Publications by authors named "Xu Wei"

4,468 Publications

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Evaluating the prognostic contributions of TNM classifications and building novel staging schemes for middle ear squamous cell carcinoma.

Cancer Med 2021 Sep 24. Epub 2021 Sep 24.

Department of Oto-Rhino-Laryngology, West China Hospital, Sichuan University, Chengdu, China.

Background: A universally acknowledged cancer staging system considering all aspects of the T-, N-, and M-classifications for middle ear squamous cell carcinoma (MESCC) remains absent, limiting the clinical management of MESCC patients.

Materials And Methods: A total of 214 MESCC patients were extracted from the SEER (the Surveillance, Epidemiology, and End Results) database between 1973 and 2016. The relationships between patient's characteristics and prognoses were analyzed by Kaplan-Meier and Cox proportional hazards regression models. Novel staging schemes for MESCC were designed by adjusted hazard ratio (AHR) modeling method according to the combinations of Stell's T-classification and the eighth AJCC N- and M-classifications, of which performances were evaluated based on five criteria: hazard consistency, hazard discrimination, explained variation, likelihood difference, and balance.

Results: T-classification was the most significant prognostic factor for MESCC patients in multivariable analysis (p = 0.021). The N- and M-classifications also had obvious prognostic effect but were not statistically significant by multivariate analysis due to the limited metastasis events. Three novel staging schemes (AHR-Ⅰ-Ⅲ models, different combination of T- and N-classifications) and ST (solely derived from Stell's T-classification) were developed, among which the AHR-Ⅰ staging scheme performed best.

Conclusions: Tumor extension, quantified by Stell's T-classification, is the most significant prognostic factor for MESCC patients. However, our AHR-Ⅰ staging scheme, a comprehensive staging scheme that integrating T-, N-, and M-classifications, might be an optimal option for clinical practitioners to predict MESCC patients' prognosis and make proper clinical decisions.
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http://dx.doi.org/10.1002/cam4.4306DOI Listing
September 2021

Inhibition of viral suppressor of RNAi proteins by designer peptides protects from enteroviral infection in vivo.

Immunity 2021 Sep 15. Epub 2021 Sep 15.

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences (CAS), Wuhan 430071, China. Electronic address:

RNA interference (RNAi) is the major antiviral mechanism in plants and invertebrates, but the absence of detectable viral (v)siRNAs in mammalian cells upon viral infection has questioned the functional relevance of this pathway in mammalian immunity. We designed a series of peptides specifically targeting enterovirus A71 (EV-A71)-encoded protein 3A, a viral suppressor of RNAi (VSR). These peptides abrogated the VSR function of EV-A71 in infected cells and resulted in the accumulation of vsiRNAs and reduced viral replication. These vsiRNAs were functional, as evidenced by RISC-loading and silencing of target RNAs. The effects of VSR-targeting peptides (VTPs) on infection with EV-A71 as well as another enterovirus, Coxsackievirus-A16, were ablated upon deletion of Dicer1 or AGO2, core components of the RNAi pathway. In vivo, VTP treatment protected mice against lethal EV-A71 challenge, with detectable vsiRNAs. Our findings provide evidence for the functional relevance of RNAi in mammalian immunity and present a therapeutic strategy for infectious disease.
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http://dx.doi.org/10.1016/j.immuni.2021.08.027DOI Listing
September 2021

Association analysis of B7-H3 and B7-H4 gene single nucleotide polymorphisms in susceptibility to ankylosing spondylitis in eastern Chinese Han population.

Int J Immunogenet 2021 Sep 23. Epub 2021 Sep 23.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.

This study was conducted to describe the association between the genetic variation of the recently identified immune checkpoint molecules B7-H3 and B7-H4, and the susceptibility to ankylosing spondylitis (AS). Two single nucleotide polymorphisms (SNPs) of B7-H3 gene and three SNPs of B7-H4 gene were genotyped in 649 AS patients and 646 age- and sex-matched healthy controls. Allele, genotype frequencies and different inheritance models were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and the demographic and clinical parameters of patients were recorded. Our data indicated that B7-H4 rs10801935 and rs3738414 polymorphisms were correlated with AS susceptibility. In the stratification analyses, the minor A allele and GA genotype of B7-H4 rs3738414 increased the risk of AS in male patients (OR = 1.244, 95%CI = 1.026-1.508; OR = 1.453, 95%CI = 1.120-1.886, respectively). However, the association did not reach statistical significance after Bonferroni correction. Furthermore, haplotype analysis revealed that B7-H4 haplotype block TAG was a risk factor for the onset of AS (OR = 1.190, 95%CI = 1.020-1.389). These findings suggested that B7-H4 gene polymorphism may contribute to AS susceptibility in eastern Chinese Han population.
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http://dx.doi.org/10.1111/iji.12559DOI Listing
September 2021

An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope.

Protein Cell 2021 Sep 23. Epub 2021 Sep 23.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences; Shanghai Institute of Infectious Disease and Biosecurity; the Fifth People's Hospital of Shanghai; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology); Institutes of Biomedical Sciences; Biosafety Level 3 Laboratory, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
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http://dx.doi.org/10.1007/s13238-021-00871-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458794PMC
September 2021

Association of Night-Time Heart Rate With Ventricular Tachyarrhythmias, Appropriate and Inappropriate Implantable Cardioverter-Defibrillator Shocks.

Front Cardiovasc Med 2021 6;8:739889. Epub 2021 Sep 6.

State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Night-time heart rate (HR) is expected to reflect more accurately the cardiac autonomic function of modulating cardiovascular activity. Few studies have been conducted on the predictive values of night-time HR in relation to cardioverter-defibrillator therapies. To explore the associations of night-time HR with the ventricular tachyarrhythmias (VTAs), appropriate and inappropriate implantable cardioverter-defibrillator (ICD) shocks. Patients from the SUMMIT registry receiving ICD or cardiac resynchronization therapy with defibrillator (CRT-D) implantation were retrospectively analyzed using archived home monitoring data. Night-time HR was recorded from 2:00 am to 6:00 am during the first 30 to 60 days after implantation. VTA events and ICD shocks were identified using the intracardiac electrograms by two independent physicians. Restricted cubic splines and smooth curve fitting were conducted to address the non-linear associations between night-time HR and adjusted hazards for clinical outcomes. Over a mean follow-up duration of 55.8 ± 22.7 months, 187 deaths were observed among 730 patients. VTAs, appropriate and inappropriate ICD shocks were observed in 422 (57.8%), 293 (40.1%), and 72 (10.0%) patients, respectively. Apparent U-shaped non-linear associations of night-time HR with VTAs (P for non-linearity = 0.007), appropriate ICD shocks (P for non-linearity = 0.003) and inappropriate ICD shocks (P for non-linearity = 0.014) were detected. When night-time HR was beyond 60 bpm, every 1 bpm increase in night-time HR could result in 3.2, 3.3, and 4.9% higher risks of VTAs and appropriate and inappropriate ICD shocks, respectively; when night-time HR was lower than 60 bpm, every 1 bpm increase in night-time HR could result in 6.0 and 10.7% lower risks of appropriate and inappropriate ICD shocks. Compared to night-time HR of ≤ 50 or ≥70 bpm, night-time HR of 50-70 bpm was associated with 24.9, 30.2, 63.5, and 31.5% reduced incidences of VTA events, appropriate ICD shocks, inappropriate ICD shocks, and all-cause mortality, respectively. Apparent non-linear associations of night-time HR with VTAs and ICD shocks were detected. An increasing incidence of VTAs and ICD shocks was observed at both low and high levels of night-time HR. Night-time HR of 50-70 bpm might be the optimal therapeutics target for the management of ICD/CRT-D recipients.
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http://dx.doi.org/10.3389/fcvm.2021.739889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450398PMC
September 2021

Rutin inhibited the advanced glycation end products-stimulated inflammatory response and extra-cellular matrix degeneration via targeting TRAF-6 and BCL-2 proteins in mouse model of osteoarthritis.

Aging (Albany NY) 2021 Sep 22;13(undefined). Epub 2021 Sep 22.

Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China.

Background: Osteoarthritis (OA) is degenerative joint disorder mainly characterized by long-term pain with limited activity of joints, the disease has no effective preventative therapy. Rutin (RUT) is a flavonoid compound, present naturally. The flavonoid shows range of biological activities such as anti-inflammatory and anti-cancer effect. We screened RUT for its activity against osteoarthritis with and models of osteoarthritis.

Methods: Animal model of OA was developed using C57BL/6 mice by surgical destabilization of medial meniscus. For studies the human articular cartilage tissues were used which were collected from osteoarthritis patients and were processed to isolate chondrocytes. The chondrocytes were submitted to advanced glycation end products (AGEs) for inducing osteoarthritis . Cell viability was done by CCK-8 assay, ELISA analysis for MMP13, collage II, PGE2, IL-6, TNF-α, ADAMTS-5 and MMP-13. Western blot analysis was done for expression of proteins and analysis was done by docking studies.

Results: Pretreatment of RT showed no cytotoxic effect and also ameliorated the AGE mediated inflammatory reaction on human chondrocytes . Treatment of RT inhibited the levels of COX-2 and iNOS in AGE exposed chondrocytes. RT decreased the AGE mediated up-regulation of IL-6, NO, TNF-α and PGE-2 in a dose dependent manner. Pretreatment of RT decreased the extracellular matrix degradation, inhibited expression of TRAF-6 and BCL-2 the NF-κB/MAPK pathway proteins. The treatment of RT in mice prevented the calcification of cartilage tissues, loss of proteoglycans and also halted the narrowing of joint space is mice subjected to osteoarthritis. The analysis suggested potential binding affinity of RT with TRAF-6 and BCL-2.

Conclusion: In brief RT inhibited AGE-induced inflammatory reaction and also degradation of ECM via targeting the NF-κB/MAPK pathway proteins BCL-2 and TRAF-6. RT can be a potential molecule in treating OA.
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http://dx.doi.org/10.18632/aging.203470DOI Listing
September 2021

A new carboxypeptidase from Aspergillus niger with good thermostability, pH stability and broad substrate specificity.

Sci Rep 2021 Sep 21;11(1):18745. Epub 2021 Sep 21.

School of Life Sciences, Liaocheng University, Liaocheng, 252000, China.

A new serine carboxypeptidase gene, capA, was identified in Aspergillus niger CBS 513.88 by reading genomic information and performing sequence alignment, and the gene was cloned and expressed in Pichia pastoris GS115. In a shake flask, the enzyme activity of the recombinant strain GS115 (pPIC9K-capA) reached 209.3 U mg. The optimal temperature and pH for enzyme activity were determined to be 45 °C and 6.0, respectively. After incubation at 40-50 °C or at pH 4.0-8.0 for 1 h, the enzyme retained more than 80% or 60% of its initial activity. The presence of 1-10 mmol L Mg enhanced the activity of CapA, whereas 1-10 mmol L Cu, Fe, or Co, 10 mmol L Mn, or 1-10 mmol L phenylmethylsulfonyl fluoride (PMSF) significantly inhibited its activity. CapA had a broad substrate specificity and preferred the hydrophobic amino acids Leu and Lys at the C terminus of proteins, and N-benzyloxycarbonyl-L-phenylalanyl-L-leucine (Cbz-Phe-Leu) was the optimal substrate, for which CapA exhibited K 0.063 mmol L and k/K 186.35 mmol L s. The good thermostability, pH stability and hydrolysis characteristics of CapA provide a solid foundation for application in the food and biotechnology fields.
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http://dx.doi.org/10.1038/s41598-021-98003-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455534PMC
September 2021

Cognitive Impairment and Delirium in Older Patients Undergoing Major Head and Neck Surgery.

Otolaryngol Head Neck Surg 2021 Sep 21:1945998211045293. Epub 2021 Sep 21.

Department of Medicine, University Health Network, University of Toronto, Toronto, Canada.

The study objective was to measure the prevalence and predictors of cognitive impairment (CI) and delirium. Adults undergoing major head and neck cancer surgery completed the Clock Draw Test to screen for CI, defined as a score of 0 or 1. Postoperative delirium was recorded. Predictors of delirium and length of stay were assessed by univariate logistic regression and the latter with multivariate linear regression. Overall 274 patients were included, of which 47% had a Clock Draw Test score of 0 or 1. Post-operative delirium occurred in 17 (6%). CI was a predictor of postoperative delirium (odds ratio, 3.9; 95% CI, 1.2-12; = .02). Postoperative delirium was a predictor of increased length of stay (adjusted odds ratio, 1.30; 95% CI, 1.07-1.57; = .0073) on multivariate regression while baseline Clock Draw Test result was not a predictor on univariate regression ( = .98). Screening for CI can help predict delirium and facilitate targeted interventions in the postoperative period.
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http://dx.doi.org/10.1177/01945998211045293DOI Listing
September 2021

Association between cardiac autonomic function and physical activity in patients at high risk of sudden cardiac death: a cohort study.

Int J Behav Nutr Phys Act 2021 Sep 20;18(1):128. Epub 2021 Sep 20.

Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Bei Li Shi Road, Xicheng District, Beijing, 100037, China.

Background: High levels of physical activity (PA) and heart rate variability (HRV) are associated with cardiovascular benefits in patients with cardiovascular diseases. HRV, representing cardiac autonomic function, is positively associated with PA. However, the impacts of PA and cardiac autonomic function on cardiovascular outcomes were not analysed in the same study population. This lack of evidence supported our hypothesis that PA might contribute to cardiovascular benefits via enhanced cardiac autonomic function.

Methods: Patients with implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy defibrillator (CRT-D) implantation were included from the SUMMIT registry. HRV and PA values were assessed during the first 30-60 days post device implantation using a continuous home monitoring system. Causal mediation analysis was conducted to explore the possible mediation function of HRV in the association of PA with long-term cardiac death and all-cause mortality in patients at a high risk of sudden cardiac death.

Results: Over a mean follow-up period of 47.7 months, 63 cardiac deaths (18.9%) and 85 all-cause death events (25.5%) were observed among 342 patients with ICD/CRT-D implantation. A positive linear association between HRV and PA was demonstrated and the β value of HRV was 0.842 (95% confidence interval [CI]: 0.261-1.425, P = 0.005) in the multiple linear regression analysis. Multivariable Cox proportional hazards analysis revealed that high levels of PA (≥11.0%) and HRV (≥75.9 ms) were independent protective factors against cardiac death (PA: hazard ratio [HR] = 0.273; 95% CI, 0.142-0.526, P < 0.001; HRV: HR = 0.224; 95% CI, 0.103-0.489, P < 0.001) and all-cause mortality (PA: HR = 0.299; 95% CI, 0.177-0.505, P < 0.001; HRV: HR = 0.394; 95% CI, 0.231-0.674, P = 0.001). Causal mediation analysis demonstrated partial mediation effects of PA that were mediated through HRV on cardiac death (mediation proportion = 12.9, 95%CI: 2.2-32.0%, P = 0.006) and all-cause mortality (mediation proportion = 8.2, 95%CI: 1.6-20.0%, P = 0.006).

Conclusions: HRV might be a modest mediator in the association between high levels of PA and the reduced risks of cardiac death and all-cause mortality in ICD/CRT-D recipients. This finding supports that enhanced cardiac autonomic function might be one of the underlying mechanisms by which regular PA contributes to cardiovascular benefits.
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http://dx.doi.org/10.1186/s12966-021-01200-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454096PMC
September 2021

Niobium carbide (MXene) reduces UHMWPE particle-induced osteolysis.

Bioact Mater 2022 Feb 1;8:435-448. Epub 2021 Jul 1.

State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, PR China.

Joint replacement surgery is one of the orthopedic surgeries with high successful rates; however, wear debris generated from prostheses can ultimately lead to periprosthetic osteolysis and failure of the implant. The implant-derived particulate debris such as ultrahigh molecular weight polyethylene (UHMWPE) can initiate the local immune response and recruit monocytic cells to phagocytose particles for generating reactive oxygen species (ROS). ROS induces osteoclastogenesis and macrophages to secrete cytokines which ultimately promote the development of osteolysis. In this work, we develop the few-layered NbC (FNC) as an antioxidant which possesses the feature of decreasing the production of cytokines and inhibiting osteoclastogenesis by its ROS adsorption. Moreover, local injection of FNC attenuates the UHMWPE-induced osteolysis in a mouse calvarial model. In sum, our results suggest that FNC can be used for treating osteolytic bone disease caused by excessive osteoclastogenesis.
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http://dx.doi.org/10.1016/j.bioactmat.2021.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429634PMC
February 2022

Struggling With Business Corporate Cynical Impression? Powerful Methods of CSR to Enhance Corporate Image and Consumer Purchase Intention.

Front Public Health 2021 3;9:726727. Epub 2021 Sep 3.

Business School, University of International Business and Economics, Business School, Beijing, China.

This study focuses on the perception of Chinese students about the image of the company and their purchase intention if the organization has a business cynical impression in the minds of its targeted customers. The study proposed three different types of corporate social responsibility (CSR) to cope up with the organizational cynical impression. These types are Economic and Legal CSR, Philanthropic CSR, and Ethical CSR. The main objective of this study is to determine which CSR type is better to reduce the corporate cynical impression on corporate image and the purchase intentions of consumers. In the study design, the bootstrap approach and AMOS 24 were employed to deal with mediation. The researchers recruited 500 individuals from different educational institutions in China using a simple random selection process. The outcomes of this study indicated that all three types of CSR are successful in mitigating the detrimental effects of corporate cynicism on the image of a firm and the purchase intentions of consumers. A more effective technique of boosting the corporate image of a company and purchase intention of a consumer is charitable CSR, which may help restore the image of a company and the purchase intention of a consumer that has been affected by corporate cynicism among its target customers.
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http://dx.doi.org/10.3389/fpubh.2021.726727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446375PMC
September 2021

Is D2 Lymphadenectomy Alone Suitable for Gastric Cancer With Bulky N2 and/or Para-Aortic Lymph Node Metastases After Preoperative Chemotherapy?

Front Oncol 2021 2;11:709617. Epub 2021 Sep 2.

Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: For gastric cancer (GC) with extensive lymph node metastasis (bulky N2 and/or para-aortic lymph node metastases), there is no standard therapy worldwide. In Japan, preoperative chemotherapy (PCT) followed by D2 gastrectomy plus para-aortic lymph node dissection (PAND) is considered the standard treatment for these patients. However, in China, the standard operation for GC patients with only bulky N2 metastases was D2 gastrectomy. Besides, after PCT, whether doing PAND improves survival or not is debatable for GC patients with para-aortic lymph node (PAN) metastases. Therefore, we conducted this study to investigate whether D2 lymphadenectomy alone is suitable for these patients after PCT.

Methods: We retrospectively collected data on patients from our electronic medical record system. GC patients with bulky N2 and/or PAN metastases who underwent D2 lymphadenectomy alone after PCT were enrolled. The survival outcomes and chemotherapy responses were analyzed and compared with the results of the JCOG0405 study.

Results: From May 2009 to December 2017, a total of 83 patients met all eligibility criteria and were enrolled. The median survival duration for all patients was 40.0 months. The 3-year and 5-year OS rates for all patients were 50.3% and 45.6%, respectively. For patients with only bulky N2 metastasis, the 3-year and 5-year OS rates were 77.1% and 71.6%, respectively, which were similar to the results of the JCOG0405 study (82.7% and 73.4%). For patients with only PAN metastases, the 3-year and 5-year OS rates were 50.0% and 50.0%, respectively, which seemed to be lower than those of the JCOG0405 study (64.3% and 57.1%). For patients with bulky N2 and PAN metastases, the 3-year and 5-year OS rates were 7.4% and 0.0%, respectively, which were lower than those of the JCOG0405 study (20.0% and 20.0%).

Conclusion: The results of our study suggest that D2 lymphadenectomy alone is suitable for GC patients with only bulky N2 metastasis after PCT. However, D2 lymphadenectomy alone perhaps is not suitable for patients with bulky N2 and PAN metastases after PCT.
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http://dx.doi.org/10.3389/fonc.2021.709617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444230PMC
September 2021

Understanding the Stony Bridge between Osteoporosis and Vascular Calcification: Impact of the FGF23/Klotho axis.

Oxid Med Cell Longev 2021 30;2021:7536614. Epub 2021 Aug 30.

School of Traditional Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

A relationship between osteoporosis (OP) and vascular calcification (VC) is now proposed. There are common mechanisms underlying the regulation of them. Fibroblast growth factor- (FGF-) 23 and Klotho are hormones associated with the metabolic axis of osteovascular metabolism. Most recently, it was suggested that the FGF23-klotho axis is associated with increasing incidence of fractures and is potentially involved in the progression of the aortic-brachial stiffness ratio. Herein, we discussed the potential role of the FGF23/Klotho axis in the pathophysiology of OP and VC. We want to provide an update review in order to allow a better understanding of the potential role of the FGF23/Klotho axis in comorbidity of OP and VC. We believe that a better understanding of the relationship between both entities can help in proposing new therapeutic targets for reducing the increasing prevalence of OP and VC in the aging population.
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http://dx.doi.org/10.1155/2021/7536614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448600PMC
August 2021

Serum Metabolome Mediates the Antiobesity Effect of Celastrol-Induced Gut Microbial Alterations.

J Proteome Res 2021 Sep 16. Epub 2021 Sep 16.

College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.

The antiobesity effect of celastrol has been reported in numerous studies, but the underlying mechanism remains unclear. It is widely accepted that gut dysbiosis is closely related to obesity. The potential effect of celastrol on microbiota is worth exploring. In this study, the celastrol-induced weight loss was validated in high-fat diet (HFD)-induced obese mice, with the detection of reported phenotypes including a reduction in food intake, augments in dyslipidemia and glucose metabolism, and adipose thermogenesis. The anti-inflammatory effect of celastrol was also proved based on the alterations in serum cytokines. Antibiotic interference showed that gut microbiota contributes to celastrol-induced weight loss. Several key bacteria were identified using shotgun metagenomic sequencing to display the alterations of the intestinal microbiome in obese mice treated with celastrol. Meanwhile, the fecal and serum metabolic profiles were generated by pseudotargeted metabolomics, and changes in some critical metabolites related to appetite and metabolism were detected. Importantly, we applied in silico bidirectional mediation analysis to identify the precise connections among the alterations in gut microbes, serum metabolome, and host phenotypes induced by celastrol treatment for the first time. Therefore, we concluded that the celastrol-induced microbial changes partially contribute to the antiobesity effect via the serum metabolome. The mass spectrometry data are deposited on MetaboLights (ID: MTBLS3278).
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http://dx.doi.org/10.1021/acs.jproteome.1c00513DOI Listing
September 2021

Genome-wide association studies of survival in 1,520 cancer patients treated with bevacizumab-containing regimens.

Int J Cancer 2021 Sep 16. Epub 2021 Sep 16.

UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Germline variants might predict cancer progression. Bevacizumab improves overall survival (OS) in patients with advanced cancers. No biomarkers are available to identify patients that benefit from bevacizumab. A meta-analysis of genome-wide association studies (GWAS) was conducted in 1,520 patients from phase III trials (CALGB 80303, 40503, 80405, and ICON7), where bevacizumab was randomized to treatment without bevacizumab. We aimed to identify genes and SNPs associated with survival independently of bevacizumab treatment or through interaction with bevacizumab. A cause-specific Cox model was used to test the SNP-OS association in both arms combined (prognostic), and the effect of SNPs-bevacizumab interaction on OS (predictive) in each study. The SNP effects across studies were combined using inverse variance. Findings were tested for replication in advanced colorectal and ovarian cancer patients from The Cancer Genome Atlas (TGCA). In the GWAS meta-analysis, patients with rs680949 in PRUNE2 experienced shorter OS compared to patients without it (p=1.02x10 , HR=1.57, 95% CI:1.33-1.86), as well as in TCGA (p=0.0219, HR=1.58, 95% CI:1.07-2.35). In the GWAS meta-analysis, patients with rs16852804 in BARD1 experienced shorter OS compared to patients without it (p=1.40x10 , HR=1.51, 95% CI:1.25-1.82) as well as in TCGA (p=1.39x10 , HR=3.09, 95% CI:1.73-5.51). Patients with rs3795897 in AGAP1 experienced shorter OS in the bevacizumab arm compared to the non-bevacizumab arm (p=1.43x10 ). The largest GWAS meta-analysis of bevacizumab treated patients identified PRUNE2 and BARD1 (tumor suppressor genes) as prognostic genes of colorectal and ovarian cancer, respectively, and AGAP1 as a potentially predictive gene that interacts with bevacizumab with respect to patient survival. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ijc.33810DOI Listing
September 2021

Mechanical ventilation-associated pneumonia caused by Acinetobacter baumannii in Northeast China region: analysis of genotype and drug resistance of bacteria and patients' clinical features over 7 years.

Antimicrob Resist Infect Control 2021 Sep 15;10(1):135. Epub 2021 Sep 15.

Department of Pediatrics, Shengjing Hospital of China Medical University, No. 36, SanHao Street, Shenyang City, 110004, Liaoning Province, People's Republic of China.

Objective: To investigate the clinical features and outcomes of patients with mechanical ventilation-associated pneumonia (VAP) caused by Acinetobacter baumannii (Ab), and to characterize the drug resistance of pathogenic strains and carbapenem resistance-associated genes.

Methods: Clinical data were collected from the PICU of Shengjing Hospital. Patients who met the diagnostic criteria of VAP and for whom Ab was a pathogen were selected as study participants. The patients were divided into carbapenem-resistant A. baumannii (CRAB) and carbapenem-sensitive A. baumannii (CSAB) groups. The genes closely associated with Ab resistance to carbapenems and the efflux pump-related genes were detected by real-time polymerase chain reaction, and results compared between the two groups.

Results: The total mechanical ventilation time and the administration time of antibiotics after a diagnosis of Ab infection were significantly higher in the CRAB group. And the CRAB group strains were only sensitive to amikacin, cephazolin, compound sulfamethoxazole, and tigecycline. Genetic test results indicated that IPM expression was not significantly different between two groups. The OXA-51 and OXA-23 in the CRAB group was markedly higher than that in the CSAB group, while OXA-24 expression was markedly lower. The expression of AdeABC and AdeFGH was significantly greater in the CRAB compared to CSAB group.

Conclusion: In pediatric patients with VAP caused by Ab infection, the detection rate of CRAB strains is far higher than that of CSAB strains; The abnormal expression of β-lactamase-producing genes (OXA-23, OXA-24, and OXA-51) and efflux pump-related genes (AdeABC and AdeFGH) is closely related to the production of CRAB.
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http://dx.doi.org/10.1186/s13756-021-01005-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444615PMC
September 2021

[Comparison of femoral neck system and inverted triangle cannulated screws fixations in treatment of Pauwels typle femoral neck fractures].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Sep;35(9):1111-1118

Department of Orthopedics and Traumatology, the First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei Anhui, 230001, P.R.China.

Objective: To compare the effectiveness of the femoral neck system (FNS) and inverted triangle cannulated screws (ITCS) for the treatment of Pauwels type Ⅲ femoral neck fractures.

Methods: The clinical data of 59 patients with Pauwels type Ⅲ femoral neck fractures treated between May 2019 and November 2020 were retrospectively analysed. The patients were divided into FNS group (28 cases) and ITCS group (31 cases) according to the different internal fixation. There was no significant difference in gender, age, affected side, body mass index, cause of injury, smoking history, alcohol abuse history, Pauwels angle, Garden classification, AO/Orthopaedic Trauma Association (AO/OTA) classification, and time from injury to operation between the two groups ( >0.05). The operation time, incision length, intraoperative blood loss, extra assisted reduction procedures (Kirschner wire prying reduction or open reduction), hospitalization stay, and early complications were recorded and compared between the two groups. Garden index and Haidukewych score were used to evaluate fracture reduction. Fracture healing time, lateral thigh irritation, time of partial or total weight-bearing postoperatively, shortening length and degree of femoral neck, change of caput-collum-diaphysis (CCD) angle (the difference of CCD angle between immediate after operation and last follow-up), incidence of osteonecrosis of femoral head and revision surgery were recorded and compared between the two groups. Hip joint function were evaluated by Harris score.

Results: The operation time of FNS group was significantly shorter than ITCS group, and the incision length was significantly longer than ITCS group ( <0.05). There was no significant difference in intraoperative blood loss, assisted reduction, Garden index, Haidukewych score, and hospitalization stay between the two groups ( >0.05). All the incisions healed by first intention. There were 2 deep vein thrombosis in the FNS group and 1 pulmonary infection and 1 deep vein thrombosis in the ITCS group. No significant difference was found in the incidence of early postoperative complications (7.1% 6.5%) between the two groups ( =1.000). Patients in both groups were followed up 3-14 months, and there was no significant difference in follow-up time between the two groups ( =-0.553, =0.582). The fracture healing time, Harris score, and the partial weight-bearing time after operation of the FNS group were significantly better than those of the ITCS group ( <0.05). However, there was no significant difference in total weight-bearing time between the two groups ( =-1.298, =0.194). No lateral thigh irritation was found in the FNS group, while 10 patients in the ITCS group had lateral thigh irritation, and the incidence between the two groups (0 32.3%) was significant ( =0.001). At last follow-up, the shortening length and degree of femoral neck and the change of CCD angle in FNS group were significantly less than those in ITCS group ( <0.05). There was no patient with osteonecrosis of femoral head or reoperation in the FNS group, while 4 patients in the ITCS group underwent reoperation (including 2 cases of osteonecrosis of the femoral head). However, the incidences (0 6.5%; 0 12.9%) between the two groups were not significant ( =0.493; =0.114).

Conclusion: Using FNS to treat Pauwels type Ⅲ femoral neck fracture is simple as well as able to reduce the shortening of the femoral neck and the change of the CCD angle. Also, FNS is conducive to the recovery of hip joint function, which should be considered as a new choice for the treatment of young femoral neck fracture patients.
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http://dx.doi.org/10.7507/1002-1892.202102046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444134PMC
September 2021

mTOR regulates cocaine-induced behavioural sensitization through the SynDIG1-GluA2 interaction in the nucleus accumbens.

Acta Pharmacol Sin 2021 Sep 14. Epub 2021 Sep 14.

National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP and PIP. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.
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http://dx.doi.org/10.1038/s41401-021-00760-yDOI Listing
September 2021

Fixed duration prolonged duration treatment after first line therapy in patients with systemic light chain amyloidosis.

Amyloid 2021 Sep 14:1-8. Epub 2021 Sep 14.

Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.

Background: The main objective of treatment in systemic light chain amyloidosis (AL amyloidosis) is to achieve the best hematological response. Deeper responses are associated with better organ responses and survival. In this study, we analysed the efficacy of prolonged duration treatment after first line in patients with AL amyloidosis.

Methods: Retrospective analysis that included patients older than 18 years with AL amyloidosis. We excluded patients with more than 30% marrow plasmacytosis or concurrent multiple myeloma. Two cohorts identified accordingly if they received or not prolonged treatment after the first line. Survival analysis regarding progression free survival (PFS) and overall survival (OS) estimated with Kaplan-Meier and comparisons between groups with log-rank.

Results: Thirty-eight patients were included in the analysis with a median age of 55 years. Twenty-one patients received prolonged duration treatment and 17 did not. In the prolonged duration group, after a median duration of 12 months, the median PFS was 58.8 months. In the fixed duration treatment group, PFS was 30.6 months. The difference was significant with  = .0045 favouring prolonged duration treatment. Organ response was sustained for a longer period in the prolonged duration treatment group. For OS, the difference was not significant.

Conclusions: Prolonged duration treatment in patients with systemic light chain amyloidosis correlated with better PFS and deeper organ responses. Prospective studies are needed to analyse this further.
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http://dx.doi.org/10.1080/13506129.2021.1978423DOI Listing
September 2021

Altered B cell compartment associated with Tfh cells in children with Henoch-Schonlein Purpura.

BMC Pediatr 2021 Sep 13;21(1):399. Epub 2021 Sep 13.

Department of Hematology, The First Affiliated Hospital of Jinzhou Medical University, No.2 Renmin Street, Liaoning, 121000, Jinzhou, People's Republic of China.

Aim: IgA-producing B cells have been found to be associated with children diagnosed with Henoch-Schonlein purpura (HSP). The aim of the present study was to determine whether children with HSP possess altered B-cell subsets.

Methods: A total of 14 children diagnosed with HSP and age- and sex-matched healthy controls (HCs) were enrolled in our study. Peripheral blood mononuclear cells were isolated, and the percentage and absolute number of B-cell subsets and Follicular helper T (Tfh) cells were determined by flow cytometry. Finally, Spearman's correlation coefficient was used to analyse the correlation between the percentage of Tfh cells and B-cell subsets.

Results: We found that compared to HCs, the frequency and absolute number of total B cells were significantly higher in children with HSP, but the percentages of plasma cells and naïve B cells were significantly lower. A significantly increased percentage and absolute number of memory nonswitched B cells were found in children with HSP compared with HCs. We observed that the expression of C-X-C chemokine receptor type 5 (CXCR5) on total CD4 T cells and the percentage of CD4CXCR5 cells were significantly increased in patients with HSP. Moreover, significantly correlations between Tfh cells and various B-cell subsets were observed.

Conclusions: Our study showed a Tfh-cell-associated altered B cell compartment in children with HSP.
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http://dx.doi.org/10.1186/s12887-021-02873-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436472PMC
September 2021

An overview of D-galactose utilization through microbial fermentation and enzyme-catalyzed conversion.

Appl Microbiol Biotechnol 2021 Sep 13. Epub 2021 Sep 13.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi , 214122, Jiangsu, China.

D-Galactose is an abundant carbohydrate monomer in nature and widely exists in macroalgae, plants, and dairy wastes. D-Galactose is useful as a raw material for biomass fuel production or low-calorie sweetener production, attracting increased attention. This article summarizes the studies on biotechnological processes for galactose utilization. Two main research directions of microbial fermentation and enzyme-catalyzed conversion from galactose-rich biomass are extensively reviewed. The review provides the recent discoveries for biofuel production from macroalgae, including the innovative methods in the pretreatment process and technological development in the fermentation process. As modern people pay more attention to health, enzyme technologies for low-calorie sweetener production are more urgently needed. D-Tagatose is a promising low-calorie alternative to sugar. We discuss the recent studies on characterization and genetic modification of L-arabinose isomerase to improve the bioconversion of D-galactose to D-tagatose. In addition, the trends and critical challenges in both research directions are outlined at the end. KEY POINTS: • The value and significance of galactose utilization are highlighted. • Biofuel production from galactose-rich biomass is accomplished by fermentation. • L-arabinose isomerase is a tool for bioconversion of D-galactose to D-tagatose.
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http://dx.doi.org/10.1007/s00253-021-11568-5DOI Listing
September 2021

Association Between Changes in Physical Activity and New-Onset Atrial Fibrillation After ICD/CRT-D Implantation.

Front Cardiovasc Med 2021 26;8:693458. Epub 2021 Aug 26.

Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Changes in physical activity (PA) after implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillators (CRT-D) implantation were unknown. The association of PA changes with new-onset atrial fibrillation (AF), cardiac death and all-cause mortality was unclear in patients at high risk of sudden cardiac death. Patients receiving ICD/CRT-D implantation from SUMMIT registry were retrospectively analyzed. Changes in PA were considered from baseline status to 1 year after implantation. New-onset AF was defined as the first atrial high-rate episode ≥1% of the daily AF burden detected after implantation. Over a mean follow-up of 50.3 months, 124 new-onset AF events (36.2%), 61 cardiac deaths (17.8%), and 87 all-cause deaths (25.4%) were observed in 343 patients with ICD/CRT-D implantation. PA at 1 year after implantation was increased compared with PA at baseline (11.97 ± 5.83% vs. 10.82 ± 5.43%, = 0.008), and PA at 1 year was improved in 210 patients (61.2%). Per 1% decrease in PA was associated with 12.4, 18.3, and 14.3% higher risks of new-onset AF, cardiac death and all-cause mortality, regardless of different baseline characteristics. Patients with decreased PA had 2-fold risks of new-onset AF (hazard ratio [HR] = 1.972, 95% confidence interval [CI]: 1.352-2.877, < 0.001) as high as those with unchanged/increased PA. Decreased PA was an independent risk factor for cardiac death (HR = 3.358, 95% CI: 1.880-5.996, < 0.001) and all-cause mortality (HR = 2.803, 95% CI:1.732-4.535, < 0.001). PA decrease after ICD/CRT-D implantation is associated with a higher incidence of new-onset AF, resulting in worsened outcomes in cardiac death and all-cause mortality.
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http://dx.doi.org/10.3389/fcvm.2021.693458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426902PMC
August 2021

Hsa_circ_0001361 facilitates the progress of lung adenocarcinoma cells via targeting miR-525-5p/VMA21 axis.

J Transl Med 2021 09 10;19(1):389. Epub 2021 Sep 10.

Department of Hematology and Oncology, Department of Geriatric Lung Cancer Laboratory, Geriatric Hospital of Nanjing Medical University, Jiangsu Province Geriatric Hospital, No.65 Jiangsu Road, Gulou District, Nanjing, 210000, Jiangsu Province, People's Republic of China.

Background: Lung adenocarcinoma (LUAD) is a common subtype of lung cancer with high recurrence rate and fatality. Circ_0001361 has been recognized as key regulators in various malignancies, but its roles in LUAD remain ambiguous.

Methods: Circ_0001361, miR-525-5p, and VMA21 levels were assessed by RT-qPCR. The growth and metastasis of LUAD cells were detected by MTT, colony formation, wound scratch, and transwell assays, respectively. The interaction between circ_0001361/VMA21 and miR-525-5p was detected by dual luciferase, RNA immunoprecipitation, and RNA pull-down assays. VMA21 protein level was detected by Western blotting. Nude mouse xenograft model was established to determine the role of circ_0001361 in tumor growth in vivo.

Results: Circ_0001361 was up-regulated, while miR-525-5p was down-regulated in LUAD tissues and cells. Functional experiments demonstrated that circ_0001361 drove LUAD cell growth and metastasis. Mechanistically, circ_0001361 functioned as a sponge of miR-525-5p to up-regulate downstream target VMA21 level. MiR-525-5p/VMA21 axis was involved in circ_0001361-mediated malignant phenotypes of LUAD cells. Finally, inhibition of circ_0001361 restrained in vivo xenograft tumor growth via regulating miR-525-5p/VMA21 axis.

Conclusion: Our findings elucidate that circ_0001361 facilitates the tumorigenesis and development of LUAD through miR-525-5p/VMA21 axis, providing evidence for circ_0001361 as a potential prognosis biomarker and therapeutic target for clinical treatment of LUAD.
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http://dx.doi.org/10.1186/s12967-021-03045-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434718PMC
September 2021

Bixasteroid, a new compound from the fruits of and its anti-inflammatory activity.

Nat Prod Res 2021 Sep 10:1-7. Epub 2021 Sep 10.

Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China.

Bixasteroid (), one new steroid together with five known compounds (-), were isolated from the ethyl acetate fraction of ethanol extract of fruits. All of these known compounds were isolated from the plant for the first time. Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configuration of compound was determined by X-ray crystallographic data analysis as well as by the quantum chemical ECD calculations. All the isolated compounds were tested for their anti-inflammatory activities. Compounds and showed inhibiting NO release activities in LPS-induced RAW 264.7 macrophages with the IC values of 4.72 ± 0.28 and 5.48 ± 1.48 M, respectively.
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http://dx.doi.org/10.1080/14786419.2021.1974436DOI Listing
September 2021

Processes and mechanisms of phosphorus mobility among sediment, water, and cyanobacteria under hydrodynamic conditions.

Environ Sci Pollut Res Int 2021 Sep 9. Epub 2021 Sep 9.

College of Environmental Engineering, Nanjing Institute of Technology, 211167, Nanjing, People's Republic of China.

Phosphorus (P) has an important role in eutrophication and it is essential to explore the processes and mechanisms of P mobility in natural waters. In this study, laboratory experiments were conducted to simulate the SW system (sediment and water) and SAW system (sediment, algae, and water) under four hydrodynamic intensity conditions (static control, 50 rpm, 125 rpm, and 200 rpm treatments), to investigate P mobility. Results in SW system showed that sediment was an important source of P for overlying water, and the released total P (TP) increased with stronger hydrodynamic intensity, when P associated with metal pools (redox-sensitive P [BD-P] and meta-oxides bound P [NaOH-P]) were the most unstable and easier to migrate into the overlying water. Stronger hydrodynamic disturbances could enhance the processes including sediment resuspension, dissolution of particles, and release of P, when P mobility had a close relationship with redox conditions near sediment-water interface (SWI). Therefore, the release of TP, BD-P, and NaOH-P from sediment increased and decreased in the control and 50-200 rpm treatments over time. In SAW system, the release of TP significantly increased from sediment comparing to SW system, and the growth of Microcystis aeruginosa could selectively enhance the release of BD-P, NaOH-P, and organic P (OP). Meanwhile, the released P from sediment was quickly accumulated by algal cells. The maximum accumulation ability of P by cells, the highest photosynthetic efficiency, and the best growth of M. aeruginosa were observed in 125 rpm treatment. But with excessively strong hydrodynamic intensity (200 rpm treatment), the accumulation ability of P and alkaline phosphatase activity (APA) of M. aeruginosa was suppressed, which might hinder algal utilization of P and inhibit algal growth. Overall, our findings demonstrated the patterns of P mobility in natural ecosystems and could contribute to the understanding of P cycling.
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http://dx.doi.org/10.1007/s11356-021-16255-6DOI Listing
September 2021

An Improved Adaptive Spatial Preprocessing Method for Remote Sensing Images.

Sensors (Basel) 2021 Aug 24;21(17). Epub 2021 Aug 24.

Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China.

Since remote sensing images are one of the main sources for people to obtain required information, the quality of the image becomes particularly important. Nevertheless, noise often inevitably exists in the image, and the targets are usually blurred by the acquisition of the imaging system, resulting in the degradation of quality of the images. In this paper, a novel preprocessing algorithm is proposed to simultaneously smooth noise and to enhance the edges, which can improve the visual quality of remote sensing images. It consists of an improved adaptive spatial filter, which is a weighted filter integrating functions of both noise removal and edge sharpness. Its processing parameters are flexible and adjustable relative to different images. The experimental results confirm that the proposed method outperforms the existing spatial algorithms both visually and quantitatively. It can play an important role in the remote sensing field in order to achieve more information of interested targets.
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http://dx.doi.org/10.3390/s21175684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434460PMC
August 2021

Chromone Derivatives with α-Glucosidase Inhibitory Activity from the Marine Fungus Maire.

Molecules 2021 Aug 31;26(17). Epub 2021 Aug 31.

School of Pharmacy, Henan University, Kaifeng 475004, China.

The fungal strain YPGA3 was isolated from the sediments of the Yap Trench and identified as . Eight new chromone derivatives, named penithochromones M-T (-), along with two known analogues, and were isolated from the strain. The structures were established by detailed analyses of the spectroscopic data. The absolute configuration of the only chiral center in compound was tentatively determined by comparing the experimental and the calculated specific rotations. Compounds and represent the first examples of chromone derivatives featuring a 5,7-dioxygenated chromone moiety with a 9-carbon side chain. Bioassay study revealed that compounds - exhibited remarkable inhibition against α-glucosidase with IC values ranging from 268 to 1017 μM, which are more active than the positive control acarbose (1.3 mmol).
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http://dx.doi.org/10.3390/molecules26175273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434415PMC
August 2021

Neoadjuvant Chemotherapy Direct Surgery for Locally Advanced Gastric Cancer With Serosal Invasion (cT4NxM0): A Propensity Score-Matched Analysis.

Front Oncol 2021 23;11:718556. Epub 2021 Aug 23.

Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: For locally advanced gastric cancer (LAGC) with serosal invasion (cT4NxM0), adjuvant chemotherapy (AC) after D2 gastrectomy is the standard therapy in Asia. However, perioperative chemotherapy (PCT) combined with D2 gastrectomy is mostly suggested in Europe and America. As a part of PCT, the value of neoadjuvant chemotherapy (NAC) is unclear. We investigated whether NAC could further improve survival and other outcomes for these patients.

Methods: Patients with cT4NxM0 gastric cancer who underwent D2 gastrectomy were analyzed. The patients were divided into two groups based on whether they received NAC: the neoadjuvant chemotherapy (NAC) and direct surgery (S) groups. After propensity score matching (1:1 ratio), survival and perioperative outcomes were analyzed between the two groups.

Results: A total of 902 patients met all the eligibility criteria and were enrolled. After propensity score matching, 221 matched pairs of patients were identified. The median overall survival (OS) and disease-free survival (DFS) of all patients were 75.10 and 43.67 months, respectively. The median OS of patients in the NAC and S groups were undefined and 29.80 months, respectively (P<0.0001). The median DFS of patients in the NAC and S groups were undefined and 22.60 months (P<0.0001). There were no significant differences in the radical degrees of operation between the two groups (P=0.07). However, there were significant differences in postoperative hospital stay (P<0.001) and complications (P=0.037) between the two groups.

Conclusion: This study suggested NAC can further improve prognosis and prevent recurrence in LAGC (cT4NxM0) patients. NAC is feasible and safe for LAGC (cT4NxM0) patients, and does not increase the risk of perioperative surgery.
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http://dx.doi.org/10.3389/fonc.2021.718556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419416PMC
August 2021

Mediterranean fruit fly genes exhibit different expression patterns between heat and cold treatments.

Bull Entomol Res 2021 Sep 9:1-7. Epub 2021 Sep 9.

Agricultural Sciences, Murdoch University, Perth, WA6150, Australia.

Invasive Tephritid fruit flies are a global threat to both agriculture and horticulture industries. Biosecurity has played a critical role in reducing their damage but becomes more and more challenging after several key chemical pesticides were banned or withdrawn for health or environmental reasons. This has led to non-chemical approaches including heat and cold treatments being broadly utilized to get rid of fruit fly infestation. However, the molecular mechanisms to kill the flies underlying these stressors are not clear yet. This knowledge will certainly help refine current post-harvest treatment strategies and develop more efficient, cost-effective and environmentally friendly approaches for fruit fly management. Previously, the molecular response of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann) to heat was examined thoroughly, in which 31 key genes were identified with significant changes in expression levels and their high-resolution expression timeline was constructed across 11 timepoints. However, whether these candidate genes respond to cold in the same way was unknown. Here, a temperature bioassay was conducted and the expression profiles of these genes were investigated across the same 11 timepoints using cold treatment. The results showed that most of candidate genes exhibited divergent expression profiles compared to heat treatment, suggesting that the fly molecular response to cold may be different from those to heat. This study provides new knowledge of Tephritid fruit fly response to cold at a molecular level, which could aid in improving current fruit fly management and facilitate the development of new strategies to control this serious horticultural insect pest.
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http://dx.doi.org/10.1017/S000748532100078XDOI Listing
September 2021

Association of interleukin-6 promoter polymorphism with rheumatoid arthritis: a meta-analysis with trial sequential analysis.

Clin Rheumatol 2021 Sep 8. Epub 2021 Sep 8.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.

Objectives: The association of interleukin-6 (IL-6) -174G/C (rs1800795) and IL-6 -572G/C (rs1800796) single-nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) was inconsistent among previous studies. This paper aims to investigate the association between IL-6 promoter polymorphism with RA in different ethnics.

Methods: Relevant studies were searched using Medline and Google Search engines; STATA software was used to perform the meta-analysis. Pooled odds ratios (OR) were calculated to estimate the potential genetic associations. Subgroup analysis and sensitivity analysis were applied to explore the sources of heterogeneity. Lastly, we used TSA (trial sequential analysis) software to verify the reliability of meta-analysis results.

Results: A total of 18 studies were included, involving 8116 subjects (3820 RA patients and 4296 controls). We found a tendency to associate RA with the IL-6 -174G/C allele in Asians (C vs G: OR = 4.56, 95% CI = 1.85-11.23; P < 0.001); with IL-6 -572G/C genotype or allele frequencies, there was no statistical differences between RA patients and controls (P > 0.05). TSA results indicate that the current meta-analysis can draw conclusions.

Conclusions: IL-6-174G/C gene polymorphism were associated with increased risk of RA in Asians, but not in Caucasians. There was no association between IL-6 -572G/C gene polymorphism and the risk of RA. Key Points • Although the association between interleukin-6 (IL-6) promoter polymorphism and rheumatic arthritis (RA) has been discussed in the previous meta-analysis, their conclusions are inconsistent. • In this study, trial sequential analysis (TSA) was introduced into the meta-analysis, and the following two important conclusions were confirmed: (1) IL-6-174G/C gene polymorphism was associated with increased risk of RA in Asians, but not in Caucasians. (2) There was no association between IL-6 -572G/C gene polymorphism and the risk of RA.
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http://dx.doi.org/10.1007/s10067-021-05886-2DOI Listing
September 2021
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