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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.
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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).
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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 ionsï¼ 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 environmentï¼ 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 ï¼4 787.46 ±4 704.31ï¼, ï¼7 663.07 ±8 395.05ï¼, and ï¼2 629.13 ±2 369.51ï¼ µg·L-1, respectively. The total equivalent concentrations of ions in 2018, 2019, and 2021 were ï¼851.68 ±649.16ï¼, ï¼973.98 ±850.94ï¼, and ï¼644.31 ±531.16ï¼ 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 ï¼9 624.25 ±7 327.92ï¼, ï¼4 088.67 ±5 710.14ï¼, ï¼3 357.68 ±3 995.64ï¼, and ï¼6 203.19 ±3 857.43ï¼ µg·L-1, respectively, and the seasonal average total equivalent concentrations of ions in spring, summer, autumn, and winter were ï¼1 014.71 ±512.21ï¼, ï¼729.83 ±589.90ï¼, ï¼724.35 ±681.40ï¼, and ï¼1 014.03 ±359.67ï¼ 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 [ï¼0.05 ±0.01ï¼ mg·ï¼m2·aï¼-1], only accounting for ï¼0.13 ±0.04ï¼% of the total wet deposition fluxes of main metal elementsï¼ 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 ï¼85.72 ±2.18ï¼% 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.
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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.
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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.
Subject(s)
Conservation of Natural Resources , Soil , China , Soil/chemistry , Ecosystem , Crops, Agricultural/growth & development , BiodiversityABSTRACT
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.
Subject(s)
Antineoplastic Agents, Phytogenic , Cardiac Glycosides , Phytochemicals , Seeds , Thevetia , Humans , Cardiac Glycosides/pharmacology , Cardiac Glycosides/isolation & purification , Cardiac Glycosides/chemistry , Seeds/chemistry , Molecular Structure , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Thevetia/chemistry , Structure-Activity Relationship , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Apoptosis/drug effectsABSTRACT
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.
Subject(s)
Antidepressive Agents , Ketamine , Motor Activity , Swimming , Animals , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Mice , Male , Ketamine/pharmacology , Ketamine/analogs & derivatives , Motor Activity/drug effects , Time Factors , Behavior, Animal/drug effects , Depression/drug therapy , Disease Models, Animal , Reproducibility of ResultsABSTRACT
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.
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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.
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[This corrects the article DOI: 10.2196/44892.].
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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.
Subject(s)
Algorithms , Antineoplastic Agents , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Humans , Drug Discovery , Drug Screening Assays, AntitumorABSTRACT
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.
Subject(s)
Anti-Bacterial Agents , Carbapenem-Resistant Enterobacteriaceae , Carbapenems , Klebsiella Infections , Klebsiella pneumoniae , Meropenem , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/pathogenicity , Klebsiella pneumoniae/genetics , Klebsiella Infections/microbiology , Klebsiella Infections/mortality , Klebsiella Infections/drug therapy , Virulence , Anti-Bacterial Agents/pharmacology , Meropenem/pharmacology , Carbapenems/pharmacology , Animals , Mice , Carbapenem-Resistant Enterobacteriaceae/drug effects , Carbapenem-Resistant Enterobacteriaceae/genetics , Humans , Macrophages/microbiology , Macrophages/immunology , beta-Lactamases/genetics , beta-Lactamases/metabolism , Sepsis/microbiology , Sepsis/mortality , Sepsis/drug therapy , Cytokines/metabolism , Microbial Sensitivity Tests , Bacterial Proteins/genetics , Disease Models, Animal , Bacterial LoadABSTRACT
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.
Subject(s)
Evolution, Molecular , Malus , Multigene Family , Phosphorus , Plant Proteins , Stress, Physiological , Malus/genetics , Malus/metabolism , Stress, Physiological/genetics , Phosphorus/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Phylogeny , Promoter Regions, Genetic , Gene Duplication , Protein Interaction MapsABSTRACT
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.
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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.
Subject(s)
Acinetobacter baumannii , Glycosyltransferases , Acinetobacter baumannii/metabolism , Glycosylation , Glycosyltransferases/metabolism , Glycosyltransferases/genetics , Sugar Acids/metabolism , Sugar Acids/chemistry , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , VirulenceABSTRACT
The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.
Subject(s)
M Phase Cell Cycle Checkpoints , Meiosis , Animals , Female , Mice , Anaphase-Promoting Complex-Cyclosome/genetics , Anaphase-Promoting Complex-Cyclosome/metabolism , Oocytes/metabolism , Ubiquitins/metabolismABSTRACT
The therapeutic effects of antibodies include neutralization of pathogens, activation of the host complement system, and facilitation of phagocytosis of pathogens. However, antibody alone has never been shown to exhibit bactericidal activity. In this study, we developed a monoclonal antibody that targets the bacterial cell surface component Pseudaminic acid (Pse). This monoclonal antibody, Pse-MAB1, exhibited direct bactericidal activity on Acinetobacter baumannii strains, even in the absence of the host complements or other immune factors, and was able to confer a protective effect against A. baumannii infections in mice. This study provides new insight into the potential of developing monoclonal antibody-based antimicrobial therapy of multidrug resistant bacterial infections, especially those which occurred among immunocompromised patients.
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BACKGROUND: In China, the prevalence of type 2 diabetes mellitus (T2DM) among diabetic patients is estimated to be between 90%-95%. Additionally, China is among the 22 countries burdened by a high number of tuberculosis cases, with approximately 4.5 million individuals affected by active tuberculosis. Notably, T2DM poses a significant risk factor for the development of tuberculosis, as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis (T2DM-PTB), which has risen from 19.3% to 24.1%. It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature. AIM: To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis (T2DM-PTB), as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM. METHODS: T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group, Simple DM patients presenting to our hospital in the same period were the control group, Controls and case groups were matched 1:2 according to the principle of the same sex, age difference ( ± 3) years and disease duration difference ( ± 5) years, patients were investigated for general demographic characteristics, diabetes-related characteristics, body immune status, lifestyle and behavioral habits, univariate and multivariate analysis of the data using conditional logistic regression, calculate the odds ratio (OR) values and 95%CI of OR values. RESULTS: A total of 315 study subjects were included in this study, including 105 subjects in the observation group and 210 subjects in the control group. Comparison of the results of both anthropometric and biochemical measures showed that the constitution index, systolic blood pressure, diastolic blood pressure and lymphocyte count were significantly lower in the case group, while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group. The results of univariate analysis showed that poor glucose control, hypoproteinemia, lymphopenia, TB contact history, high infection, smoking and alcohol consumption were positively associated with PTB in T2DM patients; married, history of hypertension, treatment of oral hypoglycemic drugs plus insulin, overweight, obesity and regular exercise were negatively associated with PTB in T2DM patients. Results of multivariate stepwise regression analysis found lymphopenia (OR = 17.75, 95%CI: 3.40-92.74), smoking (OR = 12.25, 95%CI: 2.53-59.37), history of TB contact (OR = 6.56, 95%CI: 1.23-35.03) and poor glycemic control (OR = 3.37, 95%CI: 1.11-10.25) was associated with an increased risk of developing PTB in patients with T2DM, While being overweight (OR = 0.23, 95%CI: 0.08-0.72) and obesity (OR = 0.11, 95%CI: 0.02-0.72) was associated with a reduced risk of developing PTB in patients with T2DM. CONCLUSION: T2DM-PTB patients are prone to worse glycemic control, higher infection frequency, and a higher proportion of people smoking, drinking alcohol, and lack of exercise. Lymphopenia, smoking, history of TB exposure, poor glycemic control were independent risk factors for T2DM-PTB, and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.