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IntroductionThis study aimed to explore the influence of Intimate Partner Violence (IPV) on depression, the mediating role of social support, and the moderating role of the Big Five personality traits in the relationship between social support and depression.MethodsParticipants were recruited from Mainland China, using a stratified random sampling and quota sampling method. From June to August 2022, a diverse group of 21,916 participants (ranging from 12 to 100 years old) completed the Intimate Partner Violence Scale, Patient Health Questionnaire, Perceived Social Support Scale, and Big Five Inventory-Short Version.ResultsIPV was significantly positively correlated with depression and significantly negatively correlated with perceived social support. Perceived social support plays a mediating role in the link between IPV and depression.DiscussionHealthcare workers should assess social support and provide adequate care or recommendations for increasing social support when patients with IPV report depressive symptoms. Patients can be coached by professionals to improve their resiliency by developing or nurturing more optimistic personality traits.

IntroductionIgA nephropathy (IgAN), a prevalent form of glomerulonephritis globally, exhibits complex pathogenesis. Cathepsins, cysteine proteases within lysosomes, are implicated in various physiological and pathological processes, including renal conditions. Prior observational studies have suggested a potential link between cathepsins and IgAN, yet the precise causal relationship remains unclear.MethodsWe conducted a comprehensive bidirectional and multivariable Mendelian randomization (MR) study using publicly available genetic data to explore the causal association between cathepsins and IgAN systematically. Additionally, immunohistochemical (IHC) staining and enzyme-linked immunosorbent assay (ELISA) were employed to evaluate cathepsin expression levels in renal tissues and serum of IgAN patients. We investigated the underlying mechanisms via gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immune cell infiltration analysis. Molecular docking and virtual screening were also performed to identify potential drug candidates through drug repositioning.ResultsUnivariate MR analyses demonstrated a significant link between increased cathepsin S (CTSS) levels and a heightened risk of IgAN. This was evidenced by an odds ratio (OR) of 1.041 (95% CI=1.009–1.073, P=0.012) as estimated using the inverse variance weighting (IVW) method. In multivariable MR analysis, even after adjusting for other cathepsins, elevated CTSS levels continued to show a strong correlation with an increased risk of IgAN (IVW P=0.020, OR=1.037, 95% CI=1.006–1.069). However, reverse MR analyses did not establish a causal relationship between IgAN and various cathepsins. IHC and ELISA findings revealed significant overexpression of CTSS in both renal tissues and serum of IgAN patients compared to controls, and this high expression was unique to IgAN compared with several other primary kidney diseases such as membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis. Investigations into immune cell infiltration, GSEA, and GSVA highlighted the role of CTSS expression in the immune dysregulation observed in IgAN. Molecular docking and virtual screening pinpointed Camostat mesylate, c-Kit-IN-1, and Mocetinostat as the top drug candidates for targeting CTSS.ConclusionElevated CTSS levels are associated with an increased risk of IgAN, and this enzyme is notably overexpressed in IgAN patients’ serum and renal tissues. CTSS could potentially act as a diagnostic biomarker, providing new avenues for diagnosing and treating IgAN.

BackgroundBronchopulmonary foregut malformation (BPFM) is an uncommon condition, with few case reports documented in both national and international literature. This scarcity underscores the importance of utilizing effective imaging techniques to improve our understanding and diagnostic precision concerning this disorder.Case descriptionIn the first case report, a neonate, born at full term and aged 15 days, presented with symptoms including dyspnea, coughing, wheezing, cyanosis, and vomiting. Initial diagnostic evaluations, which included chest radiography and upper gastrointestinal tract radiography, led to an erroneous initial diagnosis of a left-sided diaphragmatic hernia, accompanied by a suspicion of infection. In the second case report, another neonate, also born at full term but aged 5 days, exhibited symptoms such as coughing, choking, and mild vomiting. Utilizing a combination of computed tomography (CT) scans (plain, enhanced, and reconstructed), chest x-ray, and upper gastrointestinal tract radiography, the diagnosis of BPFM was accurately determined.ConclusionComprehensive imaging examinations play a crucial role in reducing misdiagnosis and diagnostic oversights in cases of BPFM. Given its rarity, BPFM often manifests as a sequestered lung accompanied by gastrointestinal abnormalities. Hence, the integration of CT scans with gastrointestinal tract radiography can substantially improve diagnostic precision in such cases.

Post-Traumatic Stress Disorder (PTSD) is a chronic mental disorder characterized by symptoms of panic and anxiety, depression, impaired cognitive functioning, and difficulty in social interactions. While the effect of the traditional Chinese medicine artemisinin (AR) on PTSD is unknown, its therapeutic benefits have been demonstrated by studies on models of multiple neurological disorders. This study aimed to extend such findings by investigating the effects of AR administration on a rat model of PTSD induced by a regimen of single prolonged stress (SPS). After rats were subjected to the SPS protocol, AR was administered and its impact on PTSD-like behaviors was evaluated. In the present study, rats were subjected to a multitude of behavioral tests to evaluate behaviors related to anxiety, memory function, and social interactions. The expression of hippocampal synaptic plasticity-related proteins was detected using Western blot and immunofluorescence. The ultrastructure of synapses was observed under transmission electron microscopy. The apoptosis of hippocampal neurons was examined with Western blot, TUNEL staining, and HE staining. The results showed that AR administration alleviated the PTSD-like phenotypes in SPS rats, including behavior indicative of anxiety, cognitive deficits, and diminished sociability. AR administration was further observed to improve synaptic plasticity and inhibit neuronal apoptosis in SPS rats. These findings suggest that administering AR after the onset of severe traumatic events may alleviate anxiety, cognitive deficits, and impaired social interaction, improve synaptic plasticity, and diminish neuronal apoptosis. Hence, the present study provides evidence for AR’s potential as a multi-target agent in the treatment of PTSD.

IntroductionThe well-being of patients with chronic diseases is an issue of widespread concern in public health. While social support is thought to have a positive effect on it, the mechanisms of its influence have not been fully addressed. Thus, we explored the possible mediating effects of self-efficacy and perceived stress to determine the relationship between social support and well-being in these patients.MethodsA cross-sectional study was conducted among 4,657 patients with chronic diseases in China. The PROCESS Macro model 6 of SPSS was employed to explore the intermediary role between variables.ResultsSelf-efficacy and perceived stress played a partial intermediary role between social support and subjective well-being, with an effect ratio of 48.25% and 23.61%, respectively. Self-efficacy and perceived stress had a chain intermediary effect (28.14%) between social support and subjective well-being.DiscussionThis study suggested that improving the self-efficacy of patients with chronic diseases to cope with the changes in social support caused by the disease could reduce stress and enhance subjective well-being.

IntroductionWith the increasingly serious problem of bacterial drug resistance caused by NDM-1, it is an important strategy to find effective inhibitors to assist β-lactam antibiotic treatment against NDM-1 resistant bacteria. In this study, PHT427 (4-dodecyl-N-1,3,4-thiadiazol-2-yl-benzenesulfonamide) was identified as a novel NDM-1 inhibitor and restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1.MethodsWe used a high throughput screening model to find NDM-1 inhibitor in the library of small molecular compounds. The interaction between the hit compound PHT427 and NDM-1 was analyzed by fluorescence quenching, surface plasmon resonance (SPR) assay, and molecular docking analysis. The efficacy of the compound in combination with meropenem was evaluated by determining the FICIs of Escherichia coli BL21(DE3)/pET30a(+)-blaNDM–1 and Klebsiella pneumoniae clinical strain C1928 (producing NDM-1). In addition, the mechanism of the inhibitory effect of PHT427 on NDM-1 was studied by site mutation, SPR, and zinc supplementation assays.ResultsPHT427 was identified as an inhibitor of NDM-1. It could significantly inhibit the activity of NDM-1 with an IC50 of 1.42 μmol/L, and restored the susceptibility of meropenem against E. coli BL21(DE3)/pET30a(+)-blaNDM–1 and K. pneumoniae clinical strain C1928 (producing NDM-1) in vitro. The mechanism study indicated that PHT427 could act on the zinc ions at the active site of NDM-1 and the catalytic key amino acid residues simultaneously. The mutation of Asn220 and Gln123 abolished the affinity of NDM-1 by PHT427 via SPR assay.DiscussionThis is the first report that PHT427 is a promising lead compound against carbapenem-resistant bacteria and it merits chemical optimization for drug development.

Immunotherapy of malignant tumor is a verified and crucial anti-tumor strategy to help patients with cancer for prolonging prognostic survival. It is a novel anticancer tactics that activates the immune system to discern and damage cancer cells, thereby prevent them from proliferating. However, immunotherapy still faces many challenges in view of clinical efficacy and safety issues. Various nanomaterials, especially gold nanoparticles (AuNPs), have been developed not only for anticancer treatment but also for delivering antitumor drugs or combining other treatment strategies. Recently, some studies have focused on AuNPs for enhancing cancer immunotherapy. In this review, we summarized how AuNPs applicated as immune agents, drug carriers or combinations with other immunotherapies for anticancer treatment. AuNPs can not only act as immune regulators but also deliver immune drugs for cancer. Therefore, AuNPs are candidates for enhancing the efficiency and safety of cancer immunotherapy.

Periodontitis progression is accompanied by irreversible alveolar bone absorption and leads to tooth loss. Early diagnosis is important for tooth stability and periodontal tissue preservation. However, there is no recognized miRNA diagnostic signature with convincing sensitivity and specificity for periodontitis. In this study, we obtained miRNA array expression profiles of periodontitis from the Gene Expression Omnibus (GEO) database. After screening for differentially expressed miRNAs, the least absolute shrinkage and selection operator (LASSO) method was performed to identify and construct a 17-miRNA-based diagnostic signature (hsa-miR-3917, hsa-mir-4271, hsa-miR-3156, hsa-miR-3141, hsa-miR-1246, hsa-miR-125a-5p, hsa-miR-671-5p, hcmv-mir-UL70, hsa-miR-650, hsa-miR-497-3p, hsa-miR-145-3p, hsa-miR-141-3p, hsa-miR-210-3p, hsa-miR-204-3p, hsa-miR-203a-5p, hsa-miR-99a-3p, and hsa-miR-30a-3p). Periodontal tissue samples with higher risk scores were more likely to show symptoms of periodontitis. Then, the receiver operating characteristic (ROC) curves were used to assess the diagnostic value of the miRNA signature, which indicated that the optimum cutoff value in periodontitis diagnosis was 0.5056 with an area under the ROC curve (AUC) of 0.996, a sensitivity of 97.3%, a specificity of 100.0% in the training cohort; in the testing cohort, the corresponding values were as follows: an AUC of 0.998, a sensitivity of 97.9%, and a specificity of 91.7%. We next evaluated the efficacy of the signature in differentiating disease subtype and affected range. Furthermore, we conducted functional enrichment analysis of the 17 miRNA-targeted mRNAs, including the regulation of mTOR activity and cell autophagy, Th1/Th2 cell balance and immunoregulation, cell apoptosis, and so on. In summary, our study identified and validated a 17-miRNA diagnostic signature with convincing AUC, sensitivity, and specificity for periodontitis.

The emergence of drug-resistant Mycobacterium tuberculosis (Mtb) has hampered treatments for tuberculosis, which consequently now require novel agents to overcome such drug resistance. The genetically stable D-alanine–D-alanine ligase A (DdlA) has been deemed as an excellent therapeutic target for tuberculosis. In the present study, a competitive inhibitor (IMB-0283) of DdlA was obtained via high-throughput screening. The minimum inhibitory concentrations (MIC) of IMB-0283 for the standard and clinical drug-resistant Mtb strains ranged from 0.25 to 4.00 μg/mL, whereas the conventional inhibitor of DdlA, D-cycloserine (DCS), only inhibited the growth of the standard Mtb strain at 16 μg/mL. The lethal effect of IMB-0283 on Mtb was found to act intracellularly in a DdlA-dependent manner. Specifically, IMB-0283 prevented the synthesis of neonatal cell walls but did not damage mature cell walls. Compared with those of DCS, IMB-0283 exhibited lower cytotoxicity and a higher selective index (SI). At the same dosages of treatment, IMB-0283 reduced bacterial load (log CFU/mL) in an acute animal model from 5.58 to 4.40, while DCS did not yield any such treatment efficacy. Taken together, the lower cytotoxicity and more efficacious in vivo activity of IMB-0283 suggest that it is a promising lead compound for antituberculosis drug development.

Immunotherapy of malignant tumor is a verified and crucial anti-tumor strategy to help patients with cancer for prolonging prognostic survival. It is a novel anticancer tactics that activates the immune system to discern and damage cancer cells, thereby prevent them from proliferating. However, immunotherapy still faces many challenges in view of clinical efficacy and safety issues. Various nanomaterials, especially gold nanoparticles (AuNPs), have been developed not only for anticancer treatment but also for delivering antitumor drugs or combining other treatment strategies. Recently, some studies have focused on AuNPs for enhancing cancer immunotherapy. In this review, we summarized how AuNPs applicated as immune agents, drug carriers or combinations with other immunotherapies for anticancer treatment. AuNPs can not only act as immune regulators but also deliver immune drugs for cancer. Therefore, AuNPs are candidates for enhancing the efficiency and safety of cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) contamination of agricultural soils is an increasingly serious problem. Measures need to be developed to minimize Cd entering the human food chain from contaminated soils. We report here that, under Cd exposure condition, application with low doses of (0.1-0.5µM) abscisic acid (ABA) clearly inhibited Cd uptake by roots and decreased Cd level in Arabidopsis wild-type plants (Col-0). Expression of IRT1 in roots was also strongly inhibited by ABA treatment. Decrease in Cd uptake and the inhibition of IRT1 expression were clearly lesser pronounced in an ABA-insensitive double mutant snrk2.2/2.3 than in the Col-0 in response to ABA application. The ABA-decreased Cd uptake was found to correlate with the ABA-inhibited IRT1 expression in the roots of Col-0 plants fed two different levels of iron. Furthermore, the Cd uptake of irt1 mutants was barely affected by ABA application. These results indicated that inhibition of IRT1 expression is involved in the decrease of Cd uptake in response to exogenous ABA application. Interestingly, ABA application increased the iron level in both Col-0 plants and irt1 mutants, suggesting that ABA-increased Fe acquisition does not depend on the IRT1 function, but on the contrary, the ABA-mediated inhibition of IRT1 expression may be due to the elevation of iron level in plants. From our results, we concluded that ABA application might increase iron acquisition, followed by the decrease in Cd uptake by inhibition of IRT1 activity. Thus, for crop production in Cd contaminated soils, developing techniques based on ABA application potentially is a promising approach for reducing Cd accumulation in edible organs in plants. [ABSTRACT FROM AUTHOR]