A dose-adjusted, open-label, pilot study of the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis.

Increased circulating histones correlate with sepsis severity and are a potential therapeutic target. Pre-clinical studies showed benefit with a histone-neutralizing polyanion molecule (STC3141). We aimed to investigate the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis. We studied 26 patients with sepsis divided into four cohorts of one, five, ten, and ten subjects, respectively. We conducted a dose-adjusted, open-label study to determine the safety, tolerability, and pharmacokinetics of STC3141 administered as an IV infusion for up to 72 h, with rate adjusted to estimated creatinine clearance. Four steady-state concentrations were targeted. Twenty of the 26 subjects (77%) in the study experienced at least one adverse event (AE). The most frequently reported study drug-related AE was a mildly prolonged aPTT (four events). Only one AE (pulmonary hemorrhage) led to discontinuation of the drug. After excluding patients receiving renal replacement therapy (RRT) patients, clearance ranged from 3.3 to 4.2 L/h across cohorts and was essentially completely renal in nature. Half-life values ranged from 5 to 7 h. The mean (±SD) terminal half-life for non-RRT subjects and for whom it was possible to calculate was approximately 9 (±4.77) h but increased to 19 (±7.94) h for subjects on RRT. Overall, 18 (69.2%) patients completed the study to day eight in the ICU, and 22 (84.6%) survived to 28 days. STC3141 administration appeared to have an acceptable degree of safety and tolerability and expected pharmacokinetics. Cautious, larger randomized efficacy trials in sepsis appear justified.

Nurses' acceptance of nursing information systems: A multi-center cross-sectional study in China.

BACKGROUND: In China, nursing information systems (NIS) implementation can face numerous barriers to acceptance, including the attitudes of potential users. However, few studies have evaluated this acceptance. OBJECTIVE: The aim of this study was to explain the acceptance of NIS utilizing a survey based on unified theory of acceptance and use of technology. METHODS: A multi-center cross-sectional study utilizing an online survey was conducted. SPSS AMOS was used to conduct a structural equation modelling analysis. This research followed the STROBE Checklist. RESULTS: A total of 3973 Nurses participated in the study between January 2023 and March 2023. The acceptance of NIS among nurses was overall moderate to high. The proposed model has been rigorously tested and validated using empirical data, ensuring its credibility and dependability. Performance expectancy (PE), social influence (SI), and attitude significantly and positively affected intentions to use NIS. Effort expectancy (EE) did not show any significant effects in the sample. Facilitating conditions (FCs) was found to have a negative relationship with the intention to use NIS. There was a statistically significant difference BI between the different age groups, working years, and computer training experience. The model demonstrates a good fit with the observed data. CONCLUSIONS: This study identified PE, SI, and attitude as facilitators of nurses' intentions to use NIS. The findings about EE indicates that the ease of using NIS does not seem to be a concern among nurses. Moreover, high FC might be perceived as indicative of a complex system or extensive usage, that can lead to increased workload and reduced behavioural intention (BI). The significant differences in BI among various demographic groups highlight the need for more studies understanding the preferences and barriers faced by different, levels of experience and training backgrounds. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Mendelian randomization supports causal effects of inflammatory biomarkers on myopic refractive errors.

AIMS: To determine whether inflammatory biomarkers are causal risk factors for more myopic refractive errors. METHODS: Northern Sweden Population Health Study (NSPHS), providing inflammatory biomarkers data; UK Biobank, providing refractive errors data. 95,619 European men and women aged 40 to 69 years with available information of refractive errors and inflammatory biomakers. Inflammatory biomarkers including ADA, CCL23, CCL25, CD6, CD40, CDCP-1, CST5, CXCL-5, CXCL-6, CXCL-10, IL-10RB, IL-12B, IL-15RA, IL-18R1, MCP-2, MMP-1, TGF-ß1, TNF-ß, TWEAK and VEGF-A were exposures, and spherical equivalent (SE) using the formula SE = sphere + (cylinder/2) was outcome. RESULTS: Mendelian randomization analyses showed that each unit increase in VEGF-A, CD6, MCP-2 were causally related to a more myopic refractive errors of 0.040 D/pg.mL-1 (95% confidence interval 0.019 to 0.062; P = 2.031 × 10-4), 0.042 D/pg.mL-1 (0.027 to 0.057; P = 7.361 × 10-8) and 0.016 D/pg.mL-1 (0.004 to 0.028; P = 0.009), and each unit increase in TWEAK was causally related to a less myopic refractive errors of 0.104 D/pg.mL-1 (-0.152 to -0.055; P = 2.878 × 10-5). Tested by the MR-Egger, weighted median, MR-PRESSO, Leave-one-out methods, our results were robust to horizontal pleiotropy and heterogeneity in VEGF-A, MCP-2, CD6, but not in TWEAK. CONCLUSIONS: Our Mendelian Randomization analysis supported the causal effects of VEGF-A, MCP-2, CD6 and TWEAK on myopic refractive errors. These findings are important for providing new indicators for early intervention of myopia to make myopic eyesight threatening consequences less inevitable.

The relationship between filial values and preparedness in adult -child caregivers of patients with chronic heart failure: A cross-sectional study.

OBJECTIVES: To explore the relationship between filial values (responsibility, reciprocity, and obligation) and caregiving preparedness in adult child carers of patients with chronic heart failure (CHF). METHODS: A total of 339 adult child caregivers of CHF patients were recruited from six hospitals in China. Self-report questionnaires were used to measure caregivers' filial values and their caregiving preparedness. Descriptive analysis, Spearman's correlation analysis, and hierarchical regression analysis were performed. The study adhered to the STROBE guidelines. RESULTS: Filial values were positively correlated with caregiving preparedness. Hierarchical regression analysis revealed a positive relationship between the combined variables of care and respect with caregiver preparedness, jointly explaining 7.9 % of the variance. CONCLUSIONS: Filial values promote caregiver preparedness, broadening the applicability of the Caregiver Empowerment Model.

Separation of astragaloside IV from Astragalus membranaceus based on high-speed countercurrent chromatography in continuous injection mode.

INTRODUCTION: Astragaloside IV (AS-IV) is an index for the quality evaluation of the traditional Chinese medicine Astragalus and an important material basis for Astragalus to exert its medicinal effects, and it is difficult to obtain a single AS-IV by ordinary separation methods. OBJECTIVE: To find a new isolation method that can prepare AS-IV quickly and efficiently. METHODOLOGY: AS-IV was isolated from Astragalus membranaceus extract by high-speed countercurrent chromatography using a two-phase solvent system consisting of ethyl acetate/n-butanol/water (4.2:0.8:5, v/v) at a speed of 950 rpm at a flow rate of 2 mL/min using one of the high-speed countercurrent chromatographic sequential injection models developed during the previous study. RESULTS: Compared with the common countercurrent chromatographic separation, this separation method increased the injection volume and yield by 4-fold and 4.47-fold, respectively, with only about 1.2-fold increase in solvent consumption and separation time, and the purity was basically not reduced, and 55.9 mg of AS-IV, with a purity of 96.95%, was finally prepared from 400 mg of the crude extract in 240 min. CONCLUSION: The continuous injection mode of high-speed countercurrent chromatography was able to successfully prepare a large amount of AS-IV with high purity at one time.

A new stegosaur (Dinosauria: Ornithischia) from the Middle Jurassic of Gansu Province, China.

Stegosaurs are a minor but iconic clade of ornithischian dinosaurs, yet due to a poor fossil record, their early evolution is poorly understood. Here, we describe a new stegosaur, Baiyinosaurus baojiensis, gen. et sp. nov. from the Middle Jurassic Wangjiashan Formation of the Pingchuan District, Baiyin City, Gansu Province, China. The frontal of Baiyinosaurus possesses a unique characteristic among Stegosauria: it is wider than long and contributes to both the medial and anterior margins of the supratemporal fenestra. The character combinations of dorsal vertebrae of Baiyinosaurus are also different to other stegosaurs: its neural arches are not greatly elongated, its parapophyses are well developed, and its neural spines are axially expanded in lateral. The features of the frontal and vertebrae of Baiyinosaurus are reminiscent of basally branching thyreophorans, indicating that Baiyinosaurus is transitional in morphology between early thyreophorans and early-diverging stegosaurs. Systematic analysis shows that Baiyinosaurus is an early-diverging stegosaur.

A role for YAP/FOXM1/Nrf2 axis in oxidative stress and apoptosis of cataract induced by UVB irradiation.

This study aims to investigate the hypothesis that Yes-associated protein (YAP) significantly regulates antioxidant potential and anti-apoptosis in UVB-induced cataract by exploring the underlying molecular mechanisms. To investigate the association between YAP and cataract, various experimental techniques were employed, including cell viability assessment, Annexin V FITC/PI assay, measurement of ROS production, RT-PCR, Western blot assay, and Immunoprecipitation. UVB exposure on human lens epithelium cells (HLECs) reduced total and nuclear YAP protein expression, increased cleaved/pro-caspase 3 ratios, decreased cell viability, and elevated ROS levels compared to controls. Similar Western blot results were observed in in vivo experiments involving UVB-treated mice. YAP knockdown in vitro demonstrated a decrease in the protein expression of FOXM1, Nrf2, and HO-1, which correlated with the mRNA expression, accompanied by an increase in cell apoptosis, caspase 3 activation, and the release of ROS. Conversely, YAP overexpression mitigated these effects induced by UVB irradiation. Immunoprecipitation revealed a FOXM1-YAP interaction. Notably, inhibiting FOXM1 decreased Nrf2 and HO-1, activating caspase 3. Additionally, administering the ROS inhibitor N-acetyl-L-cysteine (NAC) effectively mitigated the apoptotic effects induced by oxidative stress from UVB irradiation, rescuing the protein expression levels of YAP, FOXM1, Nrf2, and HO-1. The initial findings of our study demonstrate the existence of a feedback loop involving YAP, FOXM1, Nrf2, and ROS that significantly influences the cell apoptosis in HLECs under UVB-induced oxidative stress.

Acute primary angle closure concurrent with coronavirus disease 2019 recurrence in Northern China: A retrospective multi-centre study.

Aims and objectives: During the new coronavirus disease 2019 (COVID-19) outbreak period, there was increasing presentation in the number of patients with acute primary angle closure (APAC). This study aimed to report the occurrence of APAC during the COVID-19 post-restriction period and investigate the related characteristics of these patients with APAC. Methods: This retrospective, multi-center study included consecutive patients seeking APAC treatment at two eye centers in China from December 7, 2022 to January 13, 2023 (post-restriction period) and from December 7, 2021 to January 13, 2022 (control period). Electronic medical records were reviewed, and ocular data of the affected eye(s) were analyzed for patients with unilateral or bilateral APAC. Information including COVID-19 related symptoms, medications used for COVID-19 infection, and living habits and emotions related to the COVID-19 outbreak during the post restriction period were collected using a questionnaire. Results: Overall, 189 (219 APAC eyes) and 51 (54 APAC eyes) patients with APAC were identified during the post-restriction and control periods, respectively. The patients identified during the post-restriction period were younger (P = 0.043) and had a longer duration from symptoms to treatment (P = 0.039), shorter axial length (P = 0.002), larger pupil diameter (P = 0.004), larger vertical cup disc ratio (P = 0.004), poorer mean deviation values (P = 0.003), and more glaucomatous optic neuropathy diagnoses (P = 0.032) compared with the patients with APAC identified during the control period. Among 151 included patients with APAC who completed the questionnaires, 130 patients with APAC were diagnosed with concurrent COVID-19 infection, of which 54 (41.5 %) had coughing and/or vomiting as the main symptoms. Of these, 89.2 % spent 0 h per day on outdoor activity; 44.6 % drank more water than usual, with 14.6 % drinking more than twice the amount of water than usual; 91.5 % used antipyretics; and 20.0 % had mood swings, including anxiety, depression, and tension, during the concurrent COVID-19 infection. Conclusion: In our study, a significant increase in the number of patients presenting with APAC with certain characteristics was observed during the COVID-19 post-restriction period. And whether COVID-19 symptoms, such as coughing and vomiting, and behavioral and psychological changes caused by COVID-19 infection contributing to the concurrence of APAC and COVID-19 recurrence require further investigation.

Enhanced response over wavelength range of 7-12 µm for quantum wells in asymmetric micro-pillars.

Efficient coupling in broad wavelength range is desirable for wide-spectrum infrared light detection, yet this is a challenge for intersubband transition in semiconductor quantum wells (QWs). High-Q cavities mostly intensify the absorption at peak wavelengths but with shrinking bandwidth. Here, we propose a novel approach to expand the operating spectral range of the Quantum Well Infrared Photodetectors (QWIPs). By processing the QWs into asymmetric micro-pillar array structure, the device demonstrates a substantial enhancement in spectral response across the wavelength from 7.1 µm to 12.3 µm with guided mode resonance (GMR) effects. The blackbody responsivity is then increased by 3 times compared to that of the 45° polished edge-coupled counterpart. Meanwhile, the dark current density remains unchanged after the deep etching process, which will benefit the electrical performance of the detector with reduced volume duty ratio. In contrast to the symmetric micro-pillar array that contains simple resonance mode, the detectivity of QWIP in asymmetric pillar structure is found to be improved by 2-4 times within the range of 9.5 µm to 15 µm.

Organocatalyzed Asymmetric Michael Addition of 3-Fluorooxindole to Vinylidene Bisphosphonates.

Both the 3-fluorooxindole and germinal bisphosphonate structural motifs are prevalent in bioactive molecules because of their associated biological activities. We describe an approach to accessing 3,3-disubstituted 3-fluorooxindoles bearing a geminal bisphosphate fragment through a highly enantioselective Michael addition reaction between 3-fluorooxindoles and vinylidene bisphosphonates. These reactions are catalyzed by a commercially available cinchona alkaloid catalyst, have a broad substrate scope concerning 3-fluorooxindoles, and provide the corresponding addition products in a yield of up to 95% with an enantiomeric excess of up to 95%. A reasonable reaction pathway to explain the observed stereochemistry is also proposed.

Establishment and characterization of Lesch-Nyhan syndrome rabbit model.

Lesch-Nyhan syndrome (LNS) is a congenital defect disease that results in defective purine metabolism. It is caused by pathogenic variants of the HPRT gene. Its clinical symptoms mainly include high uric acid levels, gout, and kidney stones and damage. The mechanism of LNS has not been fully elucidated, and no cure exists. Animal models have always played an important role in exploring causative mechanisms and new therapies. This study combined CRISPR/Cas9 and microinjection to knock out the HPRT gene to create an LNS rabbit model. A sgRNA targeting exon 3 of HPRT gene was designed. Subsequently, Cas9 mRNA and sgRNA were injected into rabbit zygotes, and injected embryos were transferred to the uterus. The genotype and phenotype of rabbits were analyzed after birth. Four infant rabbits (named R1, R2, R3 and R4), which showed varying levels of gene modification, were born. The gene-editing efficiency was 100%. No wild-type sequences at the target HPRT gene were detected in R4 rabbit. Next, 6-thioguanine drug testing confirmed that HPRT enzymatic activity was deficient in R4 infant rabbit. HE staining revealed kidney abnormalities in all infant rabbits. Overall, an sgRNA capable of knocking out the HPRT gene in rabbits was successfully designed, and HPRT gene-modified rabbits were successfully constructed by using CRISPR/Cas9 technology and microinjection. This study provides a new nonrodent animal model for studying LNS syndrome.

The Accompanying Effect in Responses to Auditory Perturbations: Unconscious Vocal Adjustments to Unperturbed Parameters.

PURPOSE: The present study examined whether participants respond to unperturbed parameters while experiencing specific perturbations in auditory feedback. For instance, we aim to determine if speakers adjust voice loudness when only pitch is artificially altered in auditory feedback. This phenomenon is referred to as the "accompanying effect" in the present study. METHOD: Thirty native Mandarin speakers were asked to sustain the vowel /ɛ/ for 3 s while their auditory feedback underwent single shifts in one of the three distinct ways: pitch shift (±100 cents; coded as PT), loudness shift (±6 dB; coded as LD), or first formant (F1) shift (±100 Hz; coded as FM). Participants were instructed to ignore the perturbations in their auditory feedback. Response types were categorized based on pitch, loudness, and F1 for each individual trial, such as Popp_Lopp_Fopp indicating opposing responses in all three domains. RESULTS: The accompanying effect appeared 93% of the time. Bayesian Poisson regression models indicate that opposing responses in all three domains (Popp_Lopp_Fopp) were the most prevalent response type across the conditions (PT, LD, and FM). The more frequently used response types exhibited opposing responses and significantly larger response curves than the less frequently used response types. Following responses became more prevalent only when the perturbed stimuli were perceived as voices from someone else (external references), particularly in the FM condition. In terms of isotropy, loudness and F1 tended to change in the same direction rather than loudness and pitch. CONCLUSION: The presence of the accompanying effect suggests that the motor systems responsible for regulating pitch, loudness, and formants are not entirely independent but rather interconnected to some degree.

Identification of key mitochondria-related genes and their relevance to the immune system linking Parkinson's disease and primary Sjögren's syndrome through integrated bioinformatics analyses.

BACKGROUND: Mitochondria are the metabolic hubs of cells, regulating energy production and antigen presentation, which are essential for activation, proliferation, and function of immune cells. Recent evidence indicates that mitochondrial antigen presentation may have an impact on diseases such as Parkinson's disease (PD) and autoimmune diseases. However, there is limited knowledge about the mechanisms that regulate the presentation of mitochondrial antigens in these diseases. METHODS: In the current study, RNA sequencing was performed on labial minor salivary gland (LSG) from 25 patients with primary Sjögren's syndrome (pSS) and 14 non-pSS aged controls. Additionally, we obtained gene expression omnibus datasets associated with PD patients from NCBI Gene Expression Omnibus (GEO) databases. Single-sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE and Spearman correlations were conducted to explore the association between mitochondrial related genes and the immune system. Furthermore, we applied weighted Gene Co-expression Network Analysis (WGCNA) to identify hub mitochondria-related genes and investigate the correlated networks in both diseases. Single cell transcriptome analysis, immunohistochemical (IHC) staining and quantitative real-time PCR (qRT-PCR) were used to verify the activation of the hub mitochondria-related pathway. Pearson correlations and the CIBERSORT algorithms were employed to further reveal the correlation between hub mitochondria-related pathways and immune infiltration. RESULTS: The transcriptome analysis revealed the presence of overlapping mitochondria-related genes and mitochondrial DNA damage in patients with pSS and PD. Reactive oxygen species (ROS), the senescence marker p53, and the inflammatory markers CD45 and Bcl-2 were found to be regionally distributed in LSGs of pSS patients. WGCNA analysis identified the STING pathway as the central mitochondria-related pathway closely associated with the immune system. Single cell analysis, IHC staining, and qRT-PCR confirmed the activation of the STING pathway. Subsequent, bioinformatic analysis revealed the proportion of infiltrating immune cells in the STING-high and STING-low groups of pSS and PD. Furthermore, the study demonstrated the association of the STING pathway with innate and adaptive immune cells, as well as functional cells, in the immune microenvironment of PD and pSS. CONCLUSION: Our study uncovered a central pathway that connects mitochondrial dysfunction and the immune microenvironment in PD and pSS, potentially offering valuable insights into therapeutic targets for these conditions.

Zonular instability-associated morphologic features in eyes with primary angle closure disease using the swept-source anterior segment - optical coherence tomography system.

BACKGROUND: This study aims to investigate the morphologic features of the crystalline lens in Primary Angle Closure Disease (PACD) patients with zonular instability during cataract surgery using the swept-source CASIA 2 Anterior Segment-Optical Coherence Tomography (AS-OCT) system. METHODS: A total of 398 eyes (125 PACD eyes with zonular instability, 133 PACD eyes with zonular stability, and 140 cataract patient controls) of 398 patients who underwent cataract surgery combined or not glaucoma surgery between January 2021 and January 2023 were enrolled. The crystalline lens parameters were measured by CASIA2 AS-OCT. Then, logistic regression was performed to evaluate the risk factors associated with zonular instability. RESULTS: The results revealed that PACD eyes had a more anterior lens equator position, a steeper anterior curvature of lens, shorter Axial Length (AL), shallower Anterior Chamber Distance (ACD), higher Lens Vault (LV) and thicker Lens Thickness (LT), when compared to eyes in the cataract control group. Furthermore, PACD eyes in the zonular instability group had steeper front R, front Rs and Front Rf, flatter back Rf, thicker lens anterior part thickness, higher lens anterior-to-posterior part thickness ratios, shallower ACD, and greater LV, when compared to PACD eyes with zonular stability. The logistic regression analysis, which was adjusted for age and gender, revealed that zonular instability was positively correlated with anterior part thickness, lens anterior-to-posterior part thickness ratio, and LV, but was negatively correlated with lens anterior radius and ACD. CONCLUSION: Steeper anterior curvature, increased lens anterior part thickness, higher anterior-to-posterior part thickness ratio, shallower ACD, and greater LV are the anatomic features of PACD eyes associated with zonular instability.

The Effects of Health Education and the Sunrise Model of Nursing Care on Blood Pressure Control and Psychological Status in Elderly Patients with Hypertension.

Objective: Our aim was to investigate the effect of health education and a positive attitude nursing model on blood pressure (BP) control and psychological status in elderly patients with hypertension (HTN). Methods: A total of 80 elderly patients with HTN in the Affiliated Hangzhou First People's Hospital in China were selected as the study participants. They were randomly divided into a control group and an observation group, with 40 patients in each group. The control group received the routine nursing intervention, while the observation group received health education and the positive attitude nursing intervention based on the nursing care in the control group. The BP control effect, changes in systolic and diastolic BP, psychological status and nursing satisfaction were compared in the 2 groups. Results: The BP control rate in the control group was 77.5% and was 95.0% in the observation group, which was significantly better (P < .05). Before the intervention, there was no significant difference in average systolic and diastolic BP between the 2 groups (P > .05); after the intervention, average systolic and diastolic BP in the observation group were significantly lower than in the control group (P < .05). Before the intervention, there was no significant difference in Self-rating Anxiety Scale (SAS) and Self-rating Anxiety Scale (SDS) scores between the 2 groups (P > .05). After the intervention, the SAS and SDS scores in the observation group were significantly better than those in the control group (P < .05). The nursing satisfaction in the control group was 75.0% and was 95.0% in the observation group, which was significantly higher (P < .05). Conclusion: Compared with routine nursing intervention, the health education and positive attitude nursing intervention can further improve BP control, psychological status and satisfaction and recognition level of elderly patients with HTN; it can be an important clinical nursing intervention.

Clinical metabolomics characteristics of diabetic kidney disease: A meta-analysis of 1875 cases with diabetic kidney disease and 4503 controls.

AIMS: Diabetic Kidney Disease (DKD), one of the major complications of diabetes, is also a major cause of end-stage renal disease. Metabolomics can provide a unique metabolic profile of the disease and thus predict or diagnose the development of the disease. Therefore, this study summarises a more comprehensive set of clinical biomarkers related to DKD to identify functional metabolites significantly associated with the development of DKD and reveal their driving mechanisms for DKD. MATERIALS AND METHODS: We searched PubMed, Embase, the Cochrane Library and Web of Science databases through October 2022. A meta-analysis was conducted on untargeted or targeted metabolomics research data based on the strategy of standardized mean differences and the process of ratio of means as the effect size, respectively. We compared the changes in metabolite levels between the DKD patients and the controls and explored the source of heterogeneity through subgroup analyses, sensitivity analysis and meta-regression analysis. RESULTS: The 34 clinical-based metabolomics studies clarified the differential metabolites between DKD and controls, containing 4503 control subjects and 1875 patients with DKD. The results showed that a total of 60 common differential metabolites were found in both meta-analyses, of which 5 metabolites (p < 0.05) were identified as essential metabolites. Compared with the control group, metabolites glycine, aconitic acid, glycolic acid and uracil decreased significantly in DKD patients; cysteine was significantly higher. This indicates that amino acid metabolism, lipid metabolism and pyrimidine metabolism in DKD patients are disordered. CONCLUSIONS: We have identified 5 metabolites and metabolic pathways related to DKD which can serve as biomarkers or targets for disease prevention and drug therapy.

Association between personality traits and psychological distress among postmenopausal women with coronary heart disease: A cross-sectional survey and mediation analysis.

Postmenopausal women with negative personality characteristics are at an increased risk of psychological disorders, yet little is known about the mechanism underlying the relationship between type D personality and psychological distress in postmenopausal women with coronary disease. This study assessed the mediating roles of perceived social support and self-perceived burden in the relationship between type D and psychological distress based on the equity theory and stress-buffering model. Demographic characteristics, type D, psychological distress, perceived social support, and self-perceived burden were completed by 335 participants with self-reported questionnaires using a cross-sectional design in Southeast China. The results revealed that perceived social support and self-perceived burden both separately and serially mediated the relationship between type D personality and psychological distress. Effective intervention strategies aimed at improving perceived social support or reducing self-perceived burden may be beneficial in reducing psychological distress.

Multi-omics analysis of disulfidptosis regulators and therapeutic potential reveals glycogen synthase 1 as a disulfidptosis triggering target for triple-negative breast cancer.

Disruption of disulfide homeostasis during biological processes can have fatal consequences. Excess disulfides induce cell death in a novel manner, termed as "disulfidptosis." However, the specific mechanism of disulfidptosis has not yet been elucidated. To determine the cancer types sensitive to disulfidptosis and outline the corresponding treatment strategies, we firstly investigated the crucial functions of disulfidptosis regulators pan-cancer at multi-omics levels. We found that different tumor types expressed dysregulated levels of disulfidptosis regulators, most of which had an impact on tumor prognosis. Moreover, we calculated the disulfidptosis activity score in tumors and validated it using multiple independent datasets. Additionally, we found that disulfidptosis activity was correlated with classic biological processes and pathways in various cancers. Disulfidptosis activity was also associated with tumor immune characteristics and could predict immunotherapy outcomes. Notably, the disulfidptosis regulator, glycogen synthase 1 (GYS1), was identified as a promising target for triple-negative breast cancer and validated via in vitro and in vivo experiments. In conclusion, our study elucidated the complex molecular phenotypes and clinicopathological correlations of disulfidptosis regulators in tumors, laying a solid foundation for the development of disulfidptosis-targeting strategies for cancer treatment.

Upregulation of proBDNF/p75NTR signaling in immune cells and its correlation with inflammatory markers in patients with major depression.

ProBDNF is the precursor protein of brain-derived neurotrophic factor (BDNF) expressed in the central nervous system and peripheral tissues. Previous studies showed that the blood levels of both proBDNF and p75 neurotrophic receptors (p75NTR) in major depressive disorder (MDD) were increased, but which blood cell types express proBDNF and its receptors is not known. Furthermore, the relationship between proBDNF/p75NTR and inflammatory cytokines in peripheral blood of MDD is unclear. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from depressive patients (n = 32) and normal donors (n = 20). We examined the expression of proBDNF and inflammatory markers and their correlative relationship in patients with major depression. Using flow cytometry analysis, we examined which blood cells express proBDNF and its receptors. Finally, the role of proBDNF/p75NTR signal in inflammatory immune activity of PBMCs was verified in vitro experiments. Inflammatory cytokines in PBMC from MDD patients were increased and correlated with the major depression scores. The levels of IL-1ß and IL-10 were also positively correlated with the major depression scores, while the levels of TNF-α and IL-6 were negatively correlated with the major depression scores. Intriguingly, the levels of sortilin were positively correlated with IL-1ß. Q-PCR and Western blots showed proBDNF, p75NTR, and sortilin levels were significantly increased in PBMCs from MDD patients compared with that from the normal donors. Flow cytometry studies showed that proBDNF and p75NTR were present mainly in CD4+ and CD8+ T cells. The number of proBDNF and p75NTR positive CD4+ and CD8+ T cells from MDD patients was increased and subsequently reversed after therapeutic management. Exogenous proBDNF protein or p75ECD-Fc treatment of cultured PBMC affected the release of inflammatory cytokines in vitro. ProBDNF promoted the expression of inflammatory cytokines, while p75ECD-Fc inhibited the expression of inflammatory cytokines. Given there was an inflammatory response of lymphocytes to proBDNF, it is suggested that proBDNF/p75NTR signaling may upstream inflammatory cytokines in MDD. Our data suggest that proBDNF/p75NTR signaling may not only serve as biomarkers but also may be a potential therapeutic target for MDD.

Atrial Fibrillation Detection with Single-Lead Electrocardiogram Based on Temporal Convolutional Network-ResNet.

Atrial fibrillation, one of the most common persistent cardiac arrhythmias globally, is known for its rapid and irregular atrial rhythms. This study integrates the temporal convolutional network (TCN) and residual network (ResNet) frameworks to effectively classify atrial fibrillation in single-lead ECGs, thereby enhancing the application of neural networks in this field. Our model demonstrated significant success in detecting atrial fibrillation, with experimental results showing an accuracy rate of 97% and an F1 score of 87%. These figures indicate the model's exceptional performance in identifying both majority and minority classes, reflecting its balanced and accurate classification capability. This research offers new perspectives and tools for diagnosis and treatment in cardiology, grounded in advanced neural network technology.