The impact of mixed planting of Poaceae species in the Qinghai-Tibet plateau region on forage yield, soil nutrients, and soil microbial communities.

Establishing cultivated grassland in the Qinghai-Tibet Plateau region is an effective method to address the conflict between vegetation and livestock. However, the high altitude, low temperature, and arid climate in the region result in slow regeneration and susceptibility to degradation of mixed cultivation grassland containing perennial legumes and gramineous plants. Therefore, we aim to through field experiments, explore the feasibility of establishing mixed cultivation grassland of Poaceae species in the region by utilizing two grass species, Poa pratensis L. and Puccinellia tenuiflora. By employing a mixture of P. pratensis and P. tenuiflora to establish cultivated grassland, we observed significant changes in forage yield over time. Specifically, during the 3rd to 6th years of cultivation, the yield in the mixed grassland was higher than in monocultures. It exceeded the yield of monoculture P. tenuiflora by 19.38% to 29.14% and surpassed the monoculture of P. pratensis by 17.18% to 62.98%. Through the analysis of soil physicochemical properties and soil microbial communities in the cultivated grassland, the study suggests that the mixed grassland with Poaceae species can enhance soil enzyme activity and improve soil microbial communities. Consequently, this leads to increased soil nutrient levels, enhanced nitrogen fixation efficiency, and improved organic phosphorus conversion efficiency. Therefore, establishing mixed grasslands with Poaceae species in the Qinghai-Tibet Plateau region is deemed feasible.

Evaluation of Acarbose Bioequivalence in Healthy Chinese Populations Using Novel Pharmacodynamic End Points.

Acarbose is a widely used α-glucosidase inhibitor for the management of postprandial hyperglycemia in patients with type 2 diabetes mellitus. Recent pilot studies on acarbose bioequivalence (BE) have successfully identified additional pharmacodynamic (PD) parameters as valid end points. Nevertheless, there was a scarcity of published pivotal studies using novel PD parameters. The purpose of the study is to investigate the acarbose BE using the new PD parameters. The study was conducted with an open, randomized, 2-period crossover design. A total of 64 healthy Chinese volunteers received either the reference (R) or test (T) acarbose at a dose of 2×50 mg orally, followed by a 1-week washout period. After sucrose treatment (baseline) and sucrose/acarbose co-administration, serum glucose, and insulin concentrations were assessed. The rectifying approach yielded geometric mean ratios of 102.9% for maximum serum glucose concentration with deduction of glucose concentration at 0 hour and 105.3% for the area under the serum glucose concentration-time curve profile 0-2 hours after coadministration of sucrose and acarbose with deduction of baseline (AUC0-2 h,r ). The 90% confidence intervals of maximum serum glucose concentration with deduction of glucose concentration at 0 hour and the area under the serum glucose concentration-time curve profile 0-2 hours after coadministration of sucrose and acarbose with deduction of baseline all fell within the acceptance limits. The incidence of adverse events after the T or R drug was comparable, and healthy subjects were well tolerated. The findings of our investigation clearly show that the PD parameters of the rectifying method exhibit enhanced suitability and sensitivity when assessing acarbose BE in healthy participants. The T and R drugs were bioequivalent using the novel PD parameters, and both drugs demonstrated good safety and tolerability.

Clinical utility of tumour mutational burden on efficacy of immune checkpoint inhibitors in malignant solid tumours: protocol for a systematic review and meta-analysis.

INTRODUCTION: A major development in solid malignancy treatment is the application of immune checkpoint inhibitors (ICIs), which have produced durable responses and increased survival rates. However, the therapeutic effect of ICIs has great heterogeneity in patients with cancer. We propose a systematic review to evaluate the predictive value of tumour mutation burden (TMB) on efficacy of ICIs. METHODS AND ANALYSIS: A systematic literature search will be conducted in the PubMed, OVID, Web of Science, Embase and Cochrane Central Register of Controlled Trials Library databases up to 31 May 2022. We will compare the efficacy of ICIs between TMB high group and TMB low group in terms of the HRs of overall survival (OS) and progression-free survival (PFS), and the OR of the objective response rate/overall response rate (ORR). The HRs of PFS and OS, and the OR of ORR, will be measured by an inverse variance weighted fixed effects model (I2≤50%) or a DerSimonian-Laird random effects model (I2>50%). In addition, subgroup analysis, sensitivity analysis, heterogeneity analysis and publication bias will be conducted. We plan to conduct a subgroup analysis on age, sex, area, number of patients (high/low TMB), cancer type, tumour size, stage, line of therapy, TMB sequencing method, type of immunotherapy and follow-up period. ETHICS AND DISSEMINATION: Ethical approval and informed consent are not needed, as the study will be a literature review and will not involve direct contact with patients or alterations to patient care. This systematic review is anticipated to be finished in December 2023, and the results will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021262480.

No apparent pharmacokinetic interactions were found between henagliflozin: A novel sodium-glucose co-transporter 2 inhibitor and glimepiride in healthy Chinese male subjects.

WHAT IS KNOWN AND OBJECTIVE: Henagliflozin is a novel selective sodium-glucose co-transporter 2 (SGLT2) inhibitor with similar inhibitory effect to ertugliflozin. Glimepiride is widely used to treat type 2 diabetes mellitus (T2DM) with few cardiovascular side effects. In the present study, we aimed at evaluating the pharmacokinetic (PK) interactions between henagliflozin and glimepiride. METHODS: An open-label, single-centre, single-arm, 3-period, 3-treatment, self-control study was conducted in twelve healthy Chinese male subjects. During each study period, subjects received a single oral dose of glimepiride 2 mg, multiple oral doses of henagliflozin 10 mg or a combination of the two drugs. Serial blood samples were collected 24 h post-dosing for PK analyses. Finger-tip blood glucose was also tested for safety evaluation. RESULTS AND DISCUSSION: Co-administration of henagliflozin with glimepiride did not affect their plasma PK profiles. For henagliflozin, the 90% confidence intervals for the geometric mean ratio (GMR) for the maximum plasma concentrations at steady-state (Cmax ss ) and the area under the plasma concentration-time curve during a dosing interval at steady-state (AUCτ, ss ) of combination therapy to henagliflozin alone were 1.00 (0.93-1.08) and 1.00 (0.98-1.02), respectively. For glimepiride, the corresponding values of combination therapy to glimepiride alone were 1.00 (0.88-1.13) for maximum plasma concentrations (Cmax ), 0.91 (0.84-0.99) for the area under the plasma concentration-time curve from 0-24 h (AUC0-24h ) and 0.91 (0.83-1.00) for the plasma concentration-time curve from 0 h to infinite (AUC0-inf ), respectively. All values fell within the equivalence range of 0.8-1.25. All monotherapies and combination therapy led to no serious adverse events and were well tolerated. WHAT IS NEW AND CONCLUSION: Multiple doses of henagliflozin did not exert a significant change on glimepiride PK profiles and a single dose of glimepiride had little effect on henagliflozin blood concentration. Thus, henagliflozin can be co-administered with glimepiride without dose adjustment of either drug.

Nitrogen-doped porous carbon fiber with enriched Fe2N sites: Synthesis and application as efficient electrocatalyst for oxygen reduction reaction in microbial fuel cells.

Low-cost, stable and highly efficient oxygen reduction reactions (ORR) electrocatalysts are of great significance for microbial fuel cells to break the limit of the air cathode. The expensive noble metal catalysts are easy to be contaminated due to biofouling, which could damage the catalytic activity significantly. Among the reported non-noble metal catalysts, FeCN materials are promising substitutes that have comparable catalytic activity with Pt/C. In this article, a facile process to obtain N-doped porous carbon fibers (NPCF) with abundant Fe2N moieties from iron based metal organic framework (MOF(Fe)) embedded electrospun fibers has been developed. The fiber structure promotes the in situ conversion of Fe2N sites in embedded MOF(Fe) during pyrolysis under NH3 atmosphere. The abundant Fe2N sites, presence of pyrrolic nitrogen and hierarchical porous structure of obtained Fe2N/NPCF make it possess excellent electrocatalytic activity to ORR with comparable performance (E1/2 = 0.8648 V) and superior long term stability to commercial 20 wt% Pt/C. This work expends the toolbox for design of high performance cathodic catalysts for MFCs and also provides original insights in Fe-N active sites construction for FeNC ORR catalysts.

Severe Acute Respiratory Syndrome Coronavirus 2: From Gene Structure to Pathogenic Mechanisms and Potential Therapy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerging respiratory virus with high morbidity, which was named coronavirus disease 2019 (COVID-19) by World Health Organization (WHO). COVID-19 has triggered a series of threats to global public health. Even worse, new cases of COVID-19 infection are still increasing rapidly. Therefore, it is imperative that various effective vaccines and drugs should be developed to prevent and treat COVID-19 and reduce the serious impact on human beings. For this purpose, detailed information about the pathogenesis of COVID-19 at the cellular and molecular levels is urgently needed. In this review, we summarized the current understanding on gene structure, protein function, and pathogenic mechanisms of SARS-CoV-2. Based on the above, we refined the correlations among gene structure, protein function, and pathogenic mechanisms of SARS-CoV-2. Importantly, we further discussed potential therapeutic targets, aiming to accelerate the advanced design and development of vaccines and therapeutic drugs against COVID-19.

Effect of changes in serum levels of endogenous hydrogen sulfide on fracture healing: Study protocol clinical trial (SPIRIT compliant).

BACKGROUND: Fracture is a common disease; many factors affect fracture healing. Recent studies have confirmed that hydrogen sulfide (H2S) plays an essential role in bone formation, but most of these studies are drawing conclusions based on animal experiment; whether H2S could promote fracture healing in patients is still unclear. We aim to investigate the change of serum H2S in fracture patients, and analyze its effort on fracture healing. METHODS: This is a single-center, prospective cohort study. Patients with spinal or limb fracture will be recruited. Patient's serum and urine will be collected at baseline for examination (serum H2S, ß-CTX, OC, PINP, 25-OH-VitD3, S-CTX, urinary calcium, and urinary creatinine). All patients will be followed-up for 24 months in outpatients settings, the image of X-ray or CT will be reviewed and fracture healing will be judged by 2 experienced orthopedic physicians. The difference in serum parameters especially H2S will be compared between patients with fracture healed within 9 months and those with fracture unhealed at 9 months. DISCUSSION: Results of the trial could provide insight into influence of H2S on fracture healing. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of School of Medicine UESTC & Sichuan Provincial People's Hospital Ethics Committee. All the participants will be asked to provide written informed consent before data collection. The findings of the study will be published in peer-reviewed journals and will be presented at national or international conferences.

Carotid plaque magnetic resonance imaging and recurrent stroke risk: A systematic review and meta-analysis.

BACKGROUND: MRI findings of carotid plaque components have been studied recently as a tool to predict recurrent ischemic events. We performed a systematic review and meta-analysis to summarize the association of MRI-determined intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap with recurrent ischemic events. METHODS: Electronic search was performed in PUBMED, EMBASE, Cochrane Controlled Register of Trials (CENTRAL) from inception to Oct 30, 2018. We included cohort studies with an average follow-up time of more than 1 month in which intraplaque hemorrhage, lipid-rich necrotic core, or thinning/rupture of the fibrous cap were associated with recurrent ipsilateral stroke or ischemic events. We performed heterogeneity assessment before carrying out meta-analysis. According to the heterogeneity, we selected fixed-effect model for meta-analysis of the included cohort studies. RESULTS: Using a prespecified search strategy, of the 2128 articles, 6 studies with a total number of 621 participants met eligibility for systematic review and meta-analysis. The hazard ratios of intra-plaque hemorrhage, thinning/rupture of the fibrous cap and lipid rich necrotic core as recurrent Stroke/Transient ischemic attack (TIA) were 7.14(95% confidence interval, 4.32 to 11.82), 5.68(95% confidence interval, 2.40 to 13.47), and 2.73(95% confidence interval, 1.04 to 7.16), respectively. No significant heterogeneity was found in the 3 meta-analyses. CONCLUSIONS: The presence of intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap on MRI of carotid plaque are strong predictors of recurrent stroke events. However, due to the lack of original studies, larger cohort studies are warranted.

Preparation of nanoscale Bacillus thuringiensis chitinases using silica nanoparticles for nematicide delivery.

A series of amino, carboxylic, and aldehydic surface-grafted silica nanoparticles (SNPs) was prepared based on SiO2 NYSi40 nanoparticles to develop an efficient, biocompatible, and cost-effective biopesticide delivery system. Bacillus thuringiensis chitinase (Chi9602) was immobilized onto SNP surface to prepare nanoscale chitinases (SNPCs) through electrostatic adsorption and covalent binding. The specimens were characterized by Fourier transform infrared, scanning electron microscopy, and zeta-potential analyses. The delivery capacity of the SNPs in Caenorhabditis elegans N2 was observed by immunofluorescence. Results demonstrated that amino-grafted SiO2 nanoparticles with Chi9602 electrostatically adsorbed onto their surface (SNPC2) exhibited a relatively high enzyme immobilization rate (80.2%) and the highest (94.1%) residual enzyme activity among all SNPCs. SNPC2 also showed wider pH tolerance and relatively higher thermostability and ultraviolet radiation resistance capacity than Chi9602. Bioassays further showed that SNPC2 synergistically enhanced the nematicidal effect of B. thuringiensis YBT-020 preparation against C. elegans, with a reduced LC50 of 8.35mg/mL and a shortened LT50 of 12.04h. Immunofluorescence assays showed that SNPC2 had considerable delivery capacity to carry a large protein into C. elegans. Therefore, SNP2 can serve as an efficient nanocarrier for the delivery of macromolecular proteic biopesticides or drugs, indicating potential agricultural or biotechnological applications.