Publications by authors named "Ying Yang"

2,204 Publications

  • Page 1 of 1

Nitrogen and copper-doped carbon quantum dots with intrinsic peroxidase-like activity for double-signal detection of phenol.

Analyst 2021 Jun 9. Epub 2021 Jun 9.

Anhui Key Laboratory of Chemo-Biosensing, Key Laboratory of Functional Molecular Solids, Ministry of Education, College of Chemistry and Materials Science, Anhui Normal University, Wuhu, 241000, P R China.

Herein, a simple and facile one-step hydrothermal carbonization synthesis procedure for the fabrication of N, Cu-doped carbon quantum dots (N, Cu-CQDs) as a peroxidase-mimicking enzyme was reported. The peroxidase-like performance of N, Cu-CQDs was assessed based on the oxidative coupling reaction of phenol with 4-aminoantipyrine (4-AAP) in the presence of hydrogen peroxide (H2O2). The N, Cu-CQDs/4-AAP/H2O2 system was applied to sensing phenol based on double signals of absorption spectra (or colorimetric visualization) as well as fluorescence spectra. The obtained limits of detection (LODs) were as low as 0.12 μM and 0.02 μM, respectively. Moreover, the proposed method was successfully applied to the determination of phenol in sewage with satisfactory recovery. Our results demonstrate that the N, Cu-CQDs/4-AAP/H2O2/phenol sensing system has a great potential prospect for applications in environmental chemistry and biotechnology.
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http://dx.doi.org/10.1039/d1an00796cDOI Listing
June 2021

Improvement of sperm traits related to the high level of extra-pair fertilization in tree sparrow population under long-term environmental heavy metal pollution.

Sci Total Environ 2021 May 29;790:148109. Epub 2021 May 29.

Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou, 730000, China. Electronic address:

Environmental stress can affect sperm traits whose changes have been reported to be associated with extra-pair fertilization (EPF) level in natural animal populations. However, little is known regarding how exposure to environmental heavy metals influences sperm traits and EPF level in free-living bird populations. In a previous study, we found that a tree sparrow (Passer montanus) population that has been exposed to heavy metal pollution over 60 years (Baiyin, BY) exhibits increased sperm quality compared with a population from a relatively unpolluted area (Liujiaxia, LJX). The high sperm quality could be related to extra-pair mating rates. Therefore, the present study investigated EPF level (the ratio of extra-pair offspring) in tree sparrow populations from BY and LJX, and analyzed the relationship between sperm traits (morphology, velocity and quantity) and EPF success. EPF success of tree sparrows was significantly correlated with their sperm velocity (p = 0.048) and total sperm length (p = 0.045), indicating that these sperm traits were important for EPF success. Tree sparrows from the BY population produced longer sperm with lower head/flagellum ratio and faster swimming sperm and showed a significantly higher EPF level than conspecifics from LJX. Thus, adaptive variation of sperm characteristics was related to the high EPF level in tree sparrows under long-term environmental heavy metal pollution. The findings are of scientific significance for exploring the evolution of mating tactics in wild bird populations under environmental stress.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148109DOI Listing
May 2021

Histone demethylase PHF8 promotes cell growth and metastasis of non-small-cell lung cancer through activating Wnt/β-catenin signaling pathway.

Histol Histopathol 2021 Jun 8:18349. Epub 2021 Jun 8.

Department of Respiratory, The First People's Hospital of Zigong City, Zigong, China.

PHD finger protein 8 (PHF8), serving as a histone demethylase, is upregulated in some types of malignant tumors. The role of PHF8 in non-small-cancer lung carcinoma (NSCLC) remains unclear. This study aims to verify the effect of PHF8 in NSCLC and its molecular mechanism. We collected 20 cases of fresh NSCLC and adjacent lung tissues to assess differential expressions of PHF8 by reverse transcription-quantitative PCR (RT-qPCR). Western blot was employed to examine protein levels of PHF8, Wnt1, β-catenin and epithelial-mesenchymal transition (EMT) related proteins. Chromatin immunoprecipitation assays were executed to confirm the regulatory mechanism of PHF8 and Wnt1. Cell Counting Kit-8 assays and Transwell assays were utilized to identify the effects of PHF8/Wnt1 pathway on cell proliferation, migration and invasion. PHF8 was overexpressed in NSCLC tissues and cells and higher PHF8 expression was correlated with poorer overall survival in NSCLC patients. PHF8 overexpression promoted NSCLC cell proliferation, migration and invasion, while PHF8 knockdown exerted the opposite effect. Mechanistic investigations identified that PHF8 occupied the Wnt1 promoter, leading to a decrease of repressive histone markers H3K9me1, H3K9me2, H3K27me2 and H4K20me1 in the promoter region of the Wnt1 gene, which further promoted the transcription of the Wnt1 gene. PHF8 activated Wnt/β-catenin signaling pathway through promoting Wnt1 expression. Besides, PHF8 altered the EMT of NSCLC through regulating Wnt1 levels. PHF8, acting as an oncogene and prognostic biomarker in NSCLC, stimulated NSCLC to proliferate, metastasis and EMT by activating Wnt/β-catenin signaling.
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http://dx.doi.org/10.14670/HH-18-349DOI Listing
June 2021

Gastric cancer cell-derived exosomes can regulate the biological functions of mesenchymal stem cells by inducing the expression of circular RNA circ_0004303.

Stem Cells Dev 2021 Jun 7. Epub 2021 Jun 7.

Qingdao University, 12593, School of Basic Medicine, Qingdao, Shandong, China, 266071.

As an important component of the dynamic tumor microenvironment, mesenchymal stem cells (MSCs) can interact with tumor cells to promote tumor growth. Treatment with tumor cell-derived exosomes can change the biological functions of MSCs. We want to study the mechanism by which exosomes derived from gastric cancer cells affect the biological functions of MSCs. After MSCs were treated with AGS cell-derived exosomes, circular RNAs differentially expressed in MSCs were verified using existing RNA microarray results combined with real-time quantitative polymerase chain reaction (qRT-PCR). Then, circular RNAs were knocked down or overexpressed by plasmids, and the functions of circular RNAs were evaluated by Migration and invasion assay. Dual luciferase reporter assay was used to evaluate the potential mechanism of circular RNAs. After treatment with exosomes secreted by AGS, the results showed that some circular RNAs expressed by human adipose derived mesenchymal stem cells showed significant differences. The elevated circ_0004303 promoted the migration and invasion of human adipose derived mesenchymal stem cells in vitro. Circ_0004303 upregulated the expression of ALCAM by acting as a miR-148a-3p sponge, thereby enhancing the migration and invasion functions of human adipose derived mesenchymal stem cells. Therefore, exosomes secreted by AGS can affect the expression of circular RNAs in human adipose derived mesenchymal stem cells. Hsa_circ_0004303 can regulate the migration and invasion of human adipose derived mesenchymal stem cells via the miR-148a-3P /ALCAM axis. This study suggests that tumor cells can promote the migration and homing of MSCs in adjacent tissues by secreting exosomes.
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http://dx.doi.org/10.1089/scd.2021.0059DOI Listing
June 2021

An HECT domain ubiquitin ligase CgWWP1 regulates granulocytes proliferation in oyster Crassostrea gigas.

Dev Comp Immunol 2021 Jun 12;123:104148. Epub 2021 Jun 12.

Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Southern Laboratory of Ocean Science and Engineering (Guangdong, Zhuhai), Zhuhai, 519000, China; Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China. Electronic address:

Ubiquitination is involved in the regulation of granulocyte proliferation in vertebrate, and E3 ubiquitin ligase WWP1 has been reported to play an essential role in this process. In the present study, an HECT type E3 ubiquitin ligase (CgWWP1) was identified from oyster Crassostrea gigas, which contained a N-terminal C2 domain, four WW domains, and a C-terminal HECT domain. CgWWP1 was able to bind the activated ubiquitin (Ub) and formed CgWWP1-Ub complex in vitro. The mRNA transcripts of CgWWP1 were expressed in granulocytes, semi-granulocytes and agranulocytes, with the highest expression level in granulocytes. The expressions of potential granulocyte markers CgSOX11 (0.18-fold, p < 0.05) and CgAATase (0.2-fold, p < 0.01) in haemocytes were significantly down-regulated at 24 h after the treatment with Indole-3-carbinol (I3C), a WWP1 inhibitor. The proportions of EdU granulocytes reduced significantly at 12 h (8.1% ± 1.4%) and 24 h (9.7% ± 2.8%) after I3C treatment, which were significantly lower than that in the sterile seawater treatment (SW) group at 12 h (15.8% ± 4.2%) and 24 h (17.6% ± 0.8%), respectively. Meanwhile, the green EdU signals observed by confocal scanning microscopy in granulocytes of oysters treated by I3C became weaker compared to that in the SW group. These results indicated that CgWWP1 was involved in the regulation of granulocyte proliferation as a ubiquitin-protein ligase.
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http://dx.doi.org/10.1016/j.dci.2021.104148DOI Listing
June 2021

MiR-27a-3p enhances the cisplatin sensitivity in hepatocellular carcinoma cells through inhibiting PI3K/Akt pathway.

Biosci Rep 2021 Jun 7. Epub 2021 Jun 7.

Xinjiang Medical University Affiliated First Hospital, Urumqi, China.

MicroRNAs (miRNAs) play an important role in drug-resistance, and it's reported that MiR-27a-3p regulated the sensitivity of cisplatin in breast cancer, lung cancer and ovarian cancer. However, the relationship between miR-27a-3p and chemosensitivity of cisplatin in HCC was unclear, especially the underlying mechanism was unknown. In present study, we analyzed miR-27a-3p expression levels in 372 tumor tissues and 49 adjacent tissues in HCC samples from TCGA database, and found that the miR-27a-3p was downregulated in HCC tissues. The level of miR-27a-3p was associated with metastasis, Child-Pugh grade and race. MiR-27a-3p was regarded as a favorable prognosis indicator for HCC patients. Then, miR-27a-3p was overexpressed in HepG2 cell, and was knockdown in PLC cell. Next, we conducted a series of vitro assays, including MTT, apoptosis and cell cycle assays to observe the biological changes. Further, inhibitor rate and apoptosis rate were detected with pre- and post-cisplatin treatment in HCC. The results showed that overexpression of miR-27a-3p repressed the cell viability, promoted apoptosis and increased the percentage of cells in phase G0/G1 phase. Importantly, overexpression of miR-27a-3p significantly increased the inhibitor rate and apoptosis rate with cisplatin intervention. Besides, we found that miR-27a-3p added cisplatin sensitivity potentially through regulating PI3K/Akt signaling pathway. Taken together, MiR-27a-3p acted as a tumor suppressor gene in HCC cells, and it could be useful for modulating cisplatin sensitivity in chemotherapy therapy.
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http://dx.doi.org/10.1042/BSR20192007DOI Listing
June 2021

Dravet syndrome-associated mutations in , and define the genetic landscape of defects of GABA receptors.

Brain Commun 2021 11;3(2):fcab033. Epub 2021 Mar 11.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37240, USA.

Dravet syndrome is a rare, catastrophic epileptic encephalopathy that begins in the first year of life, usually with febrile or afebrile hemiclonic or generalized tonic-clonic seizures followed by status epilepticus. variants in genes that mediate synaptic transmission such as and are often associated with Dravet syndrome. Recently, GABA receptor subunit genes () encoding α1 (), β3 () and γ2 (), but not β2 () or β1 (), subunits are frequently associated with Dravet syndrome or Dravet syndrome-like phenotype. We performed next generation sequencing on 870 patients with Dravet syndrome and identified nine variants in three different . Interestingly, the variants were all in genes encoding the most common GABA receptor, the α1β2γ2 receptor. Mutations in (c.644T>C, p. L215P; c.640C>T, p. R214C; c.859G>A; V287I; c.641G>A, p. R214H) and (c.269C>G, p. T90R; c.1025C>T, p. P342L) presented as cases, while in two variants were (c.992T>C, p. F331S; c.542A>T, p. Y181F) and one was autosomal dominant and inherited from the maternal side (c.990_992del, p.330_331del). We characterized the effects of these variants on GABA receptor biogenesis and channel function. We found that defects in receptor gating were the common deficiency of and Dravet syndrome variants, while mainly trafficking defects were found with the (c.269C>G, p. T90R) variant. It seems that variants in α1 and β2 subunits are less tolerated than in γ2 subunits, since variant α1 and β2 subunits express well but were functionally deficient. This suggests that all of these variants are all targeting genes that encode the assembled α1β2γ2 receptor, and regardless of which of the three subunits are mutated, variants in genes coding for α1, β2 and γ2 receptor subunits make them candidate causative genes in the pathogenesis of Dravet syndrome.
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http://dx.doi.org/10.1093/braincomms/fcab033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176149PMC
March 2021

Retrospective Analysis of the Clinical Characteristics of Infection Worldwide From 2009 to 2020.

Front Microbiol 2021 20;12:658329. Epub 2021 May 20.

Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing, China.

Introduction: is an emerging multidrug-resistant fungus that may cause infections with a high mortality rate. The first case of infection was reported in 2009 and infections have been reported in 44 countries. The fungus now represents a major global public health threat. We analyzed cases from the emergence of infections up until the end of 2020. It is hoped that the results of this analysis will raise awareness in scientists to promote protection and control research pertaining to this pathogen.

Methods: PubMed and Web of Science databases were searched for all papers related to infections up until December 31, 2020. We sorted and organized these data into the following categories: date of publication, patient age and sex, underlying diseases, risk factors for infection, patient mortality information, drug sensitivity information of isolates, and genetic classification. The χ test was used to screen for factors that may affect patient mortality.

Results: A total of 912 patients were included in the analysis. There's a higher proportion of men and a high proportion of patients were premature babies and elderly people. The proportions of patients with underlying diseases such as diabetes, kidney disease, trauma, and ear disease were also high. More than half of patients had a history of central venous catheter use and a history of broad-spectrum antibiotic use. The χ test revealed that only kidney disease ( < 0.05) was an important risk factor for mortality in infected patients.

Conclusions: A comprehensive understanding of was achieved following this retrospective analysis, including the characteristics of -infected patients. In recent years, increasing numbers of multidrug-resistant isolates have been identified, and the high mortality rates associated with infection merit greater attention from the medical world.
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http://dx.doi.org/10.3389/fmicb.2021.658329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173142PMC
May 2021

Sizes and ligands tuned gold nanocluster acting as a new type of monoamine oxidase B inhibitor.

Biosens Bioelectron 2021 May 29;189:113377. Epub 2021 May 29.

College of Pharmacy, Jinan University, Guangzhou, 510632, PR China; First Affiliated Hospital of Jinan University, Guangzhou, 510632, PR China. Electronic address:

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that can be used in the treatment of Parkinson's disease, clinical depression, and anxiety by targeting monoamine oxidase B (MAO). However, the side effects of MAOIs drive the requirement of a new framework of enzyme inhibitors development. In this context, a new type of MAOI has been built on the framework of gold nanoclusters (AuNCs), realizing the transformation from no function of small molecules to MAOI function of ligand-modified AuNCs. The MAOI activity of fabricated AuNCs can be achieved by size control and specific ligands modification. In this work, AuNCs modified with cysteamine or 4-aminothiophenol, about 1-3 nm in size, were found to have MAOI activity (MAOI-like AuNCs) and their characterization has been extensively described. Meanwhile, the possible mechanism behind this MAOI activity has been explored and it is believed that the proper size of AuNCs with ligands containing amino groups can bind tightly with the entrance to active sites of MAO, blocking the enzyme interacting with its substrates, thereby realizing the function of MAOI. Last, the antimicrobial activity and the performance of the MAOI-like AuNCs in the human blood sample were explored and suggested that MAOI-like AuNCs do not possess strong antimicrobial activity and have no visualized side effect on blood cells, although the by-product peroxide of MAO reaction may reshape the white blood cells. The research in this work may shed some light on the development of a new type of enzyme inhibitor based on the framework of nanomaterials.
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http://dx.doi.org/10.1016/j.bios.2021.113377DOI Listing
May 2021

Illuminating Neural Circuits in Alzheimer's Disease.

Neurosci Bull 2021 Jun 5. Epub 2021 Jun 5.

Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and there is currently no cure. Neural circuit dysfunction is the fundamental mechanism underlying the learning and memory deficits in patients with AD. Therefore, it is important to understand the structural features and mechanisms underlying the deregulated circuits during AD progression, by which new tools for intervention can be developed. Here, we briefly summarize the most recently established cutting-edge experimental approaches and key techniques that enable neural circuit tracing and manipulation of their activity. We also discuss the advantages and limitations of these approaches. Finally, we review the applications of these techniques in the discovery of circuit mechanisms underlying β-amyloid and tau pathologies during AD progression, and as well as the strategies for targeted AD treatments.
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http://dx.doi.org/10.1007/s12264-021-00716-6DOI Listing
June 2021

Honesty-Humility and unethical behavior in adolescents: The mediating role of moral disengagement and the moderating role of system justification.

J Adolesc 2021 Jun 1;90:11-22. Epub 2021 Jun 1.

Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education (Beijing Normal University), Institute of Developmental Psychology, Beijing Normal University, Beijing, 100875, China. Electronic address:

Introduction: Honesty-Humility represents the tendency to be fair, genuine, and cooperative in social interactions. Although previous evidence has demonstrated that Honesty-Humility is related to decreased unethical behavior, little is known about the mediating and moderating mechanisms underlying this relationship, especially among adolescents. Based on social cognitive theory and system justification theory, the present study aims to examine the mediating role of moral disengagement and the moderating role of system justification in the relationship between Honesty-Humility and unethical behavior among Chinese adolescents.

Methods: A large sample of Chinese adolescents (N = 2,576, 47% boys; M = 17.00 years, SD = 1.07) was recruited from four senior high schools. The participants completed questionnaires regarding Honesty-Humility, moral disengagement, system justification, and unethical behavior.

Results: The findings suggested that Honesty-Humility was negatively associated with adolescents' unethical behavior, and moral disengagement partially mediated this negative association. Furthermore, system justification moderated the mediation model. Specifically, the negative relationships between Honesty-Humility and moral disengagement/unethical behavior were stronger among adolescents who perceive the society as fair.

Conclusion: These findings advance the understanding of when and how Honesty-Humility prevents adolescents from unethical behavior. The theoretical and practical implications of the current study as well as future research directions are discussed.
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http://dx.doi.org/10.1016/j.adolescence.2021.05.009DOI Listing
June 2021

Mutation of the novel acetylation site at K414R of BECN1 is involved in adipocyte differentiation and lipolysis.

J Cell Mol Med 2021 Jun 4. Epub 2021 Jun 4.

Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, China.

BECN1, a protein essential for autophagy, is involved in adipocyte differentiation, lipolysis and insulin resistance. The discovery of new mechanisms for modifying BECN1 in adipocytes may provide novel therapeutic targets for obesity. This study aimed to investigate the impact of mutations at the acetylation sites of BECN1 on adipocyte differentiation and lipolysis. We found that Ace-BECN1 levels were increased in 3T3-L1 adipocyte differentiation and isoproterenol-/TNF-α-stimulated lipolysis and in subcutaneous and visceral adipose tissues of high-fat diet mice. K414 was identified as an acetylation site of BECN1, which affects the stability of the BECN1 protein. Mutation at K414 of BECN1 affected autophagy, differentiation and lipolysis in 3T3-L1 adipocytes. These data indicated the potential of BECN1 K414 as a key molecule and a drug target for regulating autophagy and lipid metabolism in adipocytes.
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http://dx.doi.org/10.1111/jcmm.16692DOI Listing
June 2021

Protective effects of glycine against lipopolysaccharide-induced intestinal apoptosis and inflammation.

Amino Acids 2021 Jun 4. Epub 2021 Jun 4.

State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, 100193, China.

Intestinal dysfunction is commonly observed in humans and animals. Glycine (Gly) is a functional amino acid with anti-inflammatory and anti-apoptotic properties. The objective of this study was to test the protective effects of Gly against lipopolysaccharide (LPS)-induced intestinal injury. 28 C57BL/6 mice with a body weight (BW) of 18 ± 2 g were randomly assigned into four groups: CON (control), GLY (orally administered Gly, 5 g/kg BW/day for 6 days), LPS (5 mg/kg BW on day 7, i. p.), and GLY + LPS (Gly pretreatment and LPS administration). Histological alterations, inflammatory responses, epithelial cell apoptosis, and changes of the intestinal microbiota were analyzed. Results showed that, compared with the CON group, mice in the LPS treatment group showed decreased villus height, increased crypt depth, and decreased ratio of villus height to crypt depth, which were significantly attenuated by Gly. Neither LPS nor Gly treatment altered morphology of the distal colon tissues. LPS increased the apoptosis of jejunum and colon epithelial cells and protein abundance of cleaved caspase3 in the jejunum, which were markedly abrogated by Gly. LPS also elevated the mRNA levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MYD88), pro-inflammatory cytokines, and chemokines in the jejunum and colon. These alterations were significantly suppressed by Gly. In addition, Gly supplementation attenuated infiltration of CD4, CD8 T-lymphocytes, CD11b and F4/80 macrophages in the colon. Furthermore, Gly increased the relative abundance of Mucispirillum, Lachnospiraceae-NK4A136-group, Anaerotruncus, Faecalibaculum, Ruminococcaceae-UCG-014, and decreased the abundance of Bacteroides at genus level. Supplementation with Gly might be a nutritional strategy to ameliorate LPS-induced intestinal injury in mice.
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http://dx.doi.org/10.1007/s00726-021-03011-wDOI Listing
June 2021

Cruxome: a powerful tool for annotating, interpreting and reporting genetic variants.

BMC Genomics 2021 Jun 3;22(1):407. Epub 2021 Jun 3.

Berry Genomics Company Limited, Building 5, Courtyard 4, Shengmingyuan Road, ZGC Life Science Park, Changping District, 102200, Beijing, China.

Background: Next-generation sequencing (NGS) is an efficient tool used for identifying pathogenic variants that cause Mendelian disorders. However, the lack of bioinformatics training of researchers makes the interpretation of identified variants a challenge in terms of precision and efficiency. In addition, the non-standardized phenotypic description of human diseases also makes it difficult to establish an integrated analysis pathway for variant annotation and interpretation. Solutions to these bottlenecks are urgently needed.

Results: We develop a tool named "Cruxome" to automatically annotate and interpret single nucleotide variants (SNVs) and small insertions and deletions (InDels). Our approach greatly simplifies the current burdensome task of clinical geneticists and scientists to identify the causative pathogenic variants and build personal knowledge reference bases. The integrated architecture of Cruxome offers key advantages such as an interactive and user-friendly interface and the assimilation of electronic health records of the patient. By combining a natural language processing algorithm, Cruxome can efficiently process the clinical description of diseases to HPO standardized vocabularies. By using machine learning, in silico predictive algorithms, integrated multiple databases and supplementary tools, Cruxome can automatically process SNVs and InDels variants (trio-family or proband-only cases) and clinical diagnosis records, then annotate, score, identify and interpret pathogenic variants to finally generate a standardized clinical report following American College of Medical Genetics and Genomics/ Association for Molecular Pathology (ACMG/AMP) guidelines. Cruxome also provides supplementary tools to examine and visualize the genes or variations in historical cases, which can help to better understand the genetic basis of the disease.

Conclusions: Cruxome is an efficient tool for annotation and interpretation of variations and dramatically reduces the workload for clinical geneticists and researchers to interpret NGS results, simplifying their decision-making processes. We present an online version of Cruxome, which is freely available to academics and clinical researchers. The site is accessible at http://114.251.61.49:10024/cruxome/ .
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http://dx.doi.org/10.1186/s12864-021-07728-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173893PMC
June 2021

Association between air particulate matter pollution and blood cell counts of women preparing for pregnancy: Baseline analysis of a national birth cohort in China.

Environ Res 2021 May 30;200:111399. Epub 2021 May 30.

Environmental and Spatial Epidemiology Research Center, National Human Genetic Resources Center, Beijing, China; National Research Institute for Family Planning, Beijing, China. Electronic address:

Background: Limited evidence is known about whether long-term exposures to air borne particulate matters of 2.5 μm or less (PM) impact human hematologic index for women preparing for pregnancy. No study assessed the effect of PM, which is small enough to reach the blood circulation.

Objective: To evaluate whether exposure to PM and PM is associated with blood cell count of woman preparing for pregnancy.

Method: Based on the baseline data of a national birth cohort in China, we analysed the white blood cell (WBC), red blood cells (RBC) and thrombocyte counts of 1,203,565 women who are aged 18-45 years, being Han ethnicity, had no chronic disease and preparing for pregnancy. We matched their home addresses and examination date with daily concentrations of PM and PM which were estimated by a machine learning method with remote sensing, meteorological and land use information. Generalized additive mixed model to examine the associations between exposure to one-year average exposure to PMs prior to the health examination and the blood cells counts, after adjustment for potential individual variables.

Results: A 10 μg/m PM increment was associated with -1.49% (95%CI: 1.56%, -1.42%) difference in WBC count; with 0.33% (95%CI: 0.30%, 0.36%) difference of RBC count; and with 1.08% (95%CI: 1.01%, 1.15%) difference of thrombocyte count. For PM, the corresponding difference was -0.47% (95%CI: 0.54%, -0.39%) for WBC; was 0.06% (95%CI: 0.03%, 0.09%) for RBC; and was 1.10% (95%CI: 1.02%, 1.18%) for thrombocyte. Women working as workers, being overweight and with tobacco smoking exposure had higher associations between PMs and hematologic index than their counterparts (p < 0.05 for interaction test).

Conclusion: Long-term exposure to PMs were associated with decrement in WBC, as well as increment in RBC and thrombocytes among Han Chinese women preparing for pregnancy. Measures such as using air purifiers and wearing a mask in polluted areas should be improved to prevent women from the impact of PMs.
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http://dx.doi.org/10.1016/j.envres.2021.111399DOI Listing
May 2021

Glycine Attenuates Citrobacter rodentium-Induced Colitis by Regulating ATF6-Mediated Endoplasmic Reticulum Stress in Mice.

Mol Nutr Food Res 2021 Jun 1:e2001065. Epub 2021 Jun 1.

State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, 100193, China.

Scope: Inflammatory bowel disease (IBD) is an inflammatory gastrointestinal disorder in which endoplasmic reticulum (ER) stress and dysbiosis of the intestinal microbiota are implicated. Glycine supplementation has been reported to reduce inflammatory responses in experimental colitis. However, the underlying mechanisms responsible for the beneficial effects remain unclear.

Methods And Results: Female C57BL/6 mice were orally administered with glycine (3.5 or 5.2 g/kg body weight) for 14 continuous days. On day 8 post-glycine supplementation, the mice were orally inoculated with 2 × 10 CFU Citrobacter rodentium (C. rodentium). The results showed that glycine alleviated C. rodentium-induced body weight loss, increased disease activity index and spleen weight, colon length shortening, and colonic hyperplasia. Glycine suppressed the activation and infiltration of inflammatory cells, and secretion of pro-inflammatory cytokines in the colon tissues. The apoptosis of colon epithelial cells was also abrogated by glycine, which was associated with the inactivation of activating transcription factor 6α (ATF6α)-C/EBP homologous protein (CHOP) signaling. In addition, glycine administration increased α diversity, restored β diversity, and abolished the reduction in Lactobacillus, Bifidobacterium, Alistipes, Turicibacter, and Alloprevotella in the colon.

Conclusions: Glycine supplementation is a nutritional strategy that may ameliorate C. rodentium-induced colitis by regulating ATF6α-CHOP-mediated ER stress and enhancing the abundance of Lactobacillus. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/mnfr.202001065DOI Listing
June 2021

A potential association between immunosenescence and high COVID-19 related mortality among elderly patients with cardiovascular diseases.

Immun Ageing 2021 Jun 1;18(1):25. Epub 2021 Jun 1.

Department of Cardiology, SirRunRunShaw Hospital, College of Medicine, Zhejiang University, No.3 Qingchun East Road, Hangzhou, 310016, Zhejiang, China.

Elderly patients with cardiovascular diseases account for a large proportion of Corona virus Disease 2019(COVID-19)related deaths. COVID-19, as a new coronavirus, mainly targets the patient's lung triggering a cascade of innate and adaptive immune responses in the host. The principal causes of death among COVID-19 patients, especially elderly subjects with cardiovascular diseases, are acute respiratory distress syndrome(ARDS), multiple organ dysfunction syndrome (MODS), and microvascular thrombosis. All prompted by an excessive uncontrolled systemic inflammatory response. Immunosenescence, characterized by systemic and chronic inflammation as well as innate/adaptive immune imbalance, presents both in the elderly and cardiovascular patients. COVID-19 infection further aggravates the existing inflammatory process and lymphocyte depletion leading to uncontrollable systemic inflammatory responses, which is the primary cause of death. Based on the higher mortality, this study attempts to elucidate the pathophysiological mechanisms of COVID-19 in elderly subjects with cardiovascular diseases as well as the cause of the high mortality result from COVID-19.
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http://dx.doi.org/10.1186/s12979-021-00234-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166579PMC
June 2021

L-Proline Activates Mammalian Target of Rapamycin Complex 1 and Modulates Redox Environment in Porcine Trophectoderm Cells.

Biomolecules 2021 May 17;11(5). Epub 2021 May 17.

State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing 100193, China.

L-proline (proline) is a key regulator of embryogenesis, placental development, and fetal growth. However, the underlying mechanisms that support the beneficial effects of proline are largely unknown. This study used porcine trophectoderm cell line 2 (pTr2) to investigate the underlying mechanisms of proline in cell proliferation and redox homeostasis. Cells were cultured in the presence of 0, 0.25, 0.50, or 1.0 mmol/L proline for an indicated time. The results showed that 0.5 and 1.0 mmol/L proline enhanced cell viability. These effects of proline (0.5 mmol/L) were accompanied by the enhanced protein abundance of p-mTORC1, p-p70S6K, p-S6, and p-4E-BP1. Additionally, proline dose-dependently enhanced the mRNA expression of proline transporters [solute carrier family () , , , , and ], elevated proline concentration, and protein abundance of proline dehydrogenase (PRODH). Furthermore, proline addition (0.25 or 0.5 mmol/L) resulted in lower abundance of p-AMPK when compared with a control. Of note, proline resulted in lower reactive oxygen species (ROS) level, upregulated mRNA expression of the catalytic subunit of glutamate-cysteine ligase () and glutathione synthetase (), as well as enhanced total (T)-GSH and GSH concentration when compared with a control. These data indicated that proline activates themTORC1 signaling and modulates the intracellular redox environment via enhancing proline transport.
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http://dx.doi.org/10.3390/biom11050742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157211PMC
May 2021

DNMT3A Mutation-Induced CDK1 Overexpression Promotes Leukemogenesis by Modulating the Interaction between EZH2 and DNMT3A.

Biomolecules 2021 May 22;11(6). Epub 2021 May 22.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

mutations are frequently identified in acute myeloid leukemia (AML) and indicate poor prognosis. Previously, we found that the hotspot mutation DNMT3A R882H could upregulate CDK1 and induce AML in conditional knock-in mice. However, the mechanism by which CDK1 is involved in leukemogenesis of DNMT3A mutation-related AML, and whether CDK1 could be a therapeutic target, remains unclear. In this study, using fluorescence resonance energy transfer and immunoprecipitation analysis, we discovered that increased CDK1 could compete with EZH2 to bind to the PHD-like motif of DNMT3A, which may disturb the protein interaction between EZH2 and DNMT3A. Knockdown of CDK1 in OCI-AML3 cells with mutation markedly inhibited proliferation and induced apoptosis. CDK1 selective inhibitor CGP74514A (CGP) and the pan-CDK inhibitor flavopiridol (FLA) arrested OCI-AML3 cells in the G2/M phase, and induced cell apoptosis. CGP significantly increased CD163-positive cells. Moreover, the combined application of CDK1 inhibitor and traditional chemotherapy drugs synergistically inhibited proliferation and induced apoptosis of OCI-AML3 cells. In conclusion, this study highlights CDK1 overexpression as a pathogenic factor and a potential therapeutic target for DNMT3A mutation-related AML.
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http://dx.doi.org/10.3390/biom11060781DOI Listing
May 2021

Biomimetic tubular scaffold with heparin conjugation for rapid degradation in in situ regeneration of a small diameter neoartery.

Biomaterials 2021 Jul 12;274:120874. Epub 2021 May 12.

Department of Cardiac Surgery, The University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address:

To address the clinical need for readily available small diameter vascular grafts, biomimetic tubular scaffolds were developed for rapid in situ blood vessel regeneration. The tubular scaffolds were designed to have an inner layer that is porous, interconnected, and with a nanofibrous architecture, which provided an excellent microenvironment for host cell invasion and proliferation. Through the synthesis of poly(spirolactic-co-lactic acid) (PSLA), a highly functional polymer with a norbornene substituting a methyl group in poly(l-lactic acid) (PLLA), we were able to covalently attach biomolecules onto the polymer backbone via thiol-ene click chemistry to impart desirable functionalities to the tubular scaffolds. Specifically, heparin was conjugated on the scaffolds in order to prevent thrombosis when implanted in situ. By controlling the amount of covalently attached heparin we were able to modulate the physical properties of the tubular scaffold, resulting in tunable wettability and degradation rate while retaining the porous and nanofibrous morphology. The scaffolds were successfully tested as rat abdominal aortic replacements. Patency and viability were confirmed through dynamic ultrasound and histological analysis of the regenerated tissue. The harvested tissue showed excellent vascular cellular infiltration, proliferation, and migration with laminar cellular arrangement. Furthermore, we achieved both complete reendothelialization of the vessel lumen and native-like media extracellular matrix. No signs of aneurysm or hyperplasia were observed after 3 months of vessel replacement. Taken together, we have developed an effective vascular graft able to generate small diameter blood vessels that can function in a rat model.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120874DOI Listing
July 2021

Enhanced photocatalytic hydrogen production activity of Janus CuS-ZnS spherical nanoheterostructures.

J Colloid Interface Sci 2021 May 18;600:838-846. Epub 2021 May 18.

State Key Laboratory for Powder Metallurgy, Powder Metallurgy Research Institute, Central South University, Changsha 410083, China; Research Institute of Resource Recycling, Central South University, Changsha 410083, China.

Photocatalytic hydrogen evolution is one of the most promising approaches for efficient solar energy conversion. The light-harvesting ability and interfacial structure of heterostructured catalysts regulate the processes of photon injection and transfer, which further determines their photocatalytic performances. Here, we report a Janus CuS-ZnS nano-heterostructured photocatalyst synthesized using a facile stoichiometrically limited cation exchange reaction. Djurleite CuS and wurtzite ZnS share the anion skeleton, and the lattice mismatch between immiscible domains is ∼1.7%. Attributing to the high-quality interfacial structure, Janus CuS-ZnS nanoheterostructures (NHs) show an enhanced photocatalytic hydrogen evolution rate of up to 0.918 mmol h g under full-spectrum irradiation, which is ∼38-fold and 17-fold more than those of sole CuS and ZnS nanocrystals (NCs), respectively. The results indicate that cation exchange reaction is an efficient approach to construct well-ordered interfaces in hybrid photocatalysts, and it also demonstrates that reducing lattice mismatch and interfacial defects in hybrid photocatalysts is essential for enhancing their solar energy conversion performance.
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http://dx.doi.org/10.1016/j.jcis.2021.05.073DOI Listing
May 2021

Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes.

Sci Rep 2021 May 28;11(1):11295. Epub 2021 May 28.

Division of Animal Sciences and Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, USA.

MBD5-associated neurodevelopmental disorder (MAND) is an autism spectrum disorder (ASD) characterized by intellectual disability, motor delay, speech impairment and behavioral problems; however, the biological role of methyl-CpG-binding domain 5, MBD5, in neurodevelopment and ASD remains largely undefined. Hence, we created neural progenitor cells (NPC) derived from individuals with chromosome 2q23.1 deletion and conducted RNA-seq to identify differentially expressed genes (DEGs) and the biological processes and pathways altered in MAND. Primary skin fibroblasts from three unrelated individuals with MAND and four unrelated controls were converted into induced pluripotent stem cell (iPSC) lines, followed by directed differentiation of iPSC to NPC. Transcriptome analysis of MAND NPC revealed 468 DEGs (q < 0.05), including 20 ASD-associated genes. Comparison of DEGs in MAND with SFARI syndromic autism genes revealed a striking significant overlap in biological processes commonly altered in neurodevelopmental phenotypes, with TGFβ, Hippo signaling, DNA replication, and cell cycle among the top enriched pathways. Overall, these transcriptome deviations provide potential connections to the overlapping neurocognitive and neuropsychiatric phenotypes associated with key high-risk ASD genes, including chromatin modifiers and epigenetic modulators, that play significant roles in these disease states.
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http://dx.doi.org/10.1038/s41598-021-90798-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163803PMC
May 2021

LncRNA H19 governs mitophagy and restores mitochondrial respiration in the heart through Pink1/Parkin signaling during obesity.

Cell Death Dis 2021 May 28;12(6):557. Epub 2021 May 28.

Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120, Guangzhou, Guangdong, China.

Maintaining proper mitochondrial respiratory function is crucial for alleviating cardiac metabolic disorders during obesity, and mitophagy is critically involved in this process. Long non-coding RNA H19 (H19) is crucial for metabolic regulation, but its roles in cardiac disorders, mitochondrial respiratory function, and mitophagy during obesity are largely unknown. In this study, palmitic acid (PA)-treated H9c2 cell and Lep mice were used to investigate cardiac metabolic disorders in vitro and in vivo, respectively. The effects of H19 on metabolic disorders, mitochondrial respiratory function, and mitophagy were investigated. Moreover, the regulatory mechanisms of PA, H19, mitophagy, and respiratory function were examined. The models tested displayed a reduction in H19 expression, respiratory function and mitochondrial number and volume, while the expression of mitophagy- and Pink1/Parkin signaling-related proteins was upregulated, as indicated using quantitative real-time PCR, Seahorse mitochondrial stress test analyzer, transmission electron microscopy, fluorescence indicators and western blotting. Forced expression of H19 helped to the recoveries of respiratory capacity and mitochondrial number while inhibited the levels of mitophagy- and Pink1/Parkin signaling-related proteins. Pink1 knockdown also attenuated PA-induced mitophagy and increased respiratory capacity. Mechanistically, RNA pull-down, mass spectrometry, and RNA-binding protein immunoprecipitation assays showed that H19 could hinder the binding of eukaryotic translation initiation factor 4A, isoform 2 (eIF4A2) with Pink1 mRNA, thus inhibiting the translation of Pink1 and attenuation of mitophagy. PA significantly increased the methylation levels of the H19 promoter region by upregulation Dnmt3b methylase levels, thereby inhibiting H19 transcription. Collectively, these findings suggest that DNA methylation-mediated the downregulation of H19 expression plays a crucial role in cardiomyocyte or H9c2 cells metabolic disorders and induces cardiac respiratory dysfunction by promoting mitophagy. H19 inhibits excessive mitophagy by limiting Pink1 mRNA translation, thus alleviating this cardiac defect that occurs during obesity.
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http://dx.doi.org/10.1038/s41419-021-03821-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163878PMC
May 2021

Association of epicardial fat thickness with left ventricular diastolic function parameters in a community population.

BMC Cardiovasc Disord 2021 May 28;21(1):262. Epub 2021 May 28.

Department of Cardiovascular Disease, Peking University First Hospital, Beijing, China.

Background: We examined the relationship between epicardial fat thickness (EFT) measured by echocardiography and left ventricular diastolic function parameters in a Beijing community population.

Methods: We included 1004 participants in this study. Echocardiographic parameters including E and A peak velocity, the early diastolic velocities (e') of the septal and lateral mitral annulus using tissue doppler imaging, E/e', and EFT were measured. EFT1 was measured perpendicularly on the right ventricular free wall at end diastole in the extension line of the aortic root. EFT2 was the maximum thickness measured perpendicularly on the right ventricular free wall at end diastole. Multivariable linear regression was used to analyze the relationship between EFT and the mean e' and E/e'.

Results: The mean age of the participants was 63.91 ± 9.02 years, and 51.4% were men. EFT1 and EFT2 were negatively correlated with lateral e', septal e', and mean e' (p < 0.05), and the correlation coefficient for EFT1 and EFT2 and mean e' was - 0.138 and - 0.180, respectively. EFT1 and EFT2 were positively correlated with lateral E/e', septal E/e', and mean E/e' (p < 0.05), and the correlation coefficient for EFT1 and EFT2 and mean e' was 0.100 and 0.090, respectively. Multivariable egression analysis showed that EFT2 was independently and negatively associated with e' mean (β = - 0.078 [95% confidence interval = - 0.143, - 0.012, p = 0.020]). There were no interactions between EFT2 and any covariates, including age or heart groups, sex, BMI, or presence of hypertension, diabetes, or coronary heart disease, in relation to left ventricular diastolic dysfunction.

Conclusions: EFT2 was negatively and independently associated with e' mean, which suggests that more attention to this type of adipose fat is required for cardiovascular disease therapy.
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http://dx.doi.org/10.1186/s12872-021-02071-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162010PMC
May 2021

Corneal Epithelial Thickness Changes Following SMILE for Myopia With High Astigmatism.

J Refract Surg 2021 Apr 1;37(4):224-230. Epub 2021 Apr 1.

Purpose: To evaluate the corneal epithelial thickness (CET) profile changes after small incision lenticule extraction (SMILE) surgery for myopic astigmatism correction of greater than 2.00 diopters (D).

Methods: This prospective observational study included 40 eyes (23 patients) treated with SMILE for myopia with cylinders of -2.25 to -4.50 D. Along with standard ophthalmic examinations, CET maps with a diameter of 9 mm were measured by high-resolution spectral-domain optical coherence tomography preoperatively and postoperatively. Correlations between the degree of residual astigmatism and the difference in CET values between preoperative flat and steep meridians were analyzed.

Results: The CET showed significant changes in the central (2 mm), paracentral (2 to 5 mm), midperipheral (5 to 7 mm), and peripheral (7 to 9 mm) zones 6 months after SMILE ( < .001). Among the regions, the CET in the paracentral zones displayed the largest increase (9.75%) with the highest average thickness (57.29 µm). Moreover, symmetrical regional epithelial thickening at the preoperative astigmatism axis was observed in the midperipheral zones. The difference in CET between preoperative flat and steep meridians in the mid-peripheral zones continuously increased from postoperative 1 day to 6 months. This difference was positively correlated with the residual cylinder errors at 6 months postoperatively ( = -0.334, = .035).

Conclusions: The 9-mm diameter CET in eyes with high astigmatism significantly increased 6 months after SMILE. Additionally, the difference in CET between preoperative flat and steep meridians in midperipheral zones may be related to astigmatic undercorrection in SMILE. .
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http://dx.doi.org/10.3928/1081597X-20210126-01DOI Listing
April 2021

Efficacy and safety of Lianhuaqingwen for mild or moderate coronavirus disease 2019: A meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2021 May;100(21):e26059

Institute for Drug Evaluation, Peking University Health Science Center, Beijing, PR China.

Background: : Coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving disease, with no recommended effective anti-coronavirus treatments. Traditional Chinese Medicine (TCM) has been widely used to treat COVID-19 in China, and the most used one is Lianhuaqingwen (LH). This study aimed to assess the efficacy and safety of LH combined with usual treatment vs usual treatment alone in treating mild or moderate COVID-19 by a meta-analysis of randomized controlled trials (RCTs).

Methods And Analysis: : We systematically searched the Medline (OVID), Embase, the Cochrane Library, and 4 Chinese databases from inception to July 2020 to include the RCTs that evaluated the efficacy and safety of LH in combination with usual treatment vs usual treatment for mild or moderate COVID-19. A meta-analysis was performed to calculate the risk ratio (RR) and 95% confidence interval (CI) for binary outcomes and mean difference (MD) for continuous outcomes.

Results: : A total of 5 RCTs with 824 individuals with mild or moderate COVID 19 were included. Compared with the usual treatment alone, LH in combination with usual treatment significantly improved the overall clinical efficacy (RR = 2.39, 95% CI 1.61-3.55), increased the rate of recovery of chest computed tomographic manifestations (RR = 1.80, 95% CI 1.08-3.01), reduced the rate of conversion to severe cases (RR = 0.47, 95% CI 0.29-0.74), shorten the duration of fever (MD = -1.00, 95% CI -1.17 to -0.84). Moreover, LH in combination with usual treatment did not increase the occurrence of the adverse event compared to usual treatment alone.

Conclusion: : Our meta-analysis of RCTs indicated that LH in combination with usual treatment may improve the clinical efficacy in patients with mild or moderate COVID-19 without increasing adverse events. However, given the limitations and poor quality of included trials in this study, further large-sample RCTs or high-quality real-world studies are needed to confirm our conclusions.
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http://dx.doi.org/10.1097/MD.0000000000026059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154466PMC
May 2021

The degradation pathways of carbamazepine in advanced oxidation process: A mini review coupled with DFT calculation.

Sci Total Environ 2021 Jul 17;779:146498. Epub 2021 Mar 17.

Key Laboratory of the Three Gorges Reservoir Region's Eco-Environment of Ministry of Education, Chongqing University, Chongqing 400044, PR China. Electronic address:

Degradation pathway is important for the study of carbamazepine (CBZ) removal in advanced oxidation processes (AOPs). Generally, degradation pathways are speculated based on intermediate identification and basic chemical rules. However, this semiempirical strategy is sometimes time-consuming and baseless. To improve the situation, a mini meta-analysis was first conducted for the degradation pathways of CBZ in AOPs. Then, the rationality of the pathways was analyzed by Density Functional Theory (DFT) calculation. Results show that the degradation pathways of CBZ in various AOPs has high similarity, and the reactive sites predicted by Fukui function fitted well with the data retrieved from literatures. In addition, molecule configuration of degradation intermediates was found to play a very important roles on degradation pathway. The study reveals that computational chemistry is a useful tool for degradation pathway speculation in AOPs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146498DOI Listing
July 2021

PTCH1 mutation promotes antitumor immunity and the response to immune checkpoint inhibitors in colorectal cancer patients.

Cancer Immunol Immunother 2021 May 24. Epub 2021 May 24.

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Fu-Cheng Road 52, Hai-Dian District, Beijing, 100142, China.

Immunotherapy has emerged as an effective therapeutic strategy for various cancers, including colorectal cancer (CRC), but only a subset of MSI-H patients can benefit from such therapy. Patched1 (PTCH1) is a frequently altered gene in CRCs and its mutations contribute to unregulated Hedgehog (Hh) signaling. In the study, we evaluated the association of PTCH1 mutations with CRC immunity based on our single-center cohort and multiple cancer genomic datasets. Among 21 enrolled patients, six (28.6%) harbored a PTCH1 mutation based on WES analyses. In CRC patients, the PTCH1 mutation subgroup experienced a higher durable clinical benefit rate than the PTCH1 wild-type subgroup (100% vs. 40%, P = 0.017). In addition, patients with the PTCH1 mutation experienced greater progression-free survival (PFS, P = 0.037; HR, 0.208) and overall survival (OS, P = 0.045; HR, 0.185). A validation cohort from the MSKCC also confirmed the correlation between PTCH1 mutation and better prognosis (P = 0.022; HR, 0.290). Mechanically, diverse antitumor immune signatures were more highly enriched in PTCH1-mutated tumors than in PTCH1 wild-type tumors. Furthermore, PTCH1-mutated tumors had higher proportions of CD8 + T cells, activated NK cells, and M1 type macrophage infiltration, as well as elevated gene signatures of several steps in the cancer-immunity cycle. Notably, the PTCH1 mutation was correlated with tumor mutational burden (TMB), loss of heterozygosity score, and copy number variation burden. Our results show that the mutation of PTCH1 is a potential biomarker for predicting the response of CRC patients to immunotherapy.
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http://dx.doi.org/10.1007/s00262-021-02966-9DOI Listing
May 2021

Novel Compound Heterozygous Pathogenic Variants in Cause Isolated Sulfite Oxidase Deficiency in a Chinese Han Family.

Front Genet 2021 7;12:607085. Epub 2021 May 7.

Shaanxi Institute for Pediatric Diseases, Xi'an Children's Hospital, Xi'an, China.

Aim: To explore the clinical imaging, laboratory and genetic characteristics of a newborn boy with isolated sulfite oxidase deficiency (ISOD) in a Chinese mainland cohort.

Methods: Homocysteine and uric acid in plasma and cysteine and total homocysteine in the blood spot were assessed in a Chinese newborn patient with progressive encephalopathy, tonic seizures, abnormal muscle tone, and feeding difficulties. Whole exome sequencing and Sanger sequencing facilitated an accurate diagnosis. The pathogenicity predictions and conservation analysis of the identified mutations were conducted by bioinformatics tools.

Results: Low total homocysteine was detected in the blood spot, while homocysteine and uric acid levels were normal in the plasma. -sulfocysteine was abnormally elevated in urine. A follow-up examination revealed several progressive neuropathological findings. Also, intermittent convulsions and axial dystonia were observed. However, the coordination of sucking and swallowing was slightly improved. A novel paternal nonsense variant c.475G > T (p.Glu159) and a novel maternal missense variant c.1201A > G (p.Lys401Glu) in were identified in this case by co-segregation verification.

Conclusion: This is the second report of early-onset ISOD case in a non-consanguineous Chinese mainland family. Combined with the clinical characteristics and biochemical indexes, we speculated that these two novel pathogenic variants of the gene underlie the cause of the disease in this patient. Next-generation sequencing (NGS) and Sanger sequencing provided reliable basis for clinical and prenatal diagnoses of this family, it also enriched the mutation spectrum of the gene.
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http://dx.doi.org/10.3389/fgene.2021.607085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139553PMC
May 2021

Efficacy of Laser Therapy in Reducing Swelling and Pain Following Alveolar Bone Grafting: A Randomized Controlled Trial.

J Oral Maxillofac Surg 2021 May 2. Epub 2021 May 2.

Oral Medical Center, the Third Clinical Medical College of China Three Gorges University, Gezhouba Central Hospital of Sinopharm, Yichang City, Hubei Province, China. Electronic address:

Purpose: This randomized controlled trial aimed to explore the efficacy of laser therapy in reducing swelling and pain in female patients after alveolar bone grafting in the hope of providing a new method for the treatment of patients with swelling after alveolar bone grafting.

Patients And Methods: From August 2019 to June 2020, 82 female patients with soft tissue swelling after alveolar bone grafting in our hospital were enrolled in this prospective blinded randomized controlled trial. The patients were randomized divided into the study group (receiving laser therapy) and the control group (receiving routine postoperative intervention). Swelling and pain were evaluated at postoperative day (POD) 1, 3, and 5, and the quality-of-life at POD 1 and 5. The healing success rate and postoperative satisfaction were evaluated at 3 months postoperatively.

Results: The pain severity in the study group was lower than that in the control group at POD 3 and 5 (P<.05). The study group had significantly higher scores of general health, vitality, bodily pain, social functioning, physical functioning, role-physical, role-emotional, and mental health than the control group at POD 5 (P<.05). In addition, the scores of general health, vitality, bodily pain, social functioning, physical functioning, role-physical, role-emotional, and mental health of the 2 groups were higher at POD 5 versus POD 1 (P<.05). The study group had a significantly higher healing success rate and postoperative satisfaction rate than the control group at 3 months postoperatively (P<.05).

Conclusions: Laser therapy can effectively reduce swelling and pain and improve the quality-of-life of female patients after alveolar bone grafting.
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http://dx.doi.org/10.1016/j.joms.2021.04.017DOI Listing
May 2021