Publications by authors named "Jing Zhou"

2,229 Publications

  • Page 1 of 1

Comparison of bacterial and archaeal communities in two fertilizer doses and soil compartments under continuous cultivation system of garlic.

PLoS One 2021 14;16(5):e0250571. Epub 2021 May 14.

School of Life Sciences, Qufu Normal University, Jining, PR China.

Soil microbial communities are affected by interactions between agricultural management (e.g., fertilizer) and soil compartment, but few studies have considered combinations of these factors. We compared the microbial abundance, diversity and community structure in two fertilizer dose (high vs. low NPK) and soil compartment (rhizosphere vs. bulk soils) under 6-year fertilization regimes in a continuous garlic cropping system in China. The soil contents of NO3- and available K were significantly higher in bulk soil in the high-NPK. The 16S rRNA gene-based bacterial and archaeal abundances were positively affected by both the fertilizer dose and soil compartment, and were higher in the high-NPK fertilization and rhizosphere samples. High-NPK fertilization increased the Shannon index and decreased bacterial and archaeal richness, whereas the evenness was marginally positively affected by both the fertilizer dose and soil compartment. Soil compartment exerted a greater effect on the bacterial and archaeal community structure than did the fertilization dose, as demonstrated by both the nonmetric multidimensional scaling and redundancy analysis results. We found that rhizosphere effects significantly distinguished 12 dominant classes of bacterial and archaeal communities, whereas the fertilizer dose significantly identified four dominant classes. In particular, a Linear Effect Size analysis showed that some taxa, including Alphaproteobacteria, Rhizobiales, Xanthomonadaceae and Flavobacterium, were enriched in the garlic rhizosphere of the high-NPK fertilizer samples. Overall, the fertilizer dose interacted with soil compartment to shape the bacterial and archaeal community composition, abundance, and biodiversity in the garlic rhizosphere. These results provide an important basis for further understanding adaptive garlic-microbe feedback, reframing roots as a significant moderating influence in agricultural management and shaping the microbial community.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250571PLOS
May 2021

Potential functional variants of KIAA genes are associated with breast cancer risk in a case control study.

Ann Transl Med 2021 Apr;9(7):549

Department of Epidemiology, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

Background: KIAA genes identified in the Kazusa cDNA-sequencing project may play important roles in biological processes and are involved in carcinogenesis of many cancers. Genetic variants of KIAA genes are implicated in the abnormal expression of these genes and are linked to susceptibility of several human complex diseases.

Methods: The differentially expressed KIAA genes were screened and identified in The Cancer Genome Atlas (TCGA) database of breast cancer. A total of 48 variants located in the 28 KIAA genes were selected to investigate the associations between polymorphism and breast cancer in 1,032 cases and 1,063 cancer-free controls in a Chinese population.

Results: Two coding variants, which included a SNP rs2306369 in and a SNP rs1205434 in , were identified to be associated with the incidences of breast cancer. Logistic regression analysis showed that the SNP rs2306369 G allele was associated with a decreased risk of breast cancer (additive model: OR =0.81, 95% CI: 0.66-0.99, P=0.038), whereas the SNP rs1205434 A allele was involved with a higher risk of breast cancer (additive model: OR =1.19, 95% CI: 1.02-1.38, P= 0.025). Further stratified analysis revealed that the SNP rs1205434 showed a significant difference for age at menarche strata (heterogeneity test P=0.009). Multiplicative interaction analysis indicated that there was positive multiplicative interaction between the SNP rs1205434 and menarche age (OR =1.09, 95% CI: 1.01-1.17, P=0.036). Additionally, expression quantitative trait loci analysis revealed that the SNP rs1205434 A allele could decrease the expression in the Genotype-Tissue Expression (GTEx) database (P=0.002). The Kaplan-Meier plotter showed that breast cancer patients with high expression have significantly better outcomes than those with low levels of expression (HR =0.84, 95% CI: 0.72-0.99, P=0.033).

Conclusions: The results indicate that the genetic variants (rs2306369 and rs1205434) in the coding region of and respectively may affect Chinese females' breast cancer susceptibility and act as potential predictive biomarkers for breast cancer.
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http://dx.doi.org/10.21037/atm-20-6108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105804PMC
April 2021

Childhood Bacille Calmette-Guerin Vaccination and Its Association With Less Severe COVID-19 Pneumonia.

Am J Prev Med 2021 Apr 12. Epub 2021 Apr 12.

Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Introduction: The potential for Bacille Calmette-Guerin vaccination to mitigate COVID-19 severity and perhaps infection susceptibility has been hypothesized, attracting global attention given its off-target benefits shown in several respiratory viral infections.

Methods: In this retrospective study, patients with laboratory-confirmed COVID-19 from Wuhan Pulmonary Hospital, China were categorized into Bacille Calmette-Guerin‒vaccinated and nonvaccinated groups. Clinical records, demography, laboratory results, and chest computed tomography scans were extracted from electronic medical records and compared between the 2 groups.

Results: No adverse events were observed, except for an increased frequency of chills in the Bacille Calmette-Guerin‒vaccinated group compared with that in the unvaccinated group (p=0.014). There were no significant differences in oxygen demand for breathing, computed tomography scans, treatments, or outcomes between the 2 groups. However, Bacille Calmette-Guerin‒vaccinated group had significantly less severe pneumonia (p=0.028) and milder deficiency in liver function, consistent with a lower death rate than in the unvaccinated group.

Conclusions: Bacille Calmette-Guerin vaccination received in childhood is associated with less severe COVID-19 pneumonia and milder liver function deficiency in addition to a lower death rate in Bacille Calmette-Guerin‒vaccinated patients than in nonvaccinated individuals.
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http://dx.doi.org/10.1016/j.amepre.2021.02.025DOI Listing
April 2021

Double-sided optical coating of strongly curved glass by atomic layer deposition.

Opt Express 2021 Apr;29(9):13815-13828

A reaction chamber of atomic layer deposition (ALD) was developed for simultaneous coating on the inner and outer surfaces of a large-size and strongly curved glass bowl. The inner surface ALD process was in a showerhead reaction mode and the outer surface ALD process was in a cross-flow reaction mode. Blue reflection (BR) film of 400 nm wavelength and broadband antireflection (BBAR) film of 400-700 nm wavelength were coated on different glass bowls by ALD. The spectral uniformity of both coated bowls was studied. The measured spectra at multiple positions of the glass bowl with the BBAR coating show better spectral uniformity along the circumference than the depth. The spectral deviation is mainly caused by the non-uniformity of the film on the outer surface (<±3%), and the film on the inner surface has good uniformity along both the circumference and the depth (<±0.7%). The growth rate of the outer film was reduced by 10% on average compared to that of the inner film due to the different gas flow mode.
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http://dx.doi.org/10.1364/OE.423085DOI Listing
April 2021

Stroke outcome assessment: Optimizing cutoff scores for the Longshi Scale, modified Rankin Scale and Barthel Index.

PLoS One 2021 13;16(5):e0251103. Epub 2021 May 13.

The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.

The Longshi Scale, a visual-based scale, is reliable and valid in activity assessment, but lacks cutoff definition corresponding to classical scales such as the modified Rankin Scale and Barthel Index. Therefore, this study aimed to investigate the relationships of the Longshi Scale with the modified Rankin Scale and Barthel Index and optimize cutoff scores of these scales in stroke outcomes assessment. This is a cross-sectional study. Stroke patients were measured concurrently by the Longshi scale, modified Rankin Scale and Barthel Index. Kruskal-Wallis test and Spearman correlation analysis were used to analyze the differences and associations among the three scales. The receiver operating characteristic curve was performed to determine the optimal cutoff scores. A total of 5475 stroke patients (67.3% ischemic) were included in this study. There are close relationships of the Longshi Scale with adjusted modified Rankin Scale and Barthel Index (r = -0.861, 0.922; p<0.001, <0.001; respectively). The activity levels assessed by adjusted modified Rankin Scale and Barthel Index among different Longshi scale grades were significantly different (χ2:4217.27, 4676.55; p<0.001, <0.001; respectively). The optimal cutoff scores were adjusted modified Rankin Scale 4, 3, 3, 3, 2 for Longshi scale grade 2 to 6 (sensitivity%: 96.12, 70.24, 89.10, 96.80, 86.23, specificity%: 72.72, 98.29, 93.81, 79.82, 92.89, respectively), and Barthel Index 15, 45, 60, 75, 80 for Longshi scale grade 2 to 6 (sensitivity%: 92.54, 89.28, 91.32, 90.30, 95.65, specificity%: 95.48, 89.51, 94.02, 90.41, 90.62, respectively). In conclusion, the classification of Longshi Scale is consistent with those of modified Rankin Scale and Barthel Index. We recommend the Longshi Scale as an effective supplement for modified Rankin Scale and Barthel Index in assessing the outcome in acute stroke patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251103PLOS
May 2021

Enhancing employee creativity: Effects of choice, rewards and personality.

J Appl Psychol 2021 May 13. Epub 2021 May 13.

College of Management, National Taiwan Normal University.

We conducted a quasi-experimental field study of an organization-wide suggestion program and a follow-up laboratory experiment to examine the effects of choice of rewards on employee creativity. As hypothesized, the results of both studies showed that choice had positive, significant effects on the number of creative ideas employees generated and the creativity level of those ideas. Results of the quasi-experiment also showed that creative self-efficacy (CSE) mediated the effects of reward choice. Two general categories of rewards were examined in our studies-those that directly benefited the idea generator (Self) and those that directly benefited charities (Other). We explored the effects of these reward categories on employee creativity and whether employee creative personality interacted with the reward categories to affect employee creativity. Results showed that the reward categories did not have a significant impact on employee creativity. However, both studies demonstrated that in the Other reward condition, employees with a creative personality produced ideas higher in creativity than those with a less creative personality. The quasi-experiment also showed that CSE mediated the effects of the Reward × Creative Personality interaction. We discussed the implications of these results for the future research and practice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/apl0000900DOI Listing
May 2021

The YAP/HIF-1α/miR-182/EGR2 axis is implicated in asthma severity through the control of Th17 cell differentiation.

Cell Biosci 2021 May 12;11(1):84. Epub 2021 May 12.

Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Street, Donghu District, Nanchang, 330006, People's Republic of China.

Background: Asthma is a heterogeneous chronic inflammatory disease of the airway, involving reversible airflow limitation and airway remodeling. T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. However, there is limited understanding of the signaling pathways controlling Th17 cell differentiation in asthma. The aim of this study was to investigate if the Yes-associated protein (YAP)/hypoxia inducible factor-1α (HIF-1α)/microRNA-182 (miR-182)/early growth response 2 (EGR2) axis is involved in mediating Th17 cell differentiation and disease severity in asthma.

Methods: The study included 29 pediatric patients with asthma, 22 healthy volunteers, ovalbumin-induced murine asthma models, and mouse naive CD4 T cells. The subpopulation of Th17 cells was examined by flow cytometry. The levels of interleukin-17A were determined by enzyme linked immunosorbent assay. Chromatin immunoprecipitation-quantitative polymerase chain reaction assays and dual-luciferase reporter gene assays were performed to examine interactions between HIF-1α and miR-182, and between miR-182 and EGR2.

Results: YAP, HIF-1α, and miR-182 were upregulated but EGR2 was downregulated in human and mouse peripheral blood mononuclear cells from the asthma group. Abundant expression of YAP and HIF-1α promoted miR-182 expression and then inhibited EGR2, a target of miR-182, thus enhancing Th17 differentiation and deteriorating asthma and lipid metabolism dysfunction. In addition, in vivo overexpression of EGR2 countered the promoting effect of the YAP/HIF-1α/miR-182 axis on asthma and lipid metabolism dysfunction.

Conclusion: These results indicate that activation of the YAP/HIF-1α/miR-182/EGR2 axis may promote Th17 cell differentiation, exacerbate asthma development, and aggravate lipid metabolism dysfunction, thus suggesting a potential therapeutic target for asthma.
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http://dx.doi.org/10.1186/s13578-021-00560-1DOI Listing
May 2021

The role and mechanism of PKM2 in the development of LPS-induced acute kidney injury.

Histol Histopathol 2021 May 12:18343. Epub 2021 May 12.

Shanghai General Hospital of Nanjing Medical University, Shanghai, China.

A previous study suggested that pyruvate kinase M2 (PKM2) plays a vital role of metabolic reprogramming in the regulation of the innate inflammatory response, while PKM2 is a sensitive biomarker for nephrotoxicity. In this study, we investigated the role and mechanism of PKM2 in development of LPS-induced acute kidney injury. The AKI model of mice was established using LPS. The serum levels of blood urea nitrogen (Bun), creatinine (Cr), and Cystatin C (CysC) were identified using the enzyme-linked immunosorbent assay (ELISA). Hematoxylin and Eosin staining (H&E) was employed to assess pathological changes in kidney tissues of LPS-induced AKI model. Immunohistochemical staining and Western blot analysis were carried out to determine the expression of apoptosis-related factors at protein levels. We found that Bun, CysC, and Cr were significantly increased in the LPS group compared with the control group. The histopathological assay showed model swollen tubular epithelial cells and the presence of vacuolar degeneration in the LPS-induced AKI. In addition, expression levels of PKM2 significantly increased in the LPS group compared with the control group at both protein and mRNA levels (P<0.01). The inhibition of PKM2 by shikonin notably suppressed the expression of HIF-1α and apoptosis-related factors such as BNIP3, Bax, and Caspase-3, while the inhibition of PKM2 by shikonin significantly improved the histopathological symptoms of LPS-induced AKI. This study demonstrated the potential role of PKM2 in LPS-induced AKI and identified PKM2 as a promising therapeutic target in the treatment of AKI.
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http://dx.doi.org/10.14670/HH-18-343DOI Listing
May 2021

Ginseng ameliorates exercise-induced fatigue potentially by regulating the gut microbiota.

Food Funct 2021 May;12(9):3954-3964

Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing, Jiangsu, People's Republic of China. and Department of Pharmaceutical Analysis, Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.

The therapeutic effects of water extract of ginseng (WEG) on exercise-induced fatigue (EF) have been reported in several previous studies, but the molecular mechanisms involved remain unexplored. In this study, the anti-EF effects of WEG were studied, and the potential mechanisms were discussed. We characterized the chemical components of WEG by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD), and then examined the anti-EF effects of WEG on a rat model of weight-loaded swimming with a focus on endogenous metabolism and gut microbiota. WEG contains abundant (90.15%, w/w) saccharides and ginsenosides with structurally diverse glycosyls. WEG taken orally showed strong anti-EF effects by ameliorating energy metabolism abnormality, oxidative stress, lipid peroxidation, inflammatory response, disorders in the metabolism of bile acid, amino acid, fatty acid and lipid, as well as the gut microbiota dysbiosis. Given that gut microbiota is significantly associated with energy expenditure, systemic inflammation and host metabolism, these findings suggest a potential central role of the gut microbiota in mediating the anti-EF effect of WEG. That is, the saccharides and ginsenosides in WEG serve as energy substrates for specific intestinal bacteria, thereby beneficially regulating the gut microbiota, and the reshaped gut microbial ecosystem then triggers several molecular and cellular signaling pathways (e.g. butyrate or TGR5 signals) to achieve the therapeutic effects on EF. The outcomes highlighted here enable deeper insight into how WEG overcomes EF.
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http://dx.doi.org/10.1039/d0fo03384gDOI Listing
May 2021

Nanoprobes-Assisted Multichannel NIR-II Fluorescence Imaging-Guided Resection and Photothermal Ablation of Lymph Nodes.

Adv Sci (Weinh) 2021 05 15;8(9):2003972. Epub 2021 Feb 15.

Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou 310000 P. R. China.

Lymph node metastasis is a major metastatic route of cancer and significantly influences the prognosis of cancer patients. Radical lymphadenectomy is crucial for a successful surgery. However, iatrogenic normal organ injury during lymphadenectomy is a troublesome complication. Here, this paper reports a kind of organic nanoprobes (IDSe-IC2F nanoparticles (NPs)) with excellent second near-infrared (NIR-II) fluorescence and photothermal properties. IDSe-IC2F NPs can effectively label lymph nodes and helped achieve high-contrast lymphatic imaging. More importantly, by jointly using IDSe-IC2F nanoparticles and other kinds of nanoparticles with different excitation/emission properties, a multichannel NIR-II fluorescence imaging modality and imaging-guided lymphadenectomy is proposed. With the help of this navigation system, the iatrogenic injury can be largely avoided. In addition, NIR-II fluorescence imaging-guided photothermal treatment ("hot" strategy) can ablate those metastatic lymph nodes which are difficult to deal with during resection ("cold" strategy). Nanoprobes-assisted and multichannel NIR-II fluorescence imaging-guided "cold" and "hot" treatment strategy provides a general new basis for the future precision surgery.
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http://dx.doi.org/10.1002/advs.202003972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097375PMC
May 2021

Oridonin inhibits tumor angiogenesis and induces vessel normalization in experimental colon cancer.

J Cancer 2021 2;12(11):3257-3264. Epub 2021 Apr 2.

Department of Oncology, Shanxi Province Academy of Traditional Chinese Medicine, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, Shanxi 030012, China.

Tumor blood vessels exhibit morphological and functional aberrancies. Its maturity and functionality are closely associated with colon cancer progression and therapeutic efficacy. The direct evidence proving whether oridonin (ORI) has vascular normalization promoting effect from which combination therapies will benefit is still lacking. We established a subcutaneous xenograft model of human colon cancer. The animals were divided into the Control and ORI-treated groups. Immunohistochemical analysis and TUNEL staining was applied to evaluate the proliferation, apoptosis and angiogenesis. Western blot analysis was employed to characterize the angiogenesis-related factors and JAK2/STAT3 signaling. Then, vascular normalization and macrophage reprogramming were assessed by immunofluorescence analysis. The results showed that ORI obviously reduced tumor growth, diminished the numbers of Ki67 cells and CD31 microvessel density, while increased the numbers of TUNEL cells. The expression levels of VEGF and bFGF proteins were dramatically down-regulated while the angiostatin and endostatin levels were increased in the ORI-treated group. Moreover, ORI therapy remarkably promoted the pericyte coverage of tumor vessels from days 5 to 10, with the highest pericyte coverage rate occurred at day 7. In the time window of vascular normalization, hypoxia of the tumor microenvironment was improved by ORI, the expression of HIF-1a was downregulated. Moreover, CD206 macrophage cells were diminished in the ORI-treated group. These anticancer effects of ORI maybe partly mediated by suppressing JAK2/STAT3 signaling pathway. These results highlight the potential effect of ORI on anti-angiogenesis and inducing vessel normalization roles of ORI, and probably provide optimum time point for the ORI therapy in conjunction with the chemoradiotherapy or immunotherapy.
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http://dx.doi.org/10.7150/jca.55929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100792PMC
April 2021

Structural analogues in herbal medicine ginseng hit a shared target to achieve cumulative bioactivity.

Commun Biol 2021 May 10;4(1):549. Epub 2021 May 10.

College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.

By a pilot trial on investigating immunomodulatory activity and target of ginsenosides, the major bioactive components of ginseng, here we report that structural analogues in herbal medicines hit a shared target to achieve cumulative bioactivity. A ginsenoside analogues combination with definite immunomodulatory activity in vivo was designed by integrating pharmacodynamics, serum pharmacochemistry and pharmacokinetics approaches. The cumulative bioactivity of the ginsenoside analogues was validated on LPS/ATP-induced RAW264.7 macrophages. The potentially shared target NLRP3 involved in this immunomodulatory activity was predicted by systems pharmacology. The steady binding affinity between each ginsenoside and NLRP3 was defined by molecular docking and bio-layer interferometry assay. The activation of NLRP3 inflammasomes in LPS/ATP-induced RAW264.7 was significantly suppressed by the combination, but not by any individual, and the overexpression of NLRP3 counteracted the immunomodulatory activity of the combination. All these results demonstrate that the ginsenoside analogues jointly hit NLRP3 to achieve cumulative immunomodulatory activity.
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http://dx.doi.org/10.1038/s42003-021-02084-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110997PMC
May 2021

Handgrip Strength-Related Factors Affecting Health Outcomes in Young Adults: Association with Cardiorespiratory Fitness.

Biomed Res Int 2021 21;2021:6645252. Epub 2021 Apr 21.

The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.

Objectives: Handgrip strength (HS) is a risk factor of all-cause mortality and cardiovascular diseases. However, the influencing factors and mechanisms contributing to this correlation remain unclear. Therefore, we aimed to explore factors related to HS and investigated the mechanism underlying its risk predictive value.

Methods: This was a prospective, cross-sectional study. One hundred forty-five participants were recruited from December 2019 to November 2020. HS was measured using a hydraulic hand dynamometer and adjusted for body mass index (HS) and body surface area (HS). Body composition was assessed via bioimpedance spectroscopy. Physical fitness was measured using a cardiopulmonary exercise test system. Univariate, multiple linear regression analyses and receiver operator characteristic curve (ROC) were conducted to evaluate the associations between various participant characteristics and HS.

Results: The average participant age was 21.68 ± 2.61 years (42.8% were male). We found positive correlations between HS/HS and VO, VE, Load, and MET in both sexes ( < 0.05). Lean-tissue, protein, total water, and inorganic salt percentages were positively correlated, and fat percentage was negatively correlated with HS in men and with HS and HS in women ( < 0.05). Multiple regression revealed that VO was independently associated with HS in both sexes ( = 0.215, 0.173; 95%confidence interval [CI] = 0.032 - 0.398, 0.026-0.321; = 0.022, 0.022, respectively) and independently associated with HS in women ( = 0.016, 95%CI = 0.004 - 0.029, = 0.011). ROC analysis showed that HS and HS can moderately identify normal VO in men (area under curve [AUC] = 0.754, 0.769; = 0.002, 0.001, respectively) and marginally identify normal VO in women (AUC = 0.643, 0.635; = 0.029, 0.042, respectively).

Conclusions: BMI- and BSA-adjusted HS could serve as indicators of physical health, and HS may moderately reflect cardiorespiratory fitness levels in healthy young adults, particularly in males. Clinical trials registry site and number: China Clinical Trial Center (ChiCTR1900028228).
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http://dx.doi.org/10.1155/2021/6645252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084643PMC
April 2021

The gut microbiome is associated with brain structure and function in schizophrenia.

Sci Rep 2021 May 7;11(1):9743. Epub 2021 May 7.

Department of Biomedical Engineering, School of Material Science and Engineering, South China University of Technology, Guangzhou, 510006, China.

The effect of the gut microbiome on the central nervous system and its possible role in mental disorders have received increasing attention. However, knowledge about the relationship between the gut microbiome and brain structure and function is still very limited. Here, we used 16S rRNA sequencing with structural magnetic resonance imaging (sMRI) and resting-state functional (rs-fMRI) to investigate differences in fecal microbiota between 38 patients with schizophrenia (SZ) and 38 demographically matched normal controls (NCs) and explored whether such differences were associated with brain structure and function. At the genus level, we found that the relative abundance of Ruminococcus and Roseburia was significantly lower, whereas the abundance of Veillonella was significantly higher in SZ patients than in NCs. Additionally, the analysis of MRI data revealed that several brain regions showed significantly lower gray matter volume (GMV) and regional homogeneity (ReHo) but significantly higher amplitude of low-frequency fluctuation in SZ patients than in NCs. Moreover, the alpha diversity of the gut microbiota showed a strong linear relationship with the values of both GMV and ReHo. In SZ patients, the ReHo indexes in the right STC (r = - 0.35, p = 0.031, FDR corrected p = 0.039), the left cuneus (r = - 0.33, p = 0.044, FDR corrected p = 0.053) and the right MTC (r = - 0.34, p = 0.03, FDR corrected p = 0.052) were negatively correlated with the abundance of the genus Roseburia. Our results suggest that the potential role of the gut microbiome in SZ is related to alterations in brain structure and function. This study provides insights into the underlying neuropathology of SZ.
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http://dx.doi.org/10.1038/s41598-021-89166-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105323PMC
May 2021

Enhancing Thermocatalytic Activities via Up-shift of the d-Band Center of Exsolved Co-Ni-Fe Ternary Alloy Nanoparticles for Dry Reforming of Methane.

Angew Chem Int Ed Engl 2021 May 7. Epub 2021 May 7.

Ulsan National Institute of Science and Technology (UNIST), Department of Energy Engineering, 701-8 Natural & Sci. Bldg., 50 UNIST-Gil, Eonyang-eup, Ulju-gun, 689-798, Ulsan, KOREA, REPUBLIC OF.

Dry reforming of methane (DRM) is a feasible solution to cope with the reduction of greenhouse gas under the Paris Convention's obligations, given that it adds value by converting trivial gases of CO2 and CH4 simultaneously into useful syngas. However, conventional Ni catalyst undergoes deactivation due to carbon coking and particle agglomeration. Here we demonstrate for the first time a highly efficient and durable DRM catalyst of exsolved Co-Ni-Fe ternary alloy nanoparticles on the layered perovskite PrBaMn1.7Co0.1Ni0.2O5+d produced by topotactic exsolution. This readily allows the generation of a larger number of exsolved nanoparticles, enhancing catalytic activity above those of Ni monometallic and Co-Ni bimetallic particles. The enhancement is achieved by the optimal up-shift of the d-band center of Co-Ni-Fe than those of Co-Ni and Ni meaning easier charge donation to the adsorbate. Furthermore, the exsolved catalyst shows exceptional stability with the continuous DRM operation for about 350 hours.
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http://dx.doi.org/10.1002/anie.202101335DOI Listing
May 2021

Cooperative Heterobimetallic Zinc/Alkaline Earth Metal Catalysis: A Zn/Sr Aminophenol Sulfonamide Complex for Catalytic Asymmetric Michael Addition of 3-Acetoxy-2-oxindoles to β-Ester Enones.

J Org Chem 2021 May 7. Epub 2021 May 7.

Chongqing Research Center for Pharmaceutical Engineering, Research Center for Innovative Pharmaceutical and Excipient Analysis Technology, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China.

A heterobimetallic zinc/strontium catalyst has been developed for the asymmetric Michael addition of 3-acetoxy-2-oxindoles to β-ester enones in high yields with excellent enantioselectivities and high diastereoselectivities. This process represents that 3-acetoxy-2-oxindoles can be used as a stable air- and base-tolerant precursor for chiral 3-substituted 3-hydroxy-2-oxindoles.
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http://dx.doi.org/10.1021/acs.joc.1c00379DOI Listing
May 2021

Immunological and inflammatory profiles during acute and convalescent phases of severe/ critically ill COVID-19 patients.

Int Immunopharmacol 2021 Apr 17;97:107685. Epub 2021 Apr 17.

Department of Laboratory Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China. Electronic address:

Background: The 2019 Coronavirus (COVID-19) pandemic poses a huge threat internationally; however, the role of the host immune system in the pathogenesis of COVID-19 is not well understood.

Methods: Cytokine and chemokine levels and characterisation of immune cell subsets from 20 COVID-19 cases after hospital admission (17 critically ill and 3 severe patients) and 16 convalescent patients were determined using a multiplex immunoassay and flow cytometry, respectively.

Results: IP-10, MCP-1, MIG, IL-6, and IL-10 levels were significantly higher in acute severe/critically ill patients with COVID-19, whereas were normal in patients who had reached convalescence. CD8 T cells in severe and critically ill COVID-19 patients expressed high levels of cytotoxic granules (granzyme B and perforin)and was hyperactivated as evidenced by the high proportions of CD38. Furthermore, the cytotoxic potential of natural killer (NK) cells, and the frequencies of myeloid dendritic cells and plasmacytoid dendritic cells was reduced in patients with severe and critical COVID-19; however, these dysregulations were found to be restored in convalescent phases.

Conclusion: Thus, elicitation of the hyperactive cytokine-mediated inflammatory response, dysregulation of CD8 T and NK cells, and deficiency of host myeloid and plasmacytoid DCs, may contribute to COVID-19 pathogenesis and provide insights into potential therapeutic targets and strategies.
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http://dx.doi.org/10.1016/j.intimp.2021.107685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052478PMC
April 2021

Interleukin-9 promotes intestinal barrier injury of sepsis: a translational research.

J Intensive Care 2021 May 3;9(1):37. Epub 2021 May 3.

Department of Critical Care Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, Jiangsu Province, China.

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Intestinal mucosal barrier injury is one of the important manifestations of sepsis. Interleukin-9 (IL-9) and IL-9-producing CD4(+) T cells were emerging pro-inflammatory mediators with development of intestinal injury. However, it is unclear whether IL-9 is related to the intestinal barrier injury of sepsis.

Methods: To investigate the roles of IL-9-producing CD4(+) T cells and IL-9 in the process of barrier injury in sepsis, serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels were measured in septic patients and controls. The markers of barrier function in serum and intestinal tissue were also collected in septic rats. Moreover, the barrier injury degree and survival rate of septic rats were also investigated after increasing or interfering with IL-9 expression.

Results: The serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels were significantly higher in septic patients or rats than those in controls. IL-9-producing CD4(+) T cells and IL-9 levels were positively correlated with D-lactate levels and had a high predictive value of 28-day mortality in septic patients. The non-survivors had significantly higher serum T cell percentages, IL-9, and D-lactate levels compared with survivors. In septic rats, IL-9 increased the expression levels of D-lactate, whereas that decreased the expression levels of zonula occludens 1. Moreover, the barrier injury was aggravated or alleviated by increasing or interfering with IL-9 expression, respectively. Survival rate analysis also showed that IL-9 decreased the 14-day survival rate of septic rats.

Conclusion: IL-9 is closely related to intestinal mucosal barrier injury and mortality in sepsis. IL-9 blockade has the potential to improve the barrier injury in sepsis.

Trial Registration: The study was registered at ClinicalTrials.gov (ID: NCT03791866, Date: December 2018).
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http://dx.doi.org/10.1186/s40560-021-00550-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091144PMC
May 2021

Prediction of the compressive strength of high-performance self-compacting concrete by an ultrasonic-rebound method based on a GA-BP neural network.

PLoS One 2021 3;16(5):e0250795. Epub 2021 May 3.

School of Civil Engineering, Hunan University, ChangSha, Hunan Province, China.

To address the problem of low accuracy and poor robustness of in situ testing of the compressive strength of high-performance self-compacting concrete (SCC), a genetic algorithm (GA)-optimized backpropagation neural network (BPNN) model was established to predict the compressive strength of SCC. Experiments based on two concrete nondestructive testing methods, i.e., ultrasonic pulse velocity and Schmidt rebound hammer, were designed and test sample data were obtained. A neural network topology with two input nodes, 19 hidden nodes, and one output node was constructed, and the initial weights and thresholds of the resulting traditional BPNN model were optimized using GA. The results showed a correlation coefficient of 0.967 between the values predicted by the established BPNN model and the test values, with an RMSE of 3.703, compared to a correlation coefficient of 0.979 between the values predicted by the GA-optimized BPNN model and the test values, with an RMSE of 2.972. The excellent agreement between the predicted and test values demonstrates the model can accurately predict the compressive strength of SCC and hence reduce the cost and time for SCC compressive strength testing.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250795PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092652PMC
May 2021

Retroperitoneal or transperitoneal approach in robot-assisted partial nephrectomy, which one is better?

Cancer Med 2021 May 1. Epub 2021 May 1.

Department of Urology, West China Hospital, Sichuan University, Chengdu, China.

Purpose: To systematically assess the perioperative outcomes of retroperitoneal (RP) and transperitoneal (TP) approaches in robot-assisted partial nephrectomy (RAPN), we conducted an updated meta-analysis.

Methods: A literature retrieval of multi-database including PubMed, Web of Science, Embase, Cochrane Library, and CNKI was performed to identify eligible comparative studies from the inception dates to January 2021. Perioperative outcomes included operative time (OT), estimated blood loss (EBL), warm ischemia time (WIT), postoperative length of stay (PLOS), positive surgical margin (PSM), and complications (major complications and overall complications). Outcomes of data were pooled and analyzed with Review Manager 5.4.1.

Results: Twenty-one studies involving a total of 2482 RP and 3423 TP approach RAPN patients met the inclusion criteria. Operating time (OT) (weighted mean difference [WMD] -16.60; 95% confidence interval [CI] -23.08, -10.12; p < 0.01) and PLOS (WMD -0.46 days; 95% CI -0.69, -0.23; p < 0.01) were shorter in RP-RAPN. Besides, lower EBL (WMD -21.67; 95% CI -29.74, -13.60; p < 0.05) was also found in RP-RAPN. Meanwhile, no significant differences were found in other outcomes.

Conclusions: RP-RARN was superior to TP-RAPN in patients undergoing RAPN in terms of OT, PLOS, and estimated blood loss. Besides these two approaches have no significant differences in PSMs or perioperative complications.
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http://dx.doi.org/10.1002/cam4.3888DOI Listing
May 2021

Slot-die coating large-area formamidinium-cesium perovskite film for efficient and stable parallel solar module.

Sci Adv 2021 Apr 30;7(18). Epub 2021 Apr 30.

Wuhan National Laboratory for Optoelectronics (WNLO), Huazhong University of Science and Technology (HUST), Wuhan 430074, China.

Perovskite solar cells have emerged as one of the most promising thin-film photovoltaic (PV) technologies and have made a strong debut in the PV field. However, they still face difficulties with up-scaling to module-level devices and long-term stability issue. Here, we report the use of a room-temperature nonvolatile Lewis base additive, diphenyl sulfoxide(DPSO), in formamidinium-cesium (FACs) perovskite precursor solution to enhance the nucleation barrier and stabilize the wet precursor film for the scalable fabrication of uniform, large-area FACs perovskite films. With a parallel-interconnected module design, the resultant solar module realized a certified quasi-stabilized efficiency of 16.63% with an active area of 20.77 cm The encapsulated modules maintained 97 and 95% of their initial efficiencies after 10,000 and 1187 hours under day/night cycling and 1-sun equivalent white-light light-emitting diode array illumination with maximum power point tracking at 50°C, respectively.
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http://dx.doi.org/10.1126/sciadv.abg3749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087413PMC
April 2021

Dynamically tunable ultra-narrowband perfect absorbers for the visible-to-infrared range based on a microcavity integrated graphene pair.

Opt Lett 2021 May;46(9):2236-2239

Dynamically tunable ultra-narrowband perfect absorbers are important to next-generation active photonic devices. A composite structure of a graphene pair and a microcavity with Bragg mirrors are proposed for this purpose. Based on the electrically controllable doping of graphene and critical coupling of the incident light, the microcavity-graphene composite structure achieves peak absorptance higher than 99.5%, a relative peak width ($\Delta \lambda /{\lambda _0}$) smaller than 1.1%, and a modulation depth larger than 92.0% throughout the visible-to-mid-infrared range, surpassing other structures in comprehensive performance. By changing the number of the dielectric pairs in the Bragg mirrors, the device can become an amplitude or a spectral modulator. The results are based on the optical constants from experiment data, including the surface conductivity of graphene with relatively low mobility, so they are more useful in practical situations.
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http://dx.doi.org/10.1364/OL.423674DOI Listing
May 2021

What do "barbarians" eat? Integrating ceramic use-wear and residue analysis in the study of food and society at the margins of Bronze Age China.

PLoS One 2021 29;16(4):e0250819. Epub 2021 Apr 29.

Department of Anthropology, Harvard University, Cambridge, MA, United States of America.

The Siwa archaeological culture (ca. 3350 and 2650 cal yr BP) has often been associated with the tribes referenced in textual sources as Qiang and Rong: prized captives commonly sacrificed by the Shang and marauding hordes who toppled the Western Zhou dynasty. In early Chinese writings, food plays a key role in accentuating the 'sino-barbarian' dichotomy believed to have taken root over 3000 years ago, with the Qiang and Rong described as nomadic pastoralists who consumed more meat than grain and knew little of proper dining etiquette. To date, however, little direct archaeological evidence has allowed us to reconstruct the diet and foodways of the groups who occupied the Loess Plateau during this pivotal period. Here we present the results of the first ceramic use-wear study performed on the Siwa ma'an jars from the site of Zhanqi, combined with the molecular and isotopic characterization of lipid residues from foodcrusts, and evidence from experimental cooking. We report molecular data indicating the preparation of meals composed of millet and ruminant dairy among the Siwa community of Zhanqi. Use-wear analysis shows that Zhanqi community members were sophisticated creators of ceramic equipment, the ma'an cooking pot, which allowed them to prepare a wide number of dishes with limited fuel. These findings support recent isotope studies at Zhanqi as well as nuance the centrality of meat in the Siwa period diet.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250819PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084173PMC
April 2021

Multiple Functions of RNA Methylation in T Cells: A Review.

Front Immunol 2021 12;12:627455. Epub 2021 Apr 12.

Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

RNA modification represents one of the most ubiquitous mechanisms of epigenetic regulation and plays an essential role in modulating cell proliferation, differentiation, fate determination, and other biological activities. At present, over 170 types of RNA modification have been discovered in messenger RNA (mRNA) and noncoding RNA (ncRNA). RNA methylation, as an abundant and widely studied epigenetic modification, is crucial for regulating various physiological or pathological states, especially immune responses. Considering the biological significance of T cells as a defense against viral infection and tumor challenge, in this review, we will summarize recent findings of how RNA methylation regulates T cell homeostasis and function, discuss the open questions in this rapidly expanding field of RNA modification, and provide the theoretical basis and potential therapeutic strategies involving targeting of RNA methylation to orchestrate beneficial T cell immune responses.
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http://dx.doi.org/10.3389/fimmu.2021.627455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071866PMC
April 2021

Altered Heart Rate Variability in Patients With Schizophrenia During an Autonomic Nervous Test.

Front Psychiatry 2021 30;12:626991. Epub 2021 Mar 30.

Department of Biomedical Engineering, School of Material Science and Engineering, South China University of Technology, Guangzhou, China.

Reduced heart rate variability (HRV) and dysfunction of the autonomic nervous system (ANS) have been observed in schizophrenia patients. HRV parameters of schizophrenia patients in the resting state have been well-documented; however, these parameters of schizophrenia patients who experience continuous psychophysiological stress remain unclear. The objective of this study was to systematically explore the linear and nonlinear HRV parameters between schizophrenia patients and normal controls and to detect the adaptive capabilities of HRV of schizophrenia patients during the stimulation tests of autonomic nervous system. Forty-five schizophrenia patients and forty-five normal controls, matched for age, sex and body mass index, completed a 14 min ANS test. Thirteen linear and nonlinear HRV parameters of all subjects under the ANS test were computed and statistically analyzed between groups and between sessions. The STROBE checklist was adhered to in this study. All time-domain HRV features in the ANS test were significantly different between schizophrenia patients and normal controls ( < 0.01). The schizophrenia patients showed significantly low values in the Poincaré indices, which revealed significantly decreased heart rate fluctuation complexity compared with that of normal controls ( < 0.001). In addition, the normal controls, not schizophrenia patients, showed significant differences between the recovery and stress states in the parameters of low frequency, high frequency, and nonlinear dynamics. Schizophrenia patients showed autonomic dysfunction of the heart in a series of stimulation tests of the autonomic nervous system and could not regain normal physiological functions after stress cessation. Our findings revealed that the dynamic parameters of HRV in psychophysiological stress are sensitive and practical for a diagnosis of schizophrenia.
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http://dx.doi.org/10.3389/fpsyt.2021.626991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074969PMC
March 2021

Hydroxychloroquine/Chloroquine as Therapeutics for COVID-19: Truth under the Mystery.

Int J Biol Sci 2021 10;17(6):1538-1546. Epub 2021 Apr 10.

Department of Physiology, School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi Province, China, 530021.

The outbreak of coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved into a global pandemic. One major challenge in the battle against this deadly disease is to find effective therapy. Due to the availability and proven clinical record of hydroxychloroquine (HCQ) and chloroquine (CQ) in various human diseases, there have been enormous efforts in repurposing these two drugs as therapeutics for COVID-19. To date, substantial amount of work at cellular, animal models and clinical trials have been performed to verify their therapeutic potential against COVID-19. However, neither lab-based studies nor clinical trials have provided consistent and convincing evidence to support the therapeutic value of HCQ/CQ in the treatment of COVID-19. In this mini review we provide a systematic summary on this important topic and aim to reveal some truth covered by the mystery regarding the therapeutic value of HCQ/CQ in COVID-19.
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http://dx.doi.org/10.7150/ijbs.59547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071775PMC
April 2021

XPG is Modulated by miR-4715-3p and rs873601 Genotypes in Lung Cancer.

Cancer Manag Res 2021 19;13:3417-3427. Epub 2021 Apr 19.

Department of Environmental and Occupational Health, School of Public Health, Hainan Medical University, Haikou, 571199, Hainan, People's Republic of China.

Objective: (Xeroderma pigmentosum group G, ), a single strand-specific DNA endonuclease in the nucleotide excision repair pathway, has been implicated in lung cancer. Potentially functional rs873601 in is consistently associated with gastrointestinal cancer, and miR-4715-3p, targeting 3UTR of , also influences the process of gastrointestinal carcinogenesis, however, the relationships between and miR-4715-3p and rs873601 in lung cancer have not been elucidated.

Methods: A case-control study included 264 lung cancer patients and 264 cancer-free healthy controls and was designed to determine the relationships between rs873601 and lung cancer and the effect of miR-4715-3p on expression in lung cancer. Fifty matched cases and controls were randomly selected from the lung cancer and control groups to assess the relationships between the expression levels of miR-4715-3p and determined by using qRT-PCR. The association of rs873601 with lung cancer was analyzed by mass spectrometry, and function prediciton of rs873601 genotypes explored by web-based bioinformatics.

Results: miR-4715-3p in the lung cancer group was significantly increased compared with that in the control group ( = 0.011), upregulation of miR-4715-3p correlated with an increase in mRNA (r = 0.399, <0.05) in the lung cancer group. The AA genotype was associated with increased risk of lung cancer compared with the AG and GG genotypes of rs873601 (AG vs AA: OR = 0.231, 95% CI: 0.155-0.345, <0.001 GG vs AA: OR = 0.300, 95% CI: 0.131-0.719, = 0.003). The genetic association remained significant after adjustment for age, sex, smoking, and drinking, and rs873601-AA was associated with an increase in mRNA in the lung cancer group. The results of web-based bioinformatics analysis indicated rs873601 genotypes might change XPG-RNA stability and bindability between XPG and miR-4715-3p.

Conclusion: Our data characterized that miR-4715-3p and rs873601 genotypes modified expression in lung cancer. These findings may help to elucidate the mechanisms governing lung cancer.
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http://dx.doi.org/10.2147/CMAR.S294365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064622PMC
April 2021

[New insights into vascular mechanobiology: roles of matrix mechanics in regulating smooth muscle cell function].

Sheng Li Xue Bao 2021 Apr;73(2):160-174

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Vascular smooth muscle cell (vSMC) is the predominant cell type in the blood vessel wall and is constantly subjected to a complex extracellular microenvironment. Mechanical forces that are conveyed by changes in stiffness/elasticity, geometry and topology of the extracellular matrix have been indicated by experimental studies to affect the phenotype and function of vSMCs. vSMCs perceive the mechanical stimuli from matrix via specialized mechanosensors, translate these stimuli into biochemical signals controlling gene expression and activation, with the consequent modulation in controlling various aspects of SMC behaviors. Changes in vSMC behaviors may further cause disruption of vascular homeostasis and then lead to vascular remodeling. A better understanding of how SMC senses and transduces mechanical forces and how the extracellular mechano-microenvironments regulate SMC phenotype and function may contribute to the development of new therapeutics for vascular diseases.
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April 2021

Fc-GDF15 glyco-engineering and receptor binding affinity optimization for body weight regulation.

Sci Rep 2021 Apr 26;11(1):8921. Epub 2021 Apr 26.

BioMedicine Design, Pfizer Inc., 610 N Main Street, Cambridge, MA, USA.

GDF15 is a distant TGF-β family member that induces anorexia and weight loss. Due to its function, GDF15 has attracted attention as a potential therapeutic for the treatment of obesity and its associated metabolic diseases. However, the pharmacokinetic and physicochemical properties of GDF15 present several challenges for its development as a therapeutic, including a short half-life, high aggregation propensity, and protease susceptibility in serum. Here, we report the design, characterization and optimization of GDF15 in an Fc-fusion protein format with improved therapeutic properties. Using a structure-based engineering approach, we combined knob-into-hole Fc technology and N-linked glycosylation site mutagenesis for half-life extension, improved solubility and protease resistance. In addition, we identified a set of mutations at the receptor binding site of GDF15 that show increased GFRAL binding affinity and led to significant half-life extension. We also identified a single point mutation that increases p-ERK signaling activity and results in improved weight loss efficacy in vivo. Taken together, our findings allowed us to develop GDF15 in a new therapeutic format that demonstrates better efficacy and potential for improved manufacturability.
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http://dx.doi.org/10.1038/s41598-021-87959-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076310PMC
April 2021

Corrigendum to "Overexpression of soybean GmPLDγ enhances seed oil content and modulates fatty acid composition in transgenic Arabidopsis" [Plant Sci. 290 (2020) 110298].

Plant Sci 2021 Jun 31;307:110881. Epub 2021 Mar 31.

College of Life Sciences, State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.plantsci.2021.110881DOI Listing
June 2021