Network meta-analysis of treatment interventions for Helicobacter pylori infection in adult populations in East and Southeast Asia.

Background: Helicobacter pylori (H. pylori) infection poses a global health challenge, necessitating diverse treatment strategies. This network meta-analysis aimed to assess various treatment regimens for H. pylori in East and Southeast Asian populations. Methods: A systematic search was conducted in PubMed, Embase, and the Cochrane Library databases from inception to 20 Dec 2023, to identify relevant randomized controlled trials (RCTs) on H. pylori treatment interventions in East Asian and Southeast Asian populations. The primary outcome focused on effectiveness, specifically the rate of H. pylori eradication, while the secondary outcome evaluated overall safety, including the incidence of total and serious adverse effects. Network geometry plots were generated to illustrate direct and indirect treatment comparisons, using triple therapy (TT) as the reference standard. Odds Ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models to account for study heterogeneity and consistency models for indirect comparisons. The treatment hierarchy was assessed using the ranking probabilities and surface under the cumulative ranking curve (SUCRA) values. Results: 79 studies met the inclusion criteria, with 99 paired comparisons. The included studies, conducted in Southeast Asia and among East Asian populations, included 29,903 patients. Significant outcomes in treat effectiveness were observed in various comparisons, such as sequential therapy vs. TT, bismuth quadruple therapy (BQT) vs. TT, high-dose dual therapy (HDDT) vs. TT, concomitant therapy vs. TT, P-CAB-based therapy vs. TT, and R-HT/HT vs. TT. R-HT/HT was the top choice based on rankograms and SUCRA values (SUCRA = 96.5). Regarding overall safety, significant results were noted in comparisons involving BQT, HDDT, concomitant therapy, sequential therapy, and P-CAB-based therapy. HDDT achieved the highest overall safety based on rankograms and SUCRA values (SUCRA = 0.0). HDDT demonstrated the lowest incidence of serious adverse events, according to global rankograms and SUCRA values (SUCRA = 19.7). Conclusion: This network meta-analysis highlights the complexity of treating H. pylori in East and Southeast Asia. R-HT/HT emerged as the most effective regimen, while HDDT proved to be the safest, with the lowest incidence of serious adverse events. These findings are crucial for optimizing treatment protocols in these regions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023435318.

Chitinase and proteinase K treatments enhance the DNA yield of microsporidium Ecytonucleospora hepatopenaei spores.

Microsporidium Ecytonucleospora hepatopenaei (EHP) spores were purified from the hepatopancreas of Penaeus vannamei infected with EHP by percoll density gradient centrifugation and differential centrifugation. The EHP spores contain a thick chitin wall and might not rupture using the routine DNA extraction protocol. In this study, three enzymes were used, including chitinase, proteinase K, and DNase I. Chitinase or proteinase K digestions caused weakened fluorescence of chitin showing by a blurred edge of EHP spores stained with calcofluor white under a fluorescence microscope. Different combinations of these enzymes followed by DNA extraction with phenol-chloroform from EHP spores showed significant increases in the copy number of the EHP SSU gene per spore. The combination of the chitinase and proteinase K treatments resulted 4.46 ± 1.07 copies/spore detected, which is 31.6 ± 20.7 folds of no treatment groups, accounting to (55.7 ± 13.4)% of the total copies of the gene in the spore. The additional treatment with chitinase to the conventional extraction protocol with a proteinase K digestion step for feces and hepatopancreas samples of P. vannamei resulted in a significant difference in EHP copies in the DNA of (83.8 ± 64.1)% and (55.3 ± 88.0)% increases. The study proved that chitinase and proteinase K treatment enhance the DNA extraction from microsporidian spores resulting in high yield.

Evolution and maintenance of a large multidrug-resistant plasmid in a Salmonella enterica Typhimurium host under differing antibiotic selection pressures.

The dissemination of antibiotic resistance genes (ARGs) through plasmids is a major mechanism for the development of bacterial antimicrobial resistance. The adaptation and evolution mechanisms of multidrug-resistant (MDR) plasmids with their hosts are not fully understood. Herein, we conducted experimental evolution of a 244 kb MDR plasmid (pJXP9) under various conditions including no antibiotics and mono- or combinational drug treatments of colistin (CS), cefotaxime (CTX), and ciprofloxacin (CIP). Our results showed that long-term with or without positive selections for pJXP9, spanning approximately 600 generations, led to modifications of the plasmid-encoded MDR and conjugative transfer regions. These modifications could mitigate the fitness cost of plasmid carriage and enhance plasmid maintenance. The extent of plasmid modifications and the evolution of plasmid-encoded antibiotic resistance depended on treatment type, particularly the drug class and duration of exposure. Interestingly, prolonged exposure to mono- and combinational drugs of CS and CIP resulted in a substantial loss of the plasmid-encoded MDR region and antibiotic resistance, comparable to the selection condition without antibiotic. By contrast, combinational treatment with CTX contributed to the maintenance of the MDR region over a long period of time. Furthermore, drug selection was able to maintain and even amplify the corresponding plasmid-encoded ARGs, with co-selection of ARGs in the adjacent regions. In addition, parallel mutations in chromosomal arcA were also found to be associated with pJXP9 plasmid carriage among endpoint-evolved clones from diverse treatments. Meanwhile, arcA deletion improved the persistence of pJXP9 plasmid without drugs. Overall, our findings indicated that plasmid-borne MDR region deletion and chromosomal arcA inactivation mutation jointly contributed to co-adaptation and co-evolution between MDR IncHI2 plasmid and Salmonella Typhimurium under different drug selection pressure.IMPORTANCEThe plasmid-mediated dissemination of antibiotic resistance genes has become a significant concern for human health, even though the carriage of multidrug-resistant (MDR) plasmids is frequently associated with fitness costs for the bacterial host. However, the mechanisms by which MDR plasmids and bacterial pairs evolve plasmid-mediated antibiotic resistance in the presence of antibiotic selections are not fully understood. Herein, we conducted an experimental evolution of a large multidrug-resistant plasmid in a Salmonella enterica Typhimurium host under single and combinatorial drug selection pressures. Our results show the adaptive evolution of plasmid-encoded antibiotic resistance through alterations of the MDR region in the plasmid, in particular substantial loss of the MDR region, in response to different positive selections, especially mono- and combinational drugs of colistin and ciprofloxacin. In addition, strong parallel mutations in chromosomal arcA were associated with pJXP9 carriage in Salmonella Typhimurium from diverse treatments. Our results thus highlight promoting the loss of the plasmid's MDR region could offer an alternative approach for combating plasmid-encoded antibiotic resistance.

High expression of transcription factor EGR1 is associated with postoperative muscle atrophy in patients with knee osteoarthritis undergoing total knee arthroplasty.

BACKGROUND: Muscle atrophy is a typical affliction in patients affected by knee Osteoarthritis (KOA). This study aimed to examine the potential pathogenesis and biomarkers that coalesce to induce muscle atrophy, primarily through the utilization of bioinformatics analysis. METHODS: Two distinct public datasets of osteoarthritis and muscle atrophy (GSE82107 and GSE205431) were subjected to differential gene expression analysis and gene set enrichment analysis (GSEA) to probe for common differentially expressed genes (DEGs) and conduct transcription factor (TF) enrichment analysis from such genes. Venn diagrams were used to identify the target TF, followed by the construction of a protein-protein interaction (PPI) network of the common DEGs governed by the target TF. Hub genes were determined through the CytoHubba plug-in whilst their biological functions were assessed using GSEA analysis in the GTEx database. To validate the study, reverse transcriptase real-time quantitative polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Flow Cytometry techniques were employed. RESULTS: A total of 138 common DEGs of osteoarthritis and muscle atrophy were identified, with 16 TFs exhibiting notable expression patterns in both datasets. Venn diagram analysis identified early growth response gene-1 (EGR1) as the target TF, enriched in critical pathways such as epithelial mesenchymal transition, tumor necrosis factor-alpha signaling NF-κB, and inflammatory response. PPI analysis revealed five hub genes, including EGR1, FOS, FOSB, KLF2, and JUNB. The reliability of EGR1 was confirmed by validation testing, corroborating bioinformatics analysis trends. CONCLUSIONS: EGR1, FOS, FOSB, KLF2, and JUNB are intricately involved in muscle atrophy development. High EGR1 expression directly regulated these hub genes, significantly influencing postoperative muscle atrophy progression in KOA patients.

Tracking multidrug resistant tuberculosis: a 30-year analysis of global, regional, and national trends.

Objectives: To provide valuable insights for targeted interventions and resource allocation, our analysis delved into the multifaceted burden, trends, risks, and projections of multi drug resistant tuberculosis (MDR-TB). Methods: This research employed data from the Global Burden of Disease (GBD) 2019 dataset, which used a comparative risk assessment to quantify the disease burden resulting from risk factors. Initially, this database was utilized to extract details concerning the disability-adjusted life years (DALYs), mortality, incidence, and the number of individuals afflicted by MDR-TB. Subsequently, regression analyses were conducted using the Joinpoint program to figure average annual percent change (AAPC) to ascertain the trend. Thirdly, the age-period-cohort model (APCM) was adopted to analyze evolutions in incidence and mortality. Finally, utilizing the Nordpred model within R software, we projected the incidence and mortality of MDR-TB from 2020 to 2030. Results: MDR-TB remained a pressing global health concern in regions with lower socio-demographic indexes (SDI), where the AAPC in DALYs topped 7% from 1990 to 2019. In 2019, the cumulative DALYs attributed to MDR-TB tallied up to 4.2 million, with India, the Russian Federation, and China bearing the brunt. Notably, the incidence rates have shown a steadfast presence over the past decade, and a troubling forecast predicts an uptick in these areas from 2020 to 2030. Additionally, the risk of contracting MDR-TB grew with advancing age, manifesting most acutely among men aged 40+ in lower SDI regions. Strikingly, alcohol consumption had been identified as a significant contributor, surpassing the impacts of smoking and high fasting plasma glucose, leading to 0.7 million DALYs in 2019. Conclusions: A robust strategy is needed to end tuberculosis (TB) by 2030, especially in lower SDI areas.

A New Ferroptosis-Related Long Non-Coding RNA Risk Model Predicts the Prognosis of Patients With Papillary Thyroid Cancer.

Background: Ferroptosis is a novel form of regulated cell death that involves in cancer progression. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remains to be elucidated. The purpose of this paper was to clarify the prognostic value of ferroptosis-related lncRNAs in PTC. Methods: The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between ferroptosis-related genes (FRGs) and lncRNA was determined using Pearson correlation analysis. Multivariate Cox regression model (P < 0.01) was performed to establish a ferroptosis-related lncRNAs risk model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, risk curve and nomograms were then performed to assess the accuracy and clinical applicability of prognostic models. The correlations between the prognosis model and clinicopathological variables, immune and m6A were analyzed. Finally, in vitro assays were performed to verify the role of LINC00900, LINC01614 and PARAL1 on the proliferation, migration and invasion in TPC-1 and BCPAP cells, as well as the relationship between three lncRNAs and ferroptosis. Results: A five-ferroptosis-related lncRNAs (PARAL1, LINC00900, DPH6-DT, LINC01614, LPP-AS2) risk model was constructed. Based on the risk score, samples were divided into the high- and low-risk groups. Patients in the low-risk group had better prognosis than those in high-risk group. Compared to traditional clinicopathological features, risk score was more accurate in predicting prognosis in patients with PTC. Additionally, the difference of immune cell, function and checkpoints was observed between two groups. Moreover, experiments showed that LINC00900 promoted the proliferation, migration and invasion in TPC-1 and BCPAP cells, while LINC01614 and PARAL1 revealed opposite effects, all of which were related to ferroptosis. Conclusions: In summary, we identified a five-ferroptosis-related lncRNAs risk model to predict the prognosis of PTC. Furthermore, our study also revealed that LINC00900 functioned as a tumor suppressor lncRNA, LINC01614 and PARAL1 as an oncogenic lncRNA in PTC.

Understanding the Decamethylferrocene FeIII/IV Oxidation Process in Tris(pentafluoroethyl)trifluorophosphate-Containing Ionic Liquids at Glassy Carbon and Boron-Doped Diamond Electrodes.

Under voltammetric conditions, the neutral decamethylferrocene ([Me10Fc]) to cationic ([Me10Fc]+) FeII/III process is a well-known reversible outer-sphere reaction. A companion cationic [Me10Fc]+ to dicationic [Me10Fc]2+ FeIII/IV process has been reported under direct current (DC) cyclic voltammetric conditions at highly positive potentials in liquid SO2 at low temperatures and in a 1.5:1.0 AlCl3/1-butylpyridinium chloride melt. This study demonstrates that in room-temperature ionic liquids containing the hard to oxidize and hydrophobic tris(pentafluoroethyl)trifluorophosphate anion, the [Me10Fc]+/2+ process can be detected as a quasi-reversible reaction at glassy carbon (GC) and boron-doped diamond (BDD) electrodes. Large amplitude Fourier-transformed alternating current (FT-AC) voltammetry minimizes background current contributions occurring at potentials similar to those of the FeIII/IV process in the second and higher-order harmonics. This enables a straightforward determination of the thermodynamics and kinetics for both the FeII/III and FeIII/IV processes. Unlike the ideal outer-sphere FeII/III process, the parameters of the FeIII/IV process may be impacted by ion-interaction effects. For the faster FeII/III process, heterogeneous rate constants are approximately 10 times smaller at BDD than those at GC electrodes. This electrode dependence is less pronounced for the slower FeIII/IV process. The slower BDD kinetics may be attributed in part to a density of states lower than that at GC.

Visual analysis of abdominal aortitis treatment using the CiteSpace bibliometric method.

BACKGROUND: Abdominal aortitis can induce aneurysms, and tumor rupture can lead to organ ischemia or even sudden death. At present, there is a lack of extensive understanding and identification of key problems in the treatment of abdominal aortitis, which needs to be further analyzed using bibliometric analysis. AIM: To discuss the research hotspot and development trend of abdominal aortitis treatment. METHODS: We searched the English literature (published from January 1, 2000 to March 12, 2024) on the treatment of abdominal aortitis in the Web of Science database. Then, we identified and screened duplicate literature using CiteSpace 6.1R2 software. We conducted an analysis of the number of papers, a co-occurrence analysis of the authors and institutions, and co-occurrence and cluster analyses of the keywords. Then, we drew the author, institution, and keywords of the studies into graphs for visualization. Finally, we expounded on the author, institutional network interactions, and hot keywords of the studies on the treatment of abdominal aortitis. RESULTS: We included 210 English literature articles involving 190 authors; the author cooperation team was mainly represented by Caradu Caroline, Berard Xavier, Lu Guanyi, Harada Kenichi, and Sharma Ashish K. In the keyword analysis, high-frequency keywords include abdominal aortic aneurysm (38), abdominal aorta (24), Takayasu arteritis (22), etc. The three most central keywords were disease (0.69), classification (0.68), and abdominal aortic aneurysm (0.55). The first nine clusters of keywords are case report, abdominal aortic aneurysm, Takayasu arteritis, dyspnea hematuria, aortic elastic, IgG4-related disease, report, mid aortic dysplastic syndrome, and statin. In the keyword emergent analysis, 14 emergent words were obtained. Among them, seven keywords with strong abruptness were Takayasu arteritis, abdominal aortic aneurysm, disease, retroperitoneal fibrosis, expression, management, and large vessel vasculitis. In the past 3 years, the incidences of abdominal aortic aneurysm (intensity: 4.62) and inflammation (intensity: 1.99) were higher. CONCLUSION: The number of published papers is on the increase, but the cooperation among authors is scattered. The research focus is mainly on the pathogenesis and treatment of abdominal aortitis-related diseases.

Therapeutic application of circular RNA aptamers in a mouse model of psoriasis.

Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated protein kinase R (PKR). Here we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon-α and dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes.

Melatonin regulates circadian clock proteins expression in allergic airway inflammation.

Asthma demonstrates a strong circadian rhythm with disrupted molecular clock. Melatonin which can directly regulate circadian rhythm has been reported to alleviate asthma, but whether this effect is related to its regulation on circadian clock has not yet been known. Here, female C57BL/6 mice were challenged with ovalbumin (OVA) to establish allergic airway inflammation, and were treated with melatonin or Luzindole to investigate whether the expressions of circadian clock proteins were changed in response to OVA and were affected by exogenous/endogenous melatonin. Airway inflammation, mucus secretion, protein expressions of circadian proteins (Bmal1, Per1, Clock, Timeless, Cry1 and Cry2), melatonin biosynthetase (ASMT, AANAT) and melatonin receptor (Mel-1A/B-R) were analyzed accordingly. The results showed that in the successfully established allergic airway inflammation model, inflammatory cells infiltration, expressions of circadian clock proteins in the lung tissues of OVA-challenged mice were all notably up-regulated as compared to that of the vehicle mice. Meanwhile, the protein expression of ASMT and the level of melatonin in the lung tissues were reduced in allergic mice, while the expression of melatonin receptor Mel-1A/B-R was markedly increased. After addition of exogenous melatonin, the OVA-induced airway inflammation was pronouncedly ameliorated, while simultaneously the OVA-induced expressions of Per1 and Clock were further increased. However, a melatonin receptor antagonist Luzindole further augmented the OVA-induced airway inflammation, accompanied with remarkably decreased expressions of Per1, Bmal1, Cry1 and Cry2 but notably increased expression of Timeless. Collectively, our results demonstrated that the expression of circadian clock proteins was increased in the lungs during allergic airway inflammation, and Per1 was a clock protein that can be regulated by both exogenous and endogenous melatonin, suggesting Per1 may be an important potential circadian clock target for melatonin as a negative regulatory factor against Th2-type airway inflammation.

Dexamethasone protects against asthma via regulating Hif-1α-glycolysis-lactate axis and protein lactylation.

PURPOSE: Asthma can not be eradicated till now and its control primarily relies on the application of corticosteroids. Recently, glycolytic reprogramming has been reportedly contributed to asthma, this study aimed to reveal whether the effect of corticosteroids on asthma control is related to their regulation of glycolysis and glycolysis-dependent protein lactylation. METHODS: Ovalbumin (OVA) aeroallergen was used to challenge mice and stimulate human macrophage cell line THP-1 following dexamethasone (DEX) treatment. Airway hyperresponsiveness, airway inflammation, the expressions of key glycolytic enzymes and pyroptosis markers, the level of lactic acid, real-time glycolysis and oxidative phosphorylation (OXPHOS), and protein lactylation were analyzed. RESULTS: DEX significantly attenuated OVA-induced eosinophilic airway inflammation, including airway hyperresponsiveness, leukocyte infiltration, goblet cell hyperplasia, Th2 cytokines production and pyroptosis markers expression. Meanwhile, OVA-induced Hif-1α-glycolysis axis was substantially downregulated by DEX, which resulted in low level of lactic acid. Besides, key glycolytic enzymes in the lungs of asthmatic mice were notably co-localized with F4/80-positive macrophages, indicating metabolic shift to glycolysis in lung macrophages during asthma. This was confirmed in OVA-stimulated THP-1 cells that DEX treatment resulted in reductions in pyroptosis, glycolysis and lactic acid level. Finally, protein lactylation was found significantly increased in the lungs of asthmatic mice and OVA-stimulated THP-1 cells, which were both inhibited by DEX. CONCLUSION: Our present study revealed that the effect of DEX on asthma control was associated with its suppressing of Hif-1α-glycolysis-lactateaxis and subsequent protein lactylation, which may open new avenues for the therapy of eosinophilic asthma.

SLPA-Net: A Real-Time Recognition Network for Intelligent Stomata Localization and Phenotypic Analysis.

Plant stomatal phenotype traits play an important role in improving crop water use efficiency, stress resistance and yield. However, at present, the acquisition of phenotype traits mainly relies on manual measurement, which is time-consuming and laborious. In order to obtain high-throughput stomatal phenotype traits, we proposed a real-time recognition network SLPA-Net for stomata localization and phenotypic analysis. After locating and identifying stomatal density data, ellipse fitting is used to automatically obtain phenotype data such as apertures. Aiming at the problems of small stomata and high similarity to background, we introduced ECANet to improve the accuracy of stoma and aperture location. In order to effectively alleviate the unbalance problem in bounding box regression, we replaced the Loss function with a more effective Focal EIoU Loss. The experimental results show that SLPA-Net has excellent performance in the migration generalization and robustness of stomata and apertures detection and identification, as well as the correlation between stomata phenotype data obtained and artificial data.

Surface Lattice Modulation Enables Stable Cycling of High-Loading All-solid-state Batteries at High Voltages.

Halide solid electrolytes, known for their high ionic conductivity at room temperature and good oxidative stability, face notable challenges in all-solid-state Li-ion batteries (ASSBs), especially with unstable cathode/solid electrolyte (SE) interface and increasing interfacial resistance during cycling. In this work, we have developed an Al3+-doped, cation-disordered epitaxial nanolayer on the LiCoO2 surface by reacting it with an artificially constructed AlPO4 nanoshell; this lithium-deficient layer featuring a rock-salt-like phase effectively suppresses oxidative decomposition of Li3InCl6 electrolyte and stabilizes the cathode/SE interface at 4.5 V. The ASSBs with the halide electrolyte Li3InCl6 and a high-loading LiCoO2 cathode demonstrated high discharge capacity and long cycling life from 3 to 4.5 V. Our findings emphasize the importance of specialized cathode surface modification in preventing SE degradation and achieving stable cycling of halide-based ASSBs at high voltages.

Microplastics affect mosquito from aquatic to terrestrial lifestyles and are transferred to mammals through mosquito bites.

Microplastics (MPs) transfer from the environment to living organisms is a nonignorable global problem. As a complete metamorphosis insect, the larvae and adult Culex quinquefasciatus mosquito live in aquatic and terrestrial environments, respectively, where they easily access MPs. However, little is known about mosquitoes' potential role in MPs accumulation throughout ecosystems. Therefore, we conducted a study with different MPs particle sizes (0.1/1/10 µm) and concentrations (0.5/5/50 µg/mL) on Cx. quinquefasciatus to address this issue. Once exposed at the young larval stage, MPs could accompany the mosquitoes their entire life. The fluorescence signals of MPs in the larvae were mainly located in the intestines. Its intensity increased (from 3.72 × 106 AU to 5.45 × 107 AU) as the concentrations of MPs increases. The fluorescence signals of MPs were also detected in the blood and skin tissues of mice bitten by adult mosquitoes with MPs containing in their bodies. Mosquitos exposed to MPs showed longer larval pupation and eclosion time as well as lower adult body weight. In addition, MPs significantly reduced the lethal effect of pyrethroid insecticides (97.77 % vs. 48.88 %, p < 0.05) with 15.1 % removal of the deltamethrin concentration. After MPs exposure, the relative abundance of the Cx. quinquefasciatus gut microbiome, such as Wolbachia spp., Elizabethkingia spp., and Asaia spp., changed as the MPs size and concentration changes. Mosquitoes provide a new pathway for MPs accumulation and transfer to higher-level living organisms. Moreover, MPs significantly reduce the control effect of deltamethrin, providing new guidelines for mosquito insecticide application in MPs contamination circumstances.

Mo-doping heterojunction: interfacial engineering in an efficient electrocatalyst for superior simulated seawater hydrogen evolution.

Exploring economical, efficient, and stable electrocatalysts for the seawater hydrogen evolution reaction (HER) is highly desirable but is challenging. In this study, a Mo cation doped Ni0.85Se/MoSe2 heterostructural electrocatalyst, Mox-Ni0.85Se/MoSe2, was successfully prepared by simultaneously doping Mo cations into the Ni0.85Se lattice (Mox-Ni0.85Se) and growing atomic MoSe2 nanosheets epitaxially at the edge of the Mox-Ni0.85Se. Such an Mox-Ni0.85Se/MoSe2 catalyst requires only 110 mV to drive current densities of 10 mA cm-2 in alkaline simulated seawater, and shows almost no obvious degradation after 80 h at 20 mA cm-2. The experimental results, combined with the density functional theory calculations, reveal that the Mox-Ni0.85Se/MoSe2 heterostructure will generate an interfacial electric field to facilitate the electron transfer, thus reducing the water dissociation barrier. Significantly, the heteroatomic Mo-doping in the Ni0.85Se can regulate the local electronic configuration of the Mox-Ni0.85Se/MoSe2 heterostructure catalyst by altering the coordination environment and orbital hybridization, thereby weakening the bonding interaction between the Cl and Se/Mo. This synergistic effect for the Mox-Ni0.85Se/MoSe2 heterostructure will simultaneously enhance the catalytic activity and durability, without poisoning or corrosion of the chloride ions.

Individualized Delivery of Vancomycin by Model-Informed Bayesian Dosing Approach to Maintain an AUC24 Target in Critically Ill Patients.

INTRODUCTION: Monitoring of AUC24 was updated recommendation in the guideline for the therapeutic drug monitoring (TDM) of vancomycin in Chinese pharmacological society published in 2020. Vancomycin pharmacokinetic profiles are diverse and unique in critically ill patients because of the drastic variability of the patients' physiological parameters, while the study for population pharmacokinetic (PPK) models in Chinese critically ill patients has been rarely reported. The objectives of this study were to construct a PPK model to describe the pharmacokinetic characteristics of vancomycin in critically ill patients and to individualize vancomycin dosing by model-informed Bayesian estimation for maintenance of AUC24 target at 400-650 mg h/L recommended by the 2020 guideline. METHODS: Vancomycin with different dosing was administered intravenously over 1 h for critically ill patients, TDM was started at 48 h or 72 h since initiation of vancomycin therapy for patients. Blood samples were collected from patients for trough concentrations or Cmax. Vancomycin concentrations were determined by high-performance liquid chromatography method with ultraviolet detection. PPK model was performed using the nonlinear mixed-effect model (NONMEM®). Individual PK parameters for critically ill patients treated with vancomycin were estimated using a post hoc empirical Bayesian method based on the final PPK model. AUC24 was calculated as the total daily dose divided by the clearance (L/h). RESULTS: The PPK of vancomycin was determined by a one-compartment model with creatinine clearance as fixed effects. The PK estimates in the final model generally agreed with the median estimates and were contained within the 95% CI generated from the bootstrap results, indicating good precision and stability in the final model. The visual predictive check plots showed the adequate predictive performance of the final PK model and supported a good model fit. The model-informed Bayesian estimation was used to predict the AUC24 of critically ill patient by the acquired TDM results, and the dosing adjustment by maintenance of AUC24 at 400-650 mg h/L had made a great therapeutic effect for the case. CONCLUSION: This study established a PPK model of vancomycin in Chinese critically ill patients, and individualized dosing of vancomycin by model-informed Bayesian estimation to maintain an AUC24 target at 400-650 mg h/L has been successfully applied in clinic. This result supports the continued use of model-informed Bayesian estimation to vancomycin treatment in critically ill patients.

Stabilizing Undercoordinated Zn Active Sites through Confinement in CeO2 Nanotubes for Efficient Electrochemical CO2 Reduction.

Zn-based catalysts hold great potential to replace the noble metal-based ones for CO2 reduction reaction (CO2 RR). Undercoordinated Zn (Znδ+ ) sites may serve as the active sites for enhanced CO production by optimizing the binding energy of *COOH intermediates. However, there is relatively less exploration into the dynamic evolution and stability of Znδ+ sites during CO2 reduction process. Herein, we present ZnO, Znδ+ /ZnO and Zn as catalysts by varying the applied reduction potential. Theoretical studies reveal that Znδ+ sites could suppress HER and HCOOH production to induce CO generation. And Znδ+ /ZnO presents the highest CO selectivity (FECO 70.9 % at -1.48 V vs. RHE) compared to Zn and ZnO. Furthermore, we propose a CeO2 nanotube with confinement effect and Ce3+ /Ce4+ redox to stabilize Znδ+ species. The hollow core-shell structure of the Znδ+ /ZnO/CeO2 catalyst enables to extremely expose electrochemically active area while maintaining the Znδ+ sites with long-time stability. Certainly, the target catalyst affords a FECO of 76.9 % at -1.08 V vs. RHE and no significant decay of CO selectivity in excess of 18 h.

Vanadium-Containing Keggin-Type Polyoxometalates, [VM12O40]3- and [VVM11O40]4- (M = Mo, W): Structural Characterization and Voltammetric, NMR, and EPR Studies Related to Electrochemical Reduction at Framework and Central Vanadium Sites.

Vanadium is accommodated in both the framework (VoutV) and central positions (VinV) in the Keggin-type polyoxometalates (POMs) [VinVVoutVM11O40]4- (M = Mo, W; VinVVoutVM11) and in the central position in [VinVM12O40]3- (VinVM12). The structures of the VinVVoutVM11 class have been determined by X-ray crystallography and compared to those of VinVM12 reported previously. A major feature of interest with POMs is their capacity for very extensive reduction, particularly when protonation accompanies the electron transfer step. With VinVVoutVM11 and VinVM12 POMs, knowledge as to whether reduction occurs at V or M sites and the concomitant dependence on acidity has been obtained. Frozen solution EPR spectra obtained following bulk electrolysis showed that the one-electron reduction of VinVMo12 occurs at the molybdenum framework site to give VinVMoVMo11. In contrast, EPR spectra of one-electron reduced VinVW12 at <30 K are consistent with the electron being accommodated on the central V atom in a tetrahedral environment to give VinIVW12. In the case of VinVVoutVM11, the initial reduction occurs at the framework VoutV site to give VinVVoutIVM11. The second electron is delocalized over the Mo framework in two-electron reduced VinVVoutIVMoVMo10, whereas it is accommodated on the central V site in VinIVVoutIVW11. The distance between VinIV and VoutIV in VinIVVoutIVW11 estimated as 3.5 ± 0.2 Å from analysis of the EPR spectrum is consistent with that obtained in VinVVoutVW11 from crystallographic data. Simulations of the cyclic voltammograms as a function of CF3SO3H acid concentration for the initial reduction processes provide excellent agreement with experimental data obtained in acetonitrile (0.10 M [n-Bu4N][PF6]) and allowed acid association constants to be estimated and compared with the literature values available for [XVoutVM11O40]n- (X = S (n = 3), P and As (n= 4); M = Mo, W). The interpretation of the voltammetric data is supported by 51V NMR measurements on the oxidized VV forms of the POMs.

Clinical study of NFNC in the treatment of acute exacerbation chronic obstructive pulmonary disease patients with respiratory failure.

BACKGROUND: Most patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD) have respiratory failure that necessitates active correction and the improvement of oxygenation is particularly important during treatment. High flow nasal cannula (HFNC) oxygen therapy is a non-invasive respiratory aid that is widely used in the clinic that improves oxygenation state, reduces dead space ventilation and breathing effort, protects the loss of cilia in the airways, and improves patient comfort. AIM: To compare HFNC and non-invasive positive pressure ventilation in the treatment of patients with AECOPD. METHODS: Eighty AECOPD patients were included in the study. The patients were in the intensive care department of our hospital from October 2019 to October 2021. The patients were divided into the control and treatment groups according to the different treatment methods with 40 patients in each group. Differences in patient comfort, blood gas analysis and infection indices were analyzed between the two groups. RESULTS: After treatment, symptoms including nasal, throat and chest discomfort were significantly lower in the treatment group compared to the control group on the 3rd and 5th days (P < 0.05). Before treatment, the PaO2, PaO2/FiO2, PaCO2, and SaO2 in the two groups of patients were not significantly different (P > 0.05). After treatment, the same indicators were significantly improved in both patient groups but had improved more in the treatment group compared to the control group (P < 0.05). After treatment, the white blood cell count, and the levels of C-reactive protein and calcitonin in patients in the treatment group were significantly higher compared to patients in the control group (P < 0.05). CONCLUSION: HFNC treatment can improve the ventilation of AECOPD patients whilst also improving patient comfort, and reducing complications. HFNC is a clinically valuable technique for the treatment of AECOPD.

A Chiral Emissive Conjugated Corral for High-Affinity and Highly Enantioselective Recognition in Water.

Accurately distinguishing between enantiomeric molecules is a fundamental challenge in the field of chemistry. However, there is still significant room for improvement in both the enantiomeric selectivity (KR(S) /KS(R) ) and binding strength of most reported macrocyclic chiral receptors to meet the demands of practical application scenarios. Herein, we synthesized a water-soluble conjugated tubular host-namely, corral[4]BINOL-using a chiral 1,1'-bi-2-naphthol (BINOL) derivative as the repeating unit. The conjugated chiral backbone endows corral[4]BINOL with good fluorescent emission (QY=34 % ) and circularly polarized luminescence (|glum | up to 1.4×10-3 ) in water. Notably, corral[4]BINOL exhibits high recognition affinity up to 8.6×1010  M-1 towards achiral guests in water, and manifested excellent enantioselectivity up to 18.7 towards chiral substrates, both of which represent the highest values observed among chiral macrocycles in aqueous solution. The ultrastrong binding strength, outstanding enantioselectivity, and facile accessibility, together with the superior fluorescent and chiroptical properties, endow corral[4]BINOL with great potential for a wide range of applications.