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Abstract Shrinking the size of photoelectrodes into the nanoscale will enable the precise modulation of cellular and subcellular behaviors of a single neuron and neural circuits. However, compared to photovoltaic devices, the reduced size causes the compromised efficiencies. Here, we present a highly efficient nanoelectrode based on bimetallic zinc and gold porphyrin (ZnAuPN). Upon light excitation, we observe ultrafast energy transfer (~66 ps) and charge transfer (~0.5 ps) through the porphyrin ring, enabling 97% efficiency in separating and transferring photoinduced charges to single Au-atom centers. Leveraging these isolated Au atoms as stimulating electrode arrays, we achieve significant photocurrent injection in single neurons, triggering action potential with millisecond light pulses. Notably, Extracranial near-infrared light irradiation of the motor cortex induces neuronal firing and enhances mouse movement. These results show the potential of nanoscale optoelectrodes for high spatiotemporal modulation of neuronal networks without the need for gene transfection in optogenetics.

Abstract The study was to evaluate the clinical outcomes of azvudine versus nirmatrelvir-ritonavir against omicron strains of coronavirus disease 2019 infections and determine their comparative effectiveness. This retrospective study included 716 patients who received nirmatrelvir-ritonavir (NR group) or azvudine (FNC group) at Peking Union Medical College Hospital between 1 November 2022 and 27 February 2023. Patients in the FNC group (n = 304) were younger, exhibited less severe symptoms, started antiviral therapy later, received corticosteroids more frequently, and used tocilizumab less frequently than patients in the NR group (n = 412). Within 28 d of therapy, 40 (9.7%) and 20 (6.6%) deaths were in the NR and FNC groups, respectively. No differences were observed between drugs and mortality rates (odds ratio [OR] 0.78, 95% CI 0.40–1.5, P = 0.45), clinical improvement (OR 0.79, 95% CI 0.79–1.3, P = 0.38), and clinical progression (OR 1.0, 95% CI 0.58–1.8, P = 0.96). More patients in the NR group experienced platelet decline than those in the FNC group (17.6% vs. 8.9%, P = 0.034). This study indicated that the effectiveness and safety of azvudine were comparable to those of nirmatrelvir-ritonavir.

Background In terms of hospitalization risk for the elderly, the evidences for adverse effects and economic losses of air pollutants on different types of cardiovascular diseases (CVDs) are limited. This study aims to quantify the economic losses of five major CVDs affected by air pollutants in Southwestern China.Methods Hospitalization information of 358,271 participants in the top five CVDs among the elderly population was collected over a 4-year time span. The generalized additive model (GAM) was used to estimate the short-term exposure response relationship between air pollutants and elderly inpatients with CVDs. The cost of illness method (COI) was used to evaluate the corresponding direct and indirect costs, and we refer to this in the text as economic losses.Results Air pollutants significantly increase the risk of hospitalisation in elderly patients with coronary heart disease (CHD), myocardial ischaemia (MI), pulmonary heart disease (PHD), hypertension, and cardiac arrhythmia. CO, NO2, PM10 and SO2 were significant increase the risk of CHD, with the RRs were 0.09, 2.59, 0.31, and 6.54, respectively; CO, NO2, O3, PM10, PM2.5, and SO2 were notably increased the risk of MI， with the RRs were 0.16, 4.19, 0.76, 0.79, 0.92, and 7.49, respectively; CO, NO2, PM10, PM2.5, and SO2 were distinctly increased the risk of PHD, with the RRs were 0.14, 2.79, 0.75, 1.00, and 3.86, respectively; NO2 and SO2 significant increase the risk of hypertension, with the RRs were 1.41 and 5.94, respectively; CO, NO2, PM10, and SO2 were distinctly increased the risk of arrhythmia, with the RRs were 0.09, 2.23, 0.36, and 5.41, respectively. Furthermore, we quantify the economic losses of five major CVDs affected by air pollutants. The economic burden of air pollution on patients with CHD, hypertension, PHD, cardiac arrhythmia, and MI were 66.38, 36.58, 5.76, 5.66 5.21 million yuan, respectively.Conclusion Our study found that short-term exposure to pollutants can have a significant impact on hospital admissions for all types of CVDs in the elderly. In terms of hospitalisation rates, SO2 and NO2 had a significant effect on different types of CVDs. Moreover, we found that air pollutants cause a heavy economic burden on patients with hypertension and CHD. It follows that reducing the concentration of air pollutants is an effective way to bring potential health benefits as well as economic benefits to local residents. Government departments should actively formulate relevant policies to reduce the physical and mental damage caused by air pollution.

In the era of artificial intelligence, there has been a rise in novel computing methods due to the increased demand for rapid and effective data processing. It is of great significance to develop memristor devices capable of emulating the computational neural network of the brain, especially in the realm of artificial intelligence applications. In this work, a memristor based on NiAl-layered double hydroxides is presented with excellent electrical performance, including analog resistive conversion characteristics and the effect of multi-level conductivity modulation. In addition, the device's conductance can be continuously adjusted by varying pulse width, interval, and amplitude. The successful replication of synaptic features has been achieved. In order to implement the functions of "NOT," "AND," and "OR," a logic gate is constructed using two synaptic devices. The confirmation of the potential use of synaptic devices in brain-like computing was demonstrated. In addition, it demonstrates the potential of these devices in supporting computing models beyond von Neumann architecture. [ABSTRACT FROM AUTHOR]

ObjectiveTo understand the relationship between proactive health behaviors and quality of life among middle-aged and elderly residents in Laiwu district, Jinan city, Shandong province, and to provide a reference for improving the quality of life of middle-aged and elderly people in the region. MethodsFrom August to October 2022, a multi-stage random cluster sampling method was used to select 867 middle-aged and elderly residents aged ≥ 45 years old in Laiwu district, Jinan city for a questionnaire survey. The European Five-Dimensional Health Scale (EQ-5D) was used to obtain health utility values based on the Chinese population health utility scoring system to evaluate quality of life. A multivariate Tobit regression model was used to analyze the relationship between proactive health behaviors and quality of life among middle-aged and elderly residents. ResultsThe health utility values of the 702 middle-aged and elderly residents aged ≥ 45 years old finally included in Laiwu district, Jinan city, Shandong province ranged from – 0.216 to 1.000, with an average health utility value of 0.942 (0.862, 1.000). After adjusting for confounding factors such as gender, age, education level, marital status, average monthly household income, type of medical insurance, smoking status, and presence of chronic diseases, the results of the multivariate Tobit regression model showed that the health utility values of middle-aged and elderly residents who never drank alcohol (β = 0.019, 95%CI: 0.011 – 0.027) and had quit drinking (β = 0.015, 95%CI: 0.003 – 0.028) were higher than those of middle-aged and elderly residents who drank alcohol. The health utility values of the middle-aged and the elderly residents who ate fresh vegetables and fruits ≥ 4 times/week (β = 0.158, 95%CI: 0.017 – 0.299) were higher than those who did not eat fresh vegetables and fruits. The health utility values of middle-aged and elderly residents who engaged in moderate physical activity in the past week (β = 0.057, 95%CI: 0.023 – 0.090) were higher than those who did not exercise. The health utility values of the middle-aged and the elderly residents who went to bed between 20 : 00 – 22 : 00 (β = 0.074, 95%CI: 0.029 – 0.119) were higher than those who went to bed before 20 : 00. The health utility values of the middle-aged and the elderly residents who believed they needed health management very much (β = 0.020, 95%CI: 0.005 – 0.036) and believed they could try health management (β = 0.014, 95%CI: 0.002 – 0.030) were higher than those who held the attitude of not needing it. ConclusionThe proactive health behaviors of the middle-aged and the elderly residents in Laiwu district, Jinan city, Shandong province, such as the frequency of eating fresh vegetables and fruits per week, engaging in moderate physical activity, and the need for their own health management, were positively correlated with their quality of life.

Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to selectively degrade disease-related proteins by utilizing the ubiquitin-proteasome system. While this strategy shows great potential in preclinical and clinical settings, off-tissue effects remain a major challenge, leading to toxicity in healthy tissues. This review explores recent advancements aimed at improving PROTAC specificity, including tumor-specific ligand-directed PROTACs, pro-PROTACs activated in tumor environments, and E3 ligase overexpression strategies. Innovations such as PEGylation and nanotechnology also play a role in optimizing PROTAC efficacy. These developments hold promise for safer, more effective cancer therapies, though challenges remain for clinical translation.

Abstract Background Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. Method Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene–exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. Results According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484–5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140–14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269–5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028–0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040–1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035–1.841, P = 0.028) were directly correlated with the occurrence of PTB. Conclusions This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.

The CONSTANS-like (COL) gene plays important roles in plant growth, development, and abiotic stress. A total of 15 COL genes are unevenly distributed on eight chromosomes in the potato genome. The amino acid length of the family members was 347–453 aa, the molecular weight was 38.65–49.92 kD, and the isoelectric point was 5.13–6.09. The StCOL family can be divided into three subfamilies by evolutionary tree analysis, with conserved motifs and similar gene structure positions in each subfamily. The analysis of promoter cis-acting elements showed 17 cis-acting elements related to plant hormones, stress, and light response. Collinearity analysis of COL genes of tomato, potato, and Arabidopsis showed that 13 StCOL genes in the different species may have a common ancestor. A total of 10 conserved motifs and six kinds of post-translational modifications in the 15 StCOL proteins were identified. The 15 StCOL genes exhibit a genomic structure consisting of exons and introns, typically ranging from two to four in number. The results showed that 10 genes displayed significant expression across all potato tissues, while the remaining five genes were down-expressed in potato transcriptome data. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis exhibited differential expression of 8 StCOL genes in the potato leaves and tubers at different growth stages, as well as 7 StCOL genes under 2°C treatment conditions. These results suggested that the StCOL gene family may play an important role in regulating potato tuberization and responding to cold stress.

Abstract Background Azvudine has been approved for the treatment of coronavirus disease 2019 (COVID-19) patients in China, and this meta-analysis aims to illustrate the safety of azvudine and its effectiveness in reducing mortality. Methods PubMed, Embase, Web of science, Cochrane Library and the Epistemonikos COVID-19 Living Overview of Evidence database (L.OVE) were searched to aggregate currently published studies. Cochrane risk of bias tool and ROBINS-I tool were used to assess the risk of bias of randomized controlled study and cohort study respectively. Odds radios (ORs) with 95% confidence interval (CIs) were combined for dichotomous variables. Publication bias was assessed by Egger’s test and funnel plots. Results A total of 184 articles were retrieved from the included databases and 17 studies were included into the final analysis. Pooled analysis showed that azvudine significantly reduced mortality risk in COVID-19 patients compared with controls (OR: 0.41, 95%CI 0.31–0.54, p

Abstract Background Severe acute respiratory syndrome coronavirus 2 will coexist with humans for a long time, and it is therefore important to develop effective treatments for coronavirus disease 2019 (COVID-19). Recent studies have demonstrated that antiviral therapy is a key factor in preventing patients from progressing to severe disease, even death. Effective and affordable antiviral medications are essential for disease treatment and are urgently needed. Azvudine, a nucleoside analogue, is a potential low-cost candidate with few drug interactions. However, validation of high-quality clinical studies is still limited. Methods This is a multicentre, randomized, double-blind, placebo-controlled phase III clinical trial involving 1096 adult patients with mild-to-moderate symptoms of COVID-19 who are at high risk for progression to severe COVID-19. Patients will be randomized to (1) receive azvudine tablets 5 mg daily for a maximum of 7 days or (2) receive placebo five tablets daily. All participants will be permitted to use a standard treatment strategy except antiviral therapy beyond the investigational medications. The primary outcome will be the ratio of COVID-19-related critical illness and all-cause mortality among the two groups within 28 days. Discussion The purpose of this clinical trial is to determine whether azvudine can prevent patients at risk of severe disease from progressing to critical illness and death, and the results will identify whether azvudine is an effective and affordable antiviral treatment option for COVID-19. Trial registration ClinicalTrials.gov NCT05689034. Registered on 18 January 2023.

Owing to its high economic and nutritional value, Apostichopus japonicus is an important mariculture species in North China. Because of the rapid development of its aquaculture industry in recent years, the limitations of traditional aquaculture modes such as pond aquaculture, cofferdam aquaculture, and beach aquaculture have become increasingly prominent. Therefore, the high-efficiency and healthy northern suspension cage A. japonicus breeding model, with the best comprehensive benefits and the least management problems, came into being. Microorganisms, as an essential part of the aquaculture pond ecosystem, not only play an important role in the material circulation and energy flow of the ecosystem, but also have great significance in maintaining ecosystem balance. As a representative invertebrate, echinoderms such as A. japonicus have a simple digestive structure. Bacteria account for a large proportion of the gut microbiome of A. japonicus, providing more than 70% of their energy demand. The bacterial community is closely related to the healthy growth of the host and plays an important role in digestion and metabolism, defense against pathogens, and immune function. However, the complex bacterial community in the gut of aquaculture species depends on the culture environment, and there is a close symbiotic relationship between the environmental and gut bacterial community which affects the survival and growth of organisms, disease occurrence, and material circulation. Previous studies have shown that the complex bacterial community in the gut of A. japonicus primarily comes from their habitat and maintains a relatively stable dynamic balance with the external environmental community. In order to improve the growth capacity of A. japonicus and quality of the culture water, it is important to understand the structural characteristics of the bacterial communities of A. japonicus and their culture water to support the development of the A. japonicus aquaculture industry. This information will provide a theoretical reference for the healthy aquaculture of A. japonicus and assist with disease prevention and control. Clarifying the complex relationship between the structure and functional characteristics of bacterial communities and the aquaculture environment, as well as the important role of the bacterial community in growth, will support future research on the bacterial community mechanisms, explore ways to improve the ecological regulation of breeding yield, and promote the healthy development of the A. japonicus culture industry. To date, there have been limited studies on the correlation between the gut bacterial community structure of A. japonicus and its culture environment.At present, most of the existing studies are based on the traditional pure culture or separation and enrichment culture methods, which cannot accurately reflect natural bacterial communities. In recent years, high-throughput sequencing technology has introduced a new way to comprehensively analyze the structural and functional characteristics of bacterial communities by combining several bioinformatics methods. With the continuous development of molecular sequencing technology, 16S rRNA high-throughput sequencing technology has become a valuable tool to study the structure of bacterial communities. It has been widely used to study a variety of ecosystems and bacterial community diversity, providing a novel means to study the species diversity and quantity of bacterial communities, and the structural and functional characteristics of bacterial communities. Most of the relevant existing studies are based on the structure and diversity of the bacterial community of A. japonicus cultured in the south, whereas only a few studies have been conducted on the structure and functional characteristics of bacterial communities of A. japonicus cultured in suspension cages in the north. Therefore, in order to investigate the relationship between the bacterial community structure of A. japonicus and the culture water, this study analyzed their structural and functional characteristics in cage-cultured A. japonicus in North China using high-throughput sequencing technology, and preliminarily discussed the correlation between them. The results showed that the diversity and richness of the A. japonicus gut bacterial community were significantly higher than those of the culture water (P < 0.05). The dominant bacteria in the gut of A. japonicus and the culture water were Proteobacteria and Bacteroidetes. There were 13 common core bacteria with a relative abundance greater than 0.1%. In addition, the bacterial communities showed some independence; the specific phyla in the gut belonged to Firmicutes and Chloroflexi, represented by Bacillus, Lactobacillus, Halioglobus, Lutimonas, and Woeseia. Based on an analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway database, a total of 300 tertiary metabolic pathways was annotated, among which 146 tertiary metabolic pathways had highly significant differences (P < 0.001). The specific metabolic pathways in the gut of A. japonicus were mainly carbohydrate digestion and absorption, protein digestion and absorption, and sphingolipid metabolism. This study showed that the bacterial community in the gut of A. japonicus is similar to that of the culture water, but there were significant differences in the relative community abundance. The results of this study provide a theoretical basis for the healthy cultivation of northern A. japonicus in suspension cages.

Ship contour extraction is vital for extracting the geometric features of ships, providing comprehensive information essential for ship recognition. The main factors affecting the contour extraction performance are speckle noise and amplitude inhomogeneity, which can lead to over-segmentation and missed detection of ship edges. Polarimetric synthetic aperture radar (PolSAR) images contain rich target scattering information. Under different transmitting and receiving polarization, the amplitude and phase of pixels can be different, which provides the potential to meet the uniform requirement. This paper proposes a novel ship contour extraction framework from PolSAR images based on polarization modulation. Firstly, the image is partitioned into the foreground and background using a super-pixel unsupervised clustering approach. Subsequently, an optimization criterion for target amplitude modulation to achieve uniformity is designed. Finally, the ship’s contour is extracted from the optimized image using an edge-detection operator and an adaptive edge extraction algorithm. Based on the contour, the geometric features of ships are extracted. Moreover, a PolSAR ship contour extraction dataset is established using Gaofen-3 PolSAR images, combined with expert knowledge and automatic identification system (AIS) data. With this dataset, we compare the accuracy of contour extraction and geometric features with state-of-the-art methods. The average errors of extracted length and width are reduced to 20.09 m and 8.96 m. The results demonstrate that the proposed method performs well in both accuracy and precision.

Given that manufacturing industry is the second-largest source of carbon emissions in China, effective carbon emission reduction plans require a comprehensive examination of the spatial–temporal characteristics (STC) of manufacturing carbon emissions (MCE) from both regional and industrial perspectives. However, most studies on the STC of MCE focus solely on regional perspectives, overlooking the importance of integrating both regional and industrial perspectives to fully understand the STC of China’s MCE. Moreover, there is limited research on the spatial disparities in China’s MCE. Building on a detailed carbon emissions inventory of 27 manufacturing industries across 30 provinces in China from 2001 to 2020, this study employed descriptive statistics, natural breakpoint classification, spatial–temporal transition, and the Dagum Gini ratio with its cluster decomposition method to analyze the STC of MCE from regional and industrial perspectives. The assessment of STC of MCE includes an examination of both spatial–temporal changes and disparities. Results show that the MCE of the three regions in China follow the order of east > central > west, with most of the super-heavy-duty MCE and heavy-duty MCE provinces located in the eastern and central regions. China’s three-tier manufacturing industries exhibit a pattern of “low-end high-end industries with small carbon emissions, while mid-end industries have large carbon emissions”. The regional differences show that the gap in the high-end MCE among the three regions is gradually narrowing, while the gap between mid-end MCE in the east and those in the central and western regions is widening. The overall disparities of MCE exhibited a continuous widening trend. In terms of sources, inter-regional disparities had the highest contribution rate, followed by intra-regional disparities, and super-dense disparities had the least contribution. Based on the research findings, this paper proposes targeted policy suggestions for carbon emission reduction in the manufacturing industry.

Sulfamethoxazole (SMZ) is a frequently detected antibiotic in the environment, and there is a growing concern about its potential toxic effects on aquatic organisms. sea cucumber (Apostichopus japonicas) is a benthic invertebrate whose gut acts as a primary immune defense and serves critical protective barrier. In this study, growth performance, histology, gut microbiota, and metabolomics analyses were performed to investigate the toxic response in the intestine of sea cucumber effects caused by SMZ stress for 56 d by evaluating with different concentrations of SMZ (0, 1.2×10−3, and 1.2 mg/L). The weight gain rate of sea cucumbers under SMZ stress showed significant decrease, indicating that the growth of sea cucumbers was hindered. Analysis of the intestinal morphological features indicated that SMZ stimulation resulted in atrophy of the sea cucumber gut. In the 1.2×10−3 mg/L concentration, the thickness of muscle and mucosal layers was reduced by 12.40% and 21.39%, while in the 1.2 mg/L concentration, the reductions were 35.08% and 26.98%. The abundance and diversity of sea cucumber intestinal bacteria decreased significantly (P < 0.05) under the influence of SMZ. Notably, the intestinal bacteria of sea cucumber became homogenized with the increase in SMZ concentration, and the relative abundance of Ralstonia reached 81.64% under the stress of 1.2 mg/L concentration. The SMZ stress significantly impacted host metabolism and disrupted balance, particularly in L-threonine, L-tyrosine, neuronic acid, piperine, and docosapentaenoic acid. SMZ leads to dysregulation of metabolites, resulting in growth inhibition and potential inflammatory responses that could adversely affect the normal activities of aquatic organisms. Further metabolic pathway enrichment analyses demonstrated that impaired biosynthesis of unsaturated fatty acids and aminoacyl-tRNA biosynthesis metabolic pathway were major reasons for SMZ stress-induced intestinal bacteria dysbiosis. This research aims to provide some theoretical evidence for the ecological hazard assessment of antibiotics in water.