Publications by authors named "Yang Dong"

1,775 Publications

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SERINC2 increases the risk of bipolar disorder in the chinese population.

Depress Anxiety 2021 Jul 19. Epub 2021 Jul 19.

Guangzhou Huiai Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Background: Although common variants in a large collection of patients are associated with increased risk for bipolar disorder (BD), studies have only been able to predict 25%-45% of risks, suggesting that lots of variants that contribute to the risk for BD haven't been identified. Our study aims to identify novel BD risk genes.

Methods: We performed whole-exome sequencing of 27 individuals from 6 BD multi-affected Chinese families to identify candidate variants. Targeted sequencing of one of the novel risk genes, SERINC2, in additional sporadic 717 BD patients and 312 healthy controls (HC) validated the association. Magnetic resonance imaging (MRI) were performed to evaluate the effect of the variant to brain structures from 213 subjects (4 BD subjects from a multi-affected family, 130 sporadic BD subjects and 79 HC control).

Results: BD pedigrees had an increased burden of uncommon variants in extracellular matrix (ECM) and calcium ion binding. By large-scale sequencing we identified a novel recessive BD risk gene, SERINC2, which plays a role in synthesis of sphingolipid and phosphatidylserine (PS). MRI image results show the homozygous nonsense variant in SERINC2 affects the volume of white matter in cerebellum.

Conclusions: Our study identified SERINC2 as a risk gene of BD in the Chinese population.
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http://dx.doi.org/10.1002/da.23186DOI Listing
July 2021

Current Status of Mining, Modification, and Application of Cellulases in Bioactive Substance Extraction.

Curr Issues Mol Biol 2021 Jul 13;43(2):687-703. Epub 2021 Jul 13.

Department of Biochemical Engineering, School of Chemical Engineering & Technology, Tianjin University, Tianjin 300350, China.

Cellulases have been used to extract bioactive ingredients from medical plants; however, the poor enzymatic properties of current cellulases significantly limit their application. Two strategies are expected to address this concern: (1) new cellulase gene mining strategies have been promoted, optimized, and integrated, thanks to the improvement of gene sequencing, genomic data, and algorithm optimization, and (2) known cellulases are being modified, thanks to the development of protein engineering, crystal structure data, and computing power. Here, we focus on mining strategies and provide a systemic overview of two approaches based on sequencing and function. Strategies based on protein structure modification, such as introducing disulfide bonds, proline, salt bridges, -glycosylation modification, and truncation of loop structures, have already been summarized. This review discusses four aspects of cellulase-assisted extraction. Initially, cellulase alone was used to extract bioactive substances, and later, mixed enzyme systems were developed. Physical methods such as ultrasound, microwave, and high hydrostatic pressure have assisted in improving extraction efficiency. Cellulase changes the structure of biomolecules during the extraction process to convert them into effective ingredients with better activity and bioavailability. The combination of cellulase with other enzymes and physical technologies is a promising strategy for future extraction applications.
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http://dx.doi.org/10.3390/cimb43020050DOI Listing
July 2021

A Systematic Review and Meta-Analysis: Hyponatremia Predicted All-Cause and Cardiovascular Mortality in Dialysis Population.

Blood Purif 2021 Jul 20:1-10. Epub 2021 Jul 20.

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

Background: Hyponatremia is one of the most common disorders of electrolytes. Some research studies reported that hyponatremia was closely associated with mortality in patients with dialysis. However, this viewpoint remains controversial.

Objective: We aimed to do a systematic review and meta-analysis to assess the influence of hyponatremia on mortality in patients with dialysis.

Methods: We identified the eligible studies that investigated the association between hyponatremia and mortality risk in patients under dialysis by searching systematically a series of databases including PubMed, Embase, Cochrane, Web of science, and Ovid from January 2011 to June 2020. Adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled.

Results: From 1,116 records identified, 12 studies including prospective and retrospective cohort studies met our inclusion criteria. We found hyponatremia both at baseline (HR: 1.50 and 95% CI: 1.41-1.59) and in time-varying (HR: 1.63 and 95% CI: 1.44-1.84) were significantly correlated to all-cause mortality after multivariable adjusted. By the subgroup analysis, the same results were presented in hemodialysis (HR: 1.48 and 95% CI: 1.38-1.59) or peritoneal dialysis patients (HR: 1.52 and 95% CI: 1.37-1.70). We also observed that lower serum sodium was independently associated with cardiovascular death.

Conclusions: Hyponatremia was independently associated with all-cause and cardiovascular mortality, and it might predict adverse outcomes of patients under dialysis.
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http://dx.doi.org/10.1159/000517340DOI Listing
July 2021

NAicotinamide retains Klotho expression and ameliorates rhabdomyolysis-induced acute kidney injury.

Nutrition 2021 Jun 2;91-92:111376. Epub 2021 Jun 2.

Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address:

Objectives: Acute kidney injury (AKI) is a severe complication of rhabdomyolysis that significantly increases mortality. Unfortunately, the therapeutic approach is limited. Inflammation plays a critical role in the pathogenesis of rhabdomyolysis-induced AKI, which is a potential therapeutic target. Nicotinamide, a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide, has been shown to have potent antiinflammation effects. Klotho is a tubular highly expressed renoprotective protein. Therefore, we explored the effect of nicotinamide on rhabdomyolysis-induced AKI and the underlying mechanisms.

Methods: We intramuscularly injected glycerol to induce rhabdomyolysis, and intraperitoneally administrated nicotinamide to observe the effect on kidney injury. Interleukin-1 beta, tumor necrosis factor alpha, nuclear factor kappa B (NF-κB), and Klotho were determined by Western blot. Chromatin immunoprecipitation was used to assess the interaction of NF-κB, nuclear receptor corepressor, and histone deacetylase 1 with Klotho promoters. Small interfering RNA was used to evaluate the role of Klotho in nicotinamide-related renoprotection.

Results: The results showed that nicotinamide attenuated renal pathologic morphology, kidney functional abnormalities, and kidney inflammatory response in rhabdomyolysis. Moreover, nicotinamide effectively blocked the recruitment of NF-κB, nuclear receptor corepressor, and histone deacetylase 1 to the promoter of Klotho, and preserved Klotho expression. More importantly, the renoprotection effect of nicotinamide was abrogated when Klotho was knocked down by small interfering RNA in rhabdomyolysis mice.

Conclusions: Our study demonstrated that Klotho preservation is essential for the renoprotection effect of nicotinamide, and provides a new preventive strategy for rhabdomyolysis-induced AKI.
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http://dx.doi.org/10.1016/j.nut.2021.111376DOI Listing
June 2021

Prediction of 1-year mortality after heart transplantation using machine learning approaches: A single-center study from China.

Int J Cardiol 2021 Jul 13. Epub 2021 Jul 13.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: Heart transplantation (HTx) remains the gold-standard treatment for end-stage heart failure. The aim of this study was to establish a risk-prediction model for assessing prognosis of HTx using machine-learning approach.

Methods: Consecutive recipients of orthotopic HTx at our institute between January 1st, 2015 and December 31st, 2018 were included in this study. The primary outcome was 1-year mortality. Least absolute shrinkage and selection operator method was used to select variables and seven different machine-learning approaches were employed to develop the risk-prediction model. Bootstrap method was used for model validation. Shapley Additive exPlanations (SHAP) method was used for model interpretation.

Results: 381 recipients were included with average age of 43.783 years old. Albumin, recipient age and left atrium diameter ranked top three most important variables that affected the 1-year mortality of HTx. Other important variables included red blood cell, hemoglobin, lymphocyte%, smoking history, use of lyophilized rhBNP, use of Levosimendan, hypertension, cardiac surgery history, malignancy and endotracheal intubation history. Random Forest (RF) model achieved the best area under curves (AUC) of 0.801 and gradient boosting machine (GBM) showed the best sensitivity of 0.271. SHAP method was introduced to display the RF model's predicting processes of "survival" or "death" in individual level.

Conclusions: We established the risk-prediction model for postoperative prognosis of HTx patients by using machine learning method and demonstrated that the RF model performed the highest discrimination with the largest AUC when validated. This prediction model could help to recognize high-risk HTx recipients, provide personalized therapy plan and reduce organ wastage.
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http://dx.doi.org/10.1016/j.ijcard.2021.07.024DOI Listing
July 2021

A Polarization-Imaging-Based Machine Learning Framework for Quantitative Pathological Diagnosis of Cervical Precancerous Lesions.

IEEE Trans Med Imaging 2021 Jul 14;PP. Epub 2021 Jul 14.

Polarization images encode high resolution microstructural information even at low resolution. We propose a framework combining polarization imaging and traditional microscopy imaging, constructing a dual-modality machine learning framework that is not only accurate but also generalizable and interpretable. We demonstrate the viability of our proposed framework using the cervical intraepithelial neoplasia grading task, providing a polarimetry feature parameter to quantitatively characterize microstructural variations with lesion progression in hematoxylin-eosin-stained pathological sections of cervical precancerous tissues. By taking advantages of polarization imaging techniques and machine learning methods, the model enables interpretable and quantitative diagnosis of cervical precancerous lesion cases with improved sensitivity and accuracy in a low-resolution and wide-field system. The proposed framework applies routine image-analysis technology to identify the macro-structure and segment the target region in H&E-stained pathological images, and then employs emerging polarization method to extract the micro-structure information of the target region, which intends to expand the boundary of the current image-heavy digital pathology, bringing new possibilities for quantitative medical diagnosis.
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http://dx.doi.org/10.1109/TMI.2021.3097200DOI Listing
July 2021

Effects of Full Inhalation of Sevoflurane and Total Intravenous Anesthesia on Hemodynamics, Serum Myocardial Enzymes, and Myocardial Markers in Elderly Patients Undergoing Hysterectomy.

Biomed Res Int 2021 25;2021:9983988. Epub 2021 Jun 25.

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.

Objective: To compare the effects of sevoflurane inhalation and intravenous anesthesia on hemodynamics, serum myocardial enzymes, and myocardial markers in elderly patients undergoing hysterectomy.

Methods: Group A and group B were established randomly regarding a total of 126 elderly patients who underwent an elective hysterectomy. Patients in group A were given full anesthesia with sevoflurane, and patients in group B were given anesthesia with intravenous anesthesia. The operation time, anesthesia time, and recovery time in Postanesthesia Care Unit (PACU) were compared; plasma cortisol concentration, hemodynamics, serum myocardial enzymes, and myocardial markers were detected and compared between the two groups of patients before anesthesia ( ), after anesthesia ( ), and after surgery ( ).

Results: Group A observed a longer extubation time and recovery time in PACU than group B ( < 0.05). Results show a lower systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and plasma cortisol concentration of by comparison with those of ( < 0.05), but no significant difference remains in terms of intergroup SBP, DBP, and HR ( > 0.05), and there was no interaction effect of groups and time ( > 0.05). The two groups showed no great disparity in the levels of lactate dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase (CK), and CK-MB as a subtype of CK before surgery between the two groups of patients ( > 0.05). After surgery, LDH, AST, CK, and CK-MB levels in both groups were witnessed a surge, in which group A obtained higher levels of LDH, AST, CK, and CK-MB (all < 0.05).

Conclusion: Total intravenous anesthesia will not increase the hemodynamic fluctuation of elderly patients undergoing hysterectomy and can reduce the damage to the myocardium of patients with surgical trauma, which can protect the myocardium of elderly patients to a certain extent, so it can be adopted as the optimal anesthesia protocol for surgery.
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http://dx.doi.org/10.1155/2021/9983988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257341PMC
June 2021

Antisolvent- and Annealing-Free Deposition for Highly Stable Efficient Perovskite Solar Cells via Modified ZnO.

Adv Sci (Weinh) 2021 Jul 7;8(13):2002860. Epub 2021 May 7.

Materials Science and Engineering Pennsylvania State University University Park PA 16802 USA.

Even though ZnO is commonly used as the ETL in the perovskite solar cell (PSC), the reactivity of perovskite deposited thereupon limits its performance. Herein, an ethylene diamine tetraacetic acid-complexed ZnO (E-ZnO) is successfully developed as a significantly improved electron selective layer (ESLs) in perovskite device. It is found that E-ZnO exhibits higher electron mobility and better matched energy level with perovskite compared to ZnO. In addition, in order to eliminate the proton transfer reaction at the ZnO/perovskite interface, a high quality perovskite film fabrication process that requires neither annealing nor antisolvent is developed. By taking advantages of both E-ZnO and the new process, the highest efficiency of 20.39% is obtained for PSCs based on E-ZnO. Moreover, the efficiency of unencapsulated PSCs with E-ZnO retains 95% of its initial value exposed in an ambient atmosphere after 3604 h. This work provides a feasible path toward high performance of PSCs, and it is believed that the present work will facilitate transition of perovskite photovoltaics in flexible and tandem devices since the annealing- and antisolvent-free technology.
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http://dx.doi.org/10.1002/advs.202002860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261502PMC
July 2021

Role of NRP1 in Bladder Cancer Pathogenesis and Progression.

Front Oncol 2021 23;11:685980. Epub 2021 Jun 23.

Department of Urology, Xuzhou Central Hospital, Xuzhou, China.

Bladder urothelial carcinoma (BC) is a fatal invasive malignancy and the most common malignancy of the urinary system. In the current study, we investigated the function and mechanisms of Neuropilin-1 (NRP1), the co-receptor for vascular endothelial growth factor, in BC pathogenesis and progression. The expression of NRP1 was evaluated using data extracted from GEO and HPA databases and examined in BC cell lines. The effect on proliferation, apoptosis, angiogenesis, migration, and invasion of BC cells were validated after knockdown. After identifying differentially expressed genes (DEGs) induced by silencing, GO/KEGG and IPA bioinformatics analyses were performed and specific predicted pathways and targets were confirmed Additionally, the co-expressed genes and ceRNA network were predicted using data downloaded from CCLE and TCGA databases, respectively. High expression of NRP1 was observed in BC tissues and cells. knockdown promoted apoptosis and suppressed proliferation, angiogenesis, migration, and invasion of BC cells. Additionally, after silencing the activity of MAPK signaling and molecular mechanisms of cancer pathways were predicted by KEGG and IPA pathway analysis and validated using western blot in BC cells. knockdown also affected various biological functions, including antiviral response, immune response, cell cycle, proliferation and migration of cells, and neovascularisation. Furthermore, the main upstream molecule of the DEGs induced by knockdown may be , and was also the downstream target of and essential for regulation of expression to activate neovascularisation. was positively regulated by , and PPAR signaling was significantly associated with low expression. We also found that NRP1 was a predicted target of miR-204, miR-143, miR-145, and miR-195 in BC development. Our data provide evidence for the biological function and molecular aetiology of NRP1 in BC and for the first time demonstrated an association between NRP1 and NUPR1, FOXP3, and DCBLD2. Specifically, downregulation of contributes to BC progression, which is associated with activation of MAPK signaling and molecular mechanisms involved in cancer pathways. Therefore, NRP1 may serve as a target for new therapeutic strategies to treat BC and other cancers.
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http://dx.doi.org/10.3389/fonc.2021.685980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261128PMC
June 2021

Hypoxia associated lncRNA HYPAL promotes proliferation of gastric cancer as ceRNA by sponging miR-431-5p to upregulate CDK14.

Gastric Cancer 2021 Jul 11. Epub 2021 Jul 11.

Gastric Cancer Department, Liaoning Province Cancer Hospital and Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang City, 110042, Liaoning Province, China.

Gastric cancer (GC) is a common malignant solid tumor that is characterized by high hypoxia. The transcription of genes associated with hypoxia affects tumor occurrence and development. Long non-coding RNAs (lncRNAs) have been reported to play important roles in cancer development. In this study, we screened for differentially expressed ncRNAs (non-coding RNA) and mRNAs between hypoxia-inducible factor-1 (HIF-1α) knockdown GC cells and scrambled GC cells. Microarray data revealed that HIF-1α regulated the expression of LINC01355 (Hypoxia Yield Proliferation Associated LncRNA, HYPAL). HYPAL was found to be significantly upregulated in GC cells and tissues and was correlated with poor GC prognosis. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays revealed that HIF-1α promoted HYPAL expression by binding the promoter region. A regulatory network for the competing endogenous RNA (ceRNA) was constructed using bioinformatics tools. Mechanistic studies revealed that HYPAL acted as a ceRNA of miR-431-5p to regulate CDK14 expression. Carcinogenic effects of HYPAL were evaluated in vitro and in vivo. The HIF-1α/HYPAL/miR-431-5p/CDK14 (Cyclin-dependent kinase 14) axis activated the Wnt/β-catenin signaling pathway and induced GC cell proliferation while inhibiting apoptosis. In conclusion, HYPAL is a potential molecular target for GC therapy.
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http://dx.doi.org/10.1007/s10120-021-01213-5DOI Listing
July 2021

Off-hour effect is not significant in endovascular treatment for anterior circulation large vessel occlusion in a multicentre registry.

Stroke Vasc Neurol 2021 Jul 8. Epub 2021 Jul 8.

Department of Neurology, Southeast University, Nanjing, Jiangsu, China

Background And Purpose: Whether the off-hour effect has an impact on workflow and outcomes of endovascular treatment (EVT) for anterior circulation large vessel occlusion (AC-LVO) remains uncertain. This study aimed to compare the characteristics and outcomes of patients who presented or were treated during off-hour versus on-hour in a multi-center registry.

Methods: AC-LVO patients from 21 centres were categorised into the off-hour group and the on-hour group. Off-hour (weekends, holidays, and 18:00-7:59 on weekdays) and on-hour (8:00-17:59 on weekdays except for holidays) were defined according to arrival and groin-puncture time points, respectively. Subgroup comparisons between patients both arrived and treated during off-hour (true off-hour) and on-hour (true on-hour) were performed. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Secondary outcomes included favourable outcome (mRS 0-2 at 90 days), EVT-related time metrics, and other clinical outcomes. Ordinary and binary logistic regression and linear regression were taken to adjust for confounding factors.

Results: Of all 698 patients enrolled, 435 (62.3%) and 456 (65.3%) patients were categorised into the off-hour arrival and off-hour puncture group, respectively. Shorter onset to door time (adjusted ß coefficient: -21.56; 95% CI -39.96 to -3.16; p=0.022) was noted in the off-hour arrival group. Ordinal and dichotomous mRS scores at 90 days were comparable between the off-hour group and the on-hour group regardless of off-hour definitions. Other time metrics and outcomes were comparable between the two groups. Of 595 patients both presented and were treated during off-hour or on-hour, 394 patients were categorised into the true off-hour group and 201 into the true on-hour group. Time metrics and clinical outcomes were similar between the true off-hour and the true on-hour group.

Conclusions: The off-hour effect was not significant regarding clinical outcomes and in-hospital workflow in AC-LVO patients receiving EVT in this Chinese multicentre registry.
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http://dx.doi.org/10.1136/svn-2021-000949DOI Listing
July 2021

A robust fiber-based quantum thermometer coupled with nitrogen-vacancy centers.

Rev Sci Instrum 2021 Apr;92(4):044904

CAS Key Laboratory of Quantum Information, University of Science and Technology of China, Hefei 230026, People's Republic of China.

The nitrogen-vacancy center in diamond has been broadly applied in quantum sensing since it is sensitive to different physical quantities. Meanwhile, it is difficult to isolate disturbances from unwanted physical quantities in practical applications. Here, we present a fiber-based quantum thermometer by tracking the sharp-dip in the zero-field optically detected magnetic resonance spectrum in a high-density nitrogen-vacancy ensemble. Such a scheme can not only significantly isolate the magnetic field and microwave power drift but also improve the temperature sensitivity. Thanks to its simplicity and compatibility in implementation and robustness, this quantum thermometer is then applied to the surface temperature imaging of an electronic chip with a sensitivity of 18mK/Hz. It thus paves the way to high sensitive temperature measurements in ambiguous environments.
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http://dx.doi.org/10.1063/5.0044824DOI Listing
April 2021

Prognostic impact of chromogranin A in patients with acute heart failure.

Yeungnam Univ J Med 2021 Jul 8. Epub 2021 Jul 8.

Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.

Background: Chromogranin A (CgA) levels have been reported to predict mortality in patients with heart failure. However, information on the prognostic value and clinical availability of CgA is limited. We compared the prognostic value of CgA to that of previously proven natriuretic peptide biomarkers in patients with acute heart failure.

Methods: We retrospectively evaluated 272 patients (mean age, 68.5±15.6 years; 62.9% male) who underwent CgA test in the acute stage of heart failure hospitalization between June 2017 and June 2018. The median follow-up period was 348 days. Prognosis was assessed using the composite events of 1-year death and heart failure hospitalization.

Results: In-hospital mortality rate during index admission was 7.0% (n=19). During the 1-year follow-up, a composite event rate was observed in 12.1% (n=33) of the patients. The areas under the receiver-operating characteristic curves for predicting 1-year adverse events were 0.737 and 0.697 for N-terminal pro-B-type natriuretic peptide (NT-proBNP) and CgA, respectively. During follow-up, patients with high CgA levels (>158 pmol/L) had worse outcomes than those with low CgA levels (≤158 pmol/L) (85.2% vs. 58.6%, p<0.001). When stratifying the patients into four subgroups based on CgA and NT-proBNP levels, patients with high NT-proBNP and high CgA had the worst outcome. CgA had an incremental prognostic value when added to the combination of NT-proBNP and clinically relevant risk factors.

Conclusion: The prognostic power of CgA was comparable to that of NT-proBNP in patients with acute heart failure. The combination of CgA and NT-proBNP can improve prognosis prediction in these patients.
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http://dx.doi.org/10.12701/yujm.2020.00843DOI Listing
July 2021

Intestinal Microbiota Mediates High-Fructose and High-Fat Diets to Induce Chronic Intestinal Inflammation.

Front Cell Infect Microbiol 2021 16;11:654074. Epub 2021 Jun 16.

Tianjin Institute of Environmental and Operational Medicine, Tianjin, China.

An unhealthy diet has been linked to increased incidence of chronic diseases. To investigate the relationship between diet and intestinal inflammation, mice in two experimental groups were fed on a high-fat diet or high-fructose diet, respectively. The result showed that the defecation volume of the experimental groups was significantly reduced compared with that of the control group, and the levels of pro-inflammatory cytokines (interleukin (IL)-1β and IL-6) and IgG in serum were increased significantly. In addition, inflammatory cell infiltration was observed in intestinal tissue, indicating that a high-fructose or high-fat diet can lead to constipation and inflammation. Further analysis showed that the microbial composition of the experimental groups changed significantly, including a decrease of the ratio and increased levels of , , , and , which might be associated with inflammation. The results of pro-inflammatory metabolites analysis showed that the levels of arachidonic acid, stearic acid, and indoxylsulfuric acid were significantly increased in the experimental groups, which were related significantly to , , and . Meanwhile, the content of 5-hydroxytryptamine (5-HT) was significantly decreased, which might cause constipation by reducing intestinal peristalsis. Moreover, transplantation of fecal bacteria from inflammatory mice caused constipation and inflammation in normal mice, which could be relieved by feeding a normal diet. The results of the present study indicated that changes in intestinal microbiota and microbial metabolites may underlie chronic intestinal inflammation and constipation caused by high-fructose and high-fat diets.
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http://dx.doi.org/10.3389/fcimb.2021.654074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242949PMC
July 2021

A stark difference in the profiles of defective viral transcripts between SARS-CoV-2 and SARS-CoV.

J Infect 2021 Jul 1. Epub 2021 Jul 1.

Department of Biology, Hong Kong Baptist University, Hong Kong, China; State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.06.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245308PMC
July 2021

Hypothalamic primary cilium: A hub for metabolic homeostasis.

Exp Mol Med 2021 Jul 1. Epub 2021 Jul 1.

Departments of Oral Biology and Applied Biological Science, BK21 Four, Yonsei University College of Dentistry, Seoul, 03722, Korea.

Obesity is a global health problem that is associated with adverse consequences such as the development of metabolic disorders, including cardiovascular disease, neurodegenerative disorders, and type 2 diabetes. A major cause of obesity is metabolic imbalance, which results from insufficient physical activity and excess energy intake. Understanding the pathogenesis of obesity, as well as other metabolic disorders, is important in the development of methods for prevention and therapy. The coordination of energy balance takes place in the hypothalamus, a major brain region that maintains body homeostasis. The primary cilium is an organelle that has recently received attention because of its role in controlling energy balance in the hypothalamus. Defects in proteins required for ciliary function and formation, both in humans and in mice, have been shown to cause various metabolic disorders. In this review, we provide an overview of the critical functions of primary cilia, particularly in hypothalamic areas, and briefly summarize the studies on the primary roles of cilia in specific neurons relating to metabolic homeostasis.
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http://dx.doi.org/10.1038/s12276-021-00644-5DOI Listing
July 2021

Purification, Characterization, and Self-Assembly of the Polysaccharide from .

Foods 2021 Jun 11;10(6). Epub 2021 Jun 11.

Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science & Nutritional Engineering, China Agricultural University, 17 East Tsinghua Rd., Beijing 100083, China.

The major polysaccharide component from the stalk of (sP) was extracted and purified. Gel filtration chromatography purified sP exhibited a molecular weight of around 1.7 kDa, which was verified by MALDI-ToF-MS. The monosaccharide analysis revealed its composition as rhamnose: arabinose: galactose: glucose: mannose: fructose with a molar ratio of 0.03:2.46:3.71:3.35:1.00:9.93, respectively. The Congo-red assay indicated that there was no tertiary structure of this polysaccharide, however, it self-assembled into a homogenous nanoparticle with a diameter of ~600 nm as revealed by the dynamic light scattering measurement. The solution behavior of this polysaccharide was simulated. The association of this polysaccharide was both time dependent and concentration dependent. sP forms spherical particles spontaneously as time passes by, and when the sP concentration increased, the spherical particles increased their sizes and eventually merged into cylindrical micelles. The diversity of sP hydrodynamic behavior endowed potential versatility in its future applications.
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http://dx.doi.org/10.3390/foods10061352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230776PMC
June 2021

Distal pancreatectomy with En-bloc celiac axis resection for locally advanced pancreatic body/tail cancer: A systematic review and meta-analysis.

Asian J Surg 2021 Jun 26. Epub 2021 Jun 26.

The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Distal pancreatectomy with En-bloc celiac axis resection (DP-CAR) is a challenging procedure that has yielded certain clinical efficacy in the treatment of locally advanced pancreatic body/tail cancer, especially in patients with invasion of abdominal vessels. However, the clinical efficacy and safety of DP-CAR remain controversial. The study aimed to systematically review efficacy and safety of DP-CAR in the treatment of locally advanced pancreatic body/tail cancer. We systematically searched PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception to 1 October 2020. Two studiers independently accomplished the study selection, data extraction, and quality assessment. Initially, of 1032 studies were searched, among which 11 high quality studies including 1072 patients were finally identified. The pooled results showed that DP-CAR versus Distal pancreatectomy (DP), the rate of R0 resection (RR = 0.76; 95%CI: 0.66 to 0.88; p = 0.0002) and 3-year survival (RR = 0.65; 95%CI: 0.43 to 0.98; p = 0.04) was lower, postoperative mortality (RR = 2.48; 95%CI: 1.02 to 6.03; p = 0.04) was higher, the operation time (MD = 104.67; 95%CI: 84.70 to 124.64; p < 0.001) and hospital stay (MD = 3.94, 95% CI 1.35 to 6.53; p = 0.003) were longer. There was no statistical difference between the DP-CAR and DP group in 1-year, 2-year survival rate (RR = 0.84; 95%CI: 0.57 to 1.23; p = 0.37) (RR = 0.70; 95%CI: 0.45 to 1.10; p = 0.12). In conclusion, compared with DP, DP-CAR has worse efficacy and prognosis survival and is more dangerous, but it can obtain better survival benefit and quality of life than palliative treatment. We suggest that DP-CAR can be carefully attempted for effective margin-negative resection. However, surgeons and patients need to know its potential perioperative risk.
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http://dx.doi.org/10.1016/j.asjsur.2021.06.002DOI Listing
June 2021

A Comparative Analysis on the Structure and Function of the Rhizosphere Microbiome.

Front Microbiol 2021 9;12:673512. Epub 2021 Jun 9.

Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement, Guangxi Botanical Garden of Medicinal Plants, Nanning, China.

, an important Chinese medicinal herb, can be mainly cultivated in two planting patterns, cropland planting (DT) and understory planting (LX). We speculate that the rhizosphere microbiome may vary in DT and LX and may play an important role in promoting the growth and health of . In the present study, culture-independent Illumina HiSeq was employed to investigate the rhizosphere bacteria and fungi under DT and LX planting patterns. Predominant phyla include , , , , and in the two planting patterns. DT has higher alpha diversity index than LX. The predominant LX-core genera include , , and the predominant DT-core genera include , , and . Total relative abundance of the disease-suppression phylum (, , and ) and the potential plant growth-promoting rhizobacteria (PGPR) were both significantly higher in LX than in DT. We also identified over-presented microbial functional traits mediating plant-microbe and microbe-microbe interactions, nutrition acquisition, and plant growth promotion in rhizosphere. Our findings provide a valuable reference for studying beneficial microbes and pathogens of planted in DT and LX.
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http://dx.doi.org/10.3389/fmicb.2021.673512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219928PMC
June 2021

Cholesterol Control for Subclinical Coronary Atherosclerosis in Subjects Without Indication for Statin Therapy.

Am J Cardiol 2021 Aug 24;153:51-57. Epub 2021 Jun 24.

Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Low-risk individuals still experience adverse cardiac events. We sought to evaluate long-term cardiac events and predictors for subclinical coronary atherosclerosis in subjects without indication for statin therapy. We analyzed 3,272 individuals without indication for statin therapy who voluntarily underwent coronary computed tomography angiography as part of a general health examination. A cardiac event was defined as a composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, or late coronary revascularization. The prevalence of normal coronary arteries, nonobstructive coronary artery disease (CAD) (diameter stenosis < 50%), and obstructive CAD (diameter stenosis ≥50%) was 2,338 (71.5%), 809 (24.7%), and 125 (3.8%), respectively. During the follow-up period (median 5.3 [interquartile range, 4.3-6.3] years), the 6-year event-free survival rates were 99.2%±0.2% in subjects with normal coronary arteries, 98.2%±0.6% in those with nonobstructive CAD, and 90.2%±2.7% in those with obstructive CAD (log-rank p < 0.001). Multivariable regression analysis showed that low-density lipoprotein cholesterol (LDL-C, odds ratio [OR]: 1.012; 95% confidence interval (CI): 1.005-1.019) and high-density lipoprotein cholesterol (HDL-C, OR: 0.968; 95% CI: 0.952-0.984) levels were associated with subclinical obstructive CAD, together with age (OR: 1.080; 95% CI: 1.040-1.121) and male sex (OR: 3.102; 95% CI: 1.866-5.155) (all p < 0.05). In conclusion, LDL-C and HDL-C are significantly associated with the presence of subclinical obstructive CAD with a worse prognosis in subjects without indication for statin therapy. These findings suggest that stricter control of LDL-C and HDL-C levels may be necessary for primary prevention even in a relatively low-risk population.
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http://dx.doi.org/10.1016/j.amjcard.2021.05.019DOI Listing
August 2021

A synthesis framework using machine learning and spatial bivariate analysis to identify drivers and hotspots of heavy metal pollution of agricultural soils.

Environ Pollut 2021 Jun 17;287:117611. Epub 2021 Jun 17.

College of Environmental & Resource Sciences, Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, Zhejiang University, Hangzhou, 310058, China.

Source apportionment can be an effective tool in mitigating soil pollution but its efficacy is often limited by a lack of information on the factors that influence the accumulation of pollutants at a site. In response to this limitation and focusing on a suite of heavy metals identified as priorities for pollution control, the study established a comprehensive pollution control framework using factor identification coupled with spatial agglomeration for agricultural soils in an industrialized part of Zhejiang Province, China. In addition to elucidating the key role of industrial and traffic activities on heavy metal accumulation through implementing a receptor model, specific influencing factors were identified using a random forest model. The distance from the soil sample location to the nearest likely industrial source was the most important factor in determining cadmium and copper concentrations, while distance to the nearest road was more important for lead and zinc pollution. Soil parent materials, pH, organic matter, and clay particle size were the key factors influencing accumulation of arsenic, chromium, and nickel. Spatial auto-correlation between levels of soil metal pollution and industrial agglomeration can enable a more targeted approach to pollution control measures. Overall, the approach and results provide a basis for improved accuracy in source apportionment, and thus improved soil pollution control, at the regional scale.
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http://dx.doi.org/10.1016/j.envpol.2021.117611DOI Listing
June 2021

Phyllotaxis development: a lesson from the Asteraceae family.

Trends Plant Sci 2021 Jun 22. Epub 2021 Jun 22.

State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, the Chinese Academy of Sciences, 20 Nanxincun, Xiangshan, Beijing 100093, China. Electronic address:

Phyllotaxis refers to the spatial arrangement of leaves and flowers on a stem. A recent study by Zhang et al. described the developmental process underlying phyllotaxis establishment in the capitulum of Gerbera hybrida. This work represents a cornerstone for studying the development and diversification mechanisms of capitula in the Asteraceae.
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http://dx.doi.org/10.1016/j.tplants.2021.06.002DOI Listing
June 2021

Pair Sites on Nodes of Metal-Organic Framework hcp UiO-66 Catalyze -Butyl Alcohol Dehydration.

J Phys Chem Lett 2021 Jul 25;12(26):6085-6089. Epub 2021 Jun 25.

College of Chemical Engineering, State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, Jiangsu 21000, China.

On metal oxide cluster nodes of metal-organic frameworks (MOFs), sites not bonded to linkers (e.g., defects and structural vacancies) control reactivity and catalysis. Attention has been focused on isolated, individual sites, but pair sites have been largely overlooked. We now show that the MOF UiO-66, which incorporates dimeric ZrO nodes bridged by μ-OH groups, is an excellent platform for identifying and controlling adjacent sites consisting of OH groups and Zr sites, which catalyze -butyl alcohol dehydration much more rapidly than isolated single sites.
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http://dx.doi.org/10.1021/acs.jpclett.1c01574DOI Listing
July 2021

Non-concentrated aqueous electrolytes with organic solvent additives for stable zinc batteries.

Chem Sci 2021 Mar 15;12(16):5843-5852. Epub 2021 Mar 15.

College of Chemistry & Environmental Science, Key Laboratory of Analytical Science and Technology of Hebei Province, Hebei University Baoding 071002 China

Rechargeable aqueous zinc batteries (RAZBs) are promising for large-scale energy storage because of their superiority in addressing cost and safety concerns. However, their practical realization is hampered by issues including dendrite growth, poor reversibility and low coulombic efficiency (CE) of Zn anodes due to parasitic reactions. Here, we report a non-concentrated aqueous electrolyte composed of 2 m zinc trifluoromethanesulfonate (Zn(OTf)) and the organic dimethyl carbonate (DMC) additive to stabilize the Zn electrochemistry. Unlike the case in conventional aqueous electrolytes featuring typical Zn[HO] solvation, a solvation sheath of Zn with the co-participation of the DMC solvent and OTf anion is found in the formulated HO + DMC electrolyte, which contributes to the formation of a robust ZnF and ZnCO-rich interphase on Zn. The resultant Zn anode exhibits a high average CE of Zn plating/stripping (99.8% at an areal capacity of 2.5 mA h cm) and dendrite-free cycling over 1000 cycles. Furthermore, the HO + DMC electrolytes sustain stable operation of RAZBs pairing Zn anodes with diverse cathode materials such as vanadium pentoxide, manganese dioxide, and zinc hexacyanoferrate. Rational electrolyte design with organic solvent additives would promote building better aqueous batteries.
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http://dx.doi.org/10.1039/d0sc06734bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179661PMC
March 2021

MicroRNA-139-5p inhibits vascular endothelial cell viability and serves as a diagnostic biomarker in acute myocardial infarction patients.

Exp Gerontol 2021 Sep 16;152:111453. Epub 2021 Jun 16.

Functional Section, Jiaozhou People's Hospital, Jiaozhou 266300, Shandong, China. Electronic address:

Background: Acute myocardial infarction (AMI) is a cardiovascular disease with high morbidity and mortality, and microRNA-139-5p (miR-139-5p) has been reported to be closely related with myocardial viability. This study aimed to investigate the effects of miR-139-5p on vascular endothelial cells, detect miR-139-5p expression in AMI patients and evaluate its diagnostic value.

Methods: A dual-luciferase reporter assay was utilized to confirm the interaction of miR-139-5p with vascular endothelial growth factor receptor-1 (VEGFR-1). Quantitative real-time PCR was used to detect the levels of miR-139-5p and VEGFR-1 in serum and cells. The viability of human umbilical vein endothelial cells (HUVECs) was measured using a cell counting kit-8 assay. The correlation between miR-139-5p and VEGFR-1 was analyzed by Pearson correlation analysis. The diagnostic value of miR-139-5p, cardiac troponin I (cTnI) and creatine kinase isoenzymes (CK-MB) was identified by receiver operating characteristic analysis.

Results: miR-139-5p suppressed cell viability by directly targeting VEGFR-1 in HUVECs. Increased miR-139-5p and decreased VEGFR-1 levels were found in AMI patients and hypoxia-treated HUVECs, and miR-139-5p and VEGFR-1 were shown to be negatively correlated. The diagnostic value of miR-139-5p for AMI screening was high, and the combination of cTnI, CK-MB and miR-139-5p had the highest diagnostic accuracy. miR-139-5p inhibited cell viability by inhibiting VEGFR-1 in hypoxia-treated HUVECs.

Conclusion: miR-139-5p inhibits endothelial cell viability of AMI by inhibiting VEGFR-1, and increased miR-139-5p expression in AMI patients has high diagnostic value for AMI screening, indicating that miR-139-5p may serve as a diagnostic biomarker and molecular therapeutic target for AMI.
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http://dx.doi.org/10.1016/j.exger.2021.111453DOI Listing
September 2021

Rtt105 promotes high-fidelity DNA replication and repair by regulating the single-stranded DNA-binding factor RPA.

Proc Natl Acad Sci U S A 2021 Jun;118(25)

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences and Frontier Science Centre for Immunology and Metabolism, Wuhan University, Wuhan 320072, China;

Single-stranded DNA (ssDNA) covered with the heterotrimeric Replication Protein A (RPA) complex is a central intermediate of DNA replication and repair. How RPA is regulated to ensure the fidelity of DNA replication and repair remains poorly understood. Yeast Rtt105 is an RPA-interacting protein required for RPA nuclear import and efficient ssDNA binding. Here, we describe an important role of Rtt105 in high-fidelity DNA replication and recombination and demonstrate that these functions of Rtt105 primarily depend on its regulation of RPA. The deletion of causes elevated spontaneous DNA mutations with large duplications or deletions mediated by microhomologies. Rtt105 is recruited to DNA double-stranded break (DSB) ends where it promotes RPA assembly and homologous recombination repair by gene conversion or break-induced replication. In contrast, Rtt105 attenuates DSB repair by the mutagenic single-strand annealing or alternative end joining pathway. Thus, Rtt105-mediated regulation of RPA promotes high-fidelity replication and recombination while suppressing repair by deleterious pathways. Finally, we show that the human RPA-interacting protein hRIP-α, a putative functional homolog of Rtt105, also stimulates RPA assembly on ssDNA, suggesting the conservation of an Rtt105-mediated mechanism.
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http://dx.doi.org/10.1073/pnas.2106393118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237652PMC
June 2021

Cytochrome P450 Hydroxylase TnmL Catalyzing Sequential Hydroxylation with an Additional Proofreading Activity in Tiancimycin Biosynthesis.

ACS Chem Biol 2021 Jul 17;16(7):1172-1178. Epub 2021 Jun 17.

Tiancimycin (TNM) A belongs to the anthraquinone-fused subfamily of enediyne natural products, and selected enediynes have been translated into clinical drugs. Previously, inactivation of in sp. CB03234 resulted in the accumulation of TNM B and TNM E, supporting the functional assignment of TnmL as a cytochrome P450 hydroxylase that catalyzes A-ring modification in TNM A biosynthesis. Herein, we report in vitro characterization of TnmL, revealing that (i) TnmL catalyzes two successive hydroxylations of TNM E, resulting in sequential production of TNM F and TNM C, (ii) TnmL shows a strict substrate preference, with the C-26 side chain playing a critical role in substrate binding, and (iii) TnmL demethylates the C-7 OCH group of TNM G, affording TNM F, thereby channeling the shunt product TNM G back into TNM A biosynthesis and representing a rare proofreading logic for natural product biosynthesis. These findings shed new insights into anthraquinone-fused enediyne biosynthesis.
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http://dx.doi.org/10.1021/acschembio.1c00365DOI Listing
July 2021

Silencing Cardiac Troponin I-Interacting Kinase Reduces Lipopolysaccharide-Induced Sepsis-Induced Myocardial Dysfunction in Rat by Regulating Apoptosis-Related Proteins.

Biomed Res Int 2021 27;2021:5520051. Epub 2021 May 27.

Department of Anatomy, Hebei Medical University, Shijiazhuang 050017, China.

The aim of this study was to investigate the effect of cardiac troponin I-interacting kinase () on sepsis-induced myocardial dysfunction (SIMD) and further explore the underlying molecular mechanisms. In this study, a lipopolysaccharide- (LPS-) induced myocardial injury model was used. qRT-PCR was performed to detect the mRNA expression of . Western blot was conducted to quantitatively detect the expression of and apoptosis-related proteins (Bcl-2, Bax, and caspase-3). ELISA was performed to detect the content of lactate dehydrogenase (LDH) and creatine kinase (CK). TUNEL assay was used to detect the apoptosis of H9C2 cells. In LPS-induced H9C2 cells, was up regulated. Besides, the CK activity, the content of LDH, and the apoptosis of H9C2 cells were significantly increased after treatment with LPS. Silencing TNNI3K decreased the LDH release activity and CK activity and inhibited apoptosis of H9C2 cell. Further research illustrated that si-TNNI3K promoted the protein expression of Bcl-2 and decreased the protein expression of Bax and cleaved caspase-3. The study concluded that TNNI3K was upregulated in LPS-induced H9C2 cells. Importantly, functional research findings indicated that silencing TNNI3K alleviated LPS-induced H9C2 cell injury by regulating apoptosis-related proteins.
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http://dx.doi.org/10.1155/2021/5520051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175134PMC
May 2021

Zebrafish Chromosome 14 Gene Differential Expression in the Model of Fragile X Syndrome.

Front Genet 2021 31;12:625466. Epub 2021 May 31.

School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.

Zebrafish represent a valuable model for investigating the molecular and cellular basis of Fragile X syndrome (FXS). Reduced expression of the zebrafish orthologous gene, , causes developmental and behavioural phenotypes related to FXS. Zebrafish homozygous for the hu2787 non-sense mutation allele of are widely used to model FXS, although FXS-relevant phenotypes seen from morpholino antisense oligonucleotide (morpholino) suppression of transcript translation were not observed when hu2787 was first described. The subsequent discovery of transcriptional adaptation (a form of genetic compensation), whereby mutations causing non-sense-mediated decay of transcripts can drive compensatory upregulation of homologous transcripts independent of protein feedback loops, suggested an explanation for the differences reported. We examined the whole-embryo transcriptome effects of homozygosity for at 2 days post fertilisation. We observed statistically significant changes in expression of a number of gene transcripts, but none from genes showing sequence homology to . Enrichment testing of differentially expressed genes implied effects on lysosome function and glycosphingolipid biosynthesis. The majority of the differentially expressed genes are located, like , on Chromosome 14. Quantitative PCR tests did not support that this was artefactual due to changes in relative chromosome abundance. Enrichment testing of the "leading edge" differentially expressed genes from Chromosome 14 revealed that their co-location on this chromosome may be associated with roles in brain development and function. The differential expression of functionally related genes due to mutation of , and located on the same chromosome as , is consistent with R.A. Fisher's assertion that the selective advantage of co-segregation of particular combinations of alleles of genes will favour, during evolution, chromosomal rearrangements that place them in linkage disequilibrium on the same chromosome. However, we cannot exclude that the apparent differential expression of genes on Chromosome 14 genes was, (if only in part), caused by differences between the expression of alleles of genes unrelated to the effects of the mutation and made manifest due to the limited, but non-zero, allelic diversity between the genotypes compared.
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http://dx.doi.org/10.3389/fgene.2021.625466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203322PMC
May 2021

Targeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity.

Sci Adv 2021 06 16;7(25). Epub 2021 Jun 16.

State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.

Infection by highly pathogenic coronaviruses results in substantial apoptosis. However, the physiological relevance of apoptosis in the pathogenesis of coronavirus infections is unknown. Here, with a combination of in vitro, ex vivo, and in vivo models, we demonstrated that protein kinase R-like endoplasmic reticulum kinase (PERK) signaling mediated the proapoptotic signals in Middle East respiratory syndrome coronavirus (MERS-CoV) infection, which converged in the intrinsic apoptosis pathway. Inhibiting PERK signaling or intrinsic apoptosis both alleviated MERS pathogenesis in vivo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV induced apoptosis through distinct mechanisms but inhibition of intrinsic apoptosis similarly limited SARS-CoV-2- and SARS-CoV-induced apoptosis in vitro and markedly ameliorated the lung damage of SARS-CoV-2-inoculated human angiotensin-converting enzyme 2 (hACE2) mice. Collectively, our study provides the first evidence that virus-induced apoptosis is an important disease determinant of highly pathogenic coronaviruses and demonstrates that this process can be targeted to attenuate disease severity.
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http://dx.doi.org/10.1126/sciadv.abf8577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208716PMC
June 2021