Publications by authors named "Zheng Chen"

1,188 Publications

  • Page 1 of 1

TNFAIP3 mutation may be associated with favorable overall survival for patients with T-cell lymphoma.

Cancer Cell Int 2021 Sep 15;21(1):490. Epub 2021 Sep 15.

Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China.

Background: T-cell lymphoma (TCL) is highly aggressive and has a poor prognosis; thus, it is worth exploring biomarkers that may predict clinical outcomes and investigate their potential role in developing targeted therapies. In this study, we characterized the mutation pattern of tumor necrosis factor-alpha-inducing protein 3 (TNFAIP3) and its role in the prognosis of TCL patients.

Methods: Coding sequence (CDS) mutations in TNFAIP3 in TCL patients was explored using exome-sequencing data from 79 patients in our center (Guangdong Provincial People's Hospital, GDPH) and 544 samples from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Additionally, non-CDS mutations in TNFAIP3 in 41 TCL patients from our center (JNU) were investigated by polymerase chain reaction (PCR) and Sanger sequencing. Furthermore, non-CDS mutations in TNFAIP3 in 47 TCL patients from Gene Expression Omnibus (GEO) dataset were explored.

Results: In the COSMIC database, TNFAIP3 mutations in TCL patients were located in the CDS, and the overall mutation frequency was 2.2%. However, TNFAIP3 mutations were not detected in the CDS of any of the samples in our center's datasets. Interestingly, non-CDS TNFAIP3 mutations were found in 14.6% and 4.3% of TCL patients in the JNU and GSE15842 dataset, respectively. Importantly, there was a clear trend showing that TCL patients with a TNFAIP3 mutation were associated with a longer 5-year restricted mean survival time (RMST) and favorable OS rate compared with those without a TNFAIP3 mutation in the JNU dataset [hazard ratio (HR) = 0.29, 95% confidence interval (CI) 0.07 to 1.31, P = 0.089]. Furthermore, TNFAIP3 mutations significantly correlated with T-cell large granular lymphocytic leukemia (T-LGLL) with a favorable prognosis in the JNU dataset (P = 0.002). Notably, the different mutation patterns of TNFAIP3 when comparing our center and the COSMIC datasets might be due to different ethnic and genetic backgrounds.

Conclusions: To the best of our knowledge, we for the first time describe that TNFAIP3 mutations in non-CDS regions are associated with favorable OS for TCL patients, which might be a potential biomarker for the prognostic stratification of Chinese TCL patients.
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http://dx.doi.org/10.1186/s12935-021-02191-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444556PMC
September 2021

Predictive role of ultrasound remission for progressive ultrasonography-detected structural damage in patients with rheumatoid arthritis.

J Investig Med 2021 Sep 13. Epub 2021 Sep 13.

Department of Ultrasound, Peking University People's Hospital, Beijing, China.

Regarding the persistence of subclinical synovitis, the concept of ultrasound remission has been proposed in addition to clinical remission. However, there have been no studies that explored the different time points of ultrasound remission to predict non-progressive structural damage. Given this, the aim of our study is to explore whether early ultrasound remission in patients with rheumatoid arthritis (RA) has predictive value for non-progressive structural damage in the subsequent 12 months. Sixty-one patients with RA were prospectively studied. Synovial hypertrophy, power Doppler (PD) signal, and bone erosions of bilateral wrists, metacarpophalangeal joints I-V, and proximal interphalangeal joints II-III were assessed by ultrasonography at baseline and at 3, 6, and 12 months. Ultrasound remission was defined as no PD signal. Clinical remission was defined as Disease Activity Score in 28 Joints <2.6. Ultrasonography-detected joint damage progression was defined as increase in bone erosion score of ≥1 in the subsequent 12 months. Baseline ultrasonographic factors were not significantly correlated with progressive ultrasonography-detected joint damage in patients with RA at 12 months (all p>0.05). Ultrasound remission at 3 and 6 months was significantly correlated with non-progressive ultrasonography-detected structural damage at 12 months (p=0.006 and p=0.004), with relatively low sensitivity and high specificity. Clinical remission at 3 months was significantly correlated with non-progression of ultrasonography-detected structural damage at 12 months (p=0.029), with relatively low sensitivity and moderate specificity. Ultrasound remission at 3 and 6 months has high specificity in predicting non-progressive structural damage in patients with RA at 12 months; however, the sensitivity is limited.
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http://dx.doi.org/10.1136/jim-2021-001885DOI Listing
September 2021

MicroRNA-21 regulate the cell apoptosis and cell proliferation of polycystic ovary syndrome (PCOS) granulosa cells through target toll like receptor TLR8.

Bioengineered 2021 Dec;12(1):5789-5796

Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai, China.

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disease characterized by polycystic ovary. The aim of the study was to assess microRNA-21 regulates granulosa cell apoptosis and proliferation in polycystic ovary syndrome through target toll-like receptor 8. Granulosa cells were collected from 30 PCOS patients and 30 normal patients with tubal or male factor infertility (control) during in vitro fertilization-Embryo Transfer (IVF-ET) and were flash frozen with liquid nitrogen for storage for subsequent use. PCOS diagnosis was based on the revised standards of the American Society of Reproductive Medicine (ASRM) and the Rotterdam criteria PCOS granulosa cells and control granulosa cells were cultured in DMEM/F12 medium containing 10% fetal bovine serum and 1% antibiotic. After this RT-PCR, Western blot assessment and Detection of apoptosis by flow cytometry were conducted. The results of qPCR showed that the mRNA and protein expression of TLR8 in PCOS granulosa cells were significantly increased compared with the normal group. The results of Western blot also showed that the expression of TLR8, IFN-γ, TNF-α and IL-12 gene protein in the transfected cells was significantly higher than that in the control cells. Here, we show that miR-21 and TLR8 significantly increased in PCOS granulosa cell as compared with normal granulosa cells, and miR-21 enhances the TLR8 mRNA translation and then promotes the IFN-γ, TNF-α, and IL-12 secretion. Our study demonstrates that miR-21/ TLR8 involved in the PCOS inflammation, it provides profound insights into pathogenesis of PCOS.
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http://dx.doi.org/10.1080/21655979.2021.1969193DOI Listing
December 2021

Predictive Tool for Closure of Ductus Arteriosus with Pharmacologic or Surgical Treatment in Preterm Infants.

Pediatr Cardiol 2021 Sep 12. Epub 2021 Sep 12.

Department of NICU, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

To construct a model with the indices obtained by echocardiography to predict whether patent ductus arteriosus (PDA) was required to be treated with pharmacologic treatment or surgical ligation, we performed a prospective observational study, including all neonates with gestational age ≤ 30 weeks and assessed the hemodynamics of PDA by serial daily echocardiography examination at postnatal age of 0-12 h, 24 h, 48 h, and 72 h, respectively. The infants were classified in two groups based on whether they were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and/or surgical ligation to close the PDA from the second week after birth. We compared the echocardiographic indices between the two groups and utilized the indices to construct a model to predict which premature infants' PDA requires intervention. The results showed that a total of forty-two preterm infants were enrolled in the study. 15 (35.7%) preterms were in the intervention group and 27 (64.3%) preterms were in the non-intervention group. Compared with the non-intervention group, the intervention group had a higher proportion of left ventricular volume overload and systemic shunt effect. In addition, the combined indicators of PDA size/weight > 3.2 mm/kg and LA/Ao > 1.4 at postnatal age of 72 h had a highest value to predict whether PDA requires intervention. These findings denoted that serial daily echocardiographic assessment can be useful in predicting whether a PDA will be closed with NSAIDs and/or surgical ligation in preterm infants with gestational age ≤ 30 weeks.Trial registration Number: IRB No. 2018-IRB-073. Date: 2018/09/21, retrospectively registered.
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http://dx.doi.org/10.1007/s00246-021-02731-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435120PMC
September 2021

68Ga-Exendin-4 PET/CT Differentiates Insulinoma From Accessory Spleen in a Patient Presenting Indeterminate MRI and 68Ga-DOTATATE PET/CT Findings.

Clin Nucl Med 2021 Sep 8. Epub 2021 Sep 8.

From the Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Hospital Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, and Xiamen Clinical Medical Center for Endocrine and Metabolic Diseases, The First Affiliated Hospital of Xiamen University, Xiamen, China.

Abstract: A 55-year-old woman with endogenous hyperinsulinemia hypoglycemia was clinically diagnosed with insulinoma. Contrast-enhanced MRI revealed an inconclusive hypointense lesion in the pancreatic tail, and the enhancement pattern does not support the diagnosis of insulinoma. 68Ga-DOTATATE PET/CT showed intense radioactivity in this nodule, similar to the radioactivity of the adjacent spleen. Therefore, the diagnosis of accessory spleen cannot be excluded. Follow-up with 68Ga-exendin-4 PET/CT also showed intense uptake in this nodule, but no significant uptake in the spleen was observed at this time. Therefore, the insulinoma was unmasked from the spleen, excluding the diagnosis of accessory spleen, and allowing curative surgery.
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http://dx.doi.org/10.1097/RLU.0000000000003895DOI Listing
September 2021

Interspecific competition by non-exoelectrogenic Citrobacter freundii An1 boosts bioelectricity generation of exoelectrogenic Shewanella oneidensis MR-1.

Biosens Bioelectron 2021 Sep 3;194:113614. Epub 2021 Sep 3.

CAS Key Laboratory of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, Fujian, 361021, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China. Electronic address:

The performance of bioelectrochemical systems (BESs) is significantly influenced by metabolic interactions within a particular microbial community. Although some studies show that interspecific metabolic cooperation benefits BESs performance, the effect of interspecific substrate competition on BESs performance has not yet been discussed. Herein, the impact of interspecific competition is investigated by monitoring the extracellular electron transfer of exoelectrogenic Shewanella oneidensis MR-1 and non-exoelectrogenic Citrobacter freundii An1 alone and simultaneously. The bacterial consortia generate the highest current of 38.4 μA cm, 6 times of that produced by the single strain S. oneidensis MR-1. Though S. oneidensis MR-1 loses out to C. freundii An1 in solution, the competition enhances the metabolic activity of S. oneidensis MR-1 on electrode, which facilitates the biofilm formation and therefore helps S. oneidensis MR-1 to gain an competitive advantage over C. freundii An1. Increased metabolic activity triggers more electrons generation and flavin secretion of S. oneidensis MR-1 which contributes to its excellent exoelectrogenic capacity. The proteomics analysis confirms that the expression of proteins related to lactate metabolism, biofilm formation, and outer membrane c-type cytochromes are significantly upregulated in S. oneidensis MR-1 from bacterial consortia.
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http://dx.doi.org/10.1016/j.bios.2021.113614DOI Listing
September 2021

Fasting plasma glucose and glucose fluctuation are associated with COVID-19 prognosis regardless of pre-existing diabetes.

Diabetes Res Clin Pract 2021 Sep 6;180:109041. Epub 2021 Sep 6.

Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 401120, People's Republic of China. Electronic address:

Aims: We aimed to investigate the role of Fasting Plasma Glucose (FPG) and glucose fluctuation in the prognosis of COVID-19 patients stratified by pre-existing diabetes.

Methods: The associations of FPG and glucose fluctuation indexes with prognosis of COVID-19 in 2,642 patients were investigated by multivariate Cox regression analysis. The primary outcome was in-hospital mortality; the secondary outcome was disease progression. The longitudinal changes of FPG over time were analyzed by the latent growth curve model in COVID-19 patients stratified by diabetes and severity of COVID-19.

Results: We found FPG as an independent prognostic factor of overall survival after adjustment for age, sex, diabetes and severity of COVID-19 at admission (HR: 1.15, 95% CI: 1.06-1.25, P = 1.02 × 10). Multivariate logistic regression analysis indicated that the standard deviation of blood glucose (SDBG) and largest amplitude of glycemic excursions (LAGE) were also independent risk factors of COVID-19 progression (P = 0.03 and 0.04, respectively). The growth trajectory of FPG over the first 3 days of hospitalization was steeper in patients with critical COVID-19 in comparison to moderate patients.

Conclusions: Hyperglycemia and glucose fluctuation were adverse prognostic factors of COVID-19 regardless of pre-existing diabetes. This stresses the importance of glycemic control in addition to other therapeutic management.
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http://dx.doi.org/10.1016/j.diabres.2021.109041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420085PMC
September 2021

Autologous bone marrow-derived mesenchymal stem cells for interstitial fibrosis and tubular atrophy: a pilot study.

Ren Fail 2021 Dec;43(1):1266-1275

Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University/The Second Clinical Medicine School of Guangzhou Medical University, Guangzhou, China.

Background: Mesenchymal stem cells (MSCs)-based therapy has shown promising results for renal injury. In this study, the efficacy and safety of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating nonspecific interstitial fibrosis and tubular atrophy (IFTA) were evaluated.

Methods: From March 2011 to January 2013, 11 renal transplanted patients with IFTA were recruited. At baseline, patients were given one intra-arterial infusion of BM-MSCs; 7 days and 1 month later, another two intravenous infusions of cells were followed. Serum creatinine, creatinine clearance rate, and serum cystatin-C at baseline and 7 days, 1 month, 3 months, 6 months, and 12 months after the intra-arterial infusion of BM-MSCs were used to assess renal function. At baseline and 6 months, histological examination based on hematoxylin-eosin, Masson's trichrome and periodic acid-Schiff staining and immunohistochemistry for transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) was performed. Adverse events were recorded to evaluate the safety of BM-MSCs treatment.

Results: At 12 months, the renal function of 6 patients (54.5%) was improved, 3 (27.3%) were stable and 2 (18.2%) were worsened. At 6 months, the mean IFTA scores of all participators were similar with the baseline (1.73 ± 0.41 vs.1.50 ± 0.0.77,  = 0.242); however, it was significantly decreased when only 6 patients with improved renal function were analyzed (1.67 ± 0.41 vs. 1.08 ± 0.20,  = 0.013). Besides, decreased expression of TGF-β1 and CTGF were also observed at 6 months. During 1 year follow-up period, only two minor complications including infection and allergy were observed.

Conclusion: Our results demonstrated that autologous BM-MSCs are safe and beneficial for IFTA patients. : MSCs: mesenchymal stem cells; BM-MSCs: marrow-derived mesenchymal stem cells; IFTA: interstitial fibrosis and tubular atrophy; CAN: chronic allograft nephropathy; CNIs: calcineurin inhibitors; Scr: serum creatinine; CCr: creatinine clearance rate; Cys-C: cystatin-C; TGF-β1: transforming growth factor β1; CTGF: connective tissue growth factor.
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http://dx.doi.org/10.1080/0886022X.2021.1968432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425735PMC
December 2021

Identification of Key mRNAs as Prediction Models for Early Metastasis of Pancreatic Cancer Based on LASSO.

Front Bioeng Biotechnol 2021 17;9:701039. Epub 2021 Aug 17.

Department of Information and Electronic Engineering, Zhejiang University of Science and Technology, Hangzhou, China.

Pancreatic cancer is a highly malignant and metastatic tumor of the digestive system. Even after surgical removal of the tumor, most patients are still at risk of metastasis. Therefore, screening for metastatic biomarkers can identify precise therapeutic intervention targets. In this study, we analyzed 96 pancreatic cancer samples from The Cancer Genome Atlas (TCGA) without metastasis or with metastasis after R0 resection. We also retrieved data from metastatic pancreatic cancer cell lines from Gene Expression Omnibus (GEO), as well as collected sequencing data from our own cell lines, BxPC-3 and BxPC-3-M8. Finally, we analyzed the expression of metastasis-related genes in different datasets by the Limma and edgeR packages in R software, and enrichment analysis of differential gene expression was used to gain insight into the mechanism of pancreatic cancer metastasis. Our analysis identified six genes as risk factors for predicting metastatic status by LASSO regression, including . We used these six EMT-related genes to construct a risk-scoring model. The receiver operating characteristic (ROC) curve showed that the risk score could better predict the risk of metastasis. Univariate and multivariate Cox regression analyses revealed that the risk score was also an important predictor of pancreatic cancer. In conclusion, 6-mRNA expression is a potentially valuable method for predicting pancreatic cancer metastasis, assessing clinical outcomes, and facilitating future personalized treatment for patients with ductal adenocarcinoma of the pancreas (PDAC).
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http://dx.doi.org/10.3389/fbioe.2021.701039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415976PMC
August 2021

Critical Thickness in Superconducting LaAlO_{3}/KTaO_{3}(111) Heterostructures.

Phys Rev Lett 2021 Aug;127(8):086804

Interdisciplinary Center for Quantum Information, State Key Laboratory of Modern Optical Instrumentation, and Zhejiang Province Key Laboratory of Quantum Technology and Device, Department of Physics, Zhejiang University, Hangzhou 310027, China.

Recently, two-dimensional superconductivity was discovered at the oxide interface between KTaO_{3} and LaAlO_{3} (or EuO), whose superconducting transition temperature T_{c} is up to 2.2 K and exhibits strong crystalline-orientation dependence. However, the origin of the interfacial electron gas, which becomes superconducting at low temperatures, remains elusive. Taking the LaAlO_{3}/KTaO_{3}(111) interface as an example, we have demonstrated that there exists a critical LaAlO_{3} thickness of ∼3  nm. Namely, a thinner LaAlO_{3} film will give rise to an insulating but not conducting (or superconducting) interface. By in situ transport measurements during growth, we have also revealed that the critical thickness can be suppressed if exposure to oxygen is avoided. These observations, together with other control experiments, suggest strongly that the origination of the electron gas is dominated by the electron transfer that is from oxygen vacancies in the LaAlO_{3} film to the KTaO_{3} substrate.
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http://dx.doi.org/10.1103/PhysRevLett.127.086804DOI Listing
August 2021

Multiprincipal Component P2-Na(TiMnCoNiRu)O as a High-Rate Cathode for Sodium-Ion Batteries.

JACS Au 2021 Jan 15;1(1):98-107. Epub 2020 Dec 15.

The Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 771 Ferst Drive, Atlanta, Georgia 30332-0245, United States.

Mixing transition metal cations in nearly equiatomic proportions in layered oxide cathode materials is a new strategy for improving the performances of Na-ion batteries. The mixing of cations not only offers entropic stabilization of the crystal structure but also benefits the diffusion of Na ions with tuned diffusion activation energy barriers. In light of this strategy, a high-rate Na(TiMnCoNiRu)O cathode was designed, synthesized, and investigated, combining graph-based deep learning calculations and complementary experimental characterizations. This new cathode material delivers high discharge capacities of 164 mA g at 0.1 C and 68 mAh g at a very high rate of 86 C, demonstrating an outstanding high rate capability. and synchrotron X-ray diffraction were used to reveal the detailed structural evolution of the cathode upon cycling. Using the climbing-image nudged elastic-band calculation and Ab initio molecular dynamics simulations, we show that the optimal transition metal composition enables a percolating network of low barrier pathways for fast, macroscopic Na diffusion, resulting in the observed high rate performance.
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http://dx.doi.org/10.1021/jacsau.0c00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395632PMC
January 2021

Br-Doped CuO Multilamellar Mesoporous Nanosheets with Oxygen Vacancies and Cetyltrimethyl Ammonium Cations Adsorption for Optimizing Intermediate Species and Their Adsorption Behaviors toward CO Electroreduction to Ethanol with a High Faradaic Efficiency.

Inorg Chem 2021 Sep 30;60(18):14371-14381. Epub 2021 Aug 30.

Anhui Laboratory of Molecule-Based Materials (State Key Laboratory Cultivation Base), The Key Laboratory of Functional Molecular Solids, Ministry of Education, Key Laboratory of Electrochemical Clean Energy of Anhui Higher Education Institutes, College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, P. R. China.

It is a prospective tactic to actualize the carbon cycle via CO electroreduction reaction (COER) into ethanol, where the crucial point is to design highly active and selective electrocatalysts. In this work, Br-doped CuO multilamellar mesoporous nanosheets with oxygen vacancies and cetyltrimethyl ammonium (CTA) cations adsorption were synthesized on Cu foam by one-step liquid-phase method at room temperature. The nanosheets with numerous mesopores and rough edges provided abundant active sites for the adsorption of CO molecules and brought about a long retention time for intermediates. The dopant of Br ions induced copious oxygen vacancies on CuO lattices, thereby reducing the activation energy of CO molecules and optimizing intermediate species and their adsorption behaviors, while adsorbed CTA cations modulated the O affinity of the Cu sites, favoring *OCHCH intermediate converting to ethanol. The optimized Br-CuO can effectively catalyze COER to CHOH in 0.1 M KHCO. The faradaic efficiency of CHOH reached 53.3% with the partial current density of 7.1 mA cm at a low potential of -0.6 V. In addition, after 14 h COER test at -0.6 V, the current density and faradaic efficiency of CHOH on Br-CuO retained 99.6 and 93.9% of their original values, respectively, indicating its prominent catalytic stability. This work provided a novel strategy for designing a CuO catalyst by nonmetal doping and long-chain organic molecules adsorption with multiple active sites for optimizing intermediate species and their adsorption behaviors toward COER to ethanol.
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http://dx.doi.org/10.1021/acs.inorgchem.1c02102DOI Listing
September 2021

Probiotics Alleviated Nonalcoholic Fatty Liver Disease in High-Fat Diet-Fed Rats via Gut Microbiota/FXR/FGF15 Signaling Pathway.

J Immunol Res 2021 17;2021:2264737. Epub 2021 Aug 17.

Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006 Zhejiang, China.

Gut microbiota (GM) dysbiosis and bile acid (BA) metabolism disorder play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Probiotics had a beneficial effect on NAFLD, but further study is needed to explore probiotics as a potential therapeutic agent to NAFLD. The aim of this study was to investigate the regulatory effect of probiotics on gut microbiota in NAFLD rats and to explore the possible mechanism of probiotics regulating the bile acid receptor farnesoid X receptor/growth factor 15 (FXR/FGF15) signaling pathway in rats. We established a rat model of NAFLD fed with a high-fat diet (HFD) for 14 weeks, which was given different interventions (312 mg/kg/day probiotics or 10 mg/kg/day atorvastatin) from the 7 week. Serum lipids and total bile acids (TBA) were biochemically determined; hepatic steatosis and lipid accumulation were evaluated with HE staining. The expression levels of FXR, FGF15 mRNA, and protein in rat liver were detected. 16S rDNA was used to detect the changes of gut microbiota in rats. Compared with the HFD group, probiotics and atorvastatin significantly reduced serum lipids and TBA levels. And probiotics increased dramatically the expression of FXR, FGF15 mRNA, and protein in the liver. But there were no significant changes in the atorvastatin group. Probiotics and atorvastatin can upregulate the diversity of gut microbiota and downregulate the abundance of pathogenic bacteria in NAFLD model rats. In summary, probiotics alleviated NAFLD in HFD rats via the gut microbiota/FXR/FGF15 signaling pathway.
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http://dx.doi.org/10.1155/2021/2264737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387197PMC
August 2021

A Flexible Semi-Interpenetrating Network-Enhanced Ionogel Polymer Electrolyte for Highly Stable and Safe Lithium Metal Batteries.

ACS Appl Mater Interfaces 2021 Sep 26;13(35):41946-41955. Epub 2021 Aug 26.

College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China.

An ionogel polymer electrolyte (IGPE), which combines the merits of high ionic conductivity and excellent safety property of a liquid electrolyte and a solid electrolyte, respectively, has shown great prospects in the application of a new generation of lithium secondary batteries. However, the increase in the ionic conductivity of IGPE will inevitably be at the expense of reduced mechanical strength, and this dilemma limits its application and market promotion. Here, an IGPE with a semi-interpenetrating cross-linked network structure was synthesized by UV-cross-linking to tackle this plight. The optimal sample ME82 shows an excellent ionic conductivity of 1.19 mS cm at room temperature and robust mechanical strength (breaking strength: 1.55 MPa, elongation at break: 259%). Therefore, the assembled LiFePO/ME82/Li cion cell displays an outstanding initial specific discharge capacity of 160.9 mAh g at 55 °C 0.5 C, with a capacity retention of 94.00% after 200 cycles. In addition, ME82-based flexible batteries can withstand bending, folding, and even shearing abuse, which indicates that ME82 has application potentials in flexible electronic devices.
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http://dx.doi.org/10.1021/acsami.1c07745DOI Listing
September 2021

The Impacts of Regional Regulatory Policies on the Prevention and Control of Chronic Diseases in China: A Mediation Analysis.

Healthcare (Basel) 2021 Aug 18;9(8). Epub 2021 Aug 18.

Research Institute of Health Development Strategies, Fudan University, Shanghai 200032, China.

Regional regulatory policies (RPs) are a major factor in the prevention and control of chronic diseases (PCCDs) through the implementation of various measures. This study aimed to explore the impacts of RPs on PCCDs, with a focus on the mediating roles of community service. The soundness of the regulatory mechanism (SORM) was used to measure the soundness of RPs based on 1095 policy documents (updated as of 2015). Coverage provided by community service institutions (CSIs) and community health centres (CHCs) was used to represent community service coverage derived from the China Statistical Yearbook (2015), while the number of chronic diseases (NCDs) was used to measure the effects of PCCDs based on data taken from the 2015 China Health and Retirement Longitudinal Study survey. To assess the relationship between SORM, NCDs and community service, a negative binomial regression model and mediation analysis with bootstrapping were conducted. Results revealed that there was a negative correlation between SORM and NCDs. CSIs had a major effect on the relationship between RPs and PCCDs, while CHCs had a partial mediating effect. RPs can effectively prevent and control chronic diseases. Increased effort should also be aimed at strengthening the roles of CSIs and CHCs.
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http://dx.doi.org/10.3390/healthcare9081058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392473PMC
August 2021

Gender differences in screening self-reported psychotic symptoms in a first help-seeking population.

Arch Womens Ment Health 2021 Aug 21. Epub 2021 Aug 21.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 Wanping Nan Road, Shanghai, 200030, People's Republic of China.

Gender differences in the frequency and severity of psychotic symptoms have been widely reported. However, in the screening process for the detection of early psychosis, gender differences were largely overlooked in China. This study investigated gender differences in self-reported psychotic symptoms in a clinical population who initially visited a mental health service. In total, 1931 consecutive new patients were included in the current analysis, with a mean age of 25.3 years, including 852 (44.1%) men and 1079 (55.9%) women, of whom 388 (20.1%) had psychotic disorders and 1543 (79.9%) had non-psychotic disorders. Psychotic symptoms were assessed using the PRIME Screen-Revised (PS-R) questionnaire. The cohort was grouped according to gender, age (adolescents ≤ 21 years, adults > 21 years), and clinical diagnosis. Within the full sample, gender differences in psychotic symptoms were not significant, except that females appeared to have more severe symptoms of disorganized communication than males. However, gender differences began to appear at subgroup levels, after stratification by age and diagnosis. Female adolescents reported more severe psychotic symptoms than male adolescents, especially in the symptom of perceptual abnormalities, which refer to hallucinations. Different patterns and predictors were found to significantly discriminate between psychotic and non-psychotic disorders among age and gender groups. Our study highlights gender differences in the severity, frequency, and pattern of self-reported psychotic symptoms when screening in a first help-seeking population. Therefore, gender differences should be considered during psychotic symptoms screening.
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http://dx.doi.org/10.1007/s00737-021-01170-zDOI Listing
August 2021

Organic Semiconductor Crystal Engineering for High-Resolution Layer-Controlled 2D Crystal Arrays.

Adv Mater 2021 Aug 20:e2104166. Epub 2021 Aug 20.

Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin University & Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, 300072, China.

2D organic semiconductor crystals (2DOSCs) have extraordinary charge transport capability, adjustable photoelectric properties, and superior flexibility, and have stimulated continuous research interest for next-generation electronic and optoelectronic applications. The prerequisite for achieving large-area and high-throughput optoelectronic device integration is to fabricate high-resolution 2DOSC arrays. Patterned substrate- and template-assisted self-assembly is an effective strategy to fabricate OSC arrays. However, the film thickness is difficult to control due to the complicated crystallization process during solvent evaporation. Therefore, the manufacturing of 2DOSC arrays with high-resolution and controllable molecular-layer numbers through solution-based patterning methods remains a challenge. Herein, a two-step strategy to produce high-resolution layer-controlled 2DOSC arrays is reported. First, large-scale 2DOSCs with well-defined layer numbers are obtained by a solution-processed organic semiconductor crystal engineering method. Next, the high-resolution layer-controlled 2DOSC arrays are fabricated by a polydimethylsiloxane mold-assisted selective contact evaporation printing technique. The organic field-effect transistors (OFETs) based on 2DOSC arrays have high electrical performance and excellent uniformity. The 2,6-bis(4-hexylphenyl)anthracene 2DOSC arrays-based OFETs have a small variation of 12.5% in mobility. This strategy can be applied to various organic semiconductors and pattern arrays. These demonstrations will offer more opportunities for 2DOSCs for integrated optoelectronic devices.
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http://dx.doi.org/10.1002/adma.202104166DOI Listing
August 2021

miR-141-3p inhibits the activation of astrocytes and the release of inflammatory cytokines in bacterial meningitis through down-regulating HMGB1.

Brain Res 2021 Nov 14;1770:147611. Epub 2021 Aug 14.

Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address:

Background: Bacterial meningitis (BM) is a serious infectious disease of the central nervous system that often occurs in children and adolescents. Many studies have suggested that microRNAs (miRNAs) are involved in BM. This study aimed to address the effects of miR-141-3p on astrocyte activation and inflammatory response in BM through HMGB1.

Methods: The 3-week-old rats were injected with Streptococcus pneumoniae (SP) into the lateral ventricle to establish a BM model. Loeffler scoring method was used to evaluate the recovery of neurological function. Brain pathological damage was observed by hematoxylin and eosin (H&E) staining. Primary astrocytes were isolated from brain tissues of BM or non-infected SD rats. The levels of TNF-α, IL-1β, and IL-6 in brain tissues and astrocyte culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The targeting relationship between miR-141-3p and HMGB1 was tested using dual-luciferase reporter assay. The expression of miR-141-3p, HMGB1, and the astrocytic marker glial fibrillary acidic protein (GFAP) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blotting. Methylation-specific PCR (MSP) analysis was performed to measure the methylation status of miR-141 promoter.

Results: The results showed that lower Loeffler scores were exhibited in rats with BM. The subarachnoid space of brain tissues of BM rats was widened, and obvious inflammatory cells were observed. miR-141-3p expression was reduced in BM rats and SP-treated astrocytes. Additionally, we found that overexpression of miR-141-3p led to the downregulation of HMGB1, GFAP, and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in astrocytes. Furthermore, the results of dual-luciferase reporter assay confirmed that miR-141-3p directly targeted HMGB1. Overexpression of miR-141-3p inhibited the levels of GFAP, TNF-α, IL-1β, and IL-6 in astrocytes, which was eliminated by the up-regulation of HMGB1. The results of MSP analysis indicated that miR-141 promoter was highly methylated in brain tissues and astrocytes. DNMT1 was involved in the methylation of miR-141 promoter in BM.

Conclusion: The present study verified that miR-141-3p affected inflammatory response by suppressing HMGB1 in SP-induced astrocytes and BM rat model.
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http://dx.doi.org/10.1016/j.brainres.2021.147611DOI Listing
November 2021

Anion-exchange-mediated internal electric field for boosting photogenerated carrier separation and utilization.

Nat Commun 2021 Aug 16;12(1):4952. Epub 2021 Aug 16.

Department of Chemistry, Tsinghua University, Beijing, China.

Heterojunctions modulated internal electric field (IEF) usually result in suboptimal efficiencies in carrier separation and utilization because of the narrow IEF distribution and long migration paths of photocarriers. In this work, we report distinctive bismuth oxyhydroxide compound nanorods (denoted as BOH NRs) featuring surface-exposed open channels and a simple chemical composition; by simply modifying the bulk anion layers to overcome the limitations of heterojunctions, the bulk IEF could be readily modulated. Benefiting from the unique crystal structure and the localization of valence electrons, the bulk IEF intensity increases with the atomic number of introduced halide anions. Therefore, A low exchange ratio (~10%) with halide anions (I, Br, Cl) gives rise to a prominent elevation in carrier separation efficiency and better photocatalytic performance for benzylamine coupling oxidation. Here, our work offers new insights into the design and optimization of semiconductor photocatalysts.
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http://dx.doi.org/10.1038/s41467-021-25261-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368037PMC
August 2021

TRIM44 links the UPS to SQSTM1/p62-dependent aggrephagy and removing misfolded proteins.

Autophagy 2021 Aug 12:1-16. Epub 2021 Aug 12.

Center for Stem Cell and Regenerative Disease, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), the University of Texas-Health Science Center at Houston, Houston, Texas, USA.

Until recently, the ubiquitin-proteasome system (UPS) and macroautophagy/autophagy were considered to be two independent systems that target proteins for degradation by proteasomes or via lysosomes, respectively. Here, we report that TRIM44 (tripartite motif containing 44) is a novel link that connects the UPS system with the autophagy degradation pathway. Suppressing the UPS degradation pathway leads to TRIM44 upregulation, which further promotes aggregated protein clearance through the binding of K48 ubiquitin chains on proteins. TRIM44 expression activates autophagy via promoting SQSTM1/p62 oligomerization, which rapidly increases the rate of aggregate protein removal. Overall, our data reveal that TRIM44 is a newly identified link between the UPS system and the autophagy pathway. Delineating the cross-talk between these two degradation pathways may reveal new mechanisms of targeting aggregate-prone diseases, such as cancer and neurodegenerative disease.: 3-MA: 3-methyladenine; ACTB: actin beta; ATG5: autophagy related 5; BB: B-box domain; BECN1: beclin1; BM: bone marrow; CC: coiled-coil domain; CFTR: cystic fibrosis transmembrane conductance regulator; CON: control; CQ: chloroquine; DOX: doxycycline; DSP: dithiobis(succinimidly propionate); ER: endoplasmic reticulum; FI: fluorescence intensity; FL: full length; HIF1A/HIF-1#x3B1;: hypoxia inducible factor 1 subunit alpha; HSC: hematopoietic stem cells; HTT: huntingtin; KD: knockdown; KD-CON: knockdown construct control; MM: multiple myeloma; MTOR: mechanistic target of rapamycin kinase; NP-40: nonidet P-40; NFE2L2/NRF2: nuclear factor, erythroid 2 like 2; OE: overexpression; OE-CON: overexpression construct control; PARP: poly (ADP-ribose) polymerase; SDS: sodium dodecyl sulfate; SQSTM1/p62: sequestosome 1; Tet-on: tetracycline; TRIM44: tripartite motif containing 44; UPS: ubiquitin-proteasome system; ZF: zinc-finger.
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http://dx.doi.org/10.1080/15548627.2021.1956105DOI Listing
August 2021

[Protective effects of total saponins of on ulcerative colitis induced by TNBS in rats and its mechanism].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2021 Jul;37(4):397-401

Pharmacy Collage of Gansu University of Chinese Medicine, Lanzhou 730000.

To study the protective effects and mechanisms of total saponins of (TSC) on ulcerative colitis in rats. Fifty male Wistar rats were randomly divided into 5 groups: control group, model group, salazosulfadiazine (SASP) positive control group (0.3 g/kg), TSC high- and low-dose experimental groups(1.2, 0.4 g/kg). UC rat model was established by trinitrobenzene sulfonic acid (TNBS)/ ethanol enema. After administration for 21 days, the rats' symptoms and signs, disease activity index (DAI), colonic mucosal injury index (CMDI) and colonic tissue morphology were observed. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α) in colon tissues were determined. Protein expression of nuclear nuclear transcription factor-κB (NF-κB) in colon tissues was detected. Finally, the effect of TCS therapy was evaluated. Compared with the control group, the DAI and CMDI scores of the rats in the model group were increased significantly, meanwhile the colonic mucosa was seriously damaged, indicating that the model was successful. Compared with the model group, the TSC high and low dose groups could significantly reduce the DAI and CMDI score (<0.05) and improve the colonic mucosa form. TSC also could increase the SOD activity and decrease MDA content in colon tissues(<0.05), while inhibit the levels of IL-6 and TNF-α mRNA in the colon tissues and promote the expression of IL-10 mRNA (<0.01). At the same time, TSC reduced the expressions of NF-κB protein in the colon (<0.01). The TSC high-dose group was superior to the low-dose group (<0.05). TSC has significant protective effects on ulcerative colonic mucosal damage in UC rats, and there is a dose-dependent relationship; its mechanism may be related to anti-lipid peroxidation and inhibiting the NF-κB signaling pathway to regulate the release of inflammatory factors.
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http://dx.doi.org/10.12047/j.cjap.6051.2021.032DOI Listing
July 2021

Effects of the Clock Modulator Nobiletin on Circadian Rhythms and Pathophysiology in Female Mice of an Alzheimer's Disease Model.

Biomolecules 2021 07 9;11(7). Epub 2021 Jul 9.

Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder and the most common cause of dementia. Various pathogenic mechanisms have been proposed to contribute to disease progression, and recent research provided evidence linking dysregulated circadian rhythms/sleep and energy metabolism with AD. Previously, we found that the natural compound Nobiletin (NOB) can directly activate circadian cellular oscillators to promote metabolic health in disease models and healthy aging in naturally aged mice. In the current study, using the amyloid-β AD model APP/PS1, we investigated circadian, metabolic and amyloid characteristics of female mice and the effects of NOB. Female APP/PS1 mice showed reduced sleep bout duration, and NOB treatment exhibited a trend to improve it. While glucose tolerance was unchanged, female APP/PS1 mice displayed exaggerated oxygen consumption and CO2 production, which was mitigated by NOB. Likewise, cold tolerance in APP/PS1 was impaired relative to WT, and interestingly was markedly enhanced in NOB-treated APP/PS1 mice. Although circadian behavioral rhythms were largely unchanged, real-time qPCR analysis revealed altered expression of several core clock genes by NOB in the cerebral cortex, notably , , and . Moreover, NOB was also able to activate various clock-controlled metabolic genes involved in insulin signaling and mitochondrial function, including , , , , , and . Finally, we observed that NOB attenuated the expression of several AD related genes including , , and , reduced APP protein levels, and strongly ameliorated Aβ pathology in the cortex. Collectively, these results reveal novel genotype differences and importantly beneficial effects of a natural clock-enhancing compound in biological rhythms and related pathophysiology, suggesting the circadian clock as a modifiable target for AD.
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http://dx.doi.org/10.3390/biom11071004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301787PMC
July 2021

Scutellarein induces apoptosis and inhibits proliferation, migration, and invasion in ovarian cancer via inhibition of EZH2/FOXO1 signaling.

J Biochem Mol Toxicol 2021 Aug 5:e22870. Epub 2021 Aug 5.

Department of Obstetrics and Gynecology, Shanghai Fourth People's Hospital, Tongji University, Shanghai, China.

Scutellarein, a flavone found in the perennial herb Scutellaria baicalensis, has antitumorigenic activity in multiple human cancers. However, whether scutellarein can attenuate ovarian cancer (OC) is unclear. This study investigated the effects of scutellarein in OC. In vitro cell viability was assessed using MTT assay whereas proliferation was assessed using 5-ethynyl-2'-deoxyuridine and colony formation assays. Cell apoptosis was detected by an Annexin V-fluorescein isothiocyanate/propidium iodide assay. Wound-healing and Transwell assays were used to determine cell migration and invasion. The differential expression of enhancer of zeste homolog 2 (EZH2) and forkhead box protein O1 (FOXO1) was measured by Quantitative real-time PCR and western blot analysis. We found that scutellarein inhibited viability, migration, invasion of A2780 and SKOV-3 cells, and reduced the expression of EZH2 in OC cells. In addition, FOXO1 was downregulated in OC tissues and cells and negatively regulated by EZH2. Also, scutellarein inhibited tumor growth and metastasis in vivo. In conclusion, scutellarein alleviates OC by the regulation of EZH2/FOXO1 signaling.
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http://dx.doi.org/10.1002/jbt.22870DOI Listing
August 2021

Effects of sap (Sangre de Drago) on AGEs formation, LDL oxidation and oxidative stress related to vascular diseases.

Nat Prod Res 2021 Aug 2:1-5. Epub 2021 Aug 2.

Department of Pharmaceutical and Pharmacological Sciences (DSF), University of Padova, Padova, Italy.

The sap of Müll. Arg. (Euphorbiaceae) is well-known in South American traditional medicine. This research investigated its activity against glycation and oxidative stress (glycoxidation) to estimate its usefulness in ROS-related diseases. The activity of the sap on albumin glycation, LDL oxidation and ROS formation was detected. sap inhibited BSA glycation and exhibited a protective effect against LDL oxidation; at the concentration of 0.8 µg/mL, it extended the Lag phase of almost 60%. Furthermore, the sap was studied on cell viability and ROS production in HUVEC showing valuable free-radical scavenging activity. In detail, the sap (1.0 and 10.0 μg/mL) significantly decreased the baseline level and HO-induced ROS production in HUVEC. This research showed for the first time the ability of sap to decrease the albumin glycation, LDL oxidation and ROS formation in HUVEC, supporting its potential in vascular diseases.
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http://dx.doi.org/10.1080/14786419.2021.1960520DOI Listing
August 2021

Effects of customized resin base on bonding strength of spherical self-ligating brackets.

J Orofac Orthop 2021 Jul 26. Epub 2021 Jul 26.

Department of Orthodontics, Hubei-MOST KLOS & KLOBM, School and Hospital of Stomatology, Wuhan University, Luoyu Road 237, 430079, Hongshan District, Wuhan, Hubei, People's Republic of China.

Purpose: Fabricating resin bases has become an easy and economical method to achieve the customization of brackets. This study aimed to assess the effect of the resin base on bonding strength of spherical self-ligating brackets.

Methods: A defined amount of adhesive was bonded to the bracket base and constituted the new resin base. The thickness of the adhesive was measured and controlled at 0.5, 1.0, 1.5 and 2.0 mm, and a group without a resin base was used as a control. Sixty extracted human premolars were randomly divided into five groups. The brackets in each group were bonded to the specimen, and debonding tests were conducted. The shear bond strength (SBS) was calculated according to the measured debonding force in relation to the base area. The adhesive remnant index (ARI) score and the residual location of the fractured resin base were recorded. Enamel damage was also analyzed by scanning electron microscopy. After assessing for data normality and homogeneity, statistical comparisons between the groups and correlations among parameters were determined. P < 0.05 was regarded as significant.

Results: The correlation analysis revealed an inverse correlation between the resin base thickness and the SBS (Coeff = -0.719, P < 0.01). The highest SBS was 9.33 MPa, in the control group, which was significantly greater than the lowest SBS (6.03 MPa), in the 2.0-mm group (P < 0.05). Multiple comparisons analysis revealed no differences in SBS between the 1.0-, 1.5- and 2.0-mm groups. Nonparametric analysis found that only the ARI score in the 0.5-mm group (2.92) was significantly different (P < 0.05) from that in the control group (1.25). As the thickness of the resin base increased, the fractured resin base tended to remain at the bracket base, and the risk of enamel damage decreased.

Conclusions: As the thickness of the resin base increased, the bonding strength of the spherical bracket decreased. However, the required clinical bonding strength was still satisfied when the thickness was less than 2.0 mm. The existence of a resin base could protect the enamel surface from damage caused by debonding. The customization of spherical brackets by tailoring a resin base can be applied in clinical practice because of the clinically acceptable bonding strength.
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http://dx.doi.org/10.1007/s00056-021-00329-8DOI Listing
July 2021

Genetics and Functional Mechanisms of STAT3 Polymorphisms in Human Tuberculosis.

Front Cell Infect Microbiol 2021 7;11:669394. Epub 2021 Jul 7.

Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Institute for Advanced Study, Tongji University School of Medicine, Shanghai, China.

Signal transducer and activator of transcription-3 (STAT3) plays an important role in biological balance. Our and others previous studies implied that STAT3 had a great effect on fast-acting innate immunity against tuberculosis (TB). We hypothesized that SNP down-regulation of STAT3 leads to a change in susceptibility to TB in humans. To test this hypothesis, we investigated STAT3 SNPs using SNP scan™ technique in a case-control study of TB patients (n = 470) and HC subjects (n = 356), and then conducted functional studies of them using cellular models. We found that SNPs in STAT3 3`-UTR of rs1053004 TT and rs1053005 AA genotypes or T-A haplotype were associated with susceptibility to TB or TB severity. While the TT/AA genotype correlated with the low constitutive expression of and in PBMC, the variant of rs1053004-rs1053005 T-A haplotype indeed reduced expression in reporter assays. Interestingly, host PBMC expressing the rs1053005 AA genotype and low constitutive exhibited the reduced ability to mount fast-acting innate immunity against mycobacterial infection in cellular models. Finally, mechanistic experiments showed that the STAT3 down-regulation broadly depressed STAT3 downstream anti-mycobacterial activities involving VDR-related CAMP pathway as well as IL-32, iNOS and autophagy mechanisms, leading to an enhanced mycobacterial infection. The findings of this study suggest that low constitutive stat3 derived from the TT/AA genotype/T-A haplotype acts to down-regulate STAT3, depressing multiple anti-mycobacterial pathways/mechanisms downstream, which leads to an enhanced mycobacterial infection or TB in high-risk individuals.
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http://dx.doi.org/10.3389/fcimb.2021.669394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294188PMC
July 2021

Enhancement of Resistance Against Dehydration-Induced Leaf Senescence via Metabolite/Phytohormone-Gene Regulatory Networks Modulated by Melatonin.

Front Plant Sci 2021 6;12:686062. Epub 2021 Jul 6.

College of Tobacco Science, Henan Agricultural University, Zhengzhou, China.

Melatonin (MEL) is a pleiotropic agent with crucial functions reported in a variety of stress responses and developmental processes. Although MEL involvement in plant defense against natural leaf senescence has been widely reported, the precise regulatory mechanisms by which it delays stress-induced senescence remain unclear. In this study, we found that foliar spraying of melatonin markedly ameliorated dehydration-induced leaf senescence in , accompanied by attenuated oxidative damage, expression of senescence-related genes, and reduced endogenous ABA production. Metabolite profiling indicated that melatonin-treated plants accumulated higher concentrations of sugars, sugar alcohol, and organic acids, but fewer concentrations of amino acids in the leaves, than untreated plants after exposure to dehydration. Gene expression analysis revealed that the delayed senescence of stressed plants achieved by melatonin treatment might be partially ascribed to the upregulated expression of genes involved in ROS scavenging, chlorophyll biosynthesis, photosynthesis, and carbon/nitrogen balances, and downregulated expression of senescence-associated genes. Furthermore, hormone responses showed an extensively modulated expression, complemented by carotenoid biosynthesis regulation to achieve growth acceleration in melatonin-treated plants upon exposure to dehydration stress. These findings may provide more comprehensive insights into the role of melatonin in alleviating leaf senescence and enhancing dehydration resistance.
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http://dx.doi.org/10.3389/fpls.2021.686062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291779PMC
July 2021

CD8 Tregs ameliorate inflammatory reactions in a murine model of allergic rhinitis.

Allergy Asthma Clin Immunol 2021 Jul 22;17(1):74. Epub 2021 Jul 22.

Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, No. 12 Wulumuqi Middle Road, Shanghai, 200040, China.

Background: CD8CD25fork-head box transcription factor (Foxp3) regulatory T cells (CD8 Tregs) play a role in immune tolerance. However, the role of these cells in allergic rhinitis (AR) has not been elucidated. The study aimed to evaluate influences of CD8 Tregs on inflammatory conditions in a murine model of AR.

Methods: A murine model of AR was established. CD8 Tregs were isolated from mice nasal mucosa and cultured in vitro. We examined interleukin (IL)-10 and transforming growth factor (TGF)-β in cell cultures. Then, we administered CD8 Tregs into mice nasal mucosal cultures, and examined eosinophil cation protein (ECP), IL-4, IL-5 and IL-13 in these cultures. Finally, we adoptively transferred CD8 Tregs into mice models, and evaluated percentages of CD8 Tregs, numbers of sneezing and nasal rubbing, and counts of eosinophils and contents of ECP, IL-4, IL-5, IL-13, IL-10 and TGF-β in nasal lavage fluid (NLF) in mice.

Results: The percentage of CD8 Tregs from AR mice was reduced. IL-10 and TGF-β were increased in cell cultures from AR mice. ECP, IL-4, IL-5 and IL-13 were decreased after the AR mice CD8 Tregs administration in mucosal cultures. However, their contents were not changed after normal CD8 Tregs treatment. Additionally, the adoptive transfer of AR CD8 Tregs enhanced the percentage of CD8 Tregs and levels of IL-10 and TGF-β in NLF, reduced numbers of sneezing and nasal rubbing, and counts of eosinophils and concentrations of ECP, IL-4, IL-5 and IL-13 in NLF. However, normal CD8 Tregs could not change above parameters.

Conclusion: These findings show that CD8 Tregs may inhibit inflammatory responses in the AR condition.
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http://dx.doi.org/10.1186/s13223-021-00577-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296699PMC
July 2021

Prognostic signature and immune efficacy of m A-, m C- and m A-related regulators in cutaneous melanoma.

J Cell Mol Med 2021 Sep 21;25(17):8405-8418. Epub 2021 Jul 21.

Department of Plastic Surgery of Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

Cutaneous melanoma (CM) is an aggressive cancer; given that initial and specific signs are lacking, diagnosis is often late and the prognosis is poor. RNA modification has been widely studied in tumour progression. Nevertheless, little progress has been made in the signature of N -methyladenosine (m A), 5-methylcytosine (m C), N -methyladenosine (m A)-related regulators and the tumour microenvironment (TME) cell infiltration in CM. Our study identified the characteristics of m A-, m C- and m A-related regulators based on 468 CM samples from the public database. Using univariate, multivariate and LASSO Cox regression analysis, a risk model of regulators was established and validated by a nomogram on independent prognostic factors. The gene set variation analysis (GSVA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) clarified the involved functional pathways. A combined single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT approach revealed TME of regulator-related prognostic signature. The nine-gene signature stratified the patients into distinct risk subgroups for personalized prognostic assessment. Additionally, functional enrichment, immune infiltration and immunotherapy response analysis indicated that the high-risk group was correlated with T-cell suppression, while the low-risk group was more sensitive to immunotherapy. The findings presented here contribute to our understanding of the TME molecular heterogeneity in CM. Nine m A-, m C- and m A-related regulators may also be promising biomarkers for future research.
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http://dx.doi.org/10.1111/jcmm.16800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419166PMC
September 2021

Unnecessity of Routine Dissection of Right Central Lymph Nodes in cN0 Papillary Thyroid Carcinoma Located at the Left Thyroid Lobe.

Front Oncol 2021 1;11:685708. Epub 2021 Jul 1.

Department of Thyroid and Head Neck, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

Objective: The lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) is an important part of the central lymph nodes (LNs). We aimed to explore the rate and predictors of LN-prRLN metastasis in cN0 papillary thyroid carcinoma (PTC) located at the left thyroid lobe.

Methods: Patients with surgically treated primary left lobe PTC were retrospectively enrolled. The metastatic distribution of LN-prRLN and postoperative complications were assessed. The association between LN-prRLN metastasis and clinicopathological variables was evaluated by univariate and multivariate analyses.

Results: A total of 857 patients were included for the analysis. Central LN metastasis was noted in 310 (35.3%) cases. The most (27.6%) and least (1.7%) commonly involved LNs were the left paratracheal LN and the LN-prRLN. In the univariate analysis, the tumor size, multifocality, the extent of extrathyroidal extension (none macroscopic macroscopic maximal), and perineural invasion were associated with positive LN-prRLN. In the multivariate analysis, tumor size of >40.0 mm and macroscopic maximal invasion were found as the only two independent predictors. Transient and permanent hypoparathyroidism were noted in 90 (10.2%) and 13 (1.5%) patients, respectively. Voice change was noted in 40 (4.6%) patients, and 20 patients recovered.

Conclusions: In cN0 PTC located at the left lobe, LN-prRLN metastasis was very uncommon. We found that LN-prRLN dissection is not required routinely, but should be performed if the tumor size is >40.0 mm and macroscopic maximal extrathyroidal extension is present.
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http://dx.doi.org/10.3389/fonc.2021.685708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281883PMC
July 2021
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