system and metabolic-related diseases. Our previous research found that a ketogenic diet exerts a protective effect and promotes functional recovery after spinal cord injury. However, the mechanism of action is still unclear. In this study, different dietary feeding methods were used, and myelin expression and gene level changes were detected among different groups. We established 15 RNA-seq cDNA libraries from among 4 different groups. First, KEGG pathway enrichment of upregulated differentially expressed genes and gene set enrichment analysis of the ketogenic diet and normal diet groups indicated that a ketogenic diet significantly improved the steroid anabolic pathway in rats with spinal cord injury. Through cluster analysis, protein-protein interaction analysis and visualization of iPath metabolic pathways, it was determined that Sqle, Sc5d, Cyp51, Dhcr24, Msmo1, Hsd17b7, and Fdft1 expression changed significantly. Second, through weighted gene co-expression network analysis showed that rats fed a ketogenic diet showed a significant reduction in the expression of genes involved in immune-related pathways, including those associated with immunity and infectious diseases. A ketogenic diet may improve the immune microenvironment and myelin growth in rats with spinal cord injury through reprogramming of steroid metabolism.
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http://dx.doi.org/10.18632/aging.202969DOI Listing
May 2021

Do the successful revision surgery for humeral nonunion solve all the effects on health-related quality of life? A retrospective cohort study.

BMC Musculoskelet Disord 2021 May 5;22(1):414. Epub 2021 May 5.

Department of Orthopaedics and Trauma, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, No. 555, East Youyi Road, Shaanxi, 710000, Xi'an, China.

Background: The aim of this study is to evaluate the effects of successful revision operation on health quality of life(QoL) and functional outcome in humeral nonunion patients.

Methods: This retrospective study included 62 patients with humeral nonunion from Northwest China, who were admitted to the Department of Trauma Surgery, Honghui Hospital between March 2013 and September 2019. The following data were retrospectively evaluated: demographic data, clinical data, imaging findings, and treatment methods. The QoL assessment indicators for humeral nonunion patients included the SF-12 mental component summary (MCS) and physical component summary (PCS),brief pain inventory-severity(BPI-S) and brief pain inventory-interference (BPI-I). The mayo elbow performance score (MEPS) was used to assess the elbow function of the patients.

Results: Successful revision surgery significantly improved the patient's PCS, MCS, BPI-S and BPI-I scores (p<0.001). According to the MEPS criteria, the excellent and good rates were 95.16% in this study. The impact of humeral nonunion on mental health was comparable with the reported impact of stroke and type II diabetes (p>0.05).The impact of post-op on physical health was comparable with the reported impact of COPD, silicosis, hypertension, barrentt's esophagus and lower urinary tract symptoms(p>0.05).

Conclusion: Humeral nonunion is a devastating chronic medical condition that negatively affects both physical and mental health as well as quality of life. Although the effects of pain in the body can be completely relieved by treatment, the entire medical process may cause everlasting psychological trauma to the patient.
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http://dx.doi.org/10.1186/s12891-021-04283-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097853PMC
May 2021

Establishment of a prognostic model based on the Sequential Organ Failure Assessment score for patients with first-time acute myocardial infarction.

J Int Med Res 2021 May;49(5):3000605211011976

Department of Geriatric Medicine, Seventh Medical Center of Chinese PLA General Hospital, Beijing, China.

Objective: This study aimed to identify the prognostic factors of patients with first-time acute myocardial infarction (AMI) and to establish a nomogram for prognostic modeling.

Methods: We studied 985 patients with first-time AMI using data from the Multi-parameter Intelligent Monitoring for Intensive Care database and extracted their demographic data. Cox proportional hazards regression was used to examine outcome-related variables. We also tested a new predictive model that includes the Sequential Organ Failure Assessment (SOFA) score and compared it with the SOFA-only model.

Results: An older age, higher SOFA score, and higher Acute Physiology III score were risk factors for the prognosis of AMI. The risk of further cardiovascular events was 1.54-fold higher in women than in men. Patients in the cardiac surgery intensive care unit had a better prognosis than those in the coronary heart disease intensive care unit. Pressurized drug use was a protective factor and the risk of further cardiovascular events was 1.36-fold higher in nonusers.

Conclusion: The prognosis of AMI is affected by age, the SOFA score, the Acute Physiology III score, sex, admission location, type of care unit, and vasopressin use. Our new predictive model for AMI has better performance than the SOFA model alone.
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http://dx.doi.org/10.1177/03000605211011976DOI Listing
May 2021

Genomic polymorphisms at the crhr2 locus improve feed conversion efficiency through alleviation of hypothalamus-pituitary-interrenal axis activity in gibel carp (Carassius gibelio).

Sci China Life Sci 2021 Apr 30. Epub 2021 Apr 30.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.

Improvement in fish feed conversion efficiency (FCE) is beneficial for sustaining global food fish supplies. Here, we show that a set of polymorphisms at locus of the corticotropin releasing hormone receptor 2 (crhr2), which is involved in hypothalamus-pituitary-interrenal (HPI) axis signaling, is associated with improved FCE in farmed allogynogenetic gibel carp strain CAS III compared with that in the wild gibel carp strain Dongting (DT). This set of polymorphisms downregulates the expression levels of crhr2 mRNA in the brain and pituitary tissues in gibel carp strain CAS III compared with those in strain DT. Furthermore, compromised HPI axis signaling is observed in gibel carp strain CAS III, such as decreased α-melanocyte stimulating hormone protein levels, plasma cortisol content, and stress responses. Moreover, enhanced activation of protein kinase B/mammalian target of rapamycin complex 1 signaling observed in the muscle tissue of strain CAS III in comparison to that in strain DT indicated elevated anabolic metabolism in strain CAS III. Thus, these studies demonstrate that the genetic markers associated with compromised HPI axis signaling, such as crhr2, are potentially useful for genetic selection toward improvement in farmed fish growth and FCE, which would reduce fishmeal consumption and thereby indirectly facilitate sustainable fisheries.
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http://dx.doi.org/10.1007/s11427-020-1924-4DOI Listing
April 2021

Optimizing the sulfonic groups of a polymer to coat the zinc anode for dendrite suppression.

Chem Commun (Camb) 2021 May 4. Epub 2021 May 4.

School of Advanced Materials, Peking University Shenzhen Graduate School, Shenzhen 518055, P. R. China.

The zinc metal anodes in aqueous zinc-ion batteries suffer from low cycling performance caused by uncontrolled dendrite. We have designed sulfonated poly-ether-ether-ketone (SPEEK) polymers as a surface coating layer on the zinc anode for dendrite suppression, in which the sulfonic groups in polymers act as effective active sites for zinc-ion diffusion. In SPEEK, the un-sulfonated domain serves as the framework and the sulfonated domain serves as the functional part to re-distribute the zinc ions. By optimizing the degree of SPEEK sulfonation, the best zinc anode coating has been achieved to present a high reversibility of over 1600 hours in symmetric cells and improved performance in full cells.
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http://dx.doi.org/10.1039/d1cc00924aDOI Listing
May 2021

Effects of Ambient Air Pollution on Blood Pressure Among Children and Adolescents: A Systematic Review and Meta-Analysis.

J Am Heart Assoc 2021 May 4:e017734. Epub 2021 May 4.

Center of Clinical Pharmacology The Third Xiangya Hospital, Central South University Changsha China.

Background Previous studies have investigated the association of ambient air pollution with blood pressure (BP) in children and adolescents, however, the results are not consistent. We conducted a systematic review and meta-analysis to assess the relationship between short-term and long-term ambient air pollutant exposure with BP values among children and adolescents. Methods and Results We searched PubMed, Web of Science, and Embase before September 6, 2020. Two reviewers independently searched and selected studies, extracted data, and assessed study quality. The studies were divided into groups by composition of air pollutants (NO, particulate matter (PM) with diameter ≤10 μm or ≤2.5 μm) and length of exposure. The beta regression coefficients (β) and their 95% CIs were calculated to evaluate the strength of the effect with each 10 μg/m increase in air pollutants. Out of 36 650 articles, 14 articles were included in this meta-analysis. The meta-analysis showed short-term exposure to PM with diameter ≤10 μm (β=0.267; 95% CI, 0.033‒0.501) was significantly associated with elevated systolic BP values. In addition, long-term exposure to PM with diameter ≤2.5 μm (β=1.809; 95% CI, 0.962‒2.655), PM with diameter ≤10 μm (β=0.526; 95% CI, 0.095‒0.958), and NO (β=0.754; 95% CI, 0.541‒0.968) were associated with systolic BP values and long-term exposure to PM with diameter ≤2.5 μm (β=0.931; 95% CI, 0.157‒1.705), and PM with diameter ≤10 μm (β=0.378; 95% CI, 0.022‒0.735) was associated with diastolic BP. Conclusions Our study indicates that both short-term and long-term exposure to some ambient air pollutants may increase BP values among children and adolescents.
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http://dx.doi.org/10.1161/JAHA.120.017734DOI Listing
May 2021

Locking compression plate fixation of femoral intertrochanteric fractures in patients with preexisting proximal femoral deformity: a retrospective study.

J Orthop Surg Res 2021 Apr 29;16(1):285. Epub 2021 Apr 29.

Department of Orthopedics Trauma, Xi'an Honghui Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710054, P.R. China.

Background: To investigate the clinical efficacy of locking compression plate fixation for the treatment of femoral intertrochanteric fractures in patients with preexisting proximal femoral deformity.

Methods: A retrospective analysis was conducted on 37 patients with femoral intertrochanteric fractures combined with preexisting proximal femoral deformity between January 2013 and July 2019. The patients included 24 males and 13 females aged from 23 to 69 years old, with an average age of 47.5 years. The preexisting proximal femoral deformities resulted from poliomyelitis sequela, proximal femoral fibrous dysplasia, malunion and implant failure combined with coxa vara after intramedullary nailing fixation. There were 6 cases of 31-A2.1, 6 cases of 31-A2.2, 20 cases of 31-A3.1, and 5 cases of 31-A3.2, determined based on the AO classification of intertrochanteric fractures. All fractures were managed through open reduction and locking plate fixation. The hip disability and osteoarthritis outcome score (HOOS) was used to assess hip function before injury and at the last postoperative follow-up. The short form 36 (SF-36) Health Survey Questionnaire was used to assess quality of life.

Results: Thirty-seven patients were followed up for 12 to 27 months (average, 20.7 months). All patients achieved bone healing within 5.1 months on average (range, 3 to 6 months). Postoperative complications included deep vein thrombosis in three patients, bedsores in one and delayed union in one patient. No other complications, such as surgical site infection, fat embolism, nonunion and re-fracture, were presented. There was no significant difference in the HOOS scores and the SF-36 Health Questionnaire outcomes at pre-injury and at the last postoperative follow-up (p > 0.05).

Conclusions: It is difficult to perform intramedullary fixation of femoral intertrochanteric fractures in patients with preexisting proximal femoral deformity, while locking compression plate fixation is a simple and effective method of treatment.
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http://dx.doi.org/10.1186/s13018-021-02430-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082780PMC
April 2021

Prognostic Modeling of Patients Undergoing Surgery Alone for Esophageal Squamous Cell Carcinoma: A Histopathological and Computed Tomography Based Quantitative Analysis.

Front Oncol 2021 12;11:565755. Epub 2021 Apr 12.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China.

Objective: To evaluate the effectiveness of a novel computerized quantitative analysis based on histopathological and computed tomography (CT) images for predicting the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients.

Methods: We retrospectively reviewed the medical records of 153 ESCC patients who underwent esophagectomy alone and quantitatively analyzed digital histological specimens and diagnostic CT images. We cut pathological images (6000 × 6000) into 50 × 50 patches; each patient had 14,400 patches. Cluster analysis was used to process these patches. We used the pathological clusters to all patches ratio (PCPR) of each case for pathological features and we obtained 20 PCPR quantitative features. Totally, 125 computerized quantitative (20 PCPR and 105 CT) features were extracted. We used a recursive feature elimination approach to select features. A Cox hazard model with L1 penalization was used for prognostic indexing. We compared the following prognostic models: Model A: clinical features; Model B: quantitative CT and clinical features; Model C: quantitative histopathological and clinical features; and Model D: combined information of clinical, CT, and histopathology. Indices of concordance (C-index) and leave-one-out cross-validation (LOOCV) were used to assess prognostic model accuracy.

Results: Five PCPR and eight CT features were treated as significant indicators in ESCC prognosis. C-indices adjusted for LOOCV were comparable among four models, 0.596 (Model A) vs. 0.658 (Model B) vs. 0.651 (Model C), and improved to 0.711with Model D combining information of clinical, CT, and histopathology (all p<0.05). Using Model D, we stratified patients into low- and high-risk groups. The 3-year overall survival rates of low- and high-risk patients were 38.0% and 25.0%, respectively (p<0.001).

Conclusion: Quantitative prognostic modeling using a combination of clinical data, histopathological, and CT images can stratify ESCC patients with surgery alone into high-risk and low-risk groups.
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http://dx.doi.org/10.3389/fonc.2021.565755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072145PMC
April 2021

Selective Deposition of Catalytic Metals on Plasmonic Au Nanocups for Room-Light-Active Photooxidation of -Phenylenediamine.

ACS Appl Mater Interfaces 2021 Apr 28. Epub 2021 Apr 28.

Department of Physics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

Plasmonic hotspots can enhance hot charge carrier generation, offering new opportunities for improving the photocatalytic activity. In this work, eight types of heteronanostructures are synthesized by selectively depositing catalytic metals at the different sites of highly asymmetric Au nanocups for the photocatalytic oxidation of -phenylenediamine. The oxidation of this molecule has so far mainly relied on the use of HO as an oxidizing agent in the presence of an appropriate catalyst. The photocatalytic oxidation under visible light has not been reported before. The Au nanocups with AgPt nanoparticles grown at the opening edge and bottom exhibit the highest photocatalytic activity. The generated hot electrons and holes both participate in the reaction. The hot carriers from the interband and intraband transitions are both utilized. The optimal catalyst shows a favorable activity even under room light. Simulations reveal that the profound electric field enhancement at the hotspots boosts the hot-carrier density in the catalytic nanoparticles, explaining the overwhelming photocatalytic activity of the optimal catalyst.
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http://dx.doi.org/10.1021/acsami.1c03806DOI Listing
April 2021

Landscape of Adverse Events Related to Peroral Endoscopic Myotomy in 3,135 Patients and A Risk-Scoring System to Predict Major Adverse Events.

Clin Gastroenterol Hepatol 2021 Apr 24. Epub 2021 Apr 24.

Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:

Background And Aims: We aimed to 1) systemically describe the landscape of Peroral Endoscopic Myotomy (POEM) related adverse events (AE) and compare the different grading systems; 2) establish and validate a combined risk factor model and a simplified risk-scoring system to predict POEM related major AEs (mAEs).

Methods: 3,135 achalasia patients treated with POEM were included and the AEs were systemically described and graded. A predictive model and risk-scoring system was developed using logistic regression and then internally validated using bootstrapping approaches.

Results: 258 out of 3,135 patients, accounting for 8.23% of the total patients, presented with 292 adverse events. According to Clavien-Dindo grading, 175 (67.83%), 23 (8.91%), 56 (21.71%), 4 (1.55%) and 0 (0.00%) patients were graded as grade I-V, respectively. By ASGE lexicon, 175 (67.83%) patients were classified with mild AE, 66 (25.58%) were classified with moderate AE, and 17 (6.59%) were classified with severe AE, respectively. 68 (2.17%) patients were classified with mAE. Air insufflation, selective myotomy, mucosal injury, and long operation time were selected into the predictive model with an area under the operator curve (AUC) of 0.795. They were assigned with scores of 18, 5, 3, and 5 in the risk-scoring system, respectively. By applying the risk scoring system, patients with higher scores had higher rates of mAE. The model showed little evidence for overfitting and was well-calibrated CONCLUSIONS: Based on a systematic landscape analysis, POEM is a safe procedure with low rates of severe AEs. Our prediction model and risk-scoring system demonstrated good performance in predicting mAEs.
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http://dx.doi.org/10.1016/j.cgh.2021.04.033DOI Listing
April 2021

Effects of yeast β-glucans for the prevention and treatment of upper respiratory tract infection in healthy subjects: a systematic review and meta-analysis.

Eur J Nutr 2021 Apr 26. Epub 2021 Apr 26.

Center for Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, People's Republic of China.

Purpose: Yeast β-glucans are known for their immune-modulating effects; however, their effects on human upper respiratory tract infections (URTIs) remain unclear. The aim of the present study was to use a systematic review and meta-analysis approach to investigate the effects of yeast β-glucans for the prevention and treatment of URTIs in healthy subjects.

Methods: Databases including Pubmed, Web of Science, EMBASE and the Cochrane Library were searched and 13 RCTs investigating the effects of yeast β-glucans on the incidence, duration, and severity of URTIs in healthy subjects were included.

Results: The results showed that compared to the placebo group, yeast β-glucan could significantly reduce the incidence of URTIs (OR = 0.345, 95% CI = 0.192 to 0.620, p < 0.001), decrease the average number of URTI episodes (SMD =  - 0.315, 95% CI =  - 0.500 to  - 0.130, p < 0.05), and decrease the duration of URTIs (SMD =  - 0.312, 95% CI =  - 0.561 to  - 0.064, p < 0.001). Improved severity of symptoms was found in yeast β-glucan group compared to the placebo group in the majority of included studies. In addition, yeast β-glucan was well tolerated and safe in general.

Conclusion: These findings suggest a positive effect of yeast β-glucans on human URTIs. However, due to the high heterogeneity and small number of included studies, more high-quality research and clinical trials are warranted.
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http://dx.doi.org/10.1007/s00394-021-02566-4DOI Listing
April 2021

Antifungal activity of silver nanoparticles synthesized by iturin against Candida albicans in vitro and in vivo.

Appl Microbiol Biotechnol 2021 May 26;105(9):3759-3770. Epub 2021 Apr 26.

Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyi West Road, Xi'an, 710072, Shaanxi Province, China.

Candida albicans (C. albicans) is a fungal pathogen that is difficult to cure clinically due to lack of effective antifungal agents with low toxicity. In this study, iturin, a cyclic peptide having wide antifungal spectrum, was used to synthesize nanosilver particles (AgNPs), and a complex of iturin-AgNPs was formed. The antifungal activity of iturin-AgNPs against C. albicans and its mechanisms were tested in vitro. Iturin-AgNPs were also loaded in chitosan (CS) composite dressing and applied to skin wound healing in mice. As results, iturin-AgNPs showed excellent antifungal activity with the minimum inhibitory concentrations (MIC) of 1.25, 2.5, and 5 μg/mL at C. albicans concentrations of 1×10, 1×10, and 1×10 CFU/mL, respectively. The MIC value still kept at 2.5 μg/mL against C. albicans (10 CFU/mL) after 15 regeneration, showing less induction of drug resistance to the pathogenic fungus. The antifungal mechanisms of iturin-AgNPs against C. albicans were identified as the increase of membrane permeability, damage of cell membrane integrity, and leakage of cellular protein and nucleic acids. No toxicity was found for iturin-AgNPs to HaCaT cells at concentrations of lower than 10 μg/mL. In wound healing application, iturin-AgNP CS composite dressing significantly accelerated the healing of C. albicans infected skin wounds at the early 10 days. In conclusion, iturin-AgNPs were developed as an efficient antifungal agent against C. albicans in vitro and in vivo and showed potential application in wound healing promotion.
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http://dx.doi.org/10.1007/s00253-021-11296-wDOI Listing
May 2021

Antibacterial and wound healing-promoting effect of sponge-like chitosan-loaded silver nanoparticles biosynthesized by iturin.

Int J Biol Macromol 2021 Apr 21;181:1183-1195. Epub 2021 Apr 21.

Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyi West Road, Xi'an, Shaanxi Province 710072, China. Electronic address:

Silver nanoparticles (AgNPs) are widely used in wound dressing, but are limited in the application due to its high toxicity at effective concentrations. iturin-AgNPs was previously found to have much higher antibacterial activity at lower AgNPs content than the commercial AgNPs. To verify its potential application in the promotion of wound healing, a chitosan (CS) composite sponge dressing-loaded iturin-AgNPs was developed and evaluated for their antibacterial activity in vitro and used for wound healing in vivo. As results, the synthesized CS dressing had high porosity and water absorption. As expected, the antibacterial activity of CS dressing was significantly promoted by the incorporation of iturin-AgNPs. The CS dressing-loaded iturin-AgNPs showed more effective inhibition of bacterial infection and promotion of wound healing processing and quality than the commercial wound dressing loaded AgNPs in vivo. The mechanisms for the promotion of wound healing by the CS dressing-loaded iturin-AgNPs were found as the enhancement of re-epithelialization and collagen formation, as well as the increased antibacerial activity. No toxicity was found to all organs of mice. The study developed an efficient way to enhance the antibacterial activity of CS dressing loaded AgNPs at low toxicity, which has great potential in wound care application.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.119DOI Listing
April 2021

The challenges, achievements and applications of submersible superhydrophobic materials.

Chem Soc Rev 2021 Apr 23. Epub 2021 Apr 23.

Department of Chemistry, School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK.

Superhydrophobic materials have been widely reported throughout the scientific literature. Their properties originate from a highly rough morphology and inherently water repellent surface chemistry. Despite promising an array of functionalities, these materials have seen limited commercial development. This could be attributed to many factors, like material compatibility, low physical resilience, scaling-up complications, etc. In applications where persistent water contact is required, another limitation arises as a major concern, which is the stability of the air layer trapped at the surface when submerged or impacted by water. This review is aimed at examining the diverse array of research focused on monitoring/improving air layer stability, and highlighting the most successful approaches. The reported complexity of monitoring and enhancing air layer stability, in conjunction with the variety of approaches adopted, results in an assortment of suggested routes to achieving success. The review is addressing the challenge of finding a balance between maximising water repulsion and incorporating structures that protect air pockets from removal, along with challenges related to the variant approaches to testing air-layer stability across the research field, and the gap between the achieved progress and the required performance in real-life applications.
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http://dx.doi.org/10.1039/d0cs01056aDOI Listing
April 2021

Combining Mechanical High-Intensity Focused Ultrasound Ablation with Chemotherapy for Augmentation of Anticancer Immune Responses.

Mol Pharm 2021 05 22;18(5):2091-2103. Epub 2021 Apr 22.

School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.

As a noninvasive therapy, high-intensity focused ultrasound (HIFU) shows great potential in inducing anticancer immune responses. However, the overall anticancer efficacy of HIFU is still limited due to the rapid attenuation of ultrasound waves and inadequacy of ultrasound waves to spread to the whole tumor. Here, we combined HIFU with the ultrasound contrast agent/chemotherapeutic drug co-delivery nanodroplets to achieve synergistic enhancement of anticancer efficacy. Different from the widely used thermal HIFU irradiation, by which excessive heating would result in inactivation of immune stimulatory molecules, we used short acoustic pulses to trigger HIFU (mechanical HIFU, mHIFU) to improve anticancer immune responses. The nanodroplets displayed a mHIFU/glutathione (GSH)-dual responsive drug release property, and their cellular uptake efficacy and toxicity against cancer cells increased upon mHIFU irradiation. The generated immunogenic debris successfully induced the exposure of damage-associated molecular patterns on the cell surface for dendritic cells (DCs) maturation. In vivo experiments with tumor-bearing mice showed that the co-delivery nanodroplets in combination with mHIFU could effectively inhibit tumor growth by inducing immunogenic cell death, activating DCs maturation, and enhancing the effector T-cell infiltration within tumors. This work reveals that combined treatment with nanodroplets and mHIFU is a promising approach to eradicate tumors.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00229DOI Listing
May 2021

Conductive electrodes of metallic-organic compound CHCuS nanowires for all-solid-state flexible supercapacitors.

Nanoscale 2021 Apr 6;13(14):6921-6926. Epub 2021 Apr 6.

Beijing Advanced Innovation Center for Materials Genome Engineering, Beijing Key Laboratory for Magneto-Photoelectrical Composite and Interface Science, School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China.

Development of wearable electronics puts forward higher requirements for flexible energy storage devices. Lighter and thinner electrodes with high conductivity are one of the key factors to meet this demand. Herein, a conductive paper-based electrode, assembled from metallic-organic compound CHCuS nanowires prepared by a one-step thermal solution process, is reported. By using the conductive electrodes of CHCuS nanowires, the fabricated all-solid-state supercapacitor device delivers an excellent electrochemical performance: an areal capacitance of 90.5 μF cm at a current density of 0.5 mA cm, an energy density of 5.2 μW h cm, and 98% retention of initial capacitance after undergoing 10 000 cycles. In particular, the fabricated all-solid-state supercapacitor device can work normally under a bent state. The no-additive, cost-effective, and eco-friendly paper-based electrodes present a potential application prospect in the field of flexible energy storage devices.
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http://dx.doi.org/10.1039/d1nr00593fDOI Listing
April 2021

The proportion and effect of corticosteroid therapy in patients with COVID-19 infection: A systematic review and meta-analysis.

PLoS One 2021 21;16(4):e0249481. Epub 2021 Apr 21.

Department of Orthopedics, Honghui Hospital, Xi'anJiaotong University, Xi'an, PR China.

Objectives: Coronavirus disease 2019 (COVID-19) remains a global challenge. Corticosteroids constitute a group of anti-inflammatory and immunosuppressive drugs that are widely used in the treatment of COVID-19. Comprehensive reviews investigating the comparative proportion and efficacy of corticosteroid use are scarce. Therefore, we conducted a systematic review and meta-analysis of clinical trials to evaluate the proportion and efficacy of corticosteroid use for the treatment of COVID-19.

Methods: We conducted a comprehensive literature review and meta-analysis of research articles, including observational studies and clinical trials, by searching the PubMed, EMBASE, Cochrane Controlled Trials Registry, and China Academic Journal Network Publishing databases. Patients treated between December 1, 2019, and January 1, 2021, were included. The outcome measures were the proportion of patients treated with corticosteroids, viral clearance and mortality. The effect size with the associated 95% confidence interval is reported as the weighted mean difference for continuous outcomes and the odds ratio for dichotomous outcomes.

Results: Fifty-two trials involving 15710 patients were included. The meta-analysis demonstrated that the proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids (35.19% vs. 64.49%). In addition, our meta-analysis demonstrated no significant difference in the proportions of severe and nonsevere cases treated with corticosteroids (27.91% vs. 20.91%). We also performed subgroup analyses stratified by whether patients stayed in the intensive care unit (ICU) and found that the proportion of patients who received corticosteroids was significantly higher among those who stayed in the ICU than among those who did not. The results of our meta-analysis indicate that corticosteroid treatment significantly delayed the viral clearance time. Finally, our meta-analysis demonstrated no significant difference in the use of corticosteroids for COVID-19 between patients who died and those who survived. This result indicates that mortality is not correlated with corticosteroid therapy.

Conclusion: The proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids. Corticosteroid use in subjects with severe acute respiratory syndrome coronavirus 2 infections delayed viral clearance and did not convincingly improve survival; therefore, corticosteroids should be used with extreme caution in the treatment of COVID-19.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249481PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059814PMC
April 2021

Overexpression of circRNA SNRK targets miR-103-3p to reduce apoptosis and promote cardiac repair through GSK3β/β-catenin pathway in rats with myocardial infarction.

Cell Death Discov 2021 Apr 19;7(1):84. Epub 2021 Apr 19.

Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

Ischemic cardiomyopathy seriously endangers human health leading to a poor prognosis. Acute myocardial infarction (AMI) is the primary etiology, and the pathophysiological process concludes with the death of cardiomyocytes caused by acute and persistent ischemia and hypoxia in the coronary arteries. We identified a circRNA (circSNRK) which was downregulated in rats with myocardial infarction (MI), however, the role it plays in the MI environment is still unclear. This study contained experiments to investigate the role of circSNRK in the regulation of cardiac survival and explore the mechanisms underlying circSNRK functions. Quantitative real-time PCR (qRT-PCR) was performed to determine the circSNRK expression patterns in hearts. Gain-of-function assays were also conducted in vitro and in vivo to determine the role of circSNRK in cardiac repair. qRT-PCR, western blot, and luciferase reporter assays were used to study circRNA interactions with micro RNAs (miRNAs). Overexpression of circSNRK in cardiomyocytes reduced apoptosis and increased proliferation. Adeno associated virus 9 (AAV9) mediated myocardium overexpression of circSNRK in post MI hearts reduced cardiomyocyte apoptosis, promoted cardiomyocyte proliferation, enhanced angiogenesis, and improved cardiac functions. Overall, upregulation of circSNRK promotes cardiac survival and functional recovery after MI. Mechanistically, circSNRK regulates cardiomyocyte apoptosis and proliferation by acting as a miR-103-3p sponge and inducing increased expression of SNRK which can bind GSK3β to regulate its phosphorylated activity. And thus circSNRK may be a promising therapeutic target for improving clinical prognosis after MI.
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http://dx.doi.org/10.1038/s41420-021-00467-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055694PMC
April 2021

Transforming growth factor β as a possible independent factor in chronic hepatitis B.

Arch Virol 2021 Apr 19. Epub 2021 Apr 19.

Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.

To investigate the association between immune-cell-related cytokines and the development of chronic hepatitis B (CHB), patients with chronic hepatitis B virus (HBV) infection in the immunotolerant (IT) phase (n = 30) or hepatitis B envelope antigen (HBeAg)-positive CHB (n = 250) were enrolled in this study. Serological indicators and plasma cytokine levels were measured at the time of enrollment. The results showed that there were significant differences in the median age of the patients (27 vs. 31 years), alanine aminotransferase levels (ALT, 29.85 vs. 234.70 U/L), alanine aminotransferase levels (AST, 23.40 vs. 114.90 U/L), HBsAg levels (4.79 vs. 3.88 log IU/ml), HBeAg levels (1606.36 vs. 862.47 S/CO), and the HBV DNA load (8.17 vs. 6.71 log IU/ml) between the IT and CHB groups (all P < 0.01). The median values of Fms-like tyrosine kinase 3 ligand (FLT3-L), interferon-gamma (IFN-γ), interleukin- 17A (IL-17A), and transforming growth factor beta (TGF-β1) were significantly higher in the IT group than in the CHB group (FLT3-L, 41.62 vs. 27.47 pg/ml; IFN-γ, 42.48 vs. 33.18 pg/ml; IL-17A, 15.66 vs. 8.90 pg/ml; TGF-β1, 4921.50 vs. 2234 pg/ml; all P < 0.01). The median IFN-α2, TGF-β3 and IL-10 levels in the IT group were significantly lower than those in the CHB group (IFN-α2, 15.24 vs. 35.78 pg/ml, P = 0.000; TGF-β3, 131.69 vs. 162.61 pg/ml, P = 0.025; IL-10, 5.02 vs. 7.9 pg/ml, P = 0.012). Multivariate logistic regression analysis indicated that TGF-β 1 (OR = 0.999, 95% CI 0.999-1.000, P < 0.001) and TGF-β2 levels (OR = 1.008, 95%CI 1.004-1.012, P < 0.001) were modestly but significantly associated with the incidence of CHB. The results suggest that TGF-β level might be an independent factor related to the occurrence of CHB.
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http://dx.doi.org/10.1007/s00705-021-05062-6DOI Listing
April 2021

Global identification of the cellular targets for a multi-molecule system by a photochemically-induced coupling reaction.

Chem Commun (Camb) 2021 Apr 19;57(28):3449-3452. Epub 2021 Mar 19.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

Current target identification strategies mainly focus on single compounds. However, no practical experimental methodologies have been developed for multi-molecule systems. Herein, we established a cellular target identification technology for a multi-molecule system by preparing 4,4'-dihydroxybenzophenone (DHBP)-bound FeO nanoparticles (NPs) with photochemically induced crosslinking capacity. DHBP-bound NPs reacted with the chemicals from the medicinal plant extract as a multi-molecule system under ultraviolet radiation by forming carbon-carbon bonds, thus generating extract-crosslinked NPs for capturing target proteins from cell lysates. The technology, which is named the Zhao-Yao (ZY) strategy, may promote the comprehensive interpretation of the pharmacological mechanism of multi-molecule systems via the global identification of cellular targets.
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http://dx.doi.org/10.1039/d1cc00392eDOI Listing
April 2021

Circulating Exosomal miR-1-3p from Rats with Myocardial Infarction Plays a Protective Effect on Contrast-Induced Nephropathy via Targeting ATG13 and activating the AKT Signaling Pathway.

Int J Biol Sci 2021 2;17(4):972-985. Epub 2021 Mar 2.

Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

With the widespread development of the interventional technique for cardiovascular diseases and the widespread use of contrast medium (CM), the incidence of contrast-induced nephropathy (CIN) has been increasing, which is associated with poor prognosis for cardiovascular diseases. This study aims to explore the effect of circulating exosomal microRNA from patients with myocardial infarction (MI) on CIN and related molecular mechanism. A rat MI model was established by ligating the left anterior descending coronary artery. Circulating exosomes were isolated from control (Exo-NC) and MI rats (Exo-MI) using a commercial kit. The and models of CIN were created using iodixanol. Reverse transcription quantitative PCR (RT-qPCR) was utilized to detect the expression of miR-1-3p. Western blot (WB) was used to detect the expression of exosomal surface markers, and apoptosis-related and autophagy-related proteins. The apoptosis rate was examined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining and flow cytometry (FC). Transmission electron microscopy (TEM) was utilized to observe the exosomes and autophagosomes. Rat kidney injury was assessed by hematoxylin and eosin (H&E) staining and kidney injury molecule-1 (KIM-1) immunohistochemical staining. Renal function of rats was assessed by detecting the levels of blood urea nitrogen (BUN) and serum creatinine (Cr). The dual luciferase reporter assay was performed to identify the target gene of miR-1-3p. The treatment of CM induced NRK-52E cell damage, which manifested as enhanced cell autophagy and enhanced apoptosis. The Exo-MI treatment significantly inhibited the CM-induced autophagy and apoptosis of NRK-52E cells. Furthermore, the Exo-MI treatment increased the Bcl-2 expression, but decreased the Bax expression and the ratio of LC3II/LC3I. Furthermore, the results of the TUNEL staining and FC showed that Exo-MI can reduce apoptotic rate. Through TEM, it was found that Exo-MI reduced the number of autophagosomes in NRK-52E cells. The rescue experiments revealed that the function of Exo-MI is to inhibit the CM-induced autophagy and apoptosis of NRK-52E cells, which can be inhibited by the miR-1-3p inhibitor. Furthermore, it was found that the overexpression of miR-1-3p can also inhibit the CM-induced autophagy and apoptosis of NRK-52E cells. Through dual luciferase reporter assay, ATG13 was found to be the target of miR-1-3p. In addition, the overexpression of miR-1-3p significantly reversed the CM-induced decrease in phosphorylation level of AKT. Furthermore, ATG13 silencing can also inhibit the CM-induced autophagy and apoptosis of NRK-52E cells. , Exo-MI significantly alleviated the renal injury, reduced the renal fibrosis, and improved the renal function of CIN rats. The circulating exosomal miR-1-3p after MI inhibited the CM-induced apoptosis and autophagy of renal tubular epithelial cells, and improved the renal function of rats by targeting ATG13 and activating the AKT signaling pathway.
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http://dx.doi.org/10.7150/ijbs.55887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040303PMC
March 2021

Tracking-based deep learning method for temporomandibular joint segmentation.

Ann Transl Med 2021 Mar;9(6):467

School of Mathematics, Sun Yat-sen University, Guangzhou, China.

Background: The shape, size, and surface information relating to the glenoid fossae and condyles in temporomandibular joints (TMJ) are essential for diagnosing and treating. Patients with TMJ disease often have surface abrasion which may cause fuzzy edges in computed tomography (CT) imaging, especially for low-dose CT, making TMJ segmentation more difficult.

Methods: In this paper, an automatic segmentation algorithm based on deep learning and post-processing was introduced. First, U-Net was used to divide images into 3 categories: glenoid fossae, condyles, and background. For structural fractures in these divided images, the internal force constraint of a snake model was used to replenish the integrity of the fracture boundary in a post-processing operation, and the initial boundary of the snake was obtained based on the basis of the tracking concept. A total of 206 cases of low-dose CT were used to verify the effectiveness of the algorithm, and such indicators as the Dice coefficient (DC) and mean surface distance (MSD) were used to evaluate the agreement between experimental results and the gold standard.

Results: The proposed method is tested on a self-collected dataset. The results demonstrate that proposed method achieves state-of-the-art performance in terms of DCs = 0.92±0.03 (condyles) and 0.90±0.04 (glenoid fossae), and MSDs =0.20±0.19 mm (condyles) and 0.19±0.08 mm (glenoid fossae).

Conclusions: This study is the first to focus on the simultaneous segmentation of TMJ glenoid fossae and condyles. The proposed U-Net + tracking-based algorithm showed a relatively high segmentation efficiency, enabling it to achieve sought-after segmentation accuracy.
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http://dx.doi.org/10.21037/atm-21-319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039636PMC
March 2021