Publications by authors named "Xin He"

1,394 Publications

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A gene signature comprising seven pyroptosis-related genes predicts prognosis in pediatric patients with acute myeloid leukemia.

Acta Haematol 2022 Aug 5. Epub 2022 Aug 5.

Introduction: To construct a pyroptosis-related risk score (RS) model for the prognosis of acute myeloid leukemia (AML).

Methods: The TARGET (training) and E-MTAB-1216 (validation) datasets were downloaded. Pyroptosis-related genes with differences in expression were identified between the recurrent and non-recurrent samples of the training dataset. An RS prognostic model comprising seven pyroptosis-related genes was constructed using LASSO regression coefficients. The samples were classified into the high- and low-risk groups using the RS model; the differentially expressed genes (DEGs) between these groups were identified, followed by DEG functional analysis and the immunological evaluation of these groups.

Results: Forty-nine pyroptosis-related genes, including 22 DEGs, were screened. WT1, NPM, FLT3/ITD, and CEBPA mutations were found in most pediatric AML samples. An RS prognostic model was constructed using seven pyroptosis-related genes. The two risk groups and prognostic data were significantly related. FLT3/ITD mutations, CEBPA mutations, and RS model status were identified as independent prognostic factors, using the clinical information. The DEGs between the two groups were correlated with immune-related pathways. Moreover, the immune cell distribution and occurrence of immune-related pathways were notably decreased in the high-risk group.

Discussion/conclusion: Seven pyroptosis-related genes, CHMP2A, PRKACA, CASP9, IRF2, CHMP3, HMGB1, and AIM2, can predict the prognosis and recurrence of childhood AML.
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http://dx.doi.org/10.1159/000526346DOI Listing
August 2022

TAT&RGD Peptide-Modified Naringin-Loaded Lipid Nanoparticles Promote the Osteogenic Differentiation of Human Dental Pulp Stem Cells.

Int J Nanomedicine 2022 28;17:3269-3286. Epub 2022 Jul 28.

Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, People's Republic of China.

Background: Naringin is a naturally occurring flavanone that promotes osteogenesis. Owing to the high lipophilicity, poor in vivo bioavailability, and extensive metabolic alteration upon administration, the clinical efficacy of naringin is understudied. Additionally, information on the molecular mechanism by which it promotes osteogenesis is limited.

Methods: In this study, we prepared TAT & RGD peptide-modified naringin-loaded nanoparticles (TAT-RGD-NAR-NPs), evaluated their potency on the osteogenic differentiation of human dental pulp stem cells (hDPSCs), and studied its mechanism of action through metabolomic analysis.

Results: The particle size and zeta potential of TAT-RGD-NAR-NPs were 160.70±2.05 mm and -20.77±0.47mV, respectively. The result of cell uptake assay showed that TAT-RGD-NAR-NPs could effectively enter hDPSCs. TAT-RGD-NAR-NPs had a more significant effect on cell proliferation and osteogenic differentiation promotion. Furthermore, in metabolomic analysis, naringin particles showed a strong influence on the glycerophospholipid metabolism pathway of hDPSCs. Specifically, it upregulated the expression of and (two isozymes of phospholipase A2, PLA2), increased the biosynthesis of lysophosphatidic acid (LPA).

Conclusion: These results suggested that TAT-RGD-NPs might be used for transporting naringin to hDPSCs for modulating stem cell osteogenic differentiation. The metabolomic analysis was used for the first time to elucidate the mechanism by which naringin promotes hDPSCs osteogenesis by upregulating PLA2G3 and PLA2G1B.
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http://dx.doi.org/10.2147/IJN.S371715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342892PMC
August 2022

Influencing Factors of Physical Activity in Patients with Lung Cancer Surgery and Its Correlation with Exercise Self-Efficacy and Perceived Social Support.

Evid Based Complement Alternat Med 2022 19;2022:7572530. Epub 2022 Jul 19.

Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing 100021, China.

Purpose: The aim of the study is to understand the current status of physical activity in patients with lung cancer surgery, explore its influencing factors, and analyze the correlation between physical activity and exercise self-efficacy and perception of social support.

Methods: The General Information Questionnaire was designed for 145 patients, Chinese version of EPIC-PAQ physical activity scale for lung cancer patients. The Exercise Self-Efficacy Scale (SEE) is used to evaluate the ability of people to organize and execute motor behaviors in various difficult situations. The Perceived Social Support Scale (PSSS) was used to emphasize individual self-understanding and self-feeling.

Results: The median and quartile of total physical activity scores in lung cancer surgery patients were 73.0 (34.8, 129.7) points; univariate analysis showed that there were statistically significant differences in physical activity levels among lung cancer surgery patients with different ages, work status before hospitalization, and perceived disease severity. The results of multivariate analysis showed that age, perceived disease severity, exercise self-efficacy, and total score of perceived social support affected the physical activity level of patients ( < 0.05). Efficacy were positively correlated with perceived social support ( < 0.01).

Conclusion: The level of physical activity of patients undergoing lung cancer surgery needs to be further improved. Physical activity is affected by patient age, perceived disease severity, exercise self-efficacy, and perceived social support and is positively correlated with exercise self-efficacy and perceived social support. Medical staff should provide targeted activity guidance according to the age and other characteristics of patients undergoing lung cancer surgery, enhance patients' exercise self-efficacy and comprehend social support, and improve their physical activity level, thereby promoting patients' early recovery.
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http://dx.doi.org/10.1155/2022/7572530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325606PMC
July 2022

Rapid recovery of male cats with postrenal acute kidney injury by treating with allogeneic adipose mesenchymal stem cell-derived extracellular vesicles.

Stem Cell Res Ther 2022 Jul 28;13(1):379. Epub 2022 Jul 28.

College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, 712100, China.

Background: Acute kidney injury (AKI) is a complex disease and can be generally divided into prerenal, intrarenal, and postrenal AKI (PR-AKI). Previous studies have shown that mesenchymal stem cells (MSCs)-derived extracellular vesicles have protective function on prerenal and intrarenal AKI treatment, but whether they have therapeutic efficacy on PR-AKI remains unclear. In this study, we investigated the therapeutic efficacy of allogeneic adipose mesenchymal stem cell-derived extracellular vesicles (ADMSCEVs) on cat models of PR-AKI.

Methods: The cat models of PR-AKI were established by using artificial urinary occlusion and then treated with ADMSCEVs. Histopathological section analysis, blood routine analysis, plasma biochemical test, imaging analysis, and plasma ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) were performed to evaluate the therapeutic efficacy of ADMSCEVs.

Results: Physiological and biochemical test showed that the ADMSCEVs could recover creatinine, urea nitrogen and plasma phosphorus to homeostasis efficiently. Blood routine analysis showed that leukocytes in PR-AKI cats with ADMSCEVs treatment returned to normal physiological range more quickly than that of control. UHPLC-MS/MS analysis revealed that the plasma metabolome profile of PR-AKI cats treated with ADMSCEVs was highly similar to that of normal cats. Furthermore, UHPLC-MS/MS analysis also revealed six metabolites (carnitine, melibiose, D-Glucosamine, cytidine, dihydroorotic acid, stachyose) in plasma were highly correlated with the dynamic process of PR-AKI on cats.

Conclusions: We demonstrate the efficacy of ADMSCEVs in the treatment of PR-AKI on cats. Our study also suggests six metabolites to be novel PR-AKI markers and to be potential targets for ADMSCEVs therapy. Our findings will be useful to improve clinical treatment of both animal and human PR-AKI patients with ADMSCEVs in the future.
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http://dx.doi.org/10.1186/s13287-022-03039-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331582PMC
July 2022

Transition Path Flight Times and Nonadiabatic Electronic Transitions.

J Phys Chem Lett 2022 Aug 25;13(30):6966-6974. Epub 2022 Jul 25.

Chemical and Biological Physics Department, Weizmann Institute of Science, 76100 Rehovot, Israel.

Transition path flight times are studied for scattering on two electronic surfaces with a single crossing. These flight times reveal nontrivial quantum effects such as resonance lifetimes and nonclassical passage times and reveal that nonadiabatic effects often increase flight times. The flight times are computed using numerically exact time propagation and compared with results obtained from the Fewest Switches Surface Hopping (FSSH) method. Comparison of the two methods shows that the FSSH method is reliable for transition path times only when the scattering is classically allowed on the relevant adiabatic surfaces. However, where quantum effects such as tunneling and resonances dominate, the FSSH method is not adequate to accurately predict the correct times and transition probabilities. These results highlight limitations in methods which do not account for quantum interference effects, and suggest that measuring flight times is important for obtaining insights from the time-domain into quantum effects in nonadiabatic scattering.
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http://dx.doi.org/10.1021/acs.jpclett.2c01425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358656PMC
August 2022

Effect Evaluation and Action Mechanism Analysis of "Profile Control + Plugging Removal" after Chemical Flooding.

Gels 2022 Jun 22;8(7). Epub 2022 Jun 22.

Key Laboratory of Enhanced Oil and Gas Recovery of Ministry of Education, Northeast Petroleum University, Daqing 163318, China.

The existing plugging removal operation in JZ9-3 oilfield has the disadvantages of small amount of plugging remover, fast injection speed, and short construction time. Under the condition of injection well suction profile reversal, plugging remover is difficult to enter the low permeability part and play the role of deep plugging removal. In order to improve the plugging removal effect, this paper used the physical simulation method to carry out the experimental study and mechanism analysis on the effect of water flooding, chemical flooding, and plugging removal measures of the multi-layer system combination model. The results showed that the recovery of general plugging removal after chemical flooding increases by only 0.70%, while the recovery of 'profile control + plugging removal' increases by '9.34% + 2.59%', and the amount of produced liquid decreases by more than 40%. It can be seen that the combined operation of profile control and plugging removal has dual effects of plugging and dredging and synergistic effect, which not only expands the swept volume, but also reduces the inefficient and ineffective cycles. On this basis, the optimization design and effect prediction of the target well W4-2 plugging removal scheme were carried out by using the numerical simulation method. Recommended scheme: inorganic gel profile control agent volume 13,243.6 m, produced by the main agent (NaO·nSiO), isolation fluid (Water), and auxiliary agent (CaCl) through multiple rounds of alternating injection into the reservoir. The plug removal agent (KSO) injection volume is 100 m, the concentration is 0.8%. The post-implementation 'Output/Input' ratio is expected to be 3.7.
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http://dx.doi.org/10.3390/gels8070396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324513PMC
June 2022

Whole plant microbiome profiling reveals a novel geminivirus associated with soybean stay-green disease.

Plant Biotechnol J 2022 Jul 22. Epub 2022 Jul 22.

National Key Laboratory of Plant Molecular Genetics, Chinese Academy of Sciences Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200032, China.

Microbiota colonize every accessible plant tissue and play fundamental roles in plant growth and health. Soybean stay-green syndrome (SGS), a condition that causes delayed leaf senescence (stay-green), flat pods and abnormal seeds of soybean, has become the most serious disease of soybean in China. However, the direct cause of SGS is highly debated, and little is known about how SGS affect soybean microbiome dynamics, particularly the seed microbiome. We studied the bacterial, fungal, and viral communities associated with different soybean tissues with and without SGS using a multi-omics approach, and investigated the possible pathogenic agents associated with SGS and how SGS affects the assembly and functions of plant-associated microbiomes. We obtained a comprehensive view of the composition, function, loads, diversity, and dynamics of soybean microbiomes in the rhizosphere, root, stem, leaf, pod, and seed compartments, and discovered that soybean SGS was associated with dramatically increased microbial loads and dysbiosis of the bacterial microbiota in seeds. Furthermore, we identified a novel geminivirus that was strongly associated with soybean SGS, regardless of plant cultivar, sampling location, or harvest year. This whole plant microbiome profiling of soybean provides the first demonstration of geminivirus infection associated with microbiota dysbiosis, which might represent a general microbiological symptom of plant diseases.
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http://dx.doi.org/10.1111/pbi.13896DOI Listing
July 2022

Analysis of Current Situation and Influencing Factors of Psychological Distress in Patients with Lung Cancer during Perioperative Period.

Evid Based Complement Alternat Med 2022 12;2022:1925668. Epub 2022 Jul 12.

Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Objective: To explore the degree of psychological distress in patients with lung cancer during the perioperative period and analyze its influencing factors.

Method: A cross-sectional survey was conducted on 372 perioperative patients with lung cancer admitted to our hospital by a convenience sampling method using general data collection and psychological pain thermometer scores.

Results: The psychological distress score of 372 patients with lung cancer in the perioperative period was 4.10 ± 2.88. The psychological distress of patients was related to physical problems, practical problems, medical expenses, and family communication problems. Logistic regression analysis showed that gender, economic burden caused by disease, child care, lack of interest in daily activities, and anxiety were the main factors affecting the degree of suffering of lung cancer patients.

Conclusion: The proportion of perioperative lung cancer patients with a psychological distress score ≥4 points was 55.6%, and more than half of the perioperative patients with lung cancer had a moderate level of psychological distress. Medical staff should pay attention to the management of the psychological distress of patients with lung cancer during the perioperative period, help patients solve practical problems in the process of cancer treatment, strengthen society's attention to female lung cancer patients, and establish a comprehensive cancer public welfare organization group.
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http://dx.doi.org/10.1155/2022/1925668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296278PMC
July 2022

[Anti-photoaging effects and mechanisms of active ingredients of Chinese medicine: a review].

Zhongguo Zhong Yao Za Zhi 2022 Jul;47(14):3709-3717

Guangdong Pharmaceutical University Guangzhou 510006, China State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050, China.

Skin photoaging is exogenous aging caused by long-term ultraviolet radiation, which not only affects skin appearance, but also has a close relationship with the development of skin cancer. Saponins, flavonoids, polyphenols, polysaccharides, and extracts of Chinese medicine have been found to have anti-skin photoaging effects in recent studies. Various mechanisms such as anti-oxidative stress damage, inhibition of matrix metalloproteinase expression, promotion of collagen synthesis, inhibition of inflammatory response, DNA damage repair, enhancement of cell autophagy, and inhibition of melanin synthesis can improve the symptoms of skin photoaging and delay the photoaging process. With the active ingredients of Chinese medicine for anti-skin photoaging as the entry point, the study systematically discussed the research progress of the mechanisms underlying the anti-photoaging effects of active ingredients of Chinese medicine in recent years, in order to provide theoretical reference for the development of new anti-photoaging drugs and methods.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20220415.601DOI Listing
July 2022

Imbalance of flight-freeze responses and their cellular correlates in the Nlgn3 rat model of autism.

Mol Autism 2022 07 18;13(1):34. Epub 2022 Jul 18.

Centre for Discovery Brain Sciences, Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, 5 George Square, Edinburgh, EH8 9XD, UK.

Background: Mutations in the postsynaptic transmembrane protein neuroligin-3 are highly correlative with autism spectrum disorders (ASDs) and intellectual disabilities (IDs). Fear learning is well studied in models of these disorders, however differences in fear response behaviours are often overlooked. We aim to examine fear behaviour and its cellular underpinnings in a rat model of ASD/ID lacking Nlgn3.

Methods: This study uses a range of behavioural tests to understand differences in fear response behaviour in Nlgn3 rats. Following this, we examined the physiological underpinnings of this in neurons of the periaqueductal grey (PAG), a midbrain area involved in flight-or-freeze responses. We used whole-cell patch-clamp recordings from ex vivo PAG slices, in addition to in vivo local-field potential recordings and electrical stimulation of the PAG in wildtype and Nlgn3 rats. We analysed behavioural data with two- and three-way ANOVAS and electrophysiological data with generalised linear mixed modelling (GLMM).

Results: We observed that, unlike the wildtype, Nlgn3 rats are more likely to response with flight rather than freezing in threatening situations. Electrophysiological findings were in agreement with these behavioural outcomes. We found in ex vivo slices from Nlgn3 rats that neurons in dorsal PAG (dPAG) showed intrinsic hyperexcitability compared to wildtype. Similarly, stimulating dPAG in vivo revealed that lower magnitudes sufficed to evoke flight behaviour in Nlgn3 than wildtype rats, indicating the functional impact of the increased cellular excitability.

Limitations: Our findings do not examine what specific cell type in the PAG is likely responsible for these phenotypes. Furthermore, we have focussed on phenotypes in young adult animals, whilst the human condition associated with NLGN3 mutations appears during the first few years of life.

Conclusions: We describe altered fear responses in Nlgn3 rats and provide evidence that this is the result of a circuit bias that predisposes flight over freeze responses. Additionally, we demonstrate the first link between PAG dysfunction and ASD/ID. This study provides new insight into potential pathophysiologies leading to anxiety disorders and changes to fear responses in individuals with ASD.
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http://dx.doi.org/10.1186/s13229-022-00511-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290228PMC
July 2022

Tunable Confined Aliphatic Pore Environment in Robust Metal-Organic Frameworks for Efficient Separation of Gases with a Similar Structure.

J Am Chem Soc 2022 Aug 18;144(31):14322-14329. Epub 2022 Jul 18.

Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, 310027 Hangzhou, Zhejiang, China.

The fine-tuning of the pore structure of metal-organic frameworks (MOFs) is of critical importance to developing energy-efficient processes for the challenging separation of structurally similar molecules. Herein, we demonstrate a strategy to realize a quasi-three-dimensional refinement of the pore structure that utilizes the tunability of ring size and number in polycycloalkane-dicarboxylate ligands. Two hydrolytically stable MOFs with a confined aliphatic pore environment, ZUL-C1 and ZUL-C2, were, for the first time, synthesized and applied in separating low-concentration C2-C3 hydrocarbons from natural gas and ultralow-concentration Xe from used nuclear fuel (UNF) off-gas. Validated by X-ray diffraction and modeling, an expansion of the polycycloalkane moiety enables sub-angstrom contraction in specific directions and forms a pore surface with more alkyl sites, which affords stronger trapping of guest molecules with relatively higher polarizability. The resultant material exhibits record CH/CH and CH/CH selectivities coupled with a benchmark low-pressure CH capacity in alkane mixture separation and also a benchmark Xe capacity at extremely diluted feed concentration and record Kr productivity for the Xe/Kr (20:80, v/v) mixture in Xe/Kr separation.
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http://dx.doi.org/10.1021/jacs.2c05448DOI Listing
August 2022

Preference for experiences: Regulatory focus and the trade-offs between experiential and material purchases.

J Exp Psychol Appl 2022 Jun;28(2):329-340

Department of Marketing, College of Business Administration, University of Central Florida.

Consumers often make trade-offs between experiential and material purchases, a choice which has important implications for consumers as well as marketers. The current research explores the effect of regulatory focus on such trade-offs. We find that promotion-driven individuals have a higher preference for experiential purchases than people with a prevention focus. This effect is demonstrated with a set of nine studies that utilize different operationalizations of regulatory focus and purchase type, including seven studies in the main text that use experimental data and two studies in the online Supplemental Materials that use real-world data (Instagram and Google Trends). Due to the variable nature of an experiential purchase, promotion-focused individuals are drawn to its numerous upside potentials, whereas prevention-focused people focus on its many downside potentials. Using both the mediation and moderation approaches, we show that the focus of attention on experiential purchases drives the observed effect. Finally, we demonstrate the evidential value of our findings with a p-curve analysis. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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http://dx.doi.org/10.1037/xap0000438DOI Listing
June 2022

Allosteric activation of the metabolic enzyme GPD1 inhibits bladder cancer growth via the lysoPC-PAFR-TRPV2 axis.

J Hematol Oncol 2022 07 14;15(1):93. Epub 2022 Jul 14.

Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.

Background: Bladder cancer is the most common malignant tumor of the urinary system. Surgical resection and chemotherapy are the two mainstream treatments for bladder cancer. However, the outcomes are not satisfactory for patients with advanced bladder cancer. There is a need to further explore more effective targeted therapeutic strategies.

Methods: Proteomics were performed to compare protein expression differences between human bladder cancer tissues and adjacent normal tissues. The function of GPD1 on bladder cancer cells were confirmed through in vivo and in vitro assays. Transcriptomics and metabolomics were performed to reveal the underlying mechanisms of GPD1. Virtual screening was used to identify allosteric activator of GPD1.

Results: Here, we used proteomics to find that GPD1 expression was at low levels in bladder cancer tissues. Further investigation showed that GPD1 overexpression significantly promoted apoptosis in bladder cancer cells. Based on transcriptomics and metabolomics, GPD1 promotes Ca influx and apoptosis of tumor cells via the lysoPC-PAFR-TRPV2 axis. Finally, we performed a virtual screening to obtain the GPD1 allosteric activator wedelolactone and demonstrated its ability to inhibit bladder tumor growth in vitro and in vivo.

Conclusions: This study suggests that GPD1 may act as a novel tumor suppressor in bladder cancer. Pharmacological activation of GPD1 is a potential therapeutic approach for bladder cancer.
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http://dx.doi.org/10.1186/s13045-022-01312-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284842PMC
July 2022

Findings on the Relationship Between Intestinal Microbiome and Vasculitis.

Front Cell Infect Microbiol 2022 27;12:908352. Epub 2022 Jun 27.

Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Beijing, China.

The microbiome has been implicated in small-, medium-, large-, and variable-vessel vasculitis. Dysbiosis can frequently be found in vasculitis patients with altered microbial diversity and abundance, compared with those with other diseases and healthy controls. Dominant bacteria discovered in different studies vary greatly, but in general, the intestinal microbiome in vasculitis patients tends to contain more pathogenic and less beneficial bacteria. Improvement or resolution of dysbiosis has been observed after treatment in a few longitudinal studies. In addition, some molecular changes in intestinal permeability and immune response have been found in animal models of vasculitis diseases.
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http://dx.doi.org/10.3389/fcimb.2022.908352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271958PMC
July 2022

Predominantly epithelial-type synovial sarcoma with overwhelming neuroendocrine differentiation: a potential diagnostic pitfall.

Diagn Pathol 2022 Jul 11;17(1):59. Epub 2022 Jul 11.

Department of Pathology, Guiqian International General Hospital, Guiyang, Guizhou Province, China.

Background: Synovial sarcoma is an uncommon soft tissue tumor of soft tissue, characterized by a specific SS18 rearrangement. It generally manifests as a lesion composed of monomorphic spindle cells and sometimes shows variable epithelial differentiation. Epithelial-type synovial sarcoma is rare, and synovial sarcoma with overwhelming neuroendocrine differentiation has not been reported previously.

Case Presentation: Here, we present a case of a young man with an epithelial-type synovial sarcoma of the right leg that showed an overwhelming neuroendocrine differentiation. The diagnosis was confirmed by the detection of targeted fusion re-arrangement associated with synovial sarcoma.

Conclusions: This study emphasizes the importance of molecular approaches in modern soft tissue pathology. Detecting the expression of neuroendocrine antigens in synovial sarcoma is a pre-requisite to avoid misdiagnosis of metastatic neuroendocrine tumor, malignant peripheral nerve sheath tumor with glandular differentiation, and carcinosarcoma.
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http://dx.doi.org/10.1186/s13000-022-01243-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277931PMC
July 2022

A systematic review and meta-analysis of circulating cell-free DNA as a diagnostic biomarker for non-small cell lung cancer.

J Thorac Dis 2022 Jun;14(6):2103-2111

Department of Respiratory Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Background: Early diagnosis of non-small cell lung cancer (NSCLC) is crucial for treatment. Circulating cell-free DNA (cfDNA) is an extracellular nucleic acid found in serum, and tumor cfDNA circulating in the blood may be used as a biomarker for early diagnosis. The purpose of this study was to evaluate the application value of cfDNA as a biomarker for the diagnosis of NSCLC through meta-analysis.

Methods: We searched the China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science databases using the following search terms: lung cancer, NSCLC, biomarkers, circulating cfDNA, cfDNA, circulating tumor DNA (ctDNA), circulating cell-free tumor DNA, and diagnosis. The retrieval period was set until September 2021. According to PICOS (patients, intervention, comparison, outcomes, and study design) principles the inclusion criteria were: aged ≥18 years; at least 10 NSCLC cases; NSCLC patients diagnosed by histopathology or cytology; circulating cfDNA was detected; outcome data could be completely extracted. Bias risk assessment was conducted according to the QUADAS (Quality Assessment of Diagnostic Accuracy Studies). RevMan 5.3 was used for meta-analysis.

Results: Eight studies met the inclusion criteria, including a total of 618 NSCLC patients and 635 healthy subjects. The overall sensitivity and specificity were 0.79 [95% confidence interval (CI): 0.75-0.82] and 0.81 (95% CI: 0.78-0.84), respectively. The area under the curve (AUC) of the summary receiving operating characteristic (SROC) curve was 0.8941. The pooled positive likelihood ratio, pooled negative likelihood ratio, and pooled diagnostic odds ratio were 5.37 (95% CI: 2.67-10.81), 0.24 (95% CI: 0.15-0.38), and 24.68 (95% CI: 8.85-68.84), respectively. The patient selection bias was high in two articles was high, unclear in one article, and low in the remaining five ones. The risk of bias in the research index test was unclear in one article, and low in the remaining seven articles. The reference standard bias, and flow and time bias of all articles was low.

Conclusions: Circulating cfDNA is an efficacy biomarker in diagnosis of NSCLC. Its clinical application technology is worthy of further research.
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http://dx.doi.org/10.21037/jtd-22-646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264058PMC
June 2022

Dopamine signaling promotes tissue-resident memory differentiation of CD8+ T cells and antitumor immunity.

Cancer Res 2022 Jul 8. Epub 2022 Jul 8.

Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Tissue-resident memory CD8+ T (TRM)-cells have been associated with robust protective anti-tumor immune responses and improved prognosis of cancer patients. Therefore, therapeutic strategies that modulate either the production or activity of TRM cells could be effective for treating cancer. Using a high-throughput drug screen, we showed that the neurotransmitter dopamine drives differentiation of CD8+ T cells into CD103+ TRM cells. In murine syngeneic tumor xenograft models and clinical human colon cancer samples, DRD5 served as the major functional dopamine receptor on CD8+ T cells and positively correlated with TRM cell density. DRD5 deficiency led to a failure of CD8+ T cells to accumulate in tissues, resulting in impaired TRM cell formation, reduced effector function, and uncontrolled disease progression. Moreover, dopamine treatment promoted the antitumor activity of CD8+ T cells and suppressed colorectal cancer growth in immunocompentent mouse models, and ex-vivo pre-conditioning with dopamine enhanced the in vivo efficacy of CAR-T cells. Finally, in a colorectal cancer patient cohort, dopamine expression was positively associated with patient survival and CD8+ T cell infiltration. These findings suggest that dopaminergic immunoregulation plays an important role in the differentiation of CD8+ cells into CD103+ TRM cells and thereby modulates TRM-elicited antitumor immunity in colorectal cancer.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-4084DOI Listing
July 2022

SARS-CoV-2 Omicron: a new challenge for pandemic and vaccine.

Signal Transduct Target Ther 2022 07 5;7(1):211. Epub 2022 Jul 5.

Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, China.

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http://dx.doi.org/10.1038/s41392-022-01088-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255455PMC
July 2022

Protective effects of apple polyphenols on bone loss in mice with high fat diet-induced obesity.

Food Funct 2022 Aug 1;13(15):8047-8055. Epub 2022 Aug 1.

School of Public Health, Qingdao University, Qingdao 266071, China.

Obesity-induced inflammation can lead to an imbalance in bone formation and resorption. Our previous studies have demonstrated that apple polyphenols (APs) can reduce body weight and inflammation. But their effect on bone is still unclear. In this study, we investigated the protective effects of APs on bone loss in mice with high-fat-diet (HFD)-induced obesity. Forty male C57BL/6J mice were divided into control group (10% fat diet), HFD group (60% fat diet), resveratrol group (60% fat diet), and AP group (60% fat diet). Micro-computed tomography revealed a significant increase in bone volume fraction and bone mineral density, and more trabecular bone and less trabecular bone separation in the AP group compared with the HFD group. In addition, serum tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and tartrate-resistant acid phosphatase (TRACP) levels were decreased; runt-related transcription factor 2 (Runx2) levels were increased; the collagen area was enlarged; and femur biomechanical property was enhanced in the AP group compared with the HFD group. APs significantly increased the ratio of osteoprotegerin to the receptor activator for the nuclear factor-κB ligand (OPG/RANKL) compared with the HFD group. Resveratrol could also improve the glucolipid regulation, but poorer osteogenic promotion was found compared to APs. The present study demonstrated that APs prevent loss of bone mass induced by obesity, which has potential implications for the prevention and treatment of obesity-related osteoporosis.
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http://dx.doi.org/10.1039/d2fo01332kDOI Listing
August 2022

[Inhibitory effect of autophagy on apoptosis of rat cerebral cortical neurons after oxygen-glucose deprivation and reoxygenation (OGD/R)].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2022 Jul;38(7):590-597

Department of Maxillofacial Surgery, Urumqi Stomatological Hospital, Xinjiang Province, Urumqi 830000, China.

Objective To observe the effect of autophagy on apoptosis of cerebral cortical neurons after oxygen-glucose deprivation and reoxygenation (OGD/R). Methods Eighteen newborn SD rats born within 24 hours were selected. The cortical neurons were extracted by mechanical trypsin digestion and cultured for 7 days. The OGD/R model was established. The rats were randomly divided into 3 groups: control group, OGD/R group, and OGD/R combined with Bafilomycin A1(BafA1) group. Cell viability was detected by CCK-8 assay and lactate dehydrogenase (LDH) assay, and apoptosis was detected by flow cytometry combined with fluorescein isothiocyanate labeled annexin V/propidium iodide (annexin V-FITC/PI) double labeling. The mRNA expressions of microtubule associated protein 1 light chain 3 (LC3), P62 and cystatin 3 (caspase-3) were detected by reverse transcription PCR, and the protein expressions of LC3, P62 and caspase-3 were detected by Western blot analysis. The autophagy fluorescence intensity of neurons infected with red fluorescent protein-green fluorescent protein-LC3 (RFP-GFP-LC3) adenovirus was measured, and the ultrastructural changes of autophagosomes were observed by transmission electron microscopy. Results Compared with the control group, the activity of nerve cells in OGD/R group decreased significantly while the release level of LDH increased significantly and the apoptosis increased significantly; It was also detected the increased mRNA and protein expressions of LC3, P62 and caspase-3, increased fluorescence intensity of RFP, increased autophagosomes and more gathered autophagy lysosomes. The fluorescence intensity of RFP decreased significantly after adding late autophagy inhibitor BafA1. Conclusion OGD/R induces autophagy and apoptosis of neurons, and aggravates neuronal injury and apoptosis after inhibition of autophagy.
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July 2022

HBx Mediated Increase of DDX17 Contributes to HBV-Related Hepatocellular Carcinoma Tumorigenesis.

Front Immunol 2022 16;13:871558. Epub 2022 Jun 16.

Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.

HBV is strongly associated with HCC development and DEAD-box RNA helicase 17 (DDX17) is a very important member of the DEAD box family that plays key roles in HCC development by promoting cancer metastasis. However, the important role of DDX17 in the pathogenesis of HBV-related HCC remains unclear. In this study, we investigated the role of DDX17 in the replication of HBV and the development of HBV-associated HCC. Based on data from the GEO database and HBV-infected cells, we found that DDX17 was upregulated by the HBV viral protein X (HBx). Mechanistically, increased DDX17 expression promoted HBV replication and transcription by upregulating ZWINT. Further study showed that DDX17 could promote HBx-mediated HCC metastasis. Finally, the promotive effect of DDX17 on HBV and HBV-related HCC was confirmed . In summary, the results revealed the novel role of DDX17 in the replication of HBV and the metastasis of HBV-associated HCC.
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http://dx.doi.org/10.3389/fimmu.2022.871558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243429PMC
June 2022

Alters Gut Microbiota and Immune System to Improve Cardiovascular Diseases in Murine Model.

Front Microbiol 2022 14;13:906920. Epub 2022 Jun 14.

Department of General and Vascular Surgery, Xiangya Hospital, Central South University, Changsha, China.

The gut microbiota plays an important role in a variety of cardiovascular diseases. The probiotics screened based on microbiota can effectively improve metabolism and immune function of the body, which is of great value in the field of cardiovascular disease treatment. Abdominal aortic aneurysms (AAA) refer to the lesion or injury of the abdominal aortic wall resulting in a localized bulge, which is one of the cardiovascular diseases with pulsing mass as the main clinical symptom. Previous studies have confirmed that was depleted in the guts of AAA patients or mice. is a potential probiotic for the treatment of intestinal microbiome-related diseases. Therefore, this study aims to investigate the effects of on gut microbiota and disease-related biomarkers in AAA mice. C57BL/6J mice were used to construct the AAA model and treated with . Aortic aneurysm formation in the AAA group is associated with the increased diameter of the abdominal aorta and inflammatory infiltration. inhibited the formation of AAA and repaired tissue damage. The number of gut microbiota and α diversity index were decreased in the model group. increased the number of gut microbiota and α diversity in AAA mice. The abundance of and were increased, while the abundance of the was reduced in the AAA group. Compared with the control group, the levels of MMP-1, MMP-9, IL-33, CTSB, and CTSL in tissue and the levels of IL-6, IFN-γ, and CRP in blood were significantly increased, and the levels of IL-4, IL-10, and IL-17A in blood were significantly decreased in the AAA group. The intervention of reversed these changes. The gut microbiota function prediction showed changes in , and metabolism-related functional pathways. was negatively correlated with and and positively correlated with and at the genus level. In conclusion, inhibited the formation of AAA by restoring gut microbiota diversity, altering the expression of peripheral immune factors, and the functions of , and , which may provide a new theoretical basis for the application of probiotics in cardiovascular diseases.
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http://dx.doi.org/10.3389/fmicb.2022.906920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237526PMC
June 2022

Association Between Circulating Cell-Free DNA Level at Admission and the Risk of Heart Failure Incidence in Acute Myocardial Infarction Patients.

DNA Cell Biol 2022 Aug 28;41(8):742-749. Epub 2022 Jun 28.

Department of Cardiology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.

Plasma cell-free DNA (cfDNA) was elevated in patients with acute myocardial infarction (AMI) or heart failure (HF). However, whether cfDNA could serve as a predictor for risk of HF after AMI remains unknown. In this study, we conducted a pilot prospective cohort study in which 98 AMI patients were enrolled from a single center to assess the association between cfDNA levels at admission and risk of HF in an AMI population. Patients with cfDNA above the median level (14.39 ng/mL) showed higher low-density lipoprotein cholesterol, cardiac troponin I (cTnI), and soluble suppression of tumorigenicity 2 (sST2) levels compared with patients below the median. cfDNA was positively correlated with cTnI ( = 0.377,  < 0.001) and sST2 ( = 0.443,  < 0.001). Within a median follow-up of about 345 days, 46 patients (52.6%) developed HF. Multivariate Cox analysis showed that a higher cfDNA (above the cutoff value: 9.227 ng/mL) was an effective risk predictor (C-index = 0.74, 95% confidence interval [CI]: 0.733-0.748) for HF incidence after AMI (adjusted hazard ratio [HR]: 2.805; 95% CI: 1.087-7.242;  = 0.033). Moreover, a linear association was observed between cfDNA and risk of HF incidence adjusted for by age, gender, and history of chronic kidney disease ( for linear trend = 0.044). Taken together, the cfDNA levels at admission are associated with the incidence of HF in AMI patients. A positive correlation between cfDNA and the fibrotic factor sST2 was proved, but the underlying mechanisms require further study.
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http://dx.doi.org/10.1089/dna.2022.0238DOI Listing
August 2022

Renal amyloidosis secondary to ANCA-associated vasculitis: a case report.

Chin Med Sci J 2022 Jun 28. Epub 2022 Jun 28.

Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, China.

Renal amyloidosis secondary to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is extremely rare. Here, we reported a 77-year-old woman with ANCA-associated vasculitis. Renal biopsy with Masson trichrome staining showed pauci-immune crescentic glomerulonephritis, and electron microscopy showed amyloid deposition in the mesangial area. Immunofluorescence revealed kappa light chain and lambda light chain were negative. Bone marrow biopsy revealed no clonal plasma cell. Finally, she was diagnosed as ANCA-associated vasculitis with secondary renal amyloid A amyloidosis.
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http://dx.doi.org/10.24920/003999DOI Listing
June 2022

VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration Enhancing Osteogenesis-Angiogenesis Coupling.

Front Bioeng Biotechnol 2022 8;10:915181. Epub 2022 Jun 8.

Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, China.

Bone tissue defect, one of the common orthopaedicdiseases, is traumatizing and affects patient's lifestyle. Although autologous and xenograft bone transplantations are performed in bone tissue engineering, clinical development of bone transplantation is limited because ofvarious factors, such as varying degrees of immune rejection, lack of bone sources, and secondary damage to bone harvesting. We synthesised a heparinised gelatine-hydroxyapatite-tricalcium phosphate (HG-HA-TCP) scaffold loaded with sustained-release vascular endothelial growth factor (VEGF) analysed their structure, mechanical properties, and biocompatibility. Additionally, the effects of HG-HA-TCP (VEGF) scaffolds on osteogenic differentiation and vascularisation of stem cells from human exfoliated deciduous teeth (SHED) and bone regeneration were investigated. HG-HA-TCP scaffold possessed good pore structure, mechanical properties, and biocompatibility. HG-HA-TCP scaffold loaded with VEGF could effectively promote SHED proliferation, migration, and adhesion. Moreover, HG-HA-TCP (VEGF) scaffold increased the expression of osteogenesis- and angiogenesis-related genes and promoted osteogenic differentiation and vascularisation in cells. results demonstrated that VEGF-loaded HG-HA-TCP scaffold improved new bone regeneration and enhanced bone mineral density, revealed byhistological, micro-CT and histochemical straining analyses. Osteogenic and angiogenic abilities of the three biological scaffolds wereranked as follows: HG-HA-TCP (VEGF) > G-HA-TCP (VEGF) > G-HA-TCP. HG-HA-TCP (VEGF) scaffold with good biocompatibility could create an encouraging osteogenic microenvironment that could accelerate vessel formation and osteogenesis, providing an effective scaffold for bone tissue engineering and developing new clinical treatment strategies for bone tissue defects.
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http://dx.doi.org/10.3389/fbioe.2022.915181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9216719PMC
June 2022

Canonical Wnt signaling works downstream of iron overload to prevent ferroptosis from damaging osteoblast differentiation.

Free Radic Biol Med 2022 Aug 23;188:337-350. Epub 2022 Jun 23.

Laboratory of Skeletal Development and Regeneration, Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China; Department of Orthopedics, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. Electronic address:

Excessive iron has emerged in a large population of patients suffering from degenerative or hematological diseases with a common outcome, osteoporosis. However, its underlying mechanism remains to be clarified in order to formulate effective prevention and intervention against the loss of bone-forming osteoblasts. We show herein that increased intracellular iron by ferric ammonium citrate (FAC) mimicking the so-called non-transferrin bound iron concentrations leads to ferroptosis and impaired osteoblast differentiation. FAC upregulates the expression of Trfr and DMT1 genes to increase iron uptake, accumulating intracellular labile ferrous iron for iron overload status. Then, the excessive ferrous iron generates reactive oxygen species (ROS) and lipid peroxidation products (LPO), causing ferroptosis with its typical mitochondrial morphological changes, such as shrinkaged and condensed membrane with diminution and loss of crista and outer membrane rupture. We further examined that ferroptosis is the main cause responsible for FAC-disrupted osteoblast differentiation, although apoptosis and senescence are concurrently induced as well. Mechanistically, we revealed that iron dose-dependently down-regulates the expression of Wnt target genes and inhibits the transcription of Wnt reporter TopFlash construct, so as to inhibit the canonical Wnt signaling. Wnt agonist, ferroptosis inhibitor, or antioxidant melatonin reverses iron-inhibited canonical Wnt signaling to restore osteoblast differentiation by reducing ROS and LPO production to prevent ferroptosis notably without reducing iron overload. This study proposes a working model against excessive iron-induced osteoporosis: iron chelator deferoxamine or the above three drugs prevent ferroptosis, restore traditional Wnt signaling to maintain osteoblast differentiation no matter whether iron overload is removed or not. Additionally, iron chelator should be used to a suitable extent because iron itself is necessary for osteogenic differentiation.
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http://dx.doi.org/10.1016/j.freeradbiomed.2022.06.236DOI Listing
August 2022

CuO-Modified Nanoporous Cu Foil as a Self-Supporting Electrode for Supercapacitor and Oxygen Evolution Reaction.

Nanomaterials (Basel) 2022 Jun 20;12(12). Epub 2022 Jun 20.

School of Applied Physics and Materials, Wuyi University, 99 Yingbin Road, Jiangmen 529020, China.

Designing and modifying nanoporous metal foils to make them suitable for supercapacitor and catalysis is significant but challenging. In this work, CuO nanoflakes have been successfully in situ grown on nanoporous Cu foil via a facile electrooxidation method. A Ga-assisted surface Ga-Cu alloying-dealloying is adopted to realize the formation of a nanoporous Cu layer on the flexible Cu foil. The following electrooxidation, at a constant potential, modifies the nanoporous Cu layer with CuO nanoflakes. The optimum CuO/Cu electrode (O-Cu-2h) delivers the maximum areal capacitance of 0.745 F cm (410.27 F g) at 0.2 mA cm and maintains 94.71% of the capacitance after 12,000 cycles. The supercapacitor consisted of the O-Cu-2h as the positive electrode and activated carbon as the negative electrode has an energy density of 24.20 Wh kg and power density of 0.65 kW kg. The potential of using the electrode as oxygen evolution reaction catalysts is also investigated. The overpotential of O-Cu-2h at 10 mA cm is 394 mV; however, the long-term stability still needs further improvement.
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http://dx.doi.org/10.3390/nano12122121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227449PMC
June 2022

Past lesson works: SARS memory moderates the relationship between media use and protective behavior during COVID-19 pandemic in China.

J Health Psychol 2022 Jun 22:13591053221105349. Epub 2022 Jun 22.

Peking University, China.

COVID-19 has become one of the top global health concerns. The present research examined the relationship between media use and protective behavior. The moderating role of SARS memory was also examined. A cross-sectional study found that media use was associated with more protective behaviors (i.e. preventive behavior, and avoidant behavior). We further found that SARS memory moderated the association between media use and avoidant behavior. Moreover, the moderating role of SARS memory on the relationship between daily media use and daily protective behavior was again tested using a daily design in Study 2. Theoretical and practical implications are discussed.
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http://dx.doi.org/10.1177/13591053221105349DOI Listing
June 2022

Inorganic Crystal Structure Prototype Database Based on Unsupervised Learning of Local Atomic Environments.

J Phys Chem A 2022 Jul 22;126(26):4300-4312. Epub 2022 Jun 22.

State Key Laboratory of Integrated Optoelectronics, Key Laboratory of Automobile Materials of MOE, School of Materials Science and Engineering, and Jilin Provincial International Cooperation Key Laboratory of High-Efficiency Clean Energy Materials, Jilin University, Changchun 130012, China.

Recognition of structure prototypes from tremendous known inorganic crystal structures has been an important subject beneficial for materials science research and new materials design. The existing databases of inorganic crystal structure prototypes were mostly constructed by classifying materials in terms of the crystallographic space group information. Herein, we employed a distinct strategy to construct the inorganic crystal structure prototype database, relying on the classification of materials in terms of local atomic environments (LAEs) accompanied by unsupervised machine learning method. Specifically, we adopted a hierarchical clustering approach onto all experimentally known inorganic crystal structure data to identify structure prototypes. The criterion for hierarchical clustering is the LAE represented by the state-of-the-art structure fingerprints of the improved bond-orientational order parameters and the smooth overlap of atomic positions. This allows us to build up a LAE-based Inorganic Crystal Structure Prototype Database (LAE-ICSPD) containing 15,613 structure prototypes with defined stoichiometries. In addition, we have developed a Structure Prototype Generator Infrastructure (SPGI) package, which is a useful toolkit for structure prototype generation. Our developed SPGI toolkit and LAE-ICSPD are beneficial for investigating inorganic materials in a global way as well as accelerating the materials discovery process in the data-driven mode.
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http://dx.doi.org/10.1021/acs.jpca.2c03416DOI Listing
July 2022

E2F7 promotes mammalian target of rapamycin inhibitor resistance in hepatocellular carcinoma after liver transplantation.

Am J Transplant 2022 Jun 21. Epub 2022 Jun 21.

Zhejaing University, School of Medicine, Hangzhou, China.

The mammalian target of rapamycin (mTOR) pathway is frequently deregulated and has critical roles in cancer progression. mTOR inhibitor has been widely used in several kinds of cancers and is strongly recommended in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). However, the poor response to mTOR inhibitors due to resistance remains a challenge. Hypoxia-associated resistance limits the therapeutic efficacy of targeted drugs. The present study established models of HCC clinical samples and cell lines resistance to mTOR inhibitor sirolimus and screened out E2F7 as a candidate gene induced by hypoxia and promoting sirolimus resistance. E2F7 suppressed mTOR complex 1 via directly binding to the promoter of the TSC1 gene and stabilizes hypoxia-inducible factor-1α activating its downstream genes, which are responsible for E2F7-dependent mTOR inhibitor resistance. Clinically, low E2F7 expression could be an effective biomarker for recommending patients with HCC for anti-mTOR-based therapies after LT. Targeting E2F7 synergistically inhibited HCC growth with sirolimus in vivo. E2F7 is a promising target to reverse mTOR inhibition resistance. Collectively, our study points to a role for E2F7 in promoting mTOR inhibitor resistance in HCC and emphasizes its potential clinical significance in patients with HCC after LT.
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http://dx.doi.org/10.1111/ajt.17124DOI Listing
June 2022
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