Publications by authors named "Li Wen"

2,871 Publications

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CAG RNAs induce DNA damage and apoptosis by silencing expression in polyglutamine degeneration.

Proc Natl Acad Sci U S A 2021 May;118(19)

Laboratory of Drosophila Research, The Chinese University of Hong Kong, Hong Kong, China;

DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington's disease (HD). In this study, we showed that the expression of untranslatable expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the () gene was down-regulated in mutant CAG RNA-expressing cells. The loss of NUDT16 function results in a misincorporation of damaging nucleotides into DNAs and leads to DNA damage. We showed that small CAG (sCAG) RNAs, species generated from expanded CAG transcripts, hybridize with CUG-containing mRNA and form a CAG-CUG RNA heteroduplex, resulting in gene silencing of and leading to the DNA damage and cellular apoptosis. These results were further validated using expanded CAG RNA-expressing mouse primary neurons and in vivo R6/2 HD transgenic mice. Moreover, we identified a bisamidinium compound, DB213, that interacts specifically with the major groove of the CAG RNA homoduplex and disfavors the CAG-CUG heteroduplex formation. This action subsequently mitigated RNA-induced silencing complex (RISC)-dependent silencing in both in vitro cell and in vivo mouse disease models. After DB213 treatment, DNA damage, apoptosis, and locomotor defects were rescued in HD mice. This work establishes NUDT16 deficiency by CAG repeat RNAs as a pathogenic mechanism of polyQ diseases and as a potential therapeutic direction for HD and other polyQ diseases.
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http://dx.doi.org/10.1073/pnas.2022940118DOI Listing
May 2021

Next-generation sequence-based preimplantation genetic testing for monogenic disease resulting from maternal mosaicism.

Mol Genet Genomic Med 2021 May 4:e1662. Epub 2021 May 4.

Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China.

Background: Mosaicism poses challenges for genetic counseling and preimplantation genetic testing for monogenic disorders (PGT-M). NGS-based PGT-M has been extensively used to prevent the transmission of monogenic defects, but it has not been evaluated in the application of PGT-M resulting from mosaicism.

Methods: Four women suspected of mosaicism were confirmed by ultra-deep sequencing. Blastocyst trophectoderm cells and polar bodies were collected for whole genome amplification, followed by pathogenic variants detection and haplotype analysis based on NGS. The embryos free of the monogenic disorders were transplantable.

Results: Ultra-deep sequencing confirmed that the four women harbored somatic mosaic variants, with the proportion of variant cells at 1.12%, 9.0%, 27.60%, and 91.03%, respectively. A total of 25 blastocysts were biopsied and detected during four PGT cycles and 5 polar bodies were involved in one cycle additionally. For each couple, a wild-type embryo was successfully transplanted and confirmed by prenatal diagnosis, resulting in the birth of four healthy infants.

Conclusions: Mosaic variants could be effectively evaluated via ultra-deep sequencing, and could be prevented the transmission by PGT. Our work suggested that an NGS-based PGT approach, involving pathogenic variants detection combined with haplotype analysis, is crucial for accurate PGT-M with mosaicism.
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http://dx.doi.org/10.1002/mgg3.1662DOI Listing
May 2021

Investigating function of long noncoding RNA of HOTAIRM1 in progression of SKOV3 ovarian cancer cells.

Drug Dev Res 2021 May 3. Epub 2021 May 3.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, Sichuan, China.

Ovarian cancer is one of the most heterogeneous malignancies in the field of gynecologic oncology. Deregulation of long noncoding RNAs (lncRNAs) is implicated in carcinogenesis. Therefore, the present study was conducted to investigate the possible role of lncRNA of HOXA transcript antisense intergenic RNA myeloid-specific 1(HOTAIRM1) in progression of SKOV3 cells in ovarian cancer and also its underlying molecular mechanisms. HOTAIRM1 expression level will be measured by real-time polymerase chain reaction (PCR) in SKOV3 cells. For determining the effect of HOTAIRM1 silencing on progression of SKOV3 cells, siHOTAIRM1 will be designed and transfected into cells using a liposomal approach. MTT and trypan blue assays will be used to determine the effect of HOTAIRM1 silencing on cell proliferation. Apoptosis of the cells will be detected by flow cytometry. Furthermore, expressions of apoptosis-related genes and Wnt pathway-related proteins and genes will be analyzed by Western blot and real-time PCR. HOTAIRM1 was overexpressed in SKOV3 cells. Silencing of HOTAIRM1 alleviated cell proliferation, and increased cell apoptosis of SKOV3 cells. Moreover, siHOTAIRM1 significantly increased expression of pro-apoptotic agents, such as Bad and Bax, while it decreased expressions of Bid and Bcl-2 (anti-apoptotic agents). Also, silencing of HOTAIRM1 resulted in a suppressed expression of Wnt pathway-related proteins and also expression of its downstream target gene, matrix metalloproteinase 9(MMP9). Our findings provided new insights into function of lncRNA of HOTAIRM1 in progression of ovarian cancer by modulating Wnt pathway and its downstream target gene, MMP9.
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http://dx.doi.org/10.1002/ddr.21821DOI Listing
May 2021

Recent advances on 2'-fucosyllactose: physiological properties, applications, and production approaches.

Crit Rev Food Sci Nutr 2020 Dec 1:1-10. Epub 2020 Dec 1.

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

The trisaccharide, 2'-fucosyllactose (Fucα1-2Galβ1-4Glc; 2'-FL), is the most abundant oligosaccharide in human milk. It has numerous significant biological properties including prebiotics, antibacterial, antiviral, and immunomodulating effects, and has been approved as "generally recognized as safe" (GRAS) by the Food and Drug Administration (FDA) and as a novel food (NF) by the European Food Safety Authority (EFSA). 2'-FL not only serves as a food ingredient added in infant formula, but also as a dietary supplement and medical food material in food bioprocesses. There is considerable commercial interest in 2'-FL for its irreplaceable nutritional applications. This review aims at systematically elaborating key functional properties of 2'-FL as well as its applications. In addition, several approaches for 2'-FL production are described in this review, including chemical, chemo-enzymatical, and cell factory approaches, and the pivotal research results also have been summarized. With the rapid development of metabolic engineering and synthetic biology strategies, using the engineered cell factory for 2'-FL large-scale production might be a promising approach. From an economic and safety point of view, microbial selection for cell factory engineering in 2'-FL bioprocess also should be taken into consideration.
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http://dx.doi.org/10.1080/10408398.2020.1850413DOI Listing
December 2020

Editorial: Integrated Multi-modal and Sensorimotor Coordination for Enhanced Human-Robot Interaction.

Front Neurorobot 2021 15;15:673659. Epub 2021 Apr 15.

Embodied Artificial Intelligence and Neurorobotics Lab, University of Southern Denmark Biorobotics, The Maersk Mc-Kinney Moller Institute, University of Southern Denmark, Odense, Denmark.

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http://dx.doi.org/10.3389/fnbot.2021.673659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083979PMC
April 2021

Grandparental care and sleep disturbances in preschool children: a population-based prospective cohort study.

Sleep Med 2021 Apr 10;82:165-171. Epub 2021 Apr 10.

Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai, China; Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Objectives: Sleep disturbances are common in preschoolers, and profoundly affected by parenting. Grandparents are increasingly involved in childcare and have attracted worldwide attention for their potential impacts on child well-being. However, no studies have explored child sleep health within the context of grandparental care. We aimed to explore the association between grandparents as primary caregivers and children's sleep disturbances.

Methods: Participants included 20,324 preschoolers from the Shanghai Children's Health, Education and Lifestyle Evaluation-Preschool (SCHEDULE-P) in Shanghai, China. They were initially assessed in November 2016 and were reassessed in April 2018 and April 2019. Children's primary caregivers were collected at each survey. Sleep disturbances were assessed by the Children's Sleep Habits Questionnaire (CSHQ).

Results: At baseline, 84.4% of children had global sleep disturbances (CSHQ total score >41). Compared with parents, random-effects model indicated that grandparents as primary caregivers increased the adjusted odds ratio (OR) for children's global sleep disturbances by 30% (OR [95%CI]: 1.30 [1.21, 1.40]). To the specific domains of CSHQ, two-way repeated-measures ANOVA showed significant "caregiver transition" group × wave interaction in the behavioral sleep disturbances, such as "Bedtime Resistance" (p < 0.001). At each survey, children with grandparents as primary caregivers demonstrated significant higher behavioral sleep disturbances than their counterparts with parental care.

Conclusions: Grandparental care is associated with increased sleep disturbances, particularly behavioral sleep disturbances, in preschoolers. Future studies should explore the underlying mechanisms and whether sleep programs targeting grandparents can decrease children's sleep disturbances.
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http://dx.doi.org/10.1016/j.sleep.2021.03.033DOI Listing
April 2021

First-Generation EGFR-TKI Plus Chemotherapy Versus EGFR-TKI Alone as First-Line Treatment in Advanced NSCLC With EGFR Activating Mutation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Front Oncol 2021 13;11:598265. Epub 2021 Apr 13.

Lung Cancer Center & Institute, West China Hospital, Sichuan University, Chengdu, China.

Objective: The aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy (CT) compared to EGFR-TKI monotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutation.

Methods: A systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated as effect values for progress-free survival (PFS) and overall survival (OS). Risk ratio (RR) and Odds ratio (OR) were calculated as effect values for objective response rate (ORR) and toxicity, respectively.

Results: A total of eight randomized trials involving 1,349 advanced NSCLC patients with sensitive EGFR mutation were included in the meta-analysis. All patients in both groups received first-generation TKI as first-line treatment. The pooled HR of PFS and OS was 0.56 (95% CI = 0.50-0.64; P <0.00001) and 0.70 (95% CI = 0.54-0.90; P = 0.005), respectively. Subgroup analysis showed significantly higher OS advantages in patients receiving doublet CT (P = 0.02) and concurrent therapy (P = 0.002). The ORR in the EGFR-TKI plus CT group was significantly higher than in the EGFR-TKI monotherapy group (RR = 1.18, 95% CI = 1.10-1.26). The combination regimen showed a higher incidence of chemotherapy-induced toxicities. Subgroup analysis indicated that doublet chemotherapy rather than single-agent chemotherapy significantly increased incidence of grade 3 or higher leukopenia, neutropenia and anemia.

Conclusions: Compared with EGFR-TKI monotherapy, the combination of first-generation EGFR-TKI and CT, especially when applying concurrent delivery of platinum-based doublet chemotherapeutic drugs, significantly improve ORR and prolong PFS and OS in first-line treatment for advanced EGFR-mutated NSCLC. Although increasing incidence of chemotherapy-induced toxicities occurs in the combination group, it is well tolerated and clinically manageable.
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http://dx.doi.org/10.3389/fonc.2021.598265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076535PMC
April 2021

Protective Effects of Necrostatin-1 in Acute Pancreatitis: Partial Involvement of Receptor Interacting Protein Kinase 1.

Cells 2021 Apr 27;10(5). Epub 2021 Apr 27.

Department of Molecular Physiology & Cell Signalling, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.

Acute pancreatitis (AP) is a severe and potentially fatal disease caused predominantly by alcohol excess and gallstones, which lacks a specific therapy. The role of Receptor-Interacting Protein Kinase 1 (RIPK1), a key component of programmed necrosis (Necroptosis), is unclear in AP. We assessed the effects of RIPK1 inhibitor Necrostatin-1 (Nec-1) and RIPK1 modification (RIPK1: kinase dead) in bile acid (TLCS-AP), alcoholic (FAEE-AP) and caerulein hyperstimulation (CER-AP) mouse models. Involvement of collateral Nec-1 target indoleamine 2,3-dioxygenase (IDO) was probed with the inhibitor Epacadostat (EPA). Effects of Nec-1 and RIPK1 were also compared on pancreatic acinar cell (PAC) fate in vitro and underlying mechanisms explored. Nec-1 markedly ameliorated histological and biochemical changes in all models. However, these were only partially reduced or unchanged in RIPK1 mice. Inhibition of IDO with EPA was protective in TLCS-AP. Both Nec-1 and RIPK1 modification inhibited TLCS- and FAEE-induced PAC necrosis in vitro. Nec-1 did not affect TLCS-induced Ca entry in PACs, however, it inhibited an associated ROS elevation. The results demonstrate protective actions of Nec-1 in multiple models. However, RIPK1-dependent necroptosis only partially contributed to beneficial effects, and actions on targets such as IDO are likely to be important.
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http://dx.doi.org/10.3390/cells10051035DOI Listing
April 2021

Functional soil organic matter fraction in response to short-term tillage management under the double-cropping rice paddy field in southern of China.

Environ Sci Pollut Res Int 2021 Apr 28. Epub 2021 Apr 28.

Hunan Soil and Fertilizer Institute, Changsha, 410125, China.

Soil organic matter (SOM) and its fraction play an important role in maintaining and improving soil fertility of paddy field. However, there is still limited information about how SOM fraction response to carbon (C) sequestration with different short-term tillage practices under the double-cropping rice paddy field in southern of China. Therefore, the effects of 5-year short-term tillage treatments on different SOM fractions (physically protected, physico-chemically protected, physico-biochemically protected, chemically protected, biochemically protected, and unprotected) under the double-cropping rice paddy field in southern of China were studied in this paper. The field experiment included four different tillage treatments: rotary tillage with crop residue removed as a control (RTO), conventional tillage with crop residue incorporation (CT), rotary tillage with crop residue incorporation (RT), and no-tillage with crop residue retention (NT). The results showed that soil unprotected (cPOM), biochemically (NH-dSilt), physically-biochemically (NH-μSilt), and chemically protected (H-dSilt) fractions with different tillage treatments were the mainly C storage fraction in paddy field. The soil organic carbon (SOC) content in unprotected (cPOM and fPOM), physically protected (iPOM), and physico-chemically protected (H-μClay) fractions with CT treatment was increased by 1.45, 2.13, 1.91, and 1.42 times higher than that of RTO treatment, respectively. The results showed that largest proportion of fraction to SOC content was biochemically protected, followed by unprotected and physically-biochemically protected, and physically protected was the lowest. These results indicated that soil physically protected, physically-chemically protected, and physically-biochemically protected fractions with CT and RT treatments were higher than that of NT and RTO treatments. In summary, it was a benefit practice for increasing SOM fraction under the double-cropping rice paddy field in southern of China by combined application of conventional tillage and rotary tillage with crop residue incorporation management.
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http://dx.doi.org/10.1007/s11356-021-14173-1DOI Listing
April 2021

Should people with severe mental illness be prioritized for the COVID-19 vaccination?

Int J Biol Sci 2021 10;17(6):1443-1445. Epub 2021 Apr 10.

Unit of Psychiatry, Department of Public Health and Medicinal Administration, & Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, China.

The coronavirus disease-19 (COVID-19) has spread throughout the world, affecting many vulnerable populations including patients with severe mental illness (SMI). Recent studies have found that patients with SMI compared to the general population could have a greater risk of morbidity and mortality from COVID-19 due to cognitive impairment, poor awareness of risk, and difficulties in complying with infection control measures. Although some researchers have suggested that patients with SMI should be prioritized for COVID-19 vaccination to reduce the risk of infection, this issue remains controversial.
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http://dx.doi.org/10.7150/ijbs.57750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071759PMC
April 2021

Cerebroprotection by dioscin after experimental subarachnoid hemorrhage via inhibiting NLRP3 inflammasome through SIRT1-dependent pathway.

Br J Pharmacol 2021 Apr 26. Epub 2021 Apr 26.

Department of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China.

Background And Purpose: Dioscin possesses multiple biologic activities and is beneficial for cardiovascular and cerebral vascular diseases. Here we investigated the protective effects of dioscin against subarachnoid hemorrhage (SAH) and the involvement of underlying molecular mechanisms.

Experimental Approach: Dioscin was administered after SAH. MCC950, a potent selective nod-like receptor pyrin domain-containing 3 (NLRP3) inhibitor, was used to suppress NLRP3. EX527 was adopted to inhibit sirtuin 1 (SIRT1).

Key Results: In vivo, dioscin markedly inhibited acute inflammatory response, oxidative damage, neurological impairment, and neural cell degeneration after SAH. Meanwhile, dioscin dramatically suppressed NLRP3 inflammasome activation. Additionally, pretreatment with MCC950 ameliorated inflammatory response and improved neurological outcomes but did not mitigate reactive oxygen species (ROS) production after SAH. In contrast, dioscin reduced acute brain damage, as well as the ROS production in the SAH rats with MCC950 pretreatment. Moreover, dioscin increased SIRT1 expression after SAH, whereas EX527 abolished the upregulation of SIRT1 induced by dioscin and offset the inhibitory effects of dioscin on NLRP3 inflammasome activation. EX527 pretreatment also reversed the neuroprotective effects of dioscin against SAH. Similarly, in vitro, dioscin dose-dependently suppressed inflammatory response, oxidative damage, and neuronal degeneration, and improved cell viability in neurons and microglia co-culture system. These effects were associated with inhibition of the NLRP3 inflammasome and stimulation of SIRT1 signaling, which could be reversed by EX527 pretreatment.

Conclusion And Implications: Dioscin provides protection against SAH via the suppression of NLRP3 inflammasome activation through SIRT1-dependent pathway. Dioscin may be a new candidate to ameliorate EBI after SAH.
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http://dx.doi.org/10.1111/bph.15507DOI Listing
April 2021

Racial and Ethnic Disparities in Incidence of SARS-CoV-2 Infection, 22 US States and DC, January 1-October 1, 2020.

Emerg Infect Dis 2021 ;27(5):1477-1481

We examined disparities in cumulative incidence of severe acute respiratory syndrome coronavirus 2 by race/ethnicity, age, and sex in the United States during January 1-October 1, 2020. Hispanic/Latino and non-Hispanic Black, American Indian/Alaskan Native, and Native Hawaiian/other Pacific Islander persons had a substantially higher incidence of infection than non-Hispanic White persons.
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http://dx.doi.org/10.3201/eid2705.204523DOI Listing
January 2021

Reg4 regulates pancreatic regeneration following pancreatitis via modulating the Notch signaling.

J Cell Physiol 2021 Apr 26. Epub 2021 Apr 26.

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pancreatic regeneration after acute pancreatitis is critical in the normal restoration of pancreatic exocrine function, the inhibition of which can cause severe complications including pancreatic exocrine insufficiency. However, the regulators of pancreatic regeneration and the underlying mechanisms remain uncovered. Here, using the inducible Tet-on system, we found that regenerating family member 4 (Reg4) knockdown significantly impaired pancreatic regeneration after pancreatitis. Both acinar-to-ductal metaplasia and the resolution of pancreatitis during regeneration were affected by Reg4 knockdown. Further investigations confirmed that Reg4 exerted its function through regulating Notch activation both in vitro and in vivo. Our study revealed Reg4 as a new regulator and potential therapeutic target for pancreatic regeneration.
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http://dx.doi.org/10.1002/jcp.30397DOI Listing
April 2021

Repositioned Drugs for COVID-19-the Impact on Multiple Organs.

SN Compr Clin Med 2021 Apr 21:1-18. Epub 2021 Apr 21.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI USA.

This review summarizes published findings of the beneficial and harmful effects on the heart, lungs, immune system, kidney, liver, and central nervous system of 47 drugs that have been proposed to treat COVID-19. Many of the repurposed drugs were chosen for their benefits to the pulmonary system, as well as immunosuppressive and anti-inflammatory effects. However, these drugs have mixed effects on the heart, liver, kidney, and central nervous system. Drug treatments are critical in the fight against COVID-19, along with vaccines and public health protocols. Drug treatments are particularly needed as variants of the SARS-Cov-2 virus emerge with some mutations that could diminish the efficacy of the vaccines. Patients with comorbidities are more likely to require hospitalization and greater interventions. The combination of treating severe COVID-19 symptoms in the presence of comorbidities underscores the importance of understanding the effects of potential COVID-19 treatments on other organs.

Supplementary Information: The online version contains supplementary material available at 10.1007/s42399-021-00874-8.
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http://dx.doi.org/10.1007/s42399-021-00874-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057921PMC
April 2021

Association between Vitamin D Levels and the Risk of Metabolic Syndrome in a Rural Chinese Population.

Biomed Environ Sci 2021 Apr;34(4):330-333

Department of Nutrition and Food Hygiene, College of Public Health of Zhengzhou University, Zhengzhou 450001, Henan, China.

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http://dx.doi.org/10.3967/bes2021.043DOI Listing
April 2021

The association between RGS4 and choline in cardiac fibrosis.

Cell Commun Signal 2021 Apr 23;19(1):46. Epub 2021 Apr 23.

Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (The University Key Laboratory of Drug Research, Heilongjiang Province), Harbin, 150086, People's Republic of China.

Background: Myocardial fibrosis is caused by the adverse and powerful remodeling of the heart secondary to the death of cardiomyocytes after myocardial infarction. Regulators of G protein Signaling (RGS) 4 is involved in cardiac diseases through regulating G protein-coupled receptors (GPCRs).

Methods: Cardiac fibrosis models were established through cardiac fibroblasts (CFs) treatment with transforming growth factor (TGF)-β1 in vitro and mice subjected to myocardial infarction in vivo. The mRNA expression of RGS4, collagen I/III and α-SMA detected by qRT-PCR. Protein level of RGS4, collagen I, CTGF and α-SMA detected by Western blot. The ejection fraction (EF%) and fractional shortening (FS%) of mice were measured by echocardiography. Collagen deposition of mice was tested by Masson staining.

Results: The expression of RGS4 increased in CFs treatment with TGF-β1 and in MI mice. The model of cardiac fibrosis detected by qRT-PCR and Western blot. It was demonstrated that inhibition of RGS4 expression improved cardiac fibrosis by transfection with small interfering RNA in CFs and injection with lentivirus shRNA in mice. The protective effect of choline against cardiac fibrosis was counteracted by overexpression of RGS4 in vitro and in vivo. Moreover, choline inhibited the protein level of TGF-β1, p-Smad2/3, p-p38 and p-ERK1/2 in CFs treated with TGF-β1, which were restored by RGS4 overexpression.

Conclusion: This study demonstrated that RGS4 promoted cardiac fibrosis and attenuated the anti-cardiac fibrosis of choline. RGS4 may weaken anti-cardiac fibrosis of choline through TGF-β1/Smad and MAPK signaling pathways. Video Abstract: Video Byte of this article.
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http://dx.doi.org/10.1186/s12964-020-00682-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063380PMC
April 2021

Recent progress in electrochemical performance of binder-free anodes for potassium-ion batteries.

Nanoscale 2021 Mar 19;13(12):5965-5984. Epub 2021 Mar 19.

School of Materials Science and Engineering, Shenyang University of Technology, Shenyang 110870, China.

Potassium ion batteries (PIBs) are regarded as one of the most promising candidates for large-scale stationary energy storage beyond lithium-ion batteries (LIBs), owing to the abundance of potassium resources and low cost. Unfortunately, the practical application of PIBs is severely restricted by their poor rate capacity and unsatisfactory cycle performance. In traditional electrodes, a binder usually plays an important role in integrating individual active materials with conductive additives. Nevertheless, binders are not only generally electrochemically inactive but also insulating, which is unfavorable for improving overall energy density and cycling stability. To this end, in terms of both improved electronic conductivity and electrochemical reaction reversibility, binder-free electrodes offer great potential for high-performance PIBs. Moreover, the anode is a crucial configuration to determine full cell electrochemical performance. Therefore, this review analyzes in detail the electrochemical properties of the different type binder-free anodes, including carbon-based substrates (graphene, carbon nanotubes, carbon nanofibers, and so on), MXene-based substrates and metal-based substrates (Cu and Ni). More importantly, the recent progress, critical issues, challenges, and perspectives in binder-free electrodes for PIBs are further discussed. This review will provide theoretical guidance for the synthesis of high-performance anode materials and promote the further development of PIBs.
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http://dx.doi.org/10.1039/d1nr00077bDOI Listing
March 2021

Roles of endothelial lipase gene related single nucleotide polymorphisms in patients with coronary artery disease.

Gene 2021 Apr 18;788:145669. Epub 2021 Apr 18.

Department of Comprehensive Internal Medicine, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011 China. Electronic address:

The current work focused on evaluating the roles of endothelial lipase gene (LIPG) related single nucleotide polymorphisms (SNPs) in patients with coronary artery disease (CAD). This study involved 1,883 subjects with 959 CAD patients and 924 healthy controls. Data were harvested to assess the association of LIPG related SNPs including rs3744841, rs3744843, rs3813082 and rs2000813 with the risk of CAD. The CC + AC genotype in rs3813082 played a protective role for CAD [odds ratio (OR) = 0.709, P = 0.039]. Differences existed in apolipoprotein-A1 (Apo-A1) and high-density lipoprotein-cholesterol (HDL-C) levels in rs3744843 variant between control and CAD groups. The rs3744841 variant increased the levels of total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C), Apo-A1 and Lipoprotein a (LPa) in the CAD group and TC, LDL-C, HDL-C, Apo-B, Apo-A1 in the control group. The triglyceride (TG) level was lower in rs2000813 variant in the CAD group and elevated in the control group. The rs2000813 variant decreased the number of vascular stenosis while rs3744843 and rs3744841 variants increased the number of vascular stenosis in CAD patients. This study explored the roles of LIPG related SNPs in CAD, showing that CC + AC genotype in rs3813082 was a protective factor for CAD. The rs3744843, rs3744841 and rs2000813 variants were associated with the levels of lipid parameters in CAD patients. The rs3744843, rs3744841 and rs2000813 variants influenced the number of vascular stenosis in CAD patients. The results of our study might be a promising reference for preventing CAD.
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http://dx.doi.org/10.1016/j.gene.2021.145669DOI Listing
April 2021

Highly interconnected inverse opal extracellular matrix scaffolds enhance stem cell therapy in limb ischemia.

Acta Biomater 2021 Apr 17. Epub 2021 Apr 17.

College of Life Sciences, Key Laboratory of Bioactive Materials (Ministry of Education), State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China. Electronic address:

The therapeutic effectiveness of cell transplantation in treatment of diseases and injuries is often limited by low cell retention, survivability, and engraftment. Extracellular matrix (ECM)-derived scaffolds are capable of controlling cell responses, thereby offering potential solutions to current challenges associated with cell therapy. However, it remains a technical challenge to produce ECM scaffolds with highly interconnected porous structure specifically required for cell transplantation. Here, we developed inverse opal porous extracellular matrix (ioECM) scaffolds through subcutaneous implantation of sacrificial templates assembled from polymer microspheres, followed by removal of the microsphere template and cellular content. Such highly interconnected porous ioECM scaffolds supported the anchorage, survival, viability, anti-apoptotic and paracrine activities of rat bone marrow mesenchymal stem cells (BMSCs), which further promoted endothelial cell migration and tube formation and viability. Upon transplantation into nude mouse critical limb ischemic model, ioECM promoted the engraftment of laden BMSCs, facilitated interconnected vascular network formation with accelerated recovery of blood perfusion and inhibited muscle atrophy and fibrosis. Our study demonstrates a unique strategy to engineer highly porous yet well-interconnected ECM scaffolds specifically for cell transplantation with marked improvement of survivability and vascularization, which offers an essential step toward the success of cell therapy and regenerative medicine. Statement of Significance: Cell-based therapy has a good developing foreground applied in a variety of tissue regeneration. Extracellular matrix (ECM) scaffolds is an optimal choice for cell delivery duo to its superior biocompatibility and favorable immune responses. However, the current ECM scaffolds lacking of the controllable pore structure restrict the cell delivery efficiency and therapeutic outcome. Here, we fabricated highly interconnected inverse opal extracellular matrix (ioECM) scaffolds, which can enhance the effect of stem cell therapy in limb ischemic model by improving the survival, viability, and paracrine activities of stem cells. Our study provides reference value for the design and fabrication of ECM based biomaterials for cell transplantation.
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http://dx.doi.org/10.1016/j.actbio.2021.04.025DOI Listing
April 2021

A Highly Specific Multiple Enhancement Theranostic Nanoprobe for PET/MRI/PAI Image-Guided Radioisotope Combined Photothermal Therapy in Prostate Cancer.

Small 2021 Apr 18:e2100378. Epub 2021 Apr 18.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, 100142, China.

An integrated molecular probe for combined tumor-targeted multimodal imaging and therapy in the era of precision medicine requires a multiplexed platform that simultaneously has high targeting specificity, versatile conjugation capability, and biocompatibility. Here, a novel biocompatible melanin nanoprobe (PMNs-II-813) coupled with a highly specific prostate-specific membrane antigen small molecule inhibitor is developed for the targeted multimodal diagnosis and treatment of prostate cancer. The melanin nanoparticles demonstrate photoacoustic imaging and photothermal therapy (PTT) functionalities via strong near-infrared absorption. The imaging contrast agents Zr and Mn are stably conjugated to the nanoparticles for positron emission tomography (PET) and magnetic resonance imaging (MRI). Fusion PET/MRI with PMNs-II-813 enables the monitoring of treatment effects in real time and lasts for more than 1 week, demonstrating the capability for multimodal theranostics in prostate cancer. Labeling with a therapeutic radionuclide, I, simultaneously endows the nanoprobe with the capability for radioisotope therapy (RIT) and PTT under triple-modal imaging guidance. Combined PTT and RIT has an inhibitory effect on prostate cancer growth (tumor inhibition rate of ≈93% 20 days after treatment), which is significantly better than that with the single treatment. Overall, it is believed that PMNs-II-813 has potential for clinical translation to treat prostate cancer.
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http://dx.doi.org/10.1002/smll.202100378DOI Listing
April 2021

BMSC-Derived Small Extracellular Vesicles Induce Cartilage Reconstruction of Temporomandibular Joint Osteoarthritis Autotaxin-YAP Signaling Axis.

Front Cell Dev Biol 2021 1;9:656153. Epub 2021 Apr 1.

The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, China.

Temporomandibular joint osteoarthritis (TMJOA) seriously affects the health of patients, and the current treatments are invasive and only used for advanced cases. Bone marrow mesenchymal stem cell (BMSC)-derived small extracellular vesicles (BMSC-sEVs) may represent a safer and more effective treatment, but their role in TMJOA has not been elucidated. This study attempted to analyze the cartilage reconstruction effect of BMSC-sEVs on TMJOA and the mechanism underlying this effect. BMSC-sEVs were isolated and purified by microfiltration and ultrafiltration and were subsequently characterized by nanoparticle tracking analysis, electron microscopy, and immunoblotting. TMJOA models were established and , and hematoxylin-eosin staining, immunohistochemistry, and histological scoring were performed to analyze the histological changes in TMJOA cartilage tissues treated with BMSC-sEVs. The proliferation, migratory capacity, and cell cycle distribution of TMJOA cartilage cells treated with BMSC-sEVs were detected. Furthermore, the related mechanisms were studied by bioinformatic analysis, immunoblotting, and quantitative PCR, and they were further analyzed by knockdown and inhibitor techniques. The acquisition and identification of BMSC-sEVs were efficient and satisfactory. Compared with the osteoarthritis (OA) group, the condylar tissue of the OA group treated with BMSC-sEV (OA) showed an increase in cartilage lacuna and hypertrophic cartilage cells in the deep area of the bone under the cartilage. Significantly upregulated expression of proliferating cell nuclear antigen and cartilage-forming factors and downregulated expression of cartilage inflammation-related factors in OA were observed. In addition, we found higher rates of cell proliferation and migratory activity and alleviated G1 stagnation of the cell cycle of OA. Autotaxin was found in the BMSC-sEVs, and key factors of the Hippo pathway, Yes-associated protein (YAP), phosphorylated Yes-associated protein (p-YAP), etc. were upregulated in the OA group. Treatment with BMSC-sEVs after autotaxin knockdown or inhibition no longer resulted in expression changes in cartilage-forming and inflammation-related factors and key factors of the Hippo pathway. These results suggest that the autotaxin-YAP signaling axis plays an important role in the mechanism by which BMSC-sEVs promote cartilage reconstruction in TMJOA, which may provide guidance regarding their therapeutic applications as early and minimally invasive therapies for TMJOA, and provide insight into the internal mechanisms of TMJOA.
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http://dx.doi.org/10.3389/fcell.2021.656153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047210PMC
April 2021

Magnetic Resonance Biomarkers in Radiation Oncology.

Med Phys 2021 Apr 17. Epub 2021 Apr 17.

Department of Radiation Oncology, Anderson Cancer Center, University of Texas, Houston, Texas, USA.

A magnetic resonance (MR) biologic marker (biomarker) is a measurable quantitative characteristic that is an indicator of normal biological and pathogenetic processes or a response to therapeutic intervention derived from the MR imaging process. There is significant potential for MR biomarkers to facilitate personalized approaches to cancer care through more precise disease targeting by quantifying normal versus pathologic tissue function as well as toxicity to both radiation and chemotherapy. Both of which have the potential to increase the therapeutic ratio and provide earlier, more accurate monitoring of treatment response. The ongoing integration of MR into routine clinical radiation therapy (RT) planning and the development of MR guided radiation therapy systems is providing new opportunities for MR biomarkers to personalize and improve clinical outcomes. Their appropriate use, however, must be based on knowledge of the physical origin of the biomarker signal, the relationship to the underlying biological processes, and their strengths and limitations. The purpose of this report is to provide an educational resource describing MR biomarkers, the techniques used to quantify them, their strengths and weakness within the context of their application to radiation oncology so as to ensure their appropriate use and application within this field.
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http://dx.doi.org/10.1002/mp.14884DOI Listing
April 2021

Exploring communication between the thalamus and cognitive control-related functional networks in the cerebral cortex.

Cogn Affect Behav Neurosci 2021 Apr 17. Epub 2021 Apr 17.

Department of Psychology, Renmin University of China, Beijing, 100872, China.

It has been suggested by multiple studies (postmortem studies, invasive animal studies, and diffusion tensor imaging in the human brain) that the thalamus is important for communication among cortical regions. Many functional magnetic resonance imaging (fMRI) studies, including noninvasive and whole-brain studies, have reported thalamic co-activation with several cognitive control-related cortical systems. This forms a complex network that may be important for advanced cognitive control-related processes, such as working memory and attention. Nevertheless, how the thalamus communicates with the cognitive control-related network in the intact human brain is an essential question and needs further investigation. To address this question, we conducted a study using dynamic functional connectivity analysis and effective connectivity analysis based on fMRI data from young, healthy adult participants. The results showed that the middle thalamus exhibited both high in- and out-degree regarding the complex network related to cognitive control during both rest and task conditions. Furthermore, intrinsic communication via the middle thalamic regions showed dynamically co-varying patterns, and the thalamic regions showed high flexibility in dynamic community analysis. These results indicated that the mid-thalamic region is an important station for communication between nodes in cognitive control-related networks.
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http://dx.doi.org/10.3758/s13415-021-00892-yDOI Listing
April 2021

Natural product 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose is a reversible inhibitor of glyceraldehyde 3-phosphate dehydrogenase.

Acta Pharmacol Sin 2021 Apr 13. Epub 2021 Apr 13.

Drug Discovery and Design Center, the Center for Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer cell glucose metabolism and plays a crucial role in the activation of various types of immune cells. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of D-glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate in the 6th critical step in glycolysis. GAPDH exerts metabolic flux control during aerobic glycolysis and therefore is an attractive therapeutic target for cancer and autoimmune diseases. Recently, GAPDH inhibitors were reported to function through common suicide inactivation by covalent binding to the cysteine catalytic residue of GAPDH. Herein, by developing a high-throughput enzymatic screening assay, we discovered that the natural product 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) is an inhibitor of GAPDH with K = 0.5 μM. PGG blocks GAPDH activity by a reversible and NAD and Pi competitive mechanism, suggesting that it represents a novel class of GAPDH inhibitors. In-depth hydrogen deuterium exchange mass spectrometry (HDX-MS) analysis revealed that PGG binds to a region that disrupts NAD and inorganic phosphate binding, resulting in a distal conformational change at the GAPDH tetramer interface. In addition, structural modeling analysis indicated that PGG probably reversibly binds to the center pocket of GAPDH. Moreover, PGG inhibits LPS-stimulated macrophage activation by specific downregulation of GAPDH-dependent glucose consumption and lactate production. In summary, PGG represents a novel class of GAPDH inhibitors that probably reversibly binds to the center pocket of GAPDH. Our study sheds new light on factors for designing a more potent and specific inhibitor of GAPDH for future therapeutic applications.
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http://dx.doi.org/10.1038/s41401-021-00653-0DOI Listing
April 2021

Land cover alteration shifts ecological assembly processes in floodplain lakes: Consequences for fish community dynamics.

Sci Total Environ 2021 Mar 25;782:146724. Epub 2021 Mar 25.

School of Ecology and Nature Conservation, Beijing Forestry University, Beijing 100083, China; Science Division, NSW Department of Planning, Industry and Environment, Sydney 2124, Australia. Electronic address:

Habitat degradation is expected to alter community structure and consequently, ecosystem functions including the maintenance of biodiversity. Understanding the underlying abiotic and biotic assembly mechanisms controlling temporal and spatial community structure and patterns is a central issue in biodiversity conservation. In this study, using monthly time series of fish abundance data collected over a three-year period, we compared the temporal community dynamics in natural habitats and poplar plantations in one of the largest river-lake floodplain ecosystems in China, the Dongting Lake. We found a prevailing strong positive species covariance, i.e. species abundance changes in the same way, in all communities that was significantly negatively impacted by higher water nutrient levels. In contrast to species covariance, community stability, which was measured by the average of aggregated abundance divided by temporal standard deviation, was significantly higher in poplar plantations than in natural habitats. The positive species covariance, which was consistent for both wet and dry years and among habitat types, had significantly negative effects on community stability. Furthermore, our results demonstrated that the ecological stochasticity (i.e. community assembly processes generating diversity patterns that are indistinguishable from random chance) was significantly higher in natural sites than in poplar plantations, suggesting that deterministic processes might control the community composition (richness and abundance) at the modified habitat through reducing species synchrony and positive species covariance observed in the natural habitats, leading to significantly lower temporal β-diversity. When combined, our results suggest that habitat modification created environmental conditions for the development of stable fish community in the highly dynamic floodplains, leading to niche-based community with lower temporal β-diversity.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146724DOI Listing
March 2021

Gender-specific prevalence and influencing factors of depression in elderly in rural China: A cross-sectional study.

J Affect Disord 2021 Apr 2;288:99-106. Epub 2021 Apr 2.

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China; Department of Social Medicine and Health Administration, School of Public Health, Tianjin Medical University, Tianjin, China. Electronic address:

Background: With an aging population, late-life depression has been a major health problem in rural China. This study aims to explore the gender-specific prevalence of geriatric depression in rural Tianjin, its influencing factors, and to provide a scientific basis for the prevention and intervention of depression in the elderly.

Methods: A cross-sectional study of 4,933 elderly individuals in rural Tianjin was conducted using the cluster sampling method. The independent samples t-test and chi-squared test were used to assess differences in participants' characteristics by depressive symptoms, while multiple linear regressions and multiple logistic regressions were used to analyze the potential influencing factors of depression.

Results: The prevalence of geriatric depression was found to be 12.2% in the study participants (9.5% in men and 14.5% in women). Gender, education, household income, employment, living alone, social activities, physical exercise and chronic diseases were associated with depression (P<0.05). In addition to the above factors, sleep duration was also related with scores on self-rating depression scale (P<0.05).

Limitations: The study used a cross-sectional approach, so causation cannot be concluded.

Conclusions: Late-life depression is a serious mental health issue in rural China, highlighting the importance of appropriate diagnosis and treatment as a priority to improve the quality of mental health.
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http://dx.doi.org/10.1016/j.jad.2021.03.078DOI Listing
April 2021

General Synthesis of Hierarchically Macro/Mesoporous Fe,Ni-Doped CoSe/N-Doped Carbon Nanoshells for Enhanced Electrocatalytic Oxygen Evolution.

Inorg Chem 2021 May 12;60(9):6782-6789. Epub 2021 Apr 12.

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012, P. R. China.

Constructing hierarchical porosity and designing rational hybrid composition are effective strategies for enhancing the electrocatalytic performance of hybrid catalysts for electrochemical energy conversion. Here, we develop a multistep "molecule/ion-exchange" strategy toward the synthesis of hierarchically macro/mesoporous Fe,Ni-doped CoSe/N-doped carbon nanoshells with tunable pore structures and compositions. Polystyrene (PS)@Co-based amorphous coordination polymer (Co-CP) core-shell particles with hierarchically macro/mesoporous nanoshells are first prepared by ligand-molecule-exchange etching of the outer layers in PS@Co-based metal-organic framework precursors. Afterward, a liquid-solid dual-ion-exchange reaction of PS@Co-CP particles with [Fe(CN)] and [Ni(CN)] ions leads to the formation of PS@Co-CP/Co-Fe Prussian blue analogue (PBA)/Co-Ni PBA particles, which are further transformed into hierarchically macro/mesoporous Fe,Ni-doped CoSe/N-doped carbon particles via a vapor-solid selenization reaction. Moreover, this approach could be extended to synthesize different hierarchically porous core-shell composites with various morphologies and tailored compositions. Because of their unique hierarchically porous nanoarchitecture, these Fe,Ni-doped CoSe/N-doped carbon particles with optimized composition show enhanced performance for electrocatalytic oxygen evolution.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00620DOI Listing
May 2021

Prognosis and Risk Factors of Sepsis Patients in Chinese Icus: A Retrospective Analysis of A Cohort Database.

Shock 2021 Mar 31. Epub 2021 Mar 31.

Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University. 20A Fuxingmenwai Street, Xicheng District, Beijing 100038, China Department of Statistics, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University. 10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China Department of Critical Care Medicine, Xuanwu Hospital, Capital Medical University. 45 Changchun Road, Xicheng District, Beijing 100045, China.

Background: Sepsis-3 proposed a new definition of septic shock that excluded patients without hyperlactacidemia. The data from China might help to elucidate the prognosis of this special patient group.

Objective: To study the clinical prognosis and factors affecting patients with sepsis based on data from Chinese intensive care units (ICUs).

Methods: We conducted a retrospective, multicentre observational study in a larger Chinese cohort from January 1, 2014, to August 31, 2015. The patients were divided into 4 groups according to the presence or absence of hypotension/vasopressor delivery and hyperlactacidemia after fluid resuscitation. Descriptive statistics for the clinical characteristics were presented. The differences between groups were assessed. A survival curve was then plotted using the Kaplan-Meier method. Finally, to better understand the risk factors for the 28-day hospital mortality rates, Cox regression analysis was performed.

Results: In total, 1194 patients with sepsis were included: 282 with hypotension and hyperlactacidemia, 250 with hypotension but without hyperlactacidemia, 161 with hyperlactacidemia but without hypotension, and 501 without hypotension and hyperlactacidemia. The 28-day hospital mortality rates of the four groups were 48.2%, 43.2%, 26.1% and 24.8%, respectively. Age, the Acute Physiology And Chronic Health Evaluation (APACHE) II score, hyperlactacidemia, hypotension, intra-abdominal infection and cancer increased the risk of the 28-day mortality, while soft tissue infection and coming from the operating room were associated with a decreased risk of mortality.

Conclusions: Patients with hypotension but without hyperlactacidemia in the ICU also show a high 28-day mortality, and some clinical factors may affect their prognosis and must be treated carefully in the future.
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http://dx.doi.org/10.1097/SHK.0000000000001784DOI Listing
March 2021

Effects of enzymatic reaction on the generation of key aroma volatiles in shiitake mushroom at different cultivation substrates.

Food Sci Nutr 2021 Apr 26;9(4):2247-2256. Epub 2021 Feb 26.

Institute of Edible Fungi Shanghai Academy of Agricultural Sciences National Engineering Research Center of Edible Fungi Key Laboratory of Edible Fungi Resources and Utilization (South) Ministry of Agriculture Shanghai China.

Aroma is an important factor affecting mushroom character and quality. According to the different reaction pathway, the key aroma metabolites (sulfur and eight-carbon volatiles) formation can be classified into enzymatic reactions and nonenzymatic reactions. Aroma volatiles are generated from precursors via the biocatalytic activities of various synthases during the growth stages of shiitake mushrooms. Understanding the specific relationships between the key aroma metabolites and their synthases is key to improving shiitake mushroom quality. At the same time, to reduce forest logging and burning of agricultural by-products in farmland, agricultural by-products have been applied to shiitake mushroom cultivation. Nevertheless, how to further improve the production of aroma volatiles in mushroom cultivated with agricultural waste is still a challenge. In order to understand the biosynthesis of volatiles via enzymatic reactions and screen the agricultural by-products that can improve the production of aroma volatiles in mushroom cultivation, the mechanism of producing aroma volatiles needs to be further elucidated. In this study, the activities and gene expression levels of the key synthases involved in volatile metabolism, the contents of key aroma volatiles, and the correlations between related synthetase, volatiles, and cultivation substrate (CS) were investigated. Network models for visualizing the links between synthetase, volatiles, and CSs were built through partial least squares (PLS) regression analysis. The correlation coefficients among three related synthetase and enzymatic gene expression were high, and the combined effects of multiple synthetase promoted the production of volatiles. PLS analysis showed that the corncob and corn meal were more related to the production of volatiles and synthetase gene expression, and they can be added to the CSs as flavor promoting substances. The enrichment of key aroma volatiles in shiitake mushroom cultivated by the gradient of 20% corn meal combination CS was noticeable.
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http://dx.doi.org/10.1002/fsn3.2198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020957PMC
April 2021

Effect of combined application of iguratimod in the treatment of active rheumatoid arthritis on bone metabolism, Th17 cells and Treg cells.

Am J Transl Res 2021 15;13(3):1676-1684. Epub 2021 Mar 15.

Department of Rheumatology and Immunology, First People's Hospital Fuyang District, Hangzhou 311400, Zhejiang Province, China.

Objective: This study was designed to analyse the effect of combined application of iguratimod with methotrexate in the treatment of active rheumatoid arthritis (RA).

Methods: A total of 115 patients with active RA admitted to our hospital were enrolled and divided into group A (n=58) and group B (n=57) according to the method of random number table. Patients in group B were treated with methotrexate alone, while patients in group A were treated with methotrexate combined with iguratimod. The curative efficacy was compared between the two groups.

Results: At 6 months after treatment, the levels of CTX-1 and RANKL in group A were higher than those in group B, and the levels of OPG, IL-17 and TGF-α in group A were lower than those in group B (<0.05). The level of Th17 cells in group A was higher than that in group B, and the level of Treg cells in group A was lower than that in group B at 6 months after treatment (<0.05). Tender joints count, swollen joints count and DAS28 score in group A were less than those in group B at 6 months after treatment (<0.05). The duration of morning stiffness of the joints and the score of joint pain degree in group A were less than those in group B at 1, 2, 3, 4, 5, and 6 months after treatment (<0.05).

Conclusion: The combined application of methotrexate and iguratimod in the treatment of active RA can effectively improve bone metabolism, regulate the levels of Th17 and Treg cells, play a prominent role in anti-inflammatory effect, and relieve symptoms, and thus achieve a more satisfactory curative effect.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014432PMC
March 2021