Publications by authors named "Ming Zhang"

3,708 Publications

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Interaction mechanism between chlorinated polyfluoroalkyl ether potassium sulfonate (F-53B) and chromium on different types of soil surfaces.

Environ Pollut 2022 Aug 5:119820. Epub 2022 Aug 5.

Department of Environmental Engineering, College of Biology and Environment, Nanjing Forestry University, Nanjing, 210037, China. Electronic address:

The coexistence of per- and polyfluoroalkyl substances (PFASs) and heavy metals have been found in soils. However, the interaction between the combined pollutants in soils remains unclear. In this study, the adsorption processes of single and combined Cr(VI) and chlorinated polyfluoroalkyl ether potassium sulfonate (F-53 B) in red, yellow and black soils were simulated. When compared with the single F-53 B and Cr(VI), the adsorption amount of the combined F-53 B and Cr(VI) on soils changed with the types of soils. The interactions between F-53 B and Cr(VI) in soils affected their adsorption behavior. The adsorption of the combined F-53 B and Cr(VI) best fit second-order kinetics and the Freundlich equation. Moreover, aluminum and iron oxides are highly correlated with adsorption of F-53 B and Cr(VI). Both F-53 B and Cr(VI) can form complexes with aluminum and iron oxides through electrostatic interactions, but PFOS could be bridged with iron oxides to form an inner sphere complex and with aluminum oxides to form an outer sphere complex. The coexistence of F-53 B and Cr(VI) could change the fluorescent group of dissolved organic matter (DOM) in soils due to the complexation between F-53 B and DOM. In addition, F-53 B increased the acid-soluble portion of Cr and decreased its residual form, which promoted the environmental risk of Cr in soils.
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http://dx.doi.org/10.1016/j.envpol.2022.119820DOI Listing
August 2022

Persistent versus transient, and conventional plastic versus biodegradable plastic? -Two key questions about microplastic-water exchange of antibiotic resistance genes.

Water Res 2022 Jul 26;222:118899. Epub 2022 Jul 26.

Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address:

The ubiquitous microplastics (MPs) in water environment play an important role in the dissemination of antibiotic resistance genes (ARGs) due to their exchange between floating MPs and receiving waters. However, whether the ARG exchange is persistent or transient and what are the differences in ARG exchange between conventional plastics and biodegradable plastics are the two key issues to be addressed. In this study, biodegradable PBAT and non-biodegradable PET MPs were chosen to explore the MP-water ARG exchange after the MPs floated to the receiving waters. The results demonstrated that the active exchange of ARGs between MPs and receiving waters occurred, which, however, were transient for most of ARGs. The relative abundance of ARGs both on the MPs and in the waters rapidly decreased to the initial or lower levels within 4 weeks. Approximately 25-50% (ARG subtype number ratio) of studied ARG subtypes were introduced into the receiving waters by MPs, and 35-65% of studied ARG subtypes went through fluctuation in terms of abundance on MPs and in the receiving water. ARGs tended to converge between MPs and the receiving waters with time. Furthermore, the ARG exchange between MPs and waters facilitated horizontal gene transfer (HGT). IntI1 and tnpA05 played the crucial roles in HGT, which was indicated by their correlated change with most ARGs; in contrast, tnpA04 showed the obvious lagging responses. The biodegradable MP of PBAT generally accumulated higher levels of most ARGs including multidrug resistant genes than the non-biodegradable MP of PET. The transient exchange of most ARGs between MPs and water implies that the on-off hitchhiking of ARGs on MPs in aquatic environment may not exert significant influence on ARG transmission. However, compared with the conventional plastics, the biodegradable MPs might pose much higher ARG dissemination risks due to the higher enrichment of ARGs particularly with people's ever-increasingly usage. Enough attention must be paid to this emerging issue.
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http://dx.doi.org/10.1016/j.watres.2022.118899DOI Listing
July 2022

New insights into the genus (Gyroporaceae, Boletales), with establishment of four new sections and description of five new species from China.

Mycology 2022 5;13(3):223-242. Epub 2022 Jul 5.

State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, Guangdong Province, China.

Species of from southern China were studied in this study. Based on morphology and molecular phylogenetic analyses of DNA sequences from the nuclear ribosomal internal transcribed spacer (ITS), the nuclear ribosomal large subunit (nrLSU), and the mitochondrial adenosine triphosphate ATP synthase subunit 6 ( was divided into four main branches in the phylogenetic tree, and four sections were firstly proposed i.e. sect. . sect. . sect. and . sect. . Five new species, i.e. and , were revealed from China, and their phylogenetic positions were also analysed. Among them, and were nested into the sect. , although morphologically similar to and , with obvious cyanescent oxidation reactions, were nested into the sect. ; and characterised by its long cystidia and was nested into the sect. . The new species were formally described and illustrated in the present study, and a key to the sections and species of in China was provided.
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http://dx.doi.org/10.1080/21501203.2022.2094012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354645PMC
July 2022

Bioactivity of hamamelitannin, flavokawain A, and triacetyl resveratrol as natural compounds: Molecular docking study, anti-colon cancer and anti-Alzheimer potentials.

Biotechnol Appl Biochem 2022 Aug 7. Epub 2022 Aug 7.

Department of Gastrointestinal Surgery, Jinan Central Hospital Affiliated to Shandong University, Shangdong, Jinan, 250013, China.

In this study, we worked on anti-colon cancer effects and anti-Alzheimer's disease with molecular docking studies. Hamamelitannin, Flavokawain A, Triacetyl resveratrol compounds showed good inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. For obtaining the inhibition effects of flavokawain A, hamamelitannin, and triacetyl resveratrol on AChE and BuChE enzymes were determined spectrophotometrically conforming to Ellman. IC values of these enzymes were ranging between 0.95±0.12 to 93.27±8.14 nM for AChE and 5.71±0.77 to 52.10±8.41 nM for BuChE. The inhibitory activities of some chemical compounds such as flavokawain A, hamamelitannin, and triacetyl resveratrol were assessed by performing the molecular docking study in the presence of AChE and BChE. Also, about the features of the ligand-enzyme complex that had value of -7.722 kcal/mol for flavokawain A against AChE and -5.530 kcal/mol against BuChE. The molecular docking calculations indicated the probable interactions and their characteristics at an atomic level. Due to the outcomes gained from docking, the affinity of the chemical compounds to the enzymes was considerable. In vitro cell viabilities of Flavokawain A, Hamamelitannin, Triacetyl resveratrol with various concentrations on SW620, DLD-1, HT29, HCT8, and HCT116 were investigated by MTT assay with Dox (Doxorubicin) as the control compound. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/bab.2394DOI Listing
August 2022

The prognostic value of the ratio of standard uptake value of lymph node to primary tumor before treatment of locally advanced nasopharyngeal carcinoma.

Eur Arch Otorhinolaryngol 2022 Aug 6. Epub 2022 Aug 6.

Department of Radiotherapy, Meizhou People's Hospital, Meizhou Academy of Medical Sciences Meizhou, Meizhou, China.

Background: To evaluate the prognostic value of the ratio of the standard uptake value of the lymph node and primary tumor before the treatment of locally advanced nasopharyngeal carcinoma and examine the prognostic value of the tumor metabolic parameters (SUVmax MTV, and TLG) of the lymph node and primary tumor of locally advanced nasopharyngeal carcinoma.

Methods: A total of 180 patients with locally advanced nasopharyngeal carcinoma diagnosed pathologically from January 1, 2016 to December 31, 2018 were selected, and the MEDEX system was used to automatically delineate the SUVmax, MTV, and TLG of the lymph node metastases and nasopharyngeal carcinoma primary tumor. In addition, the ratio of LN-SUVmax (SUVmax of the lymph node metastases) to T-SUVmax (SUVmax of the nasopharyngeal carcinoma primary tumor) was calculated, and a ROC curve was drawn to obtain the best cut-off value. Kaplan-Meier and Cox regression models were used for survival and multivariate analyses, respectively.

Results: The median follow-up period for participants was 32 (4-62) months. Univariate analysis showed that age (P = 0.013), LN-SUVmax (P = 0.001), LN-TLG (P = 0.007) and NTR (P = 0.001) were factors influencing the overall survival (OS). Factors affecting local progression-free survival (LPFS) were LN-SUVmax (P = 0.005), LN-TLG (P = 0.003) and NTR (P = 0.020), while clinical stage (P = 0.023), LN-SUVmax (P = 0.007), LN-TLG (P = 0.006), and NTR (P = 0.032) were factors affecting distant metastasis-free survival (DMFS). Multivariate analysis showed that NTR was an independent influencing factor of OS (HR 3.00, 95% CI 1.06-8.4, P = 0.038), LPFS (HR 3.08, 95% CI 1.27-7.50, P = 0.013), and DMFS (HR 1.84, 95% CI 0.99-3.42, P = 0.054). Taking OS as the main observation point, the best cut-off point of NTR was 0.95. Kaplan-Meier results showed that the 3-year OS (97.0% vs 85.4%, χ = 11.25, P = 0.001), 3-year LPFS (91.3% vs 82.1%, χ = 4.035, P = 0.045), and 3-year DMFS (92.3% vs 87.9%, χ = 4.576, P = 0.032) of patients with NTR < 0.95 were higher than those with NTR > 0.95.

Conclusions: High NTR before treatment indicates a poor prognosis for patients with nasopharyngeal carcinoma. This can serve as a reference value for the reasonable treatment and prognosis monitoring of such patients.
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http://dx.doi.org/10.1007/s00405-022-07562-wDOI Listing
August 2022

Comparison of six surrogate insulin resistance indexes for predicting the risk of incident stroke: The Rural Chinese Cohort Study.

Diabetes Metab Res Rev 2022 Aug 5:e3567. Epub 2022 Aug 5.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Background: and Purpose: Some cheap and easily-used operated indexes of insulin resistance (IR) were currently available. We aimed to evaluate the association of six surrogate indexes of IR with incident stroke and to compare their predictive capacity.

Methods: We analyzed data from 14,595 eligible study participants from the Rural Chinese Cohort Study. Modified Poisson regression models were used to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) of incident stroke associated with the visceral adiposity index (VAI), the Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), triglyceride-glucose (TyG), TyG-body mass index (TyG-BMI), and TyG-waist circumference (TyG-WC). The receiver operator characteristic curve (ROC) was used to compare the ability of the abovementioned IR indexes to predict stroke.

Results: During a median follow-up of 6 years, 786 newly-diagnosed stroke cases were identified. The levels of six surrogate indexes of IR were all significantly higher in the stroke population than in the non-stroke population (p<0.001). Compared with quartile 1, the multivariable adjusted RRs (95% CIs) of incident stroke for quartile 4 were 2.01 (1.47-2.76), 1.62 (1.28, 2.04), 1.64 (1.28-2.09), and 1.92 (1.50-2.45) for CVAI, VAI, LAP, and TyG, respectively. Significant dose-response associations were also found between surrogate IR indexes and risk of stroke. The area under the curves (AUCs) for CVAI (0.674) was significantly greater than for other indexes (TyG-WC:0.622, TyG:0.614, LAP:0.606, TyG-BMI:0.598, and VAI:0.577) (p<0.001).

Conclusions: Six surrogate indexes of IR were independently associated with incident stroke. The CVAI may be the most suitable index for stroke prediction. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/dmrr.3567DOI Listing
August 2022

Recent Advances in the Molecular Design and Delivery Technology of mRNA for Vaccination Against Infectious Diseases.

Front Immunol 2022 15;13:896958. Epub 2022 Jul 15.

College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.

Vaccines can prevent many millions of illnesses against infectious diseases and save numerous lives every year. However, traditional vaccines such as inactivated viral and live attenuated vaccines cannot adapt to emerging pandemics due to their time-consuming development. With the global outbreak of the COVID-19 epidemic, the virus continues to evolve and mutate, producing mutants with enhanced transmissibility and virulence; the rapid development of vaccines against such emerging global pandemics becomes more and more critical. In recent years, mRNA vaccines have been of significant interest in combating emerging infectious diseases due to their rapid development and large-scale production advantages. However, their development still suffers from many hurdles such as their safety, cellular delivery, uptake, and response to their manufacturing, logistics, and storage. More efforts are still required to optimize the molecular designs of mRNA molecules with increased protein expression and enhanced structural stability. In addition, a variety of delivery systems are also needed to achieve effective delivery of vaccines. In this review, we highlight the advances in mRNA vaccines against various infectious diseases and discuss the molecular design principles and delivery systems of associated mRNA vaccines. The current state of the clinical application of mRNA vaccine pipelines against various infectious diseases and the challenge, safety, and protective effect of associated vaccines are also discussed.
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http://dx.doi.org/10.3389/fimmu.2022.896958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345514PMC
August 2022

Case Report: Prenatal Diagnosis of Nemaline Myopathy.

Front Pediatr 2022 19;10:937668. Epub 2022 Jul 19.

Department of Ultrasound Diagnostic, The Second Xiangya Hospital, Central South University, Changsha, China.

Nemaline myopathy (NM) is a rare, hereditary heterogeneous myopathy. Fetal NM has a more severe disease course and a poorer prognosis and is usually lethal during the first few months of life. Hence, early prenatal diagnosis is especially important for clinical interventions and patient counseling. We report the case of a fetus with NM due to gene variation leading to arthrogryposis multiplex congenita (AMC). The ultrasonography and histopathology results revealed an enhanced echo intensity and decreased muscle thickness, which may be novel features providing early clues for the prenatal diagnosis of NM. Moreover, to our knowledge, this article is the first report to describe a case of NM associated with complex congenital heart disease (CHD).
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http://dx.doi.org/10.3389/fped.2022.937668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343628PMC
July 2022

Co-infection and enterovirus B: post EV-A71 mass vaccination scenario in China.

BMC Infect Dis 2022 Aug 4;22(1):671. Epub 2022 Aug 4.

Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College (CAMS & PUMC), 935 Jiao Ling Road, Kunming, 650118, Yunnan Province, People's Republic of China.

Background: Hand, foot, and mouth disease (HFMD) is a common child infectious disease caused by more than 20 enterovirus (EV) serotypes. In recent years, enterovirus A71 (EV-A71) has been replaced by Coxsackievirus A6 (CV-A6) to become the predominant serotype. Multiple EV serotypes co-circulate in HFMD epidemics, and this study aimed to investigate the etiological epidemic characteristics of an HFMD outbreak in Kunming, China in 2019.

Methods: The clinical samples of 459 EV-associated HFMD patients in 2019 were used to amplify the VP1 gene region by the three sets of primers and identify serotypes using the molecular biology method. Phylogenetic analyses were performed based on the VP1 gene.

Results: Three hundred and forty-eight cases out of 459 HFMD patients were confirmed as EV infection. Of these 191 (41.61%) were single EV infections and 34.20% had co-infections. The EVs were assigned to 18 EV serotypes, of which CV-A6 was predominant (11.33%), followed by CV-B1 (8.93%), CV-A4 (5.23%), CV-A9 (4.58%), CV-A 16 (3.49%) and CV-A10 and CVA5 both 1.96%. Co-infection of CV-A6 with other EVs was present in 15.25% of these cases, followed by co-infection with CV-A16 and other EVs. The VP1 sequences used in the phylogenetic analyses showed that the CV-A6, CV-B1 and CV-A4 sequences belonged to the sub-genogroup D3 and genogroups F and E, respectively.

Conclusion: Co-circulation and co-infection of multiple serotypes were the etiological characteristic of the HFMD epidemic in Kunming China in 2019 with CV-A-6, CV-B1 and CV-A4 as the predominant serotypes. This is the first report of CV-B1 as a predominant serotype in China and may provide valuable information for the diagnosis, prevention and control of HFMD.
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http://dx.doi.org/10.1186/s12879-022-07661-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354358PMC
August 2022

Population pharmacokinetics model for escitalopram in Chinese psychiatric patients: effect of CYP2C19 and age.

Front Pharmacol 2022 18;13:964758. Epub 2022 Jul 18.

Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.

To establish a population pharmacokinetic model in Chinese psychiatric patients to characterize escitalopram pharmacokinetic profile to identify factors influencing drug exposure, and through simulation to compare the results with the established therapeutic reference range. Demographic information, dosing regimen, CYP2C19 genotype, concomitant medications, and liver and kidney function indicators were retrospectively collected for inpatients taking escitalopram with therapeutic drug monitoring from 2018 to 2021. Nonlinear mixed-effects modeling was used to model the pharmacokinetic characteristics of escitalopram. Goodness-of-fit plots, bootstrapping, and normalized prediction distribution errors were used to evaluate the model. Simulation for different dosing regimens was based on the final estimations. The study comprised 106 patients and 337 measurements of serum sample. A structural model with one compartment with first-order absorption and elimination described the data adequately. The population-estimated apparent volume of distribution and apparent clearance were 815 and 16.3 L/h, respectively. Age and CYP2C19 phenotype had a significant effect on the apparent clearance (CL/F). CL/F of escitalopram decreased with increased age, and CL/F of poor metabolizer patients was significantly lower than in extensive and immediate metabolizer patients. The final model-based simulation showed that the daily dose of adolescents with poor metabolizer might be as high as 15 mg or 20 mg and referring to the therapeutic range for adults may result in overdose and a high risk of adverse effects in older patients. A population pharmacokinetics model of escitalopram was successfully created for the Chinese population. Depending on the age of the patients, CYP2C19 genotype and serum drug concentrations throughout treatment are required for adequate individualization of dosing regimens. When developing a regimen for older patients, especially those who are poor metabolizers, vigilance is required.
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http://dx.doi.org/10.3389/fphar.2022.964758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340256PMC
July 2022

Title: BET Inhibition Triggers Anti-tumor Immunity by Enhancing MHC Class I Expression in Head and Neck Squamous Cell Carcinoma.

Mol Ther 2022 Aug 2. Epub 2022 Aug 2.

Hospital of Stomatology, Sun Yat-sen University, Guangzhou 51055, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, China; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 51055, China. Electronic address:

BET inhibition has been shown to have a promising anti-tumor effect in multiple tumors. However, the impact of BET inhibition on anti-tumor immunity was still not well documented in HNSCC. In this study, we aim to assess the functional role of BET inhibition in anti-tumor immunity and clarify its mechanism. We show that BRD4 is highly expressed in HNSCC and inversely correlated with the infiltration of CD8 T cells. BET inhibition potentiates CD8 T-cell based anti-tumor immunity in vitro and in vivo. Mechanistically, BRD4 acts as a transcriptional suppressor and represses the expression of MHC class I molecules by recruiting G9a. Pharmacological inhibition or genetic depletion of BRD4 potently increases the expression of MHC class I molecules in the absence and presence of IFN-γ. Moreover, compared to PD-1 blocking antibody treatment or JQ1 treatment individually, the combination of BET inhibition with anti-PD-1 antibody treatment significantly enhances the anti-tumor response in HNSCC. Taken together, our data unveils a novel mechanism by which BET inhibition potentiates anti-tumor immunity via promoting the expression of MHC class I molecules and provides a rationale for combination of ICBs with BET inhibitors for HNSCC treatment.
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http://dx.doi.org/10.1016/j.ymthe.2022.07.022DOI Listing
August 2022

Epigenetic Clock Acceleration Is Linked to Age at Onset of Parkinson's Disease.

Mov Disord 2022 Aug 3. Epub 2022 Aug 3.

The First Rehabilitation Hospital of Shanghai, Department of Medical Genetics, School of Medicine, Tongji University, Shanghai, China.

Background: Aging is the strongest risk factor for Parkinson's disease (PD), which is a clinically heterogeneous movement disorder with highly variable age at onset. DNA methylation age (DNAm age) is an epigenetic clock that could reflect biological aging.

Objectives: The aim was to evaluate whether PD age at onset is associated with DNAm-age acceleration (difference between DNAm age and chronological age).

Methods: We used the genome-wide Infinium MethylationEPIC array to assess DNAm age in discovery (n = 96) and replication (n = 182) idiopathic PD cohorts and a unique longitudinal LRRK2 cohort (n = 220) at four time points over a 3-year period, comprising 91 manifesting and 129 nonmanifesting G2019S carriers at baseline. Cox proportional hazard regression and multivariate linear regression were used to evaluate the relation between DNAm-age acceleration and PD age at onset, which was highly variable in manifesting G2019S carriers (36-75 years) and both idiopathic PD cohorts (26-77 and 35-81 years).

Results: DNAm-age acceleration remained steady over the 3-year period in most G2019S carriers. It was strongly associated with age at onset in the LRRK2 cohort (P = 2.25 × 10 ) and discovery idiopathic PD cohort (P = 5.39 × 10 ), suggesting that every 5-year increase in DNAm-age acceleration is related to about a 6-year earlier onset. This link was replicated in an independent idiopathic PD cohort (P = 1.91 × 10 ). In each cohort, the faster-aging group has an increased hazard for an earlier onset (up to 255%).

Conclusions: This study is the first to demonstrate that DNAm-age acceleration is related to PD age at onset, which could be considered in disease-modifying clinical trials. Future studies should evaluate the stability of DNAm-age acceleration over longer time periods, especially for phenoconverters from nonmanifesting to manifesting individuals. © 2022 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.29157DOI Listing
August 2022

Inhibition of APLN suppresses cell proliferation and migration and promotes cell apoptosis in esophageal cancer cells in vitro, through activating PI3K/mTOR signaling pathway.

Eur J Histochem 2022 Aug 3;66(3). Epub 2022 Aug 3.

Department of Integrated Traditional Chinese and Western Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University.

Esophageal cancer is the sixth leading cause of cancer mortalities globally with a high incidence rate. Apelin (APLN) plays regulatory roles in different organs. However, its role in esophageal cancer remains unknown. Therefore, our study aims to explore the effect of APLN on esophageal cancer. One hundred and eighty-four (184) esophageal tumor tissues samples from patients with esophageal cancer, and 11 esophageal tissues samples from healthy volunteers were analyzed for the expression of APLN. APLN was highly expressed in the tumor of patients with esophageal cancer and esophageal cancer cells.  Patients with high expressions of APLN had a lower survival rate than the ones with low to medium expressions of APLN.  Human esophageal carcinoma cell lines, TE-1 and ECA-109 cells were transfected with APLN siRNA to knockdown APLN, or transfected with pcDNA-APLN to overexpress APLN. Inhibition of APLN by siRNA-APLN reduced proliferative, migrative, and invasive abilities of esophageal cancer cells and promoted cell apoptosis, which could be all restored by pcDNA-APLN. Moreover, knocking down APLN by siRNA-APLN suppressed the PI3K/mTOR signaling pathway. These findings identify that APLN inhibition might ameliorate esophageal cancer through activating the PI3K/mTOR signaling pathway, thus APLN could be a potential target for esophageal cancer.
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http://dx.doi.org/10.4081/ejh.2022.3336DOI Listing
August 2022

The management of metastatic neck nodes following induction chemotherapy in N2/3 classification hypopharyngeal carcinoma.

Head Neck 2022 Sep;44(9):2009-2017

Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Background: For patients with less chemosensitive neck nodes, poor prognosis after chemoradiotherapy (CRT) could be predicted and neck dissection is needed.

Methods: Ninety-two N2/3 hypopharyngeal carcinoma patients were retrospectively studied. According to response after induction chemotherapy (ICT), patients were treated with neck dissection followed by concurrent CRT (CCRT) (group 1), surgery plus postoperative CRT (group 2), or CCRT for primary and regional sites (group 3).

Results: Overall survival and disease-free survival rates of group 1 were significantly higher than group 2 (p = 0.038, p = 0.031) and group 3 (both p = 0.018). Regional control rate of group 1 was significantly higher than group 3 (p = 0.041). There were no significant differences between groups 1 and 2 regarding local and regional control (p = 0.746, p = 0.302).

Conclusions: Neck dissection followed by CCRT is the best choice for patients with responsive primary but nonresponsive nodes.
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http://dx.doi.org/10.1002/hed.27106DOI Listing
September 2022

Recurrence risk stratification and treatment strategies of patients with stage IVa-b hypopharyngeal squamous cell carcinoma.

Head Neck 2022 Sep;44(9):2030-2039

ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Background: Optimal treatment strategies for patients with stage IVa-b hypopharyngeal squamous cell carcinoma (HSCC) remain controversial. This study aimed to examine the high-risk factors of postoperative tumor recurrence after surgical resection of HSCC and devise individualized postoperative adjuvant treatment (POAT).

Methods: Overall, 218 patients with stage IVa-b HSCC who received surgery as initial treatment and with negative surgical margins were evaluated. Independent risk factors of recurrence were identified, and survival outcomes were compared according to recurrence risk and POAT use.

Results: POAT significantly improved recurrence-free survival (RFS) and overall survival (OS) only in the high-risk patients (p = 0.003 and 0.018, respectively). Compared with postoperative radiotherapy alone, postoperative chemoradiotherapy (pCRT) achieved significantly better RFS (p = 0.035) and OS (p = 0.048).

Conclusions: POATs are recommended for high-risk patients with stage Iva-b HSCC, with pCRT achieving superior outcomes. Regular re-examination after tumor resection is sufficient for low-risk patients.
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http://dx.doi.org/10.1002/hed.27074DOI Listing
September 2022

C3-Selective Trifluoromethylthiolation and Difluoromethylthiolation of Pyridines and Pyridine Drugs via Dihydropyridine Intermediates.

J Am Chem Soc 2022 Aug 1. Epub 2022 Aug 1.

State Key Laboratory and Institute of Elemento-Organic Chemistry, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China.

Herein, we report a method for C3-selective C-H tri- and difluoromethylthiolation of pyridines. The method relies on borane-catalyzed pyridine hydroboration for generation of nucleophilic dihydropyridines; these intermediates react with trifluoromethylthio and difluoromethylthio electrophiles to form functionalized dihydropyridines, which then undergo oxidative aromatization. The method can be used for late-stage functionalization of pyridine drugs for the generation of new drug candidates.
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http://dx.doi.org/10.1021/jacs.2c06776DOI Listing
August 2022

TRIM66 Promotes Malignant Progression of Non-Small-Cell Lung Cancer Cells via Targeting MMP9.

Comput Math Methods Med 2022 21;2022:6058720. Epub 2022 Jul 21.

Department of Respiratory Medicine, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang Province 314001, China.

Lung cancer has a higher incidence and mortality rate than other cancers, and over 80% of lung cancer cases were classified as non-small-cell lung cancer (NSCLC). TRIM66 is one of the crucial members of TRIM, which has a deep connection with the behavior of various malignant tumors. But it remains uncertain regarding its exact function and underlying mechanism in NSCLC. In our study, qRT-PCR and Western blot were employed to validate that TRIM66 was overexpressed in NSCLC. The migration, invasion, and epithelial-mesenchymal transformation (EMT) progression of NSCLC cells were determined by Western blotting and Transwell experiments after knocking down TRIM66, and it was found that knockdown TRIM66 inhibited the migration, invasion, and EMT processes of NSCLC cells. Next, the binding relationship between TRIM66 and MMP9 was verified by Co-IP assay. After determining the interaction between them, rescue assays showed that overexpression of MMP9 was capable to promote the migration, invasion, and EMT of NSCLC cells. However, the transfection of si-TRIM66 could reverse this facilitating effectiveness. To sum up, we concluded that by targeting MMP9, TRIM66 could exert a cancer-promoting role in the progression of NSCLC cells.
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http://dx.doi.org/10.1155/2022/6058720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334090PMC
August 2022

Unraveling the antibacterial mechanism of 3-carene against Pseudomonas fragi by integrated proteomics and metabolomics analyses and its application in pork.

Int J Food Microbiol 2022 Jul 22;379:109846. Epub 2022 Jul 22.

School of Food Sciences & Engineering, Hainan University, 58 People Road, Haikou 570228, PR China. Electronic address:

Pseudomonas fragi is primarily responsible for the spoilage of various foods, especially meat. The aim of this study was to investigate the antibacterial mechanism of 3-carene against P. fragi. 3-Carene treatment decreased the phospholipid content and the fluidity of the cell membrane, induced reactive oxygen species (ROS) generation and affected respiratory chain dehydrogenase, oxoglutarate dehydrogenase and citrate synthase in P. fragi. Metabolomics and proteomics analyses further showed that in the presence of 3-carene, 519 proteins, 136 metabolites in positive ion mode and 100 metabolites in negative ion mode were differentially expressed. These proteins and metabolites were primarily involved in amino acid metabolism, fatty acid degradation, the tricarboxylic acid cycle (TCA cycle) and other processes. Consequently, the stimulation of 3-carene altered cell membrane properties, disturbed important amino acid and energy metabolism, and even caused oxidative stress. Additionally, the results of total viable counts and the total volatile base nitrogen indicated that 3-carene could significantly improve the preservation of refrigerated pork. This study suggested that 3-carene has promising potential to be developed as a food preservative.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2022.109846DOI Listing
July 2022

Integrated strategy of network analysis prediction and experimental validation to elucidate the possible mechanism of compound Turkish gall ointment in treating eczema.

Chin Med 2022 Jul 30;17(1):89. Epub 2022 Jul 30.

Department of Pharmacy, Affiliated Hospital of Traditional Chinese Medicine, Xinjiang Medical University, Xinjiang, Urumqi, 830011, China.

Background: Compound Turkish gall ointment (CTGO) has a long history of being widely used as a folk medicine in Xinjiang for the treatment of eczema. CTGO is currently in the pre-investigational new drug application stage, but its pharmacological mechanisms of action have not yet been clarified.

Methods: First, a sensitive and reliable ultra-high performance liquid chromatography-Q exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) technique was established. Second, an integrative strategy of network analysis and molecular docking based on identified and retrieved ingredients was implemented to investigate the potential targets and pathways involved in the treatment of eczema with CTGO. Finally, Sprague-Dawley (SD) rats with eczema were prepared to verify the predicted results. The skin conditions of the rats were observed, evaluated, and scored. Skin tissues were observed by hematoxylin-eosin (HE) staining, and the levels of serum interferon-γ (IFN-γ) and interleukin-4 (IL-4) were determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κB p65), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were detected by real-time quantitative polymerase chain reaction (RT-qPCR).

Results: A total of 29 compounds were identified. We found 38 active components and 58 targets for the treatment of eczema, which included 118 signaling pathways related to inflammation, immunity, and apoptosis. CTGO significantly improved the skin surface and histopathological characteristics of eczema-affected rats, downregulated the expression of IL-4, TLR4, NF-κB (p65), IL-1β, and TNF-α, and upregulated the expression level of IFN-γ.

Conclusion: We predicted and validated our prediction that CTGO may be used to treat eczema by affecting the TLR4/NF-κB signaling pathway, which provides guidance for future experimental studies.
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http://dx.doi.org/10.1186/s13020-022-00643-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338667PMC
July 2022

Rab11a-Regulated Exosomes Inhibit Bacterial Infection through the Activation of Antilipopolysaccharide Factors in Crustaceans.

J Immunol 2022 Jul 27. Epub 2022 Jul 27.

Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China;

Exosomes, secreted by most cells, are critical antimicrobial immune factors in animals. Recent studies of certain key regulators of vesicular transport, the Rab GTPases, have linked Rab dysfunction to regulation of innate immune signaling. However, the relationship between exosomes and Rab GTPases, resulting in antimicrobial activity in vertebrates and invertebrates during pathogenic infection, has not been addressed. In this study, Rab11a was reported to have a protective effect on the survival rate of mud crabs after s challenge through the stimulation of exosome secretion and modulation of anti-LPS factor (ALF) expression. Furthermore, 14-3-3 was confirmed to be densely packaged in exosomes after s infection, which could recruit the MyD88 and TLR by binding the Toll/IL-1R domain to the plasma membrane, promoting the translocation of Dorsal from the cytoplasm into the nucleus, and thereby regulating ALFs expression in the hemocytes of mud crab in response to the bacterial infection. The findings therefore provide, to our knowledge, a novel mechanism that underlies the cross-talk between Rab11a-regulated exosome formation and ALFs expression in innate immune response in invertebrates, with a crustacean species, mud crab , as a model study.
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http://dx.doi.org/10.4049/jimmunol.2200094DOI Listing
July 2022

High-Strength Collagen-Based Composite Films Regulated by Water-Soluble Recombinant Spider Silk Proteins and Water Annealing.

ACS Biomater Sci Eng 2022 Aug 27;8(8):3341-3353. Epub 2022 Jul 27.

CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, No. 189 Songling Road, Qingdao 266101, China.

Spider silk has attracted extensive attention in the development of high-performance tissue engineering materials because of its excellent physical properties, biocompatibility, and biodegradability. Although high-molecular-weight recombinant spider silk proteins can be obtained through metabolic engineering of host bacteria, the solubility of the recombinant protein products is always poor. Strong denaturants and organic solvents have thus had to be exploited for their dissolution, and this seriously limits the applications of recombinant spider silk protein-based composite biomaterials. Herein, through adjusting the temperature, ionic strength, and denaturation time during the refolding process, we successfully prepared water-soluble recombinant spider major ampullate spidroin 1 (sMaSp1) with different repeat modules (24mer, 48mer, 72mer, and 96mer). Then, MaSp1 was introduced into the collagen matrix for fabricating MaSp1-collagen composite films. The introduction of spider silk proteins was demonstrated to clearly alter the internal structure of the composite films and improve the mechanical properties of the collagen-based films and turn the opaque protein films into transparency ones. More interestingly, the composite film prepared with sMaSp1 exhibited better performance in mechanical strength and cell adhesion compared to that prepared with water-insoluble MaSp1 (pMaSp1), which might be attributed to the effect of the initial dissolved state of MaSp1 on the microstructure of composite films. Additionally, the molecular weight of MaSp1 was also shown to significantly influence the mechanical strength (enhanced to 1.1- to 2.3-fold) and cell adhesion of composite films, and 72mer of sMaSp1 showed the best physical properties with good bioactivity. This study provides a method to produce recombinant spider silk protein with excellent water solubility, making it possible to utilize this protein under environmentally benign, mild conditions. This paves the way for the application of recombinant spider silk proteins in the development of diverse composite biomaterials.
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http://dx.doi.org/10.1021/acsbiomaterials.2c00416DOI Listing
August 2022

Glycine Nano-Selenium Enhances Immunoglobulin and Cytokine Production in Mice Immunized with H9N2 Avian Influenza Virus Vaccine.

Int J Mol Sci 2022 Jul 18;23(14). Epub 2022 Jul 18.

Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.

This study was performed to investigate the immune enhancement effect of glycine nano-selenium, a microelement on H9N2 avian influenza virus vaccine (H9N2 AIV vaccine) in mice. Fifty (50) Specific Pathogen Free Kunming mice aged 4-6 weeks (18-20 g Body weight) were randomly divided into five groups: control normal group, which received no immunization + 0.5 mL 0.9% normal saline, positive control group, which received H9N2 AIV vaccine + 0.5 mL 0.9% normal saline, 0.25 mg/kg selenium group, which received H9N2 AIV vaccine + 0.5 mL 0.25 mg/kg selenium solution, 0.5 mg/kg selenium group, which received H9N2 AIV vaccine + 0.5 mL 0.5 mg/kg selenium solution, and 1 mg/kg selenium group, which received H9N2 AIV vaccine + 0.5 mL 1 mg/kg selenium solution. Hematoxylin and eosin staining, enzyme linked immunosorbent assay (ELISA), and quantitative real time polymerase chain reaction (qRT-PCR) methods were used to investigate the pathological changes, immunoglobulin levels, and cytokine gene expressions in this study. The results showed that all tested doses (0.25 mg/kg, 0.5 mg/kg and 1.00 mg/kg) of glycine nano-selenium did not lead to poisoning in mice. In addition, when compared to the positive control group, glycine nano-selenium increased the immunoglobin indexes (IgA, IgG, IgM and AIV-H9 IgG in serum) as well as the mRNA levels of IL-1β, IL-6 and INF-γ in the liver, lungs, and spleen ( < 0.05). In summary, glycine nano-selenium could enhance the efficacy of avian influenza vaccine.
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http://dx.doi.org/10.3390/ijms23147914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317336PMC
July 2022

Quantum Linear System Algorithm for General Matrices in System Identification.

Entropy (Basel) 2022 Jun 29;24(7). Epub 2022 Jun 29.

College of Information and Communication, National University of Defense Technology, Xi'an 710006, China.

Solving linear systems of equations is one of the most common and basic problems in classical identification systems. Given a coefficient matrix and a vector , the ultimate task is to find the solution such that Ax=b. Based on the technique of the singular value estimation, the paper proposes a modified quantum scheme to obtain the quantum state |x⟩ corresponding to the solution of the linear system of equations in O(κ2rpolylog(mn)/ϵ) time for a general m×n dimensional , which is superior to existing quantum algorithms, where κ is the condition number, is the rank of matrix and ϵ is the precision parameter. Meanwhile, we also design a quantum circuit for the homogeneous linear equations and achieve an exponential improvement. The coefficient matrix in our scheme is a sparsity-independent and non-square matrix, which can be applied in more general situations. Our research provides a universal quantum linear system solver and can enrich the research scope of quantum computation.
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http://dx.doi.org/10.3390/e24070893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323527PMC
June 2022

Sequence-to-Sequence Voice Reconstruction for Silent Speech in a Tonal Language.

Brain Sci 2022 Jun 23;12(7). Epub 2022 Jun 23.

State Key Laboratory of Industrial Control Technology, Institute of Cyber Systems and Control, Zhejiang University, Hangzhou 310027, China.

Silent speech decoding (SSD), based on articulatory neuromuscular activities, has become a prevalent task of brain-computer interfaces (BCIs) in recent years. Many works have been devoted to decoding surface electromyography (sEMG) from articulatory neuromuscular activities. However, restoring silent speech in tonal languages such as Mandarin Chinese is still difficult. This paper proposes an optimized sequence-to-sequence (Seq2Seq) approach to synthesize voice from the sEMG-based silent speech. We extract duration information to regulate the sEMG-based silent speech using the audio length. Then, we provide a deep-learning model with an encoder-decoder structure and a state-of-the-art vocoder to generate the audio waveform. Experiments based on six Mandarin Chinese speakers demonstrate that the proposed model can successfully decode silent speech in Mandarin Chinese and achieve a character error rate (CER) of 6.41% on average with human evaluation.
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http://dx.doi.org/10.3390/brainsci12070818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312762PMC
June 2022

Highly Efficient Organic Solar Cells Enabled by the Incorporation of a Sulfonated Graphene Doped PEDOT:PSS Interlayer.

ACS Appl Mater Interfaces 2022 Aug 25;14(30):34814-34821. Epub 2022 Jul 25.

Frontiers Science Center for Transformative Molecules, Center of Hydrogen Science, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.

An interface modification layer plays an important role in improving the performance of organic solar cells (OSCs). The structure design or doping of electrode interlayer materials can effectively inhibit interfacial carrier recombination and improve ohmic contact between the active layer and the electrodes, which is desirable for realizing high power conversion efficiencies (PCEs). Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has been extensively used as a hole-transport layer (HTL) in OSCs. Here, a modification of PEDOT:PSS is proposed using sulfonated graphene (SG) as a secondary dopant for improving the surface morphology and conductivity. The incorporation of the SG-doped PEDOT:PSS as the HTLs in OSCs leads to the increased charge extraction and shows the best PCEs of 17.48% for PM6:Y6 devices and 18.56% for PM6:L8-BO devices. The significant improvement in device performance suggests that SG-PEDOT:PSS is a promising interfacial layer for efficient charge transport and extraction toward high-efficiency OSCs.
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http://dx.doi.org/10.1021/acsami.2c10407DOI Listing
August 2022

Heterogenous Subtypes of Late-Life Depression and Their Cognitive Patterns: A Latent Class Analysis.

Front Psychiatry 2022 6;13:917111. Epub 2022 Jul 6.

Clinical Research Division, Dementia Care and Research Center, Peking University Institute of Mental Health (Sixth Hospital), Beijing, China.

Background: Late-life depression (LLD), characterized by cognitive deficits, is considered heterogeneous across individuals. Previous studies have identified subtypes with diverse symptom profiles, but their cognitive patterns are unknown. This study aimed to investigate the subtypes of LLD and the cognitive profile of each group.

Methods: In total, 109 depressed older adults were enrolled. We performed latent class analysis using Geriatric Depression Scale items as indicators to generate latent classes. We compared the sociodemographic and clinical characteristics with cognitive functions between groups and conducted regression analysis to investigate the association between class membership and variables with significant differences.

Results: Two classes were identified: the "pessimistic" group was characterized by pessimistic thoughts and the "worried" group with a relatively high prevalence of worry symptoms. The two groups did not differ in sociodemographic characteristics. The "pessimistic" group showed a higher rate of past history of depression and lower age of onset. The "worried" group had more physical comorbidities and a higher rate of past history of anxiety. The "pessimistic" group was more impaired in general cognitive function, executive function, information processing speed, and attention. Lower general and executive functions were associated with the membership in the "pessimistic" group.

Conclusions: Subjects with pessimistic symptoms and subjects with a propensity to worry may form two distinct subtypes of late-life depression with different cognitive profiles. Further, the cognitive evaluation of subjects with pessimistic symptoms is of utmost importance.
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http://dx.doi.org/10.3389/fpsyt.2022.917111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298648PMC
July 2022

Ultrasound gray scale ratio for differential diagnosis of papillary thyroid microcarcinoma from benign micronodule in patients with Hashimoto's thyroiditis.

BMC Endocr Disord 2022 Jul 22;22(1):187. Epub 2022 Jul 22.

Department of Medical Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, Yanta West Road, Xi'an, 710061, China.

Background: To investigate the diagnostic value of ultrasound gray scale ratio (UGSR) in differentiating papillary thyroid microcarcinomas (PTMCs) from benign micronodules (BMNs) in patients with Hashimoto's thyroiditis (HT).

Methods: The ultrasound images of 285 PTMCs (from 247 patients) and 173 BMNs (from 140 patients) in the HT group, as well as 461 PTMCs (from 417 patients) and 234 BMNs (from 197 patients) in the non-HT group were retrospectively analyzed. The diagnosis of all cases was confirmed by histopathological examinations. The gray scale values of the nodules and surrounding thyroid tissues were measured and subsequently the UGSRs were calculated. Receiver operating characteristic curve analysis was used to determine the area under the curve (AUC), optimal UGSR threshold, sensitivity and specificity in differentiating PTMCs and BMNs in the two groups.

Results: The UGSR of PTMC and BMN was 0.52 ± 0.12 and 0.85 ± 0.24 in the HT group (P < 0.001), and 0.57 ± 0.13 and 0.87 ± 0.20 in the non-HT group (P < 0.001), respectively. The difference in PTMC-UGSR was significant between the two groups (P < 0.001), whereas BMN-UGSR did not differ between the two groups (P = 0.416). The AUC, optimal UGSR threshold, sensitivity and specificity of UGSR for differentiating PTMC and BMN in the HT and non-HT group were 0.890 versus 0.901, 0.68 versus 0.72, 91.23% versus 90.67%, and 77.46% versus 82.05%, respectively.

Conclusions: The USGR of the HT group was lower than that of the non-HT group. Moreover, UGSR exhibited important diagnostic value in differentiating PTMC from BMN in both HT and non-HT groups.
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http://dx.doi.org/10.1186/s12902-022-01028-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306152PMC
July 2022

Influence of glucan on physicochemical and rheology properties of chitin nanofibers prepared from Shiitake stipes.

Carbohydr Polym 2022 Oct 27;294:119762. Epub 2022 Jun 27.

College of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, China. Electronic address:

Procedures for chitin nanofibers extraction from mushroom significantly modify their structure and physicochemical properties, through disintegration and surface oxidation of glucan residue, as well as surface deacetylation of chitin. Here, four kinds of chitin-glucan nanofibers (CGNF) were isolated form Shiitake stipes via different alkali treatment conditions, wherein glucan content ranged from 6.4 % to 46.8 %. Observations with transmission electron microscopy showed that CGNFs possessed average widths with 5.1 ± 1.2 to 7.1 ± 1.5 nm. The glucan showed a negative effect on the crystal index and thermal stability of CGNFs. A strong positive correlation was observed between glucan residues and zeta potential value. The phenomenon about the increase of viscosity, yield stress and elastic modulus upon glucan decrease was discussed. Overall, the residual glucan offers fungi-derived chitin nanomaterials a diversity of material properties and tuning its content is a feasible approach for customize nano chitin fibers used in nutraceutical and food industry.
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http://dx.doi.org/10.1016/j.carbpol.2022.119762DOI Listing
October 2022

Mesenchymal Stem Cells Alleviate Renal Fibrosis and Inhibit Autophagy via Exosome Transfer of miRNA-122a.

Stem Cells Int 2022 7;2022:1981798. Epub 2022 Jul 7.

Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Exosomes derived from mesenchymal stem cell (MSC) alleviate kidney damage through autophagy. This study determined whether MSCs relieve renal fibrosis and inhibit autophagy by exosome transfer of miRNA-122a. The gene expression involved in the mTOR signaling pathway and autophagy was assessed in TGF-1-treated human renal tubular epithelial cells (HK-2) and unilateral ureteral obstruction (UUO) mice before and after MSC-derived exosomes and miRNA-122a mimic treatment. Small RNA (sRNA) next-generation sequencing was also performed on TGF-1-treated HK-2 cells. MSC-derived exosomes relieve fibrosis caused by TGF in HK-2 via regulation of the mTOR signaling pathway and downstream autophagy. Furthermore, we found that MSC-derived exosomes mediate miRNA-122a to relieve renal fibrosis in HK-2 cells in response to TGF-1 through the regulation of mTOR signaling and autophagy. In the UUO mouse model, miRNA-122a mimic-transfected MSC treatment and its combination with 3-MA both recapitulated the same results as the in vitro experiments, along with reduced expansion of renal tubule, interstitial expansion, and preservation of kidney architecture. The antifibrotic activity of MSC-derived exosomes after renal fibrosis occurs partially by autophagy suppression via excreted exosomes containing mainly miRNA-122a. These findings indicate that the export of miRNA-122a via MSC-derived exosomes represents a novel strategy to alleviate renal fibrosis.
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http://dx.doi.org/10.1155/2022/1981798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289760PMC
July 2022

Hyperglycemia Aggravates Blood-Brain Barrier Disruption Following Diffuse Axonal Injury by Increasing the Levels of Inflammatory Mediators through the PPARγ/Caveolin-1/TLR4 Pathway.

Inflammation 2022 Jul 20. Epub 2022 Jul 20.

Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, People's Republic of China.

Hyperglycemia aggravates brain damage after diffuse axonal injury (DAI), but the underlying mechanisms are not fully defined. In this study, we aimed to investigate a possible role for hyperglycemia in the disruption of blood-brain barrier (BBB) integrity in a rat model of DAI and the underlying mechanisms. Accordingly, 50% glucose was intraperitoneally injected after DAI to establish the hyperglycemia model. Hyperglycemia treatment aggravated neurological impairment and axonal injury, increased cell apoptosis and glial activation, and promoted the release of inflammatory factors, including TNF-α, IL-1β, and IL-6. It also exacerbated BBB disruption and decreased the expression of tight junction-associated proteins, including ZO-1, claudin-5, and occludin-1, whereas the PPARγ agonist rosiglitazone (RSG) had the opposite effects. An in vitro BBB model was established by a monolayer of human microvascular endothelial cells (HBMECs). Hyperglycemia induction worsened the loss of BBB integrity induced by oxygen and glucose deprivation (OGD) by increasing the release of inflammatory factors and decreasing the expression of tight junction-associated proteins. Hyperglycemia further reduced the expression of PPARγ and caveolin-1, which significantly decreased after DAI and OGD. Hyperglycemia also further increased the expression of toll-like receptor 4 (TLR4), which significantly increased after OGD. Subsequently, the PPARγ agonist RSG increased caveolin-1 expression and decreased TLR4 expression and inflammatory factor levels. In contrast, caveolin-1 siRNA abrogated the protective effects of RSG in the in vitro BBB model of hyperglycemia by increasing TLR4 and Myd88 expression and the levels of inflammatory factors, including TNF-α, IL-1β, and IL-6. Collectively, we demonstrated that hyperglycemia was involved in mediating secondary injury after DAI by disrupting BBB integrity by inducing inflammation through the PPARγ/caveolin-1/TLR4 pathway.
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http://dx.doi.org/10.1007/s10753-022-01716-yDOI Listing
July 2022
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