Evaluating the protective effectiveness and risk factors of ursodeoxycholic acid on COVID-19 among outpatients.

Objective: This study aimed to assess the chemopreventive effect of ursodeoxycholic acid (UDCA) against COVID-19 and to analyze infection risk factors, symptoms, and recovery in outpatients with UDCA exposure. Methods: The study enrolled outpatients prescribed UDCA from the Second Affiliated Hospital of Chongqing Medical University, China, between 01 July 2022, and 31 December 2022. Data on demographics, comorbidities, and drug combinations were collected using electronic medical records. COVID-19 infection, symptoms, severity, prognosis, vaccinations, and UDCA administration were surveyed by telephone interviews. UDCA non-users served as controls and were matched in a 1:2 ratio with UDCA users using propensity score matching with the nearest neighbor algorithm. Infection rates, symptomatology, severity, and prognosis were compared between matched and control cohorts, and risk factors and infection and recovery symptoms were analyzed in UDCA-exposed outpatients. Results: UDCA-exposed outpatients (n = 778, 74.8%) and matched UDCA users (n = 95, 74.2%) showed significantly lower SARS-CoV-2 infection rates than control patients (n = 59, 92.2%) (p < 0.05). The matched UDCA group exhibited substantially lower fever, cough, sore throat, and fatigue rates than controls (p < 0.05). Participants with UDCA exposure generally experienced mild symptoms, while those without UDCA had moderate symptoms. The matched UDCA group also had significantly shorter durations of fever and cough (p < 0.05). Risk factors such as age over 60, less than 1 month of UDCA administration, diabetes mellitus, and coronary artery disease significantly increased SARS-CoV-2 infection rates (p < 0.05), while smoking led to a decrease (p < 0.05). Hypertension was associated with a prolonged COVID-19 recovery (p < 0.05), while smoking, vaccination, and fatty liver disease were associated with shorter recovery periods (p < 0.05). The main symptoms in the full UDCA cohort were fever, cough, and sore throat, with fatigue, cough, and hyposthenia being the most persistent. Conclusion: UDCA demonstrated chemopreventive effect against SARS-CoV-2 in outpatients by significantly reducing infection incidence and mitigating COVID-19 symptoms, severity, and recovery duration. Old age, short UDCA course, and comorbidities such as diabetes mellitus and CAD increased infection rates, while hypertension prolonged recovery. Smoking, vaccination, and fatty liver disease reduced infection rates and shortened recovery. UDCA had minimal impact on symptom types. Larger and longer-term clinical studies are needed further to assess UDCA's effectiveness in COVID-19 prevention or treatment.

Relationship between Texture, Hydrogen Content, Residual Stress and Corrosion Resistance of Electrodeposited Chromium Coating: Influence of Heat Treatment.

Electrodeposited chromium plating continues to be widely used in a number of specialized areas, such as weapons, transport, aerospace, etc. However, the formation of texture, hydrogen content and residual stress can degrade the serviceability and lead to material failure. The effect of post heat treatment processes on the relationship of texture, hydrogen content, residual stress and corrosion resistance of hexavalent [Cr(VI)] chromium coatings deposited on Cr-Ni-Mo-V steel substrates was investigated. Macrotexture was measured by XRD. Microtexture, dislocation density and grain size were studied by EBSD. With the increase of the heat treatment temperature, it was found that the fiber texture strength of the (222) plane tended to increase and subsequently decrease. Below 600 °C, the increase in the (222) plane texture carried a decrease in the hydrogen content, residual stress, microhardness and an increase in the corrosion resistance. In addition, crack density and texture strength were less affected by the heat treatment time. Notably, relatively fewer crack densities of 219/cm2, a lower corrosion current density of 1.798 × 10-6 A/dm2 and a higher microhardness of 865 HV were found under the preferred heat treatment temperature and time of 380 °C and 4 h, respectively. The hydrogen content and residual stress were 7.63 ppm and 61 MPa, with 86% and 75% reduction rates compared to the as-plated state, respectively. In conclusion, in our future judgement of the influence of heat treatment on coating properties, we can screen or determine to a certain extent whether the heat treatment process is reasonable or not by measuring only the macrotexture.

Influence of Pd-Layer Thickness on Bonding Reliability of Pd-Coated Cu Wire.

In this paper, three Pd-coated Cu (PCC) wires with different Pd-layer thicknesses were used to make bonding samples, and the influence of Pd-layer thickness on the reliability of bonded points before and after a high-temperature storage test was studied. The results show that smaller bonding pressure and ultrasonic power lead to insufficient plastic deformation of the ball-bonded point, which also leads to small contact area with the pad and low bonding strength. Excessive bonding pressure and ultrasonic power will lead to 'scratch' on the surface of the pad and large-scale Ag spatter. The wedge-bonded point has a narrowed width when the bonding pressure and ultrasonic power are too small, and the tail edge will be cocked, resulting in false bonding and low strength. When the bonding pressure or ultrasonic power is too large, it will cause stress concentration, and the pad will appear as an 'internal injury', which will improve the failure probability; a high-temperature environment can make Cu-Ag intermetallic compounds (IMCs) grow and improve the bonding strength. With the extension of high-temperature storage time, the shear force of Pd100 gradually reaches the peak and then decreases, due to Kirkendall pores caused by excessive growth of IMCs, while the shear force of Pd120 continued to increase due to the slow growth rate of IMCs. In the high-temperature storage test, the thicker the Pd layer of the bonding wire, the higher the bonding strength; in the cold/hot cycle test, the sample with the largest Pd-layer thickness has the lowest failure rate. The thicker the Pd layer, the stronger its ability to resist changes in the external environment, and the higher its stability and reliability.

Characterization of a new Camellia plant resource with low caffeine and high theobromine for production of a novel natural low-caffeine tea.

Yuanbaoshancha (YBSC) is characterized as a new wild tea relative morphologically and phytochemically distinguished from the closest wild tea plants Rongjiangcha (Camellia yungkiangensis, RJC) and Tulecha (Camellia costata, TLC). YBSC young leaves contain higher tea polyphenol and theobromine contents but lower caffeine and theanine as compared with RJC, TLC, and other tea landraces and modern cultivars. The major alkaloid detected in YBSC, TLC, and RJC is theobromine while caffeine is a minor; the primary catechins in YBSC leaves are non-galloylated catechins, significantly different from Camellia sinensis and other low-caffeine tea resources. The unique phytochemical profiles featured YBSC black tea with extremely lower caffeine and higher theobromine, as well as unique flavors and health benefits. This botanical characterization of YBSC and two related low-caffeine wild tea resources lays a foundation for future better utilization for the production of a highly valuable natural low-caffeine/high-theobromine tea. Chemical compounds: Caffeine (PubChem CID: 2519); Theobromine (PubChem CID: 5429); Catechins (PubChem CID: 9064); Epigallocatechin gallate (PubChem CID: 65064); Theanine (PubChem CID: 439378); Jasmone (PubChem CID: 1549018); cis-3-Hexenyl hexanoate (PubChem CID: 5352543); Hexyl 2-methylbutanoate (PubChem CID: 24838).

Cardiac glycosides with cytotoxic activity from the seeds of Thevetia peruviana.

Phytochemical investigation on the extract of the seeds of Thevetia peruviana resulted in the isolation of six new cardiac glycosides, namely theveperosides A-F (1-6), including a rare 19-nor-cardenolide (1), together with seven known analogues (7-13). The chemical structures of these compounds were determined based on detailed spectroscopic analysis. The cytotoxic activities of 1-13 were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cell lines, and their structure-activity relationships (SARs) were investigated. Compound 3 exhibited the significant cytotoxic effects with IC50 values ranging from 0.032 to 0.055 µΜ, which could induce HepG2 cells apoptosis in a dose-dependent manner.

Study on the antidepressant activity of (2R,6R; 2S,6S)-Hydroxynorketamine (HNK) and its derivatives.

OBJECTIVE: This study mainly explores (2R,6R; 2S,6S)-HNK and its compounds whether there are antidepressant effects. METHODS: Four HNK compounds were obtained from 2-(Chlorophenyl) Cyclopentylmethanone. Forced swimming test, locomotor sensitization test, and conditioned location preference test were used to screen the antidepressant activity of the synthesized target compounds. RESULTS: In the case of 10 mg HNK treatment, compared with saline, the immobile time of mice in the HNK group, I5 group and I6 group at 1 h and 7 days had statistical significance. In the case of 10 mg HNK treatment, compared with saline, the immobile time of compound C and D groups in the glass cylinder area was significantly different. In the locomotor sensitization test, the movement distance of compound C and D groups on day 15 and day 7 mice increased significantly compared with the first day. In the conditioned place preference experiment, compound C and compound D induced conditioned place preference in mice compared with the Veh group. CONCLUSION: The results of the forced swimming test, locomotor sensitization test, and conditioned location preference test showed that compounds C and D may have certain anti-depressant activity. However, HNK exerts a rapid and significant antidepressant effect within 1 week, but the duration is short.

[Evolution of Physical and Chemical Characteristics of Atmospheric Precipitation and Its Significant Impacts on the Environment in Beijing].

Atmospheric precipitation samples were collected in 2018, 2019, and 2021 in Beijing to study the concentrations and changes of the main metal elements and water-soluble ions； the wet deposition fluxes of heavy metals, water-soluble ions, dissolved inorganic nitrogen, and sulfur in the atmospheric precipitation and their impacts on the ecological environment； and the scavenging mechanisms of the typical precipitation to atmospheric pollutants during the study period. The results showed that the precipitation in Beijing during the study period was mostly neutral or alkaline, and the frequency of acid rain occurrence was very low, only accounting for 3.06%. The total concentrations of major metal elements in 2018, 2019, and 2021 were （4 787.46 ±4 704.31）, （7 663.07 ±8 395.05）, and （2 629.13 ±2 369.51） µg·L-1, respectively. The total equivalent concentrations of ions in 2018, 2019, and 2021 were （851.68 ±649.16）, （973.98 ±850.94）, and （644.31 ±531.16） µeq·L-1, respectively. The interannual changes in major metal elements and ions followed the order of 2019 > 2018 > 2021. The seasonal average total concentrations of major metal elements in spring, summer, autumn, and winter were （9 624.25 ±7 327.92）, （4 088.67 ±5 710.14）, （3 357.68 ±3 995.64）, and （6 203.19 ±3 857.43） µg·L-1, respectively, and the seasonal average total equivalent concentrations of ions in spring, summer, autumn, and winter were （1 014.71 ±512.21）, （729.83 ±589.90）, （724.35 ±681.40）, and （1 014.03 ±359.67） µeq·L-1, respectively, all presenting the order of spring > winter > summer > autumn. NO3- and SO42- were the main acid-causing ions in precipitation, whereas NH4+ and Ca2+ were the main acid-neutralizing ions. The wet deposition fluxes of the heavy metal Cd were very low [（0.05 ±0.01） mg·ï¼ˆm2·a）-1], only accounting for （0.13 ±0.04）% of the total wet deposition fluxes of main metal elements； however, its soil safety years were 291 years, significantly lower than those of other heavy metals, displaying that its ecological risk was relatively the highest. The total wet precipitation flux of water-soluble ions NH4+, Ca2+, NO3-, and SO42- accounted for （85.72 ±2.18）% of the wet precipitation flux of total ions, suggesting that their comprehensive impact on the ecological environment might have been higher. DIN wet deposition flux was mainly characterized by NH4+-N, which had a positive impact on the ecological environment in summer. SO42--S wet deposition flux was higher in summer, so its positive impact on the ecological environment was also greater. The scavenging effects of atmospheric precipitations to pollutants from the air were impacted by various factors, and the synergism effects of these factors could directly influence the scavenging mechanisms of precipitation to pollutants.

Exploring main soil drivers of vegetation succession in abandoned croplands of Minqin Oasis, China.

Background: The Minqin Oasis, which is located in Wuwei City, Gansu Province, China, faces a very serious land desertification problem, with about 94.5% of its total area desertified. Accordingly, it is crucial to implement ecological restoration policies such as cropland abandonment in this region. In abandoned croplands, abiotic factors such as soil properties may become more important than biotic factors in driving vegetation succession. However, the connections between soil properties and vegetation succession remain unclear. To fill this knowledge gap, this study investigated these connections to explore major factors that affected vegetation succession, which is meaningful to designing management measures to restore these degraded ecosystems. Methods: This study investigated seven 1-29-year-old abandoned croplands using the "space for time" method in Minqin Oasis. Vegetation succession was classified into different stages using a canonical correlation analysis (CCA) and two-way indicator species analysis (Twinspan). The link between soil properties and vegetation succession was analyzed using CCA. The primary factors shaping community patterns of vegetation succession were chosen by the "Forward selection" in CCA. The responses of dominant species to soil properties were analyzed using generalized additive models (GAMs). Results: Dominant species turnover occurred obviously after cropland abandonment. Vegetation succession can be classified into three stages (i.e., early, intermediate, and late successional stages) with markedly different community composition and diversity. The main drivers of vegetation succession among soil properties were soil salinity and saturated soil water content and they had led to different responses of the dominant species in early and late successional stages. During the development of vegetation succession, community composition became simpler, and species diversity decreased significantly, which was a type of regressive succession. Therefore, measures should be adopted to manage these degraded, abandoned croplands.

Characterization of Acinetobacter baumannii at a tertiary hospital in Guangzhou: a genomic and clinical study.

Acinetobacter baumannii (AB) infections have become a global public health concern due to the continued increase in the incidence of infection and the rate of resistance to carbapenems. This study aimed to investigate the genomic features of AB strains recovered from a tertiary hospital and assess the clinical implications of the findings. A total of 217 AB strains were collected between 2016 and 2018 at a tertiary hospital in Guangzhou, with 183 (84.33%) being carbapenem-resistant AB (CRAB), with the main mechanism being the carriage of the blaOXA-23 gene. The overall mortality rate of patients caused by such strains was 15.21% (n = 33). Artificial lung ventilation and the use of meropenem were mortality risk factors in AB-infected patients, while KL2 AB infection was negatively associated. Core genome multilocus sequence typing and clustering analysis were performed on the integrated AB genome collection from the NCBI database and this study to illustrate the population structure among China. The results revealed diverse core genome profiles (n = 17) among AB strains from China, and strains from this single hospital exhibited most of the core genome profiles (n = 13), suggesting genetic variability within the hospital and transmission across the country. These findings show that the high transmission potential of the CRAB strains and meropenem usage that confers a selective advantage of CRAB clinically are two major factors that pose significant challenges to the effective clinical management of AB infections. Understanding the genetic features and transmission patterns of clinical AB strains is crucial for the effective control of infections caused by this pathogen.

The Combination of Hyperuricemia and Elevated High-Sensitivity C-Reactive Protein Increased the Risk of Cardiac Conduction Block.

Objective: This study aimed to explore the impact of a combination of hyperuricemia (HUA) and excessive high-sensitivity C-reactive protein (hs-CRP) levels on the likelihood of developing cardiac conduction block (CCB). Additionally, it sought to assess whether the influence of uric acid (UA) on CCB is mediated by hs-CRP. Methods: A prospective study was executed utilizing data from the Kailuan cohort, including 81,896 individuals initially free from CCB. The participants were categorized into four groups depending on the existence of HUA and low-grade inflammation (hs-CRP>3 mg/L). Cox regression analysis was employed to ascertain hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident CCB. A mediation analysis was performed to determine if hs-CRP functioned as a mediator in the connection between UA levels and the incidence of CCB. Results: During a median observation period of 11.8 years, we identified 3160 cases of newly occurring CCB. Compared with the low UA/low CRP group, the combination of HUA and low-grade inflammation elevated the CCB risks (HR:1.56, 95% CI:1.22-1.99), atrioventricular block (AVB) (HR:1.88, 95% CI:1.27-2.77), and right bundle branch block (HR:1.47, 95% CI:1.02-2.12), respectively. Mediation analysis revealed that in the HUA group, compared with the non-HUA group, the risk of CCB elevated by 14.0%, with 10.3% of the increase mediated through hs-CRP. Conclusion: HUA combined with elevated hs-CRP increased the risk of CCB, especially AVB. The connection between UA and the CCB risk was partly mediated by hs-CRP.

Correction: A Multilabel Text Classifier of Cancer Literature at the Publication Level: Methods Study of Medical Text Classification.

[This corrects the article DOI: 10.2196/44892.].

Evolution of the SPX gene family and its role in the response mechanism to low phosphorus stress in self-rooted apple stock.

BACKGROUND: Phosphorus plays a key role in plant adaptation to adversity and plays a positive role in the yield and quality formation of apples. Genes of the SPX domain-containing family are widely involved in the regulation of phosphorus signalling networks. However, the mechanisms controlling phosphorus deficiency are not completely understood in self-rooted apple stock. RESULTS: In this study, 26 members of the apple SPX gene family were identified by genome-wide analysis, and further divided into four subfamilies (SPX, SPX-MFS, SPX-EXS, and SPX-RING) based on their structural features. The chromosome distribution and gene duplications of MdSPXs were also examined. The promoter regions of MdSPXs were enriched for multiple biotic/abiotic stresses, hormone responses and typical P1BS-related elements. Analysis of the expression levels of 26 MdSPXs showed that some members were remarkably induced when subjected to low phosphate (Pi) stress, and in particular MdSPX2, MdSPX3, and MdPHO1.5 exhibited an intense response to low Pi stress. MdSPX2 and MdSPX3 showed significantly divergent expression levels in low Pi sensitive and insensitive apple species. Protein interaction networks were predicted for 26 MdSPX proteins. The interaction of MdPHR1 with MdSPX2, MdSPX3, MdSPX4, and MdSPX6 was demonstrated by yeast two-hybrid assay, suggesting that these proteins might be involved in the Pi-signaling pathway by interacting with MdPHR1. CONCLUSION: This research improved the understanding of the apple SPX gene family and contribute to future biological studies of MdSPX genes in self-rooted apple stock.

Enhancing resistance, but not virulence attributed to the high mortality caused by carbapenem-resistant Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a global threat due to its high mortality in clinical patients. However, the specific mechanisms underlying this increased mortality remain unclear. The objective of this study is to investigate how the development of a resistance phenotype contributes to the significantly higher mortality associated with this pathogen. To achieve this, a collection of isogeneic strains was generated. The clinical carbapenem-susceptible K. pneumoniae (CSKP) strain HKU3 served as the control isolate, while HKU3-KPC was created through conjugation with a blaKPC-2-bearing plasmid and served as clinical CRKP strain. Using a sepsis model, it was demonstrated that both HKU3 and HKU3-KPC exhibited similar levels of virulence. Flow cytometry, RNA-seq, and ELISA analysis were employed to assess immune cell response, M1 macrophage polarization, and cytokine storm induction, revealing that both strains elicited comparable types and levels of these immune responses. Subsequently, meropenem was utilized to treat K. pneumoniae infection, and it was found that meropenem effectively reduced bacterial load, inhibited M1 macrophage polarization, and suppressed serum cytokine production during HKU3 (CSKP) infection. However, these effects were not observed in the case of HKU3-KPC (CRKP) infection. These findings provide evidence that the high mortality associated with CRKP is attributed to its enhanced survival within the host during antibiotic treatment, resulting in a cytokine storm and subsequent host death. The development of an effective therapy for CRKP infections could significantly reduce the mortality caused by this pathogen.

Singular value thresholding two-stage matrix completion for drug sensitivity discovery.

Incomplete data presents significant challenges in drug sensitivity analysis, especially in critical areas like oncology, where precision is paramount. Our study introduces an innovative imputation method designed specifically for low-rank matrices, addressing the crucial challenge of data completion in anticancer drug sensitivity testing. Our method unfolds in two main stages: Initially, the singular value thresholding algorithm is employed for preliminary matrix completion, establishing a solid foundation for subsequent steps. Then, the matrix rows are segmented into distinct blocks based on hierarchical clustering of correlation coefficients, applying singular value thresholding to the largest block, which has been proved to possess the largest entropy. This is followed by a refined data restoration process, where the reconstructed largest block is integrated into the initial matrix completion to achieve the final matrix completion. Compared to other methods, our approach not only improves the accuracy of data restoration but also ensures the integrity and reliability of the imputed values, establishing it as a robust tool for future drug sensitivity analysis.

KpsS1 Mediates the Glycosylation of Pseudaminic Acid in Acinetobacter Baumannii.

Pseudaminic acid (Pse) is found in the polysaccharide structures of the cell surface of various Gram-negative pathogenic bacteria including Acinetobacter baumannii and considered as an important component of cell surface glycans including oligosaccharides and glycoproteins. However, the glycosyltransferase that is responsible for the Pse glycosylation in A. baumannii remains unknown yet. In this study, through comparative genomics analysis of Pse-positive and negative A. baumannii clinical isolates, we identified a potential glycosyltransferase, KpsS1, located right downstream of the Pse biosynthesis genetic locus. Deletion of this gene in an Pse-positive A. baumannii strain, Ab8, impaired the glycosylation of Pse to the surface CPS and proteins, while the gene knockout strain, Ab8ΔkpsS1, could still produce Pse with 2.86 folds higher amount than that of Ab8. Furthermore, impairment of Pse glycosylation affected the morphology and virulence potential of A. baumannii, suggesting the important role of this protein. This study will provide insights into the further understanding of Pse in bacterial physiology and pathogenesis.

Novel Insights into Alkyl Polyglucoside Biosurfactant Promoting Anaerobic Dark Fermentation for Hydrogen Production in Sludge.

Anaerobic fermentation of excess sludge (ES) for hydrogen production is a crucial strategy for resource utilization and environmentally friendly treatment. However, the low hydrolysis efficiency of ES and the depletion of produced hydrogen have become the limiting factors for low hydrogen yield. This study innovatively applied the bio-based surfactant alkyl polyglucoside (APG) to enhance the efficiency of dark fermentation for hydrogen production from ES. When the APG content was 100 mg/g (calculated based on total suspended solids), the maximum hydrogen production reached 17.8 mL/g VSS, approximately 3.7 times that in the control group. Mechanistic analysis revealed that APG promoted the release of organic matter from ES. APG also facilitated the release of soluble protein and soluble polysaccharide, increasing the organic matter reduction rate to 34.8%, significantly higher than other groups. APG enhanced the accumulation of volatile fatty acids and promoted the proportion of small molecular carboxylic acids. Enzyme activity analysis revealed that APG promoted the activity of hydrolytic enzymes but inhibited the activity of hydrogen-consuming enzymes. The research results provide a green and environmentally friendly strategy for the efficient resource utilization of ES.

The combination of high uric acid and high C-reactive protein increased the risk of cardiovascular disease: A 15-year prospective cohort study.

BACKGROUND AND AIMS: Uric acid (UA) and C-reactive protein (CRP) may interact synergistically to accelerate the initiation and progression of cardiovascular disease (CVD). This study investigated the effects of a combination of high UA and high CRP on the risks of CVD. METHODS AND RESULTS: A total of 90,270 participants recruited from the Kailuan study were included, who were divided into four groups according to the presence/absence of hyperuricemia and inflammation. Cox regression was applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CVD. C-statistics, net classification index (NRI), and integrated discrimination improvement (IDI) were used to compare the incremental predictive of UA, CRP, and their combined effects on CVD. Mediation analysis was to explore the impact of CRP on the association between UA and CVD. Over a median follow-up of 14.95 years, we identified 11398 incident CVD cases. Compared to the low UA/low CRP group, the high UA/low CRP, low UA/high CRP and high UA/high CRP groups showed progressively higher risks of CVD, HR (95% CI): 1.18(1.10-1.27), 1.27(1.21-1.33) and 1.50 (1.33-1.69), respectively. The incorporation of UA and CRP into the traditional China-PAR model led to improvement in the C-statistic, NRI, and IDI, and was better than incorporation of either UA or CRP alone. Mediation analysis showed that CRP mediated the association between UA and CVD, accounting for 11.57% of the total effects. CONCLUSIONS: High UA/high CRP is associated with increased risks of CVD. Incorporation of both UA and CRP provided additional value for risk stratification.