Publications by authors named "Hao Xu"

1,976 Publications

  • Page 1 of 1

Impact of cytochrome P450 2C19 polymorphisms on the clinical efficacy and safety of voriconazole: an update systematic review and meta-analysis.

Pharmacogenet Genomics 2022 Sep 21;32(7):257-267. Epub 2022 Jul 21.

Department of Pharmacy, Peking University People's Hospital, Beijing.

Objective: To assess the impact of cytochrome P450 (CYP) 2C19 polymorphisms on the clinical efficacy and safety of voriconazole.

Methods: We systematically searched PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and three Chinese databases from their inception to 18 March 2021 using a predefined search algorithm to identify relevant studies. Studies that reported voriconazole-treated patients and information on CYP2C19 polymorphisms were included. The efficacy outcome was success rate. The safety outcomes included overall adverse events, hepatotoxicity, and neurotoxicity.

Results: A total of 20 studies were included. Intermediate metabolizers (IMs) and poor metabolizers (PMs) were associated with increased success rates compared with normal metabolizers (NMs) [risk ratio (RR), 1.18; 95% confidence interval (CI), 1.03-1.34; I2 = 0%; P = 0.02; RR, 1.28; 95% CI, 1.06-1.54; I2 = 0%; P = 0.01]. PMs were at increased risk of overall adverse events in comparison with NMs and IMs (RR, 2.18; 95% CI, 1.35-3.53; I2 = 0%; P = 0.001; RR, 1.80; 95% CI, 1.23-2.64; I2 = 0%; P = 0.003). PMs demonstrated a trend towards an increased incidence of hepatotoxicity when compared with NMs (RR, 1.60; 95% CI, 0.94-2.74; I2 = 27%; P = 0.08), although there was no statistically significant difference. In addition, there was no significant association between CYP2C19 polymorphisms and neurotoxicity.

Conclusion: IMs and PMs were at a significant higher success rate in comparison with NMs. PMs were significantly associated with an increased incidence of all adverse events compared with NMs and IMs. Researches are expected to further confirm these findings. Additionally, the relationship between hepatotoxicity and CYP2C19 polymorphisms deserves clinical attention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FPC.0000000000000470DOI Listing
September 2022

RNA mA demethylase ALKBH5 regulates the development of γδ T cells.

Proc Natl Acad Sci U S A 2022 Aug 8;119(33):e2203318119. Epub 2022 Aug 8.

Department of Geriatrics, Center for Immune-Related Diseases, Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

γδ T cells are an abundant T cell population at the mucosa and are important in providing immune surveillance as well as maintaining tissue homeostasis. However, despite γδ T cells' origin in the thymus, detailed mechanisms regulating γδ T cell development remain poorly understood. -methyladenosine (mA) represents one of the most common posttranscriptional modifications of messenger RNA (mRNA) in mammalian cells, but whether it plays a role in γδ T cell biology is still unclear. Here, we show that depletion of the mA demethylase ALKBH5 in lymphocytes specifically induces an expansion of γδ T cells, which confers enhanced protection against gastrointestinal infection. Mechanistically, loss of ALKBH5 favors the development of γδ T cell precursors by increasing the abundance of mA RNA modification in thymocytes, which further reduces the expression of several target genes including Notch signaling components and . As a result, impairment of Jagged1/Notch2 signaling contributes to enhanced proliferation and differentiation of γδ T cell precursors, leading to an expanded mature γδ T cell repertoire. Taken together, our results indicate a checkpoint role of ALKBH5 and mA modification in the regulation of γδ T cell early development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2203318119DOI Listing
August 2022

Association Between p.R229Q and Focal Segmental Glomerular Sclerosis/Steroid-Resistant Nephrotic Syndrome.

Front Med (Lausanne) 2022 22;9:937122. Epub 2022 Jul 22.

Department of Nephrology, Institute of Nephrology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Aim: is the coding gene of podocin. This study aims to investigate the association between p.R229Q (rs61747728), the most frequently reported missense variant of , and focal segmental glomerular sclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) based on typing the variant in a Chinese FSGS/SRNS cohort and conducting a meta-analysis.

Method: We recruited patients with FSGS or SRNS and healthy individuals. To conduct a meta-analysis, all studies on p.R229Q and FSGS/SRNS were searched from public databases.

Results: In total, we enrolled 204 patients with FSGS, 61 patients with SRNS [46 with FSGS, 9 with minimal change disease (MCD), and six patients with IgA nephropathy (IgAN)], and 100 healthy controls. Unexpectedly, p.R229Q was absent in the patients from our cohort. By meta-analysis of 21 studies including 2,489 patients with FSGS/SRNS and 6,004 healthy controls, we confirmed that the A allele of p.R229Q was significantly associated with increased risk of FSGS/SRNS (allelic OR = 1.9, 95% CI = 1.44-2.52, < 0.001). However, the subgroup analysis showed that the association between p.R229Q and FSGS/SRNS was true only in Caucasians (allelic OR = 2.14, 95%CI = 1.54-2.98, < 0.001) and in early-onset patients (allelic OR: 2.13, 95% CI = 1.21-3.76, = 0.009).

Conclusion: p.R229Q may play an important role in enhancing the susceptibility of FSGS/SRNS, especially in ethnicity of Caucasian and age of early-onset patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2022.937122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354893PMC
July 2022

Integration of probabilistic exposure assessment and risk characterization for perchlorate in infant formula and supplementary food.

Food Chem Toxicol 2022 Aug 4;168:113347. Epub 2022 Aug 4.

College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan, 430023, China; Key Laboratory for Deep Processing of Major Grain and Oil, Ministry of Education, Hubei Key Laboratory for Processing and Transformation of Agricultural Products, Wuhan Polytechnic University, Wuhan, 430023, China. Electronic address:

Infants are the primary susceptible population to perchlorate exposure-related adverse health effects, while information on their dietary intake of perchlorate via infant food remains limited. This study determined perchlorate in six categories of baby food commodities commonly consumed by 0-36 months infants. A probabilistic approach with Monte Carlo simulation was used to estimate perchlorate's daily intake (EDI) considering uncertainty and variability. Results showed that the average perchlorate concentration in infant food ranged from 3.42 to 22.26 μg/kg. The mean (SD) EDIs of perchlorate were 0.42(0.20), 0.62(0.20), and 0.46(0.14) μg/kg-bw/day for 0-6, 7-12, and 13-36-months infants, respectively. Infant formula was the major contributor (34%-74%) to EDIs of perchlorate in all age groups. Probabilistic risk characterization showed the cumulative probability of EDIs exceeding the RfD (0.70 μg/kg-bw/day) were 6.5%, 37.9%, and 4.5% for 0-6, 7-12, and 13-36-months infants, respectively. The cumulative risk of perchlorate exposure from different infant food intake should be noted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2022.113347DOI Listing
August 2022

Visible-light-driven CQDs/TiO photocatalytic simultaneous removal of Cr(VI) and organics: Cooperative reaction, kinetics and mechanism.

Chemosphere 2022 Aug 3;307(Pt 2):135897. Epub 2022 Aug 3.

School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao, 266033, China.

CQDs/TiO was synthesized with a coprecipitation method and characterized by XRD, SEM, TEM/HRTEM, BET, XPS, UV-Vis DRS and I-t curve technologies. UV-Vis DRS displayed that absorption spectrum of CQDs/TiO enlarged to visible light zone, suggesting that CQDs/TiO can be irradiated by visible light. I-t curve showed that photocurrent of CQDs/TiO was higher than that of bare TiO, revealing that the doping of CQDs accelerated the transfer of photoelectrons and restrained the recombination of photoinduced carriers. Simultaneous removal of Cr(VI) and organics with CQDs/TiO photocatalytic reaction was investigated and factors were optimized, and almost all Cr(VI) and organics were removed under the optimum conditions. Experimental results displayed that there was a distinct cooperation removal effect between Cr(VI) and organics in CQDs/TiO photocatalytic reaction. XPS analysis proved that Cr(VI) was reduced to Cr(III) in situ on CQDs/TiO surface. There were e, h,·OH and ·O active species which were detected with DMPO in ESR test during CQDs/TiO photocatalytic reaction, and scavenger experiment proved that e and h were the substantial reactants for Cr(VI) and organics, respectively. The pathway of photocatalytic simultaneous removal of Cr(VI) and organics underwent four steps: adsorption of Cr(VI) and organics on CQDs/TiO surface; production of photo electrons and holes in visible light; reduction of Cr(VI) and oxidation of organics; desorption of Cr(III) and intermediates. Photocatalytic reaction kinetics of Cr(VI) and organics were both confirmed to pseudo first-order reaction. Life span and small scale real application tests both demonstrated that CQDs/TiO had a potential application to wastewater containing Cr(VI) and organics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2022.135897DOI Listing
August 2022

Homogeneous Synthesis of Monodisperse Sequence-Defined Conjugated Oligomers by Temperature Cycling.

Angew Chem Int Ed Engl 2022 Aug 5. Epub 2022 Aug 5.

University of Toronto, Chemistry, 80 St. George Street, M5S 3H6, Toronto, CANADA.

Sequence-defined synthetic oligomers and polymers provide unprecedented opportunities for polymer chemists to finely control properties such as chain folding, self-assembly, and optoelectronic performance of materials. However, absolute control over both chain-length and monomer sequence has been a long-standing "grand challenge" for decades. Herein, we report a novel strategy to synthesize monodisperse sequence-defined conjugated oligomers in a homogeneous manner by temperature cycling, thereby achieving single-monomer precision in conjugated polyheterocycles. A series of sequence-defined oligomers with up to twelve repeating units, four different monomers, and various sequences were successfully synthesized. Monomer sequence was also proved to affect optical properties. We believe this strategy not only exhibits general applicability to the synthesis of group 16 conjugated oligomers and polymers, but also has far-reaching potential for other polymer systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202210340DOI Listing
August 2022

Identification of three novel Spätzle genes in Eriocheir sinensis and their roles during white spot syndrome virus infection.

Fish Shellfish Immunol 2022 Jul 31;128:168-180. Epub 2022 Jul 31.

Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, Jiangsu Province, 210023, China. Electronic address:

Proteins of Spätzle family play an essential role in innate immunity in invertebrates by activating the Toll pathway to induce the expression of antimicrobial peptides. However, little is known about the function of Spätzle in in the immune response of the Chinese mitten crab. In the present study, three novel Spätzle genes (named as EsSpz1, EsSpz2, and EsSpz3) were identified from Eriocheir sinensis. The genome structure of EsSpz1 contains two exons and an intron. Three Spätzle proteins all contain a Pfam Spaetzle domain. In the evolution, EsSpz1-3 cluster with other Spätzle proteins from crustaceans. EsSpz1-3 were widely distributed in multiple immune tissues. The expression levels of EsSpz1-3 in the intestine were remarkably upregulated after white spot syndrome virus (WSSV) challenge. The knockdown of EsSpz1-3 remarkably decreased the expressions of crustins and anti-lipopolysaccharide factors during WSSV infection. Moreover, EsSpz1-3 silencing remarkably increased the expression of WSSV envelope protein VP28. These findings suggest that new-found EsSpz1-3 in E. sinensis could promote the synthesis of antimicrobial peptides and inhibit the expression of VP28 during WSSV infection. Our study indicates that EsSpz1-3 in E. sinensis may participate in the innate immune defenses against WSSV by inducing the expression of antimicrobial peptides. This study provides new knowledge for the function of Spätzle in the antiviral immune defense in crustacean.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsi.2022.07.065DOI Listing
July 2022

BTApep-TAT peptide inhibits ADP-ribosylation of BORIS to induce DNA damage in cancer.

Mol Cancer 2022 08 2;21(1):158. Epub 2022 Aug 2.

School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, 310013, China.

Background: Brother of regulator of imprinted sites (BORIS) is expressed in most cancers and often associated with short survival and poor prognosis in patients. BORIS inhibits apoptosis and promotes proliferation of cancer cells. However, its mechanism of action has not been elucidated, and there is no known inhibitor of BORIS.

Methods: A phage display library was used to find the BORIS inhibitory peptides and BTApep-TAT was identified. The RNA sequencing profile of BTApep-TAT-treated H1299 cells was compared with that of BORIS-knockdown cells. Antitumor activity of BTApep-TAT was evaluated in a non-small cell lung cancer (NSCLC) xenograft mouse model. BTApep-TAT was also used to investigate the post-translational modification (PTM) of BORIS and the role of BORIS in DNA damage repair. Site-directed mutants of BORIS were constructed and used for investigating PTM and the function of BORIS.

Results: BTApep-TAT induced DNA damage in cancer cells and suppressed NSCLC xenograft tumor progression. Investigation of the mechanism of action of BTApep-TAT demonstrated that BORIS underwent ADP ribosylation upon double- or single-strand DNA damage. Substitution of five conserved glutamic acid (E) residues with alanine residues (A) between amino acids (AAs) 198 and 228 of BORIS reduced its ADP ribosylation. Inhibition of ADP ribosylation of BORIS by a site-specific mutation or by BTApep-TAT treatment blocked its interaction with Ku70 and impaired the function of BORIS in DNA damage repair.

Conclusions: The present study identified an inhibitor of BORIS, highlighted the importance of ADP ribosylation of BORIS, and revealed a novel function of BORIS in DNA damage repair. The present work provides a practical method for the future screening or optimization of drugs targeting BORIS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12943-022-01621-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344678PMC
August 2022

Dose escalation based on F-FDG PET/CT response in definitive chemoradiotherapy of locally advanced esophageal squamous cell carcinoma: a phase III, open-label, randomized, controlled trial (ESO-Shanghai 12).

Radiat Oncol 2022 Jul 29;17(1):134. Epub 2022 Jul 29.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Introduction: Definitive chemoradiotherapy has established the standard non-surgical treatment for locally advanced esophageal cancer. The standard dose of 50-50.4 Gy has been established decades ago and been confirmed in modern trials. The theorical advantage of better local control and technical advances for less toxicity have encouraged clinicians for dose escalation investigation. F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) have the potential to tailor therapy for esophageal patients not showing response to CRT and pioneers the PET-based dose escalation.

Methods And Analysis: The ESO-Shanghai 12 trial is a prospective multicenter randomized phase 3 study in which patients are randomized to either 61.2 Gy or 50.4 Gy of radiation dose by PET response. Both groups undergo concurrent chemoradiotherapy with paclitaxel/cisplatin regimen for 2 cycles followed by consolidation chemotherapy for 2 cycles. Patients with histologically confirmed ESCC [T1N1-3M0, T2-4NxM0, TxNxM1 (Supraclavicular lymph node metastasis only), (AJCC Cancer Staging Manual, 8th Edition)] and without any prior treatment of chemotherapy, radiotherapy or surgery against esophageal cancer will be eligible. The primary endpoints included overall survival in PET/CT non-responders (SUV > 4.0) and overall survival in total population. Patients will be stratified by standardized uptake volume, gross tumor volume and tumor location. The enrollment could be ended, when the number of PET/CT non-responder reached 132 and the total population reached 646 for randomization.

Ethics And Dissemination: This trial has been approved by the Fudan University Shanghai Cancer Center Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations. Trial registration The trial was initiated in 2018 and is currently recruiting patients. Trial registration number NCT03790553.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13014-022-02099-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338557PMC
July 2022

Molecular and clinical features of a potential immunotherapy target ELK3 in glioma.

Medicine (Baltimore) 2022 Jul 29;101(30):e29544. Epub 2022 Jul 29.

Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Glioma represents the most prevalent malignant primary brain cancer, and its treatment remains a tremendous challenge. Novel and efficient molecular targets are therefore required for improving diagnosis, survival prediction, and treatment outcomes. Additionally, some studies have shown that immunity is highly associated with glioma progression. Our study aimed to investigate the clinicopathological features, prognostic significance, and immunotherapeutic targetability of ELK3, a member of the erythroblast transformation-specific transcription factor family, in glioma using bioinformatics analyses. ELK3 transcript levels in glioma tissues were evaluated using the Gene Expression Omnibus and The Cancer Genome Atlas databases. Clinical and transcriptomic data of The Cancer Genome Atlas glioma patients were analyzed to identify the molecular and clinical characterizations of ELK3. The prognostic significance of ELK3 was assessed using Cox regression and Kaplan-Meier analysis. The biological pathways related to ELK3 expression were identified by gene set enrichment analysis. The relationships between ELK3 and inflammatory responses, immune cell infiltration, and immune checkpoints were explored using canonical correlation analysis and gene set variation analysis. ELK3 was upregulated in gliomas, and its high expression was correlated with advanced clinicopathologic features and unfavorable prognosis. Gene set enrichment analysis revealed that several immune-related pathways were tightly linked to high ELK3 expression. gene set variation analysis and correlograms demonstrated that ELK3 was robustly associated with inflammatory and immune responses. Correlation analyses indicated that ELK3 was positively associated with infiltrating immune cells and synergistic with several immune checkpoints. ELK3 may serve as a novel marker of poor prognosis and a potential immunotherapeutic target in glioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000029544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333475PMC
July 2022

Will climate change cause the global peatland to expand or contract? Evidence from the habitat shift pattern of Sphagnum mosses.

Glob Chang Biol 2022 Jul 28. Epub 2022 Jul 28.

Bryology Laboratory, School of Life Sciences, East China Normal University, Shanghai, China.

Peatlands play a crucial role in the global carbon cycle. Sphagnum mosses (peat mosses) are considered to be the peatland ecosystem engineers and contribute to the carbon accumulation in the peatland ecosystems. As cold-adapted species, the dominance of Sphagnum mosses in peatlands will be threatened by climate warming. The response of Sphagnum mosses to climate change is closely related to the future trajectory of carbon fluxes in peatlands. However, the impact of climate change on the habitat suitability of Sphagnum mosses on a global scale is poorly understood. To predict the potential impact of climate change on the global distribution of Sphagnum mosses, we used the MaxEnt model to predict the potential geographic distribution of six Sphagnum species that dominate peatlands in the future (2050 and 2070) under two greenhouse gas emission scenarios (SSP1-2.6 and SSP5-8.5). The results show that the mean temperature of the coldest quarter, precipitation of the driest month, and topsoil calcium carbonate are the main factors affecting the habitat availability of Sphagnum mosses. As the climate warms, Sphagnum mosses tend to migrate northward. The suitable habitat and abundance of Sphagnum mosses increase extensively in the high-latitude boreal peatland (north of 50°N) and decrease on a large scale beyond the high-latitude boreal peatland. The southern edge of boreal peatlands would experience the greatest decline in the suitable habitat and richness of Sphagnum mosses with the temperature rising and would be a risk area for the transition from carbon sink to carbon source. The spatial-temporal pattern changes of Sphagnum mosses simulated in this study provide a reference for the development of management and conservation strategies for Sphagnum bogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/gcb.16354DOI Listing
July 2022

Lipidomic identification of urinary extracellular vesicles for non-alcoholic steatohepatitis diagnosis.

J Nanobiotechnology 2022 Jul 27;20(1):349. Epub 2022 Jul 27.

The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

Background And Aims: Non-alcoholic fatty liver disease (NAFLD) is a usual chronic liver disease and lacks non-invasive biomarkers for the clinical diagnosis and prognosis. Extracellular vesicles (EVs), a group of heterogeneous small membrane-bound vesicles, carry proteins and nucleic acids as promising biomarkers for clinical applications, but it has not been well explored on their lipid compositions related to NAFLD studies. Here, we investigate the lipid molecular function of urinary EVs and their potential as biomarkers for non-alcoholic steatohepatitis (NASH) detection.

Methods: This work includes 43 patients with non-alcoholic fatty liver (NAFL) and 40 patients with NASH. The EVs of urine were isolated and purified using the EXODUS method. The EV lipidomics was performed by LC-MS/MS. We then systematically compare the EV lipidomic profiles of NAFL and NASH patients and reveal the lipid signatures of NASH with the assistance of machine learning.

Results: By lipidomic profiling of urinary EVs, we identify 422 lipids mainly including sterol lipids, fatty acyl lipids, glycerides, glycerophospholipids, and sphingolipids. Via the machine learning and random forest modeling, we obtain a biomarker panel composed of 4 lipid molecules including FFA (18:0), LPC (22:6/0:0), FFA (18:1), and PI (16:0/18:1), that can distinguish NASH with an AUC of 92.3%. These lipid molecules are closely associated with the occurrence and development of NASH.

Conclusion: The lack of non-invasive means for diagnosing NASH causes increasing morbidity. We investigate the NAFLD biomarkers from the insights of urinary EVs, and systematically compare the EV lipidomic profiles of NAFL and NASH, which holds the promise to expand the current knowledge of disease pathogenesis and evaluate their role as non-invasive biomarkers for NASH diagnosis and progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12951-022-01540-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327366PMC
July 2022

Correction to: Serum Exosomal MicroRNA-27-3p Aggravates Cerebral Injury and Inflammation in Patients with Acute Cerebral Infarction by Targeting PPARγ.

Inflammation 2022 Jul 27. Epub 2022 Jul 27.

Department of Neurology, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Liandu District of Lishui City, No. 289 Kuocang Road, Zhejiang Province, 323000, Wenzhou, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10753-022-01717-xDOI Listing
July 2022

SNAI2 promotes the malignant transformation of oral leukoplakia by modulating p-EMT.

Oral Dis 2022 Jul 27. Epub 2022 Jul 27.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, P.R. China.

Objective: Snail family transcriptional repressor 2 (SNAI2) is a key regulator of partial epithelial-mesenchymal transition (p-EMT), and is associated with tumorigenesis. Whether SNAI2 promotes oral leukoplakia (OLK) malignant transformation by modulating p-EMT is unclear.

Materials And Methods: This study utilized two clinical datasets (GSE26549 and GSE85195) from the Gene Expression Omnibus database, cytological experiments, and a 4-nitroquinoline 1-oxide-induced mice model to explore the role of SNAI2 in OLK malignant transformation.

Results: The clinical cohort found SNAI2, as a risk factor (HR = 2.50, 95% CI: 1.08 - 5.79, p = 0.033), could promote OLK malignant transformation (p = 0.012). Cytological experiments indicated that SNAI2 overexpression promoted DOK cell proliferation, invasion, migration, and increase the protein expression of p-EMT relative signatures, whereas SNAI2 silencing has opposite effects. Furthermore, the mice model and clinical datasets demonstrated the expression of SNAI2 and p-EMT relative signatures were increased with OLK malignant transformation. And SNAI2 was strongly correlated with p-EMT. Besides, co-expressed genes of SNAI2 were also enriched in p-EMT relative biological processes and signalling pathways.

Conclusions: p-EMT plays a significant role in promoting the OLK malignant transformation. As an important regulator of p-EMT, SNAI2 could be a target to block the OLK malignant transformation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.14321DOI Listing
July 2022

Aerobic Degradation Characteristics of Decabromodiphenyl ether through TAW-CT127 and Its Preliminary Genome Analysis.

Microorganisms 2022 Jul 17;10(7). Epub 2022 Jul 17.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.

Decabromodiphenyl ether (BDE-209), a polybrominated diphenyl ether (PBDE) homolog, seriously threatens human health. In this study, a strain with high BDE-209 degradation activity, named TAW-CT127, was isolated from Tong'an Bay, Xiamen. Under laboratory conditions, the strain's optimal growth temperature, pH, and salinity are 45 °C, 7.0, and 0-2.5%, respectively. Scanning electron microscopy (SEM) analysis shows that TAW-CT127 is damaged when grown in manual marine culture (MMC) medium with BDE-209 as the sole carbon source instead of eutrophic conditions. In the dark, under the conditions of 28 °C, 160 rpm, and 3 g/L (wet weight) TAW-CT127, the degradation rate of 50 mg/L BDE-209 is 81.07%. The intermediate metabolites are hexabromo-, octabromo-, and nonabromo-diphenyl ethers. Through whole-genome sequencing, multiple dehalogenases were found in the genome of TAW-CT127; these may be involved in the production of lower-brominated diphenyl ethers. Additionally, biphenyl-2,3-dioxygenase (BDO) in TAW-CT127 may catalyze the debromination reaction of BDE-209. Our research provides a new high-efficiency strain for bioremediation of BDE-209 pollution, and lays the foundation for the preliminary exploration of genes associated with BDE-209 degradation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms10071441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319644PMC
July 2022

Deep Multilabel Multilingual Document Learning for Cross-Lingual Document Retrieval.

Entropy (Basel) 2022 Jul 7;24(7). Epub 2022 Jul 7.

College of Computer Science and Technology, Jilin University, Changchun 130012, China.

Cross-lingual document retrieval, which aims to take a query in one language to retrieve relevant documents in another, has attracted strong research interest in the last decades. Most studies on this task start with cross-lingual comparisons at the word level and then represent documents via word embeddings, which leads to insufficient structure information. In this work, the cross-lingual comparison at the document level is achieved through the cross-lingual semantic space. Our method, MDL (deep multilabel multilingual document learning), leverages a six-layer fully connected network to project cross-lingual documents into a shared semantic space. The semantic distances can be calculated when the cross-lingual documents are transformed into embeddings in semantic space. The supervision signals are automatically extracted from the data and then used to construct the semantic space via a linear classifier. The ambiguity of manual labels could be avoided and the multilabel supervision signals can be acquired instead of a single label. The representation of the semantic space is enriched by multilabel supervision signals, which improves the discriminative ability of the embeddings. The MDL is easy to extend to other fields since it does not depend on specific data. Furthermore, MDL is more efficient than the models training all languages jointly, since each language is trained individually. Experiments on Wikipedia data showed that the proposed method outperforms the state-of-the-art cross-lingual document retrieval methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/e24070943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318374PMC
July 2022

Impact of Anti-Angiogenic Treatment on Bone Vascularization in a Murine Model of Breast Cancer Bone Metastasis Using Synchrotron Radiation Micro-CT.

Cancers (Basel) 2022 Jul 15;14(14). Epub 2022 Jul 15.

CREATIS, Université de Lyon, CNRS UMR5220, INSERM, U1206, Université Lyon 1, INSA-Lyon, 69100 Villeurbanne, France.

Bone metastases are frequent complications of breast cancer, facilitating the development of anarchic vascularization and induce bone destruction. Therefore, anti-angiogenic drugs (AAD) have been tested as a therapeutic strategy for the treatment of breast cancer bone metastasis. However, the kinetics of skeletal vascularization in response to tumor invasion under AAD is still partially understood. Therefore, the aim of this study was to explore the effect of AAD on experimental bone metastasis by analyzing the three-dimensional (3D) bone vasculature during metastatic formation and progression. Seventy-three eight-week-old female mice were treated with AAD (bevacizumab, vatalanib, or a combination of both drugs) or the vehicle (placebo) one day after injection with breast cancer cells. Mice were sacrificed eight or 22 days after tumor cell inoculation (time points T1 and T2, respectively). Synchrotron radiation microcomputed tomography (SR-μCT) was used to image bone and blood vessels with a contrast agent. Hence, 3D-bone and vascular networks were simultaneously visualized and quantitatively analyzed. At T1, the trabecular bone volume fraction was significantly increased ( < 0.05) in the combined AAD-treatment group, compared to the placebo- and single AAD-treatment groups. At T2, only the bone vasculature was reduced in the combined AAD-treatment group ( < 0.05), as judged by measurement of the blood vessel thickness. Our data suggest that, at the early stage, combined AAD treatment dampens tumor-induced bone resorption with no detectable effects on bone vessel organization while, at a later stage, it affects the structure of bone microvascularization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers14143443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321934PMC
July 2022

Ebselen Interferes with Alzheimer's Disease by Regulating Mitochondrial Function.

Antioxidants (Basel) 2022 Jul 11;11(7). Epub 2022 Jul 11.

Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, China.

(1) Background: With unknown causes and no effective treatment available, Alzheimer's disease (AD) places enormous pressure on families and society. Our previous study had shown that Ebselen at a high concentration (10.94 μM) improved the cognition of triple-transgenic AD (3×Tg-AD) mice and alleviated the related pathological indicators but showed toxicity to the mice. Here, we dedicated to study the therapeutic effect and molecular mechanism of Ebselen at a much lower concentration on 3×Tg-AD mice. (2) Methods: Various behavioral experiments were applied to detect the behavioral ability of mice. Western blot, thioflavin T staining and a transmission electron microscope were used to evaluate the pathology of AD mice. The mitochondrial membrane potential and respiration were assessed with the corresponding assay kit. (3) Results: Ebselen remarkably increased cognitive ability of AD mice, eliminated β-Amyloid (Aβ) oligomers and recovered the synaptic damage in AD mice brain. In addition, the destroyed mitochondrial morphologies and function were repaired by Ebselen through ameliorating mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial fusion/fission balance in N2a-SW cells and brain tissues of AD mice. (4) Conclusions: This research indicated that Ebselen might exert its therapeutic effect via protecting mitochondria in AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox11071350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312019PMC
July 2022

Evaluation of Chiral Fungicide Penflufen in Legume Vegetables: Enantioseparation and Its Mechanism, Enantioselective Behaviors, and Risk Assessment.

J Agric Food Chem 2022 Aug 25;70(30):9319-9326. Epub 2022 Jul 25.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/ Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, P. R. China.

Illustrating the enantioselective behaviors of the novel chiral fungicide penflufen was extremely important for ecological safety and human health. For penflufen enantiomers, an excellent separation method including a short analysis time (4 min), a high sensitivity (2 ng/g), and lesser consumption of an organic solvent was first established through supercritical fluid chromatography-tandem mass spectrometry. The enantioseparation mechanism was explained by computational chemistry, and the stronger binding ability of -(+)-penflufen with cellulose tris-(3-chloro-4-methylphenylcarbamate) (the chiral stationary phase OZ-3 column) contributed to the posterior elution. In legume vegetables, penflufen dissipation was the fastest in Linn plants (half-life, 1 day) and the slowest in plants (half-lives, 11.3-12.9 days). After 30, 50, and 40 days, the -penflufen residues were lower than the maximum residue level value in the Electronic Code of Federal Regulations (10 ng/g) in , Linn, and , respectively. Abundant -(+)-penflufen was found in these plants with stereoisomeric excess (se) changes being >10% in the initial stage, so the risk assessment might be driven by -(+)-penflufen. However, the se changes were <10% in plants, and the risk assessment might be calculated based on -penflufen. Moreover, penflufen enantiomers could be transferred from legume vegetables to soils, and the concentrations increased with time. The high persistence and medium mobility of penflufen in soils might lead to potential groundwater contamination, which was noteworthy. These results could contribute to a more accurate risk assessment of penflufen in legume vegetables.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.2c02238DOI Listing
August 2022

Interactive Self-Reporting as Behavioural Cue Elicitor for Online-Classroom Assessment.

Authors:
Hao Xu

Behav Sci (Basel) 2022 Jul 14;12(7). Epub 2022 Jul 14.

National Research Centre for Foreign Language Education, Beijing Foreign Studies University, Beijing 100089, China.

How teachers should elicit and draw on behavioural cues for online-classroom assessment is of much interest to both researchers and practising teachers. Aiming to explore how to enhance interactive self-reporting as a behavioural cue elicitor for online-classroom assessment, this study adopted a large-scale questionnaire survey to investigate the effects of the intensity of interaction in interactive self-reporting and teachers' professional experience on the quality of assessment data in online teaching. Results showed that only the intensity of teacher's follow-up interaction regarding interactive self-reporting had a significant impact on the quality of the assessment data. Specifically, as a behavioural cue elicitor, interactive self-reporting may be best utilised when interaction of a moderate intensity is employed by the teacher following students' self-report. The accuracy and efficiency of interactive self-reporting as a means to obtain assessment data in online teaching can only, thus, be best synergised. Otherwise, the accuracy and efficiency may be reduced to a wax-and-wane relationship, i.e., each one increases at the expense of the other.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/bs12070232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311913PMC
July 2022

High-Accuracy Oral Squamous Cell Carcinoma Auxiliary Diagnosis System Based on EfficientNet.

Front Oncol 2022 7;12:894978. Epub 2022 Jul 7.

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

It is important to diagnose the grade of oral squamous cell carcinoma (OSCC), but the current evaluation of the biopsy slide still mainly depends on the manual operation of pathologists. The workload of manual evaluation is large, and the results are greatly affected by the subjectivity of the pathologists. In recent years, with the development and application of deep learning, automatic evaluation of biopsy slides is gradually being applied to medical diagnoses, and it has shown good results. Therefore, a new OSCC auxiliary diagnostic system was proposed to automatically and accurately evaluate the patients' tissue slides. This is the first study that compared the effects of different resolutions on the results. The OSCC tissue slides from The Cancer Genome Atlas (TCGA, n=697) and our independent datasets (n=337) were used for model training and verification. In the test dataset of tiles, the accuracy was 93.1% at 20x resolution (n=306,134), which was higher than that at 10x (n=154,148, accuracy=90.9%) and at 40x (n=890,681, accuracy=89.3%). The accuracy of the new system based on EfficientNet, which was used to evaluate the tumor grade of the biopsy slide, reached 98.1% [95% confidence interval (CI): 97.1% to 99.1%], and the area under the receiver operating characteristic curve (AUROC) reached 0.998 (95%CI: 0.995 to 1.000) in the TCGA dataset. When verifying the model on the independent image dataset, the accuracy still reached 91.4% (95% CI: 88.4% to 94.4%, at 20x) and the AUROC reached 0.992 (95%CI: 0.982 to 1.000). It may benefit oral pathologists by reducing certain repetitive and time-consuming tasks, improving the efficiency of diagnosis, and facilitating the further development of computational histopathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2022.894978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302026PMC
July 2022

Senescence in osteoarthritis: from mechanism to potential treatment.

Arthritis Res Ther 2022 07 22;24(1):174. Epub 2022 Jul 22.

Department of Joint Surgery, the Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong Province, China.

Osteoarthritis (OA) is an age-related cartilage degenerative disease, and chondrocyte senescence has been extensively studied in recent years. Increased numbers of senescent chondrocytes are found in OA cartilage. Selective clearance of senescent chondrocytes in a post-traumatic osteoarthritis (PTOA) mouse model ameliorated OA development, while intraarticular injection of senescent cells induced mouse OA. However, the means and extent to which senescence affects OA remain unclear. Here, we review the latent mechanism of senescence in OA and propose potential therapeutic methods to target OA-related senescence, with an emphasis on immunotherapies. Natural killer (NK) cells participate in the elimination of senescent cells in multiple organs. A relatively comprehensive discussion is presented in that section. Risk factors for OA are ageing, obesity, metabolic disorders and mechanical overload. Determining the relationship between known risk factors and senescence will help elucidate OA pathogenesis and identify optimal treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-022-02859-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306208PMC
July 2022

Nontrivial phase matching in helielectric polarization helices: Universal phase matching theory, validation, and electric switching.

Proc Natl Acad Sci U S A 2022 Jul 12;119(29):e2205636119. Epub 2022 Jul 12.

Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, 510640 Guangzhou, China.

Second-order optical nonlinearity is the essential concept for realizing modern technologies of optical wavelength conversion. The emerging helical polarization fluid, dubbed helielectric nematic, now makes it possible to design and easily fabricate various polarization structures and control their optical responses. The matter family is demonstrated as an ideal liquid platform for nonlinear optical conversion and amplification with electric-reconfigurable tunability. We here develop a universal phase matching theory and reveal a nonclassic chirality-sensitive phase-matching condition in the polarization helices through both the numerical calculation and the experimental validations. The nonlinear optical amplification can be dramatically modulated with a contrast ratio of >100:1 by an in-plane electric field. Furthermore, we employ the director relaxation under electric fields coupled with nonlinear optical simulation to clarify the topology-light interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2205636119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304031PMC
July 2022

Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway.

Stem Cell Res Ther 2022 07 18;13(1):326. Epub 2022 Jul 18.

Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China.

Background: Bone marrow mesenchymal stem cell (BMSCs) therapy is an important cell transplantation strategy in the regenerative medicine field. However, a severely ischemic microenvironment, such as nutrient depletion and hypoxia, causes a lower survival rate of transplanted BMSCs, limiting the application of BMSCs. Therefore, improving BMSCs viability in adverse microenvironments is an important means to improve the effectiveness of BMSCs therapy.

Objective: To illustrate the protective effect of andrographolide (AG) against glucose and serum deprivation under hypoxia (1% O) (GSDH)-induced cell injury in BMSCs and investigate the possible underlying mechanisms.

Methods: An in vitro primary rat BMSCs cell injury model was established by GSDH, and cellular viability, proliferation and apoptosis were observed after AG treatment under GSDH. Reactive oxygen species levels and oxidative stress-related genes and proteins were measured by flow cytometry, RT-qPCR and Western blotting. Mitochondrial morphology, function and number were further assessed by laser confocal microscopy and flow cytometry.

Results: AG protected BMSCs against GSDH-induced cell injury, as indicated by increases in cell viability and proliferation and mitochondrial number and decreases in apoptosis and oxidative stress. The metabolic status of BMSCs was changed from glycolysis to oxidative phosphorylation to increase the ATP supply. We further observed that the NRF2 pathway was activated by AG, and treatment of BMSCs with a specific NRF2 inhibitor (ML385) blocked the protective effect of AG.

Conclusion: Our results suggest that AG is a promising agent to improve the therapeutic effect of BMSCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-022-03016-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290240PMC
July 2022

Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With Traumatic Brain Injury.

Front Genet 2022 30;13:861428. Epub 2022 Jun 30.

Department of Neurosurgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.

Traumatic brain injury (TBI) is currently a substantial public health problem and one of the leading causes of morbidity and mortality worldwide. However, the cellular and transcriptional changes in TBI at single-cell level have not been well characterized. In this study, we reanalyzed a single-cell RNA sequencing (scRNA-seq) dataset of mouse hippocampus to identify the key cellular and transcriptional changes associated with TBI. Specifically, we found that oligodendrocytes were the most abundant cell type in mouse hippocampus, and detected an expanded astrocyte population, which was significantly activated in TBI. The enhanced activity of inflammatory response-related pathways in the astrocytes of TBI samples suggested that the astrocytes, along with microglia, which were the major brain-resident immune cells, were responsible for inflammation in the acute phase of TBI. Hormone secretion, transport, and exocytosis were found upregulated in the excitatory neurons of TBI, which gave us a hint that excitatory neurons might excessively transport and excrete glutamate in response to TBI. Moreover, the ependymal subpopulation C0 was TBI-specific and characterized by downregulated cilium movement, indicating that the attenuated activity of cilium movement following TBI might decrease cerebrospinal fluid flow. Furthermore, we observed that downregulated genes in response to candesartan treatment were preferentially expressed in excitatory neurons and were related to pathways like neuronal systems and neuroactive ligand-receptor interaction, indicating that candesartan might promote recovery of neurons after traumatic brain injury mediating neuroactive ligand-receptor interactions and reducing excitotoxicity. In conclusion, our study identified key cell types in TBI, which improved our understanding of the cellular and transcriptional changes after TBI and offered an insight into the molecular mechanisms that could serve as therapeutic targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2022.861428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282873PMC
June 2022

Group 16 conjugated polymers based on furan, thiophene, selenophene, and tellurophene.

Chem Soc Rev 2022 Aug 1;51(15):6442-6474. Epub 2022 Aug 1.

Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6, Canada.

Five-membered aromatic rings containing Group 16 elements (O, S, Se, and Te), also referred as chalcogenophenes, are ubiquitous building blocks for π-conjugated polymers (CPs). Among these, polythiophenes have been established as a model system to study the interplay between molecular structure, solid-state organization, and electronic performance. The judicious substitution of alternative heteroatoms into polythiophenes is a promising strategy for tuning their properties and improving the performance of derived organic electronic devices, thus leading to the recent abundance of CPs containing furan, selenophene, and tellurophene. In this review, we first discuss the current status of Kumada, Negishi, Murahashi, Suzuki-Miyaura, and direct arylation polymerizations, representing the best routes to access well-defined chalcogenophene-containing homopolymers and copolymers. The self-assembly, optical, solid-state, and electronic properties of these polymers and their influence on device performance are then summarized. In addition, we highlight post-polymerization modifications as effective methods to transform polychalcogenophene backbones or side chains in ways that are unobtainable by direct polymerization. Finally, the major challenges and future outlook in this field are presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d2cs00139jDOI Listing
August 2022

Selective block of sensory neuronal T-type/Cav3.2 activity mitigates neuropathic pain behavior in a rat model of osteoarthritis pain.

Arthritis Res Ther 2022 07 16;24(1):168. Epub 2022 Jul 16.

Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.

Background: Peripheral and central nociceptive sensitization is a critical pathogenetic component in osteoarthritis (OA) chronic pain. T-type calcium channel 3.2 (Ca3.2) regulates neuronal excitability and plays important roles in pain processing. We previously identified that enhanced T-type/Ca3.2 activity in the primary sensory neurons (PSNs) of dorsal root ganglia (DRG) is associated with neuropathic pain behavior in a rat model of monosodium iodoacetate (MIA)-induced knee OA. PSN-specific T-type/Ca3.2 may therefore represent an important mediator in OA painful neuropathy. Here, we test the hypothesis that the T-type/Ca3.2 channels in PSNs can be rationally targeted for pain relief in MIA-OA.

Methods: MIA model of knee OA was induced in male and female rats by a single injection of 2 mg MIA into intra-knee articular cavity. Two weeks after induction of knee MIA-OA pain, recombinant adeno-associated viruses (AAV)-encoding potent Ca3.2 inhibitory peptide aptamer 2 (Ca3.2iPA2) that have been characterized in our previous study were delivered into the ipsilateral lumbar 4/5 DRG. Effectiveness of DRG-Ca3.2iPA2 treatment on evoked (mechanical and thermal) and spontaneous (conditioned place preference) pain behavior, as well as weight-bearing asymmetry measured by Incapacitance tester, in the arthritic limbs of MIA rats were evaluated. AAV-mediated transgene expression in DRG was determined by immunohistochemistry.

Results: AAV-mediated expression of Ca3.2iPA2 selective in the DRG-PSNs produced significant and comparable mitigations of evoked and spontaneous pain behavior, as well as normalization of weight-bearing asymmetry in both male and female MIA-OA rats. Analgesia of DRG-AAV-Ca3.2iPA1, another potent Ca3.2 inhibitory peptide, was also observed. Whole-cell current-clamp recordings showed that AAV-mediated Ca3.2iPA2 expression normalized hyperexcitability of the PSNs dissociated from the DRG of MIA animals, suggesting that Ca3.2iPA2 attenuated pain behavior by reversing MIA-induced neuronal hyperexcitability.

Conclusions: Together, our results add therapeutic support that T-type/Ca3.2 in primary sensory pathways contributes to MIA-OA pain pathogenesis and that Ca3.2iPAs are promising analgesic leads that, combined with AAV-targeted delivery in anatomically segmental sensory ganglia, have the potential for further development as a peripheral selective T-type/Ca3.2-targeting strategy in mitigating chronic MIA-OA pain behavior. Validation of the therapeutic potential of this strategy in other OA models may be valuable in future study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-022-02856-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287929PMC
July 2022

Oxygen Vacancy-Rich 2D TiO Nanosheets: A Bridge Toward High Stability and Rapid Hydrogen Storage Kinetics of Nano-Confined MgH.

Nanomicro Lett 2022 Jul 15;14(1):144. Epub 2022 Jul 15.

National Engineering Research Center of Light Alloys Net Forming & State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.

MgH has attracted intensive interests as one of the most promising hydrogen storage materials. Nevertheless, the high desorption temperature, sluggish kinetics, and rapid capacity decay hamper its commercial application. Herein, 2D TiO nanosheets with abundant oxygen vacancies are used to fabricate a flower-like MgH/TiO heterostructure with enhanced hydrogen storage performances. Particularly, the onset hydrogen desorption temperature of the MgH/TiO heterostructure is lowered down to 180 °C (295 °C for blank MgH). The initial desorption rate of MgH/TiO reaches 2.116 wt% min at 300 °C, 35 times of the blank MgH under the same conditions. Moreover, the capacity retention is as high as 98.5% after 100 cycles at 300 °C, remarkably higher than those of the previously reported MgH-TiO composites. Both in situ HRTEM observations and ex situ XPS analyses confirm that the synergistic effects from multi-valance of Ti species, accelerated electron transportation caused by oxygen vacancies, formation of catalytic Mg-Ti oxides, and stabilized MgH NPs confined by TiO nanosheets contribute to the high stability and kinetically accelerated hydrogen storage performances of the composite. The strategy of using 2D substrates with abundant defects to support nano-sized energy storage materials to build heterostructure is therefore promising for the design of high-performance energy materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40820-022-00891-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287516PMC
July 2022

Transcriptome analysis reveals the early resistance of zebrafish larvae to oxidative stress.

Fish Physiol Biochem 2022 Jul 15. Epub 2022 Jul 15.

College of Fisheries, Southwest University, Chongqing, 400715, China.

Oxidative stress is one of most common environmental stresses encountered by fish, especially during their fragile larval stage. More and more studies are aimed at understanding the antioxidant defense mechanism of fish larvae. Herein we characterized the early resistance of zebrafish larvae to oxidative stress and investigated the underlying transcriptional regulations using RNA-seq. We found that pre-exposure of zebrafish larvae to 2 mM HO for 1 or 3 h significantly improved their survival under higher doses of HO (3 mM), suggesting the antioxidant defenses of zebrafish larvae were rapidly built under pre-exposure of HO. Comparative transcriptome analysis showed that 310 (185 up and 125 down) and 512 (331 up and 181 down) differentially expressed genes were generated after 1 and 3 h of pre-exposure, respectively. KEGG enrichment analysis revealed that protein processing in endoplasmic reticulum is a highly enriched pathway; multiple genes (e.g., hsp70.1, hsp70.2, and hsp90aa1.2) encoding heat shock proteins in this pathway were sharply upregulated presumably to correct protein misfolding and maintaining the cellular normal functions during oxidative stress. More importantly, the Keap1/Nrf2 system-mediated detoxification enzyme system was significantly activated, which regulates the upregulation of target genes (e.g., gstp1, gsr, and prdx1) to scavenger reactive oxygen species, thereby defending against apoptosis. In addition, the MAPK, as a transmitter of stress signals, was activated, which may play an important role in activating antioxidant system in the early stages of oxidative stress. Altogether, these findings demonstrate that zebrafish larvae rapidly establish resistance to oxidative stress, and this involves changes in protein processing, stress signal transmission, and the activation of detoxification pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10695-022-01100-5DOI Listing
July 2022

Rising ecosystem water demand exacerbates the lengthening of tropical dry seasons.

Nat Commun 2022 Jul 14;13(1):4093. Epub 2022 Jul 14.

Sino-French Institute for Earth System Science, College of Urban and Environmental Sciences, Peking University, Beijing, 100871, China.

Precipitation-based assessments show a lengthening of tropical dry seasons under climate change, without considering simultaneous changes in ecosystem water demand. Here, we compare changes in tropical dry season length and timing when dry season is defined as the period when precipitation is less than: its climatological average, potential evapotranspiration, or actual evapotranspiration. While all definitions show more widespread tropical drying than wetting for 1983-2016, we find the largest fraction (48.7%) of tropical land probably experiencing longer dry seasons when dry season is defined as the period when precipitation cannot meet the need of actual evapotranspiration. Southern Amazonia (due to delayed end) and central Africa (due to earlier onset and delayed end) are hotspots of dry season lengthening, with greater certainty when accounting for water demand changes. Therefore, it is necessary to account for changing water demand when characterizing changes in tropical dry periods and ecosystem water deficits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-022-31826-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283447PMC
July 2022
-->