Modulation of High-Frequency rTMS on Reward Circuitry in Individuals with Nicotine Dependence: A Preliminary fMRI Study.

Although previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) can ameliorate addictive behaviors and cravings, the underlying neural mechanisms remain unclear. This study aimed to investigate the effect of high-frequency rTMS with the left dorsolateral prefrontal cortex (L-DLPFC) as a target region on smoking addiction in nicotine-dependent individuals by detecting the change of spontaneous brain activity in the reward circuitry. We recruited 17 nicotine-dependence participants, who completed 10 sessions of 10 Hz rTMS over a 2-week period and underwent evaluation of several dependence-related scales, and resting-state fMRI scan before and after the treatment. Functional connectivity (FC) analysis was conducted with reward-related brain regions as seeds, including ventral tegmental area, bilateral nucleus accumbens (NAc), bilateral DLPFC, and bilateral amygdala. We found that, after the treatment, individuals showed reduced nicotine dependence, alleviated tobacco withdrawal symptoms, and diminished smoking cravings. The right NAc showed increased FC with right fusiform gyrus, inferior temporal gyrus (ITG), calcarine fissure and surrounding cortex, superior occipital gyrus (SOG), lingual gyrus, and bilateral cuneus. No significant FC changes were observed in other seed regions. Moreover, the changes in FC between the right NAc and the right ITG as well as SOG before and after rTMS were negatively correlated with changes in smoking scale scores. Our findings suggest that high-frequency L-DLPFC-rTMS reduces nicotine dependence and improves tobacco withdrawal symptoms, and the dysfunctional connectivity in reward circuitry may be the underlying neural mechanism for nicotine addiction and its therapeutic target.

Effects of low temperature air exposure and immersion on antioxidant, immune, intestinal flora and metabolome of Chinese mitten crab (Eriocheir sinensis).

The aim of this study was to investigate the effects of immersion on immune enzyme activity, haemolymph index, intestinal microbiome and metabolome of E. sinensis after low temperature air exposure. The results showed that low temperature air exposure induced stress response, which led to hepatopancreas injury and increased membrane permeability, but this situation was reversible and alleviated after immersion. In addition, after exposure to low temperature air, haemolymph metabolism-related substances such as glucose and total cholesterol were significantly different from the initial value (P < 0.05), and gradually returned to the initial level after immersion. The changes of intestinal flora and hepatopancreas metabolism caused by low temperature air exposure did not fully recover after immersion, and its negative effects did not completely disappear. The sequencing results showed that the species composition and diversity of intestinal microorganisms of Chinese mitten crabs were changed after low temperature air exposure and immersion treatment. The relative abundance of Bacteroidetes and Proteobacteria were increased, while the relative abundance of Firmicutes was decreased (P < 0.05). Metabolomics analysis showed that lysine levels increased significantly, taurocholic acid levels decreased significantly, and amino acid metabolism and lipid metabolism balance were disturbed in hepatopancreas of E. sinensis after exposure to low temperature air and immersion (P < 0.05). This study will provide new insights into the recovery mechanism of water immersion on Chinese mitten crabs after exposure to air.

The Effect of Long-Term Particulate Matter Exposure on Respiratory Mortality: Cohort Study in China.

Background: Particulate matter (PM), which affects respiratory health, has been well documented; however, substantial evidence from large cohorts is still limited, particularly in highly polluted countries and for PM1. Objective: Our objective was to examine the potential causal links between long-term exposure to PMs (PM2.5, PM10, and more importantly, PM1) and respiratory mortality. Methods: A total of 580,757 participants from the Guangzhou area, China, were recruited from 2009 to 2015 and followed up through 2020. The annual average concentrations of PMs at a 1-km spatial resolution around the residential addresses were estimated using validated spatiotemporal models. The marginal structural Cox model was used to estimate the associations of PM exposure with respiratory mortality, accounting for time-varying PM exposure. Results were stratified by demographics and lifestyle behaviors factors. Results: Among the participants, the mean age was 48.33 (SD 17.55) years, and 275,676 (47.47%) of them were men. During the follow-up period, 7260 deaths occurred due to respiratory diseases. The annual average concentrations of PM1, PM2.5, and PM10 showed a declining trend during the follow-up period. After adjusting for confounders, a 6.6% (95% CI 5.6%-7.6%), 4.2% (95% CI 3.6%-4.7%), and 4.0% (95% CI 3.6%-4.5%) increase in the risk of respiratory mortality was observed following each 1-µg/m3 increase in concentrations of PM1, PM2.5, and PM10, respectively. In addition, older participants, nonsmokers, participants with higher exercise frequency, and those exposed to a lower normalized difference vegetation index tended to be more susceptible to the effects of PMs. Furthermore, participants in the low-exposure group tended to be at a 7.6% and 2.7% greater risk of respiratory mortality following PM1 and PM10 exposure, respectively, compared to the entire cohort. Conclusions: This cohort study provides causal clues of the respiratory impact of long-term ambient PM exposure, indicating that PM reduction efforts may continuously benefit the population's respiratory health.

Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial.

BACKGROUND: Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is the first sham-controlled trial investigating the safety and efficacy of RDN in China. METHODS: This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; AngioCare, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months. RESULTS: Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P<0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P<0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P=0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P=0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up. CONCLUSIONS: In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02901704.

Endo-Lysosomal Network Disorder Reprograms Energy Metabolism in SorL1-Null Rat Hippocampus.

Sortilin-related receptor 1 (SorL1) deficiency is a genetic predisposition to familial Alzheimer's disease (AD), but its pathology is poorly understood. In SorL1-null rats, a disorder of the global endosome-lysosome network (ELN) is found in hippocampal neurons. Deletion of amyloid precursor protein (APP) in SorL1-null rats could not completely rescue the neuronal abnormalities in the ELN of the hippocampus and the impairment of spatial memory in SorL1-null young rats. These in vivo observations indicated that APP is one of the cargoes of SorL1 in the regulation of the ELN, which affects hippocampal-dependent memory. When SorL1 is depleted, the endolysosome takes up more of the lysosome flux and damages lysosomal digestion, leading to pathological lysosomal storage and disturbance of cholesterol and iron homeostasis in the hippocampus. These disturbances disrupt the original homeostasis of the material-energy-subcellular structure and reprogram energy metabolism based on fatty acids in the SorL1-null hippocampus, instead of glucose. Although fatty acid oxidation increases ATP supply, it cannot reduce the levels of the harmful byproduct ROS during oxidative phosphorylation, as it does in glucose catabolism. Therefore, the SorL1-null rats exhibit hippocampal degeneration, and their spatial memory is impaired. Our research sheds light on the pathology of SorL1 deficiency in AD.

Theoretical study of adsorption of gas (CO, CO2, NH3) by metal (Au, Ag, Cu)-doped single-layer WS2.

CONTEXT: The adsorptions of gas (CO, CO2, NH3) by metal (Au, Ag, Cu)-doped single layer WS2 are studied by density functional theory. The doping of metal atoms makes WS2 behave as n-type semiconductors. The final adsorption sites for CO, CO2, and NH3 are close to the atomic sites of the doped metal. The adsorptions of CO and NH3 gases on Cu/WS2, Ag/WS2, and Au/WS2 are dominated by chemisorption. The doped metal atoms enhance the hybridization of the substrate with the gas molecular orbitals, which contributes to the charge transfer and enhances the adsorption of the gas with the material surface. The adsorptions of CO and NH3 on Cu/WS2 and Ag/WS2 allow favorable desorption in a short time after heating. The single-layer Cu/WS2 is proved to have the potential to be used as a reliable recyclable sensor for CO. This work provides a theoretical basis for developing high-performance WS2-based gas sensors. METHODS: In this paper, the adsorption energy, electronic structure, charge transfer, and recovery time of CO, CO2, and NH3 in the doped system have been investigated based on the CASTEP code of density functional theory. The exchange correlation function used is the Perdew-Burke-Ernzerhof (PBE) generalized gradient approximation (GGA). The TS (Tkatchenko-Scheffler) dispersion correction method was used to involve the effects of van der Waals interaction on the adsorption energies for all adsorption system. The ultrasoft pseudopotentials are chosen and the plane-wave cut-off energies are set to 500 eV. The k-point mesh generated by the Monkhorst package scheme is used to perform the numerical integration of the Brillouin zone and 5 × 5 × 1 k-point grid is used. The tolerances of total energy convergence, maximum ionic force, ionic displacement, and stress component are 1.0 × 10-5 eV/atom, 0.03 eV/Å, 0.001 Å, and 0.05 GPa, respectively.

Heterogeneous Nucleation Regulation Amends Unfavorable Crystallization Orientation and Defect Features of Antimony Selenosulfide Film for High-Efficient Planar Solar Cells.

Antimony selenosulfide (Sb2(S,Se)3) has obtained widespread concern for photovoltaic applications as a light absorber due to superior photoelectric features. Accordingly, various deposition technologies have been developed in recent years, especially hydrothermal deposition method, which has achieved a great success. However, device performances are limited with severe carrier recombination, relating to the quality of absorber and interfaces. Herein, bulk and interface defects are simultaneously suppressed by regulating heterogeneous nucleation kinetics with barium dibromide (BaBr2) introduction. In details, the Br adsorbs and dopes on the polar planes of cadmium sulfide (CdS) buffer layer, promoting the exposure of nonpolar planes of CdS, which facilitates the favorable growth of [hk1]-Sb2(S,Se)3 films possessing superior crystallinity and small interface defects. Additionally, the Se/S ratio is increased due to the replacement of S/Se by Br, causing a downshift of the Fermi levels with a benign band alignment and a shallow-level defect. Moreover, Ba2+ is located at grain boundaries by coordination with S and Se ions, passivating grain boundary defects. Consequently, the efficiency is increased from 7.70% to 10.12%. This work opens an avenue towards regulating the heterogeneous nucleation kinetics of Sb2(S,Se)3 film deposited via hydrothermal deposition approach to optimize its crystalline orientation and defect features.

A retrospective comparative study on the treatment of non-metastatic pancreatic cancer using high-intensity focused ultrasound versus radical surgery.

OBJECTIVE: To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) and radical surgery for non-metastatic pancreatic cancer (PC). MATERIALS AND METHODS: We retrospectively analyzed 89 stage I/II/III PC patients who underwent HIFU (n = 43) or surgery (n = 46) at the Third Xiangya Hospital from January 2020 to December 2021. Pain relief, Karnofsky Performance Scale (KPS), overall survival (OS), treatment-related complications and risk factors for OS were assessed. RESULTS: There was no significant difference in the pain relief rate at 30 days post-treatment between the two groups. However, compared with the surgery group, the HIFU group showed significantly lower post-treatment VAS scores (p = 0.019). In the surgery group, the KPS at 30 days post-treatment was lower than pretreatment KPS (70 vs 80; p = 0.015). This relationship was reversed in the HIFU group (80 vs 70; p = 0.024). Median OS favored surgery over HIFU (23 vs 10 months; p < 0.001), with a higher 1-year OS rate (69.57% vs 32.6%; p < 0.001). However, there was no significant difference in OS between the two groups for stage III patients (p = 0.177). Complications rated ≥ grade III were 2.33% in the HIFU group and 32.6% in the surgery group. Multivariate analyses showed that age, KPS, and treatment methods were independent prognostic factors for OS. CONCLUSION: HIFU demonstrates advantages over surgery in terms of early KPS, VAS improvements, and safety for pancreatic cancer; however, long-term outcomes favor surgery. For III-stage disease, HIFU was noninferior to surgery in overall survival.

Visible-Light-Induced Silk Fibroin Hydrogels with Carbon Quantum Dots as Initiators for 3D Bioprinting Applications.

Digital light processing (DLP) 3D bioprinting technology has attracted increasing attention in tissue engineering in recent years. However, it still faces significant technical and operational challenges such as cell carcinogenesis caused by prolonged exposure to ultraviolet light and the presence of heavy metal ions in complex photoinitiator systems. In this study, a novel strategy is designed to introduce carbon quantum dots into visible-light-induced silk fibroin bioink as initiators (CDs/SilMA) applied for DLP 3D bioprinting technology. The incorporation of carbon quantum dots facilitates the formation of precise hydrogel structures at 415 nm visible wavelength, enabling the creation of brain, bronchus, spine, and ear models. Replacing heavy metal photoinitiators with carbon quantum dots imparts fluorescence properties to the bioink and enhances its mechanical properties. Meanwhile, the fibroin protein-based hydrogel exhibits favorable properties, such as drug loading, slow release, degradability, and biocompatibility. This is the first study to propose the application of carbon quantum dots in silk fibroin-based bioink. Moreover, the resulting product demonstrates excellent compatibility with the DLP printing process, making it promising for practical applications in various tissue engineering scenarios with specific requirements.

Urban residential greenness and cancer mortality: Evaluating the causal mediation role of air pollution in a large cohort.

Evidence linking greenness to all-site and site-specific cancers remains limited, and the complex role of air pollution in this pathway is unclear. We aimed to fill these gaps by using a large cohort in southern China. A total of 654,115 individuals were recruited from 2009 to 2015 and followed-up until December 2020. We calculated the normalized difference vegetation index (NDVI) in a 500-m buffer around the participants' residences to represent the greenness exposure. Cox proportional-hazards models were used to evaluate the impact of greenness on the risk of all-site and site-specific cancer mortality. Additionally, we assessed both the mediation and interaction roles of air pollution (i.e., PM2.5, PM10, and NO2) in the greenness-cancer association through a causal mediation analysis using a four-way decomposition method. Among the 577,643 participants, 10,088 cancer deaths were recorded. We found a 10% (95% CI: 5-16%) reduction in all-site cancer mortality when the NDVI increased from the lowest to the highest quartile. When stratified by cancer type, our estimates suggested 18% (95% CI: 8-27%) and 51% (95% CI: 16-71%) reductions in mortality due to respiratory system cancer and brain and nervous system cancer, respectively. For the above protective effect, a large proportion could be explained by the mediation (all-site cancer: 1.0-27.7%; respiratory system cancer: 1.2-32.3%; brain and nervous system cancer: 3.6-109.1%) and negative interaction (all-site cancer: 2.1-25.7%; respiratory system cancer: 2.0-25.7%; brain and nervous system cancer: not significant) effects of air pollution. We found that particulate matter (i.e., PM2.5 and PM10) had a stronger causal mediation effect (25.0-109.1%) than NO2 (1.0-3.6%), while NO2 had a stronger interaction effect (25.7%) than particulate matter (2.0-2.8%). In summary, greenness was significantly beneficial in reducing the mortality of all-site, respiratory system, and brain and nervous system cancer in southern China, with the impact being modulated and mediated by air pollution.

Numerical and experimental investigation on debonding detection in honeycomb sandwich using air-coupled local defect resonance and coda wave analysis.

Non-contact ultrasonic testing of debonding in honeycomb sandwich structure has been a major challenge in industry. In this study, the air-coupled local defect resonance (LDR) technique with coda wave analysis is proposed for nondestructive testing (NDT) of debonding in honeycomb sandwich structure. Numerical simulations have been conducted to visualize the LDR behavior of debonding in honeycomb sandwich structure by air-coupled excitations, and a decorrelation analysis method is proposed for determining the interval of coda wave from received signals. Results indicate that the start moment of coda wave should be determined as the time corresponding to decorrelation coefficient exceed to 0.2 and the duration is 2.5 ms. Air-coupled LDR scanning experiments were conducted on the honeycomb sandwich specimens with different deboning. Experimental results indicate that the proposed technique is effective for NDT of the debonding in honeycomb sandwich structures. The research provides an efficiency non-contact ultrasonic NDT method for honeycomb sandwich structure.

Characterization of Fungal Species Isolated from Cankered Apple Barks Demonstrates the Alternaria alternata Causing Apple Canker Disease.

Apple canker disease, also named as apple Valsa canker, is one of the most destructive diseases for apples (Malus domestica Borkh.). Cytospora/Valsa spp. are the dominant causal agent of this disease, but many studies have revealed that fungi from some other genus can also cause typical apple canker symptoms. In this study, we performed fungal pathogen isolation from cankered 'Fuji' apple barks. Six representative morphologically different fungi (Strain 1-6) were further subjected to ITS sequencing and evolutionary analysis. Molecular identification results revealed that Strains 1-6 are Cytospora mali, Fusarium cf. solani, Alternaria alternata, C. mali, Diplodia seriata and F. proliferatum, respectively. All these fungi have been reported to be causal agents of apple diseases. By inoculating fungal plugs onto trunks of 'Fuji' apple trees, the pathogenicity of the six fungi were accessed. Only the inoculations of the two C. mali strains (Strain 1 and Strain 4) and the A. alternata strain (Strain 3) resulted in typical apple canker symptoms in trunks. It is worth noting that Strain 1 caused much more severe canker symptoms and higher pathogenicity incidence than the other two fungi. A. alternata has been identified as a pathogen causing diseases on apple fruits and leaves. By further assessing its pathogenicity on apple fruits and leaves, we verified that it can also cause typical fruit rot and leaf spot symptoms. To the best of our knowledge, this is the first report on apple canker disease caused by A. alternata in China. Our present study can provide a theoretical foundation for the prevention and control of apple canker disease.

Assessing oral and toothbrush microbial profiles among high-altitude individuals with and without periodontal disease: a case-control study.

BACKGROUND: Periodontitis is the sixth-most common disease worldwide. The oral microbiome composition and its association with Periodontal disease (PD) have been largely explored; however, limited studies have explored the microbial profiles of both oral and toothbrushes in patients with PD. Thus, this study aimed to ascertain the oral and toothbrushes microbial composition in high-altitude populations, hypothesizing that their correlation with periodontal health would differ from those at lower altitudes, potentially indicating links between environmental factors, microbial colonization patterns, and periodontal health in distinct geographic contexts. METHODS: In the present study, we enrolled 35 individuals including 21 healthy and 14 diagnosed with PD from the Lhasa region of Tibet, China. Saliva and toothbrush samples were collected from each participant to assess the association between toothbrush usage and oral microbiome with PD using 16 S rRNA gene-specific V3-V4 regions sequencing. To assess the oral and toothbrush microbiome composition and diversity and its possible link to PD. RESULTS: Significantly higher Alpha diversity (Shannon index) was observed between the PD group and PD toothbrushes (p = 0.00021) and between the PD group and Healthy toothbrushes (p = 0.00041). The predominant species were Proteobacteria, Bacteroidota, Firmicutes, Actinobacteria, and Fusobacteria, with genera Pseudomonas, Veillonella, Neisseria, Acinetobacter, and Haemophilus. In addition, PICRUST2 analysis unveiled 44 significant pathways differentiating the disease and healthy groups, along with 29 pathways showing significant differences between their respective toothbrush microbial profiles. The distinct oral and toothbrush microbial composition among high-altitude populations suggests potential adaptations to the challenges of high-altitude environments. CONCLUSION: This study emphasizes the importance of tailored dental care strategies, accounting for altitude and racial factors, to effectively manage periodontal health in these communities. Further research is warranted to investigate the specific microbial mechanisms and develop targeted interventions for optimizing oral health in populations across varying altitudes.

Comparison of microbiota structure in reproductive tract of Yanbian cattle and Yanhuang cattle.

Microbiota in the reproductive tract of cattle play a vital role in maintaining normal reproduction. However, the information on microbiota in different parts of reproductive tracts with different genetic background is few. The aim of the present study was to describe and compare the microbiota in vagina, cervix and uterus of Yanbian cattle and Yanhuang cattle. The results showed that microbial diversity increases from the vagina to the uterus. The top three bacterial phyla in bovine reproductive tract were Proteobacteria, Firmicutes and Bacteroidetes, accounting for more than 85%. From the vagina to the uterus, the relative abundance of Proteobacteria gradually decreased, while that of Firmicutes gradually increased. Phylum-level Firmicutes and genus-level UCG_010 were significantly enriched in the uterus of Yanbian cattle and Yanhuang cattle. Comparing the same parts of the two breeds, it was found that there was no significant difference in alpha diversity, but significant differences in beta diversity. In addition, microbiota with significant differences in the relative abundance of the reproductive tract were found. These findings lay a foundation for a comprehensive understanding of the structure of the genital tract microbiota of cows and its regulatory mechanisms.

Predictive value of number of metastatic lymph nodes and lymph node ratio for prognosis of patients with FIGO 2018 stage IIICp cervical cancer: a multi-center retrospective study.

BACKGROUND: To identify the cut-off values for the number of metastatic lymph nodes (nMLN) and lymph node ratio (LNR) that can predict outcomes in patients with FIGO 2018 IIICp cervical cancer (CC). METHODS: Patients with CC who underwent radical hysterectomy with pelvic lymphadenectomy were identified for a propensity score-matched (PSM) cohort study. A receiver operating characteristic (ROC) curve analysis was performed to determine the critical nMLN and LNR values. Five-year overall survival (OS) and disease-free survival (DFS) rates were compared using Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: This study included 3,135 CC patients with stage FIGO 2018 IIICp from 47 Chinese hospitals between 2004 and 2018. Based on ROC curve analysis, the cut-off values for nMLN and LNR were 3.5 and 0.11, respectively. The final cohort consisted of nMLN ≤ 3 (n = 2,378) and nMLN > 3 (n = 757) groups and LNR ≤ 0.11 (n = 1,748) and LNR > 0.11 (n = 1,387) groups. Significant differences were found in survival between the nMLN ≤ 3 vs the nMLN > 3 (post-PSM, OS: 76.8% vs 67.9%, P = 0.003; hazard ratio [HR]: 1.411, 95% confidence interval [CI]: 1.108-1.798, P = 0.005; DFS: 65.5% vs 55.3%, P < 0.001; HR: 1.428, 95% CI: 1.175-1.735, P < 0.001), and the LNR ≤ 0.11 and LNR > 0.11 (post-PSM, OS: 82.5% vs 76.9%, P = 0.010; HR: 1.407, 95% CI: 1.103-1.794, P = 0.006; DFS: 72.8% vs 65.1%, P = 0.002; HR: 1.347, 95% CI: 1.110-1.633, P = 0.002) groups. CONCLUSIONS: This study found that nMLN > 3 and LNR > 0.11 were associated with poor prognosis in CC patients.

Protective effects of engineered Lactobacillus johnsonii expressing bovine granulocyte-macrophage colony-stimulating factor on bovine postpartum endometritis.

Introduction: Postpartum endometritis is a prevalent reproductive disorder in bovines, leading to a prolonged open period, infertility, and other complications. While Lactobacillus strains can mitigate these conditions by reducing uterine inflammation, their effectiveness is limited due to a lack of direct anti microbial action and extended treatment duration. This study aimed to construct a recombinant Lactobacillus johnsonii strain expressing bovine Granulocyte-macrophage colony-stimulating factor (GM-CSF) to evaluate its potential in reducing postpartum uterine inflammation. Methods: The recombinant Lactobacillus johnsonii strain was engineered to express bovine GM-CSF and administered to pregnant mice via vaginal perfusion. Postpartum endometritis was induced using E. coli infection, and the protective effects of the engineered strain were assessed. Inflammatory markers (IL-6, IL-1ß, TNF-α), myeloperoxidase (MPO) activity, and nitric oxide (NO) concentration were measured. Histological examination was performed to evaluate uterine morphology and pathological damage. Results: The recombinant L. johnsonii strain expressing GM-CSF significantly reduced inflammation levels induced by E. coli infection in the uterus. This reduction was evidenced by decreased expression of IL-6, IL-1ß, TNF-α, as well as reduced MPO activity and NO concentration. Histological examination revealed improved uterine morphology and reduced pathological damage in mice treated with the recombinant GM-CSF strain. Crucially, the recombinant strain also exerts beneficial effects on bovine endometritis by reducing levels of inflammatory cytokines, suggesting a beneficial effect on clinical bovine endometritis. Conclusion: The recombinant Lactobacillus johnsonii expressing GM-CSF demonstrated protective effects against postpartum endometritis in bovines by reducing inflammatory cytokines. The findings indicate the potential clinical application of this engineered strain in preventing postpartum uterine inflammation, offering a novel and effective protective option for related disorders and improving bovine reproductive efficiency.

Expression of cytokine and Apoptosis-Associated genes in mice bone Marrow-Derived Macrophages stimulated with Brucella recombinant type IV secretion effectors.

BACKGROUND: Brucellosis is an economically important infectious caused by most commonly by Brucella. Detection of infected animals at the early stage is important for controlling the disease. The diagnostic antigens, usually protein antigens, have attracted much interest. However, the accurate mechanism of immune response is still unknown. The secretory effectors (BPE005, BPE275, and BPE123) of the type IV secretion system (T4SS) were involved in the intracellular circulation process of Brucella and the immune responses of the host. METHODS: Genes encoding three B. abortus effector proteins (BPE005, BPE275, and BPE123) of T4SS were cloned and the recombinant proteins were expressed and purified. The purified recombinant proteins were named rBPE005, rBPE275 and rBPE123. Then, the expressions of Th1- and Th2-related cytokine genes were analyzed in mice bone marrow-derived macrophages (BMDMs) after stimulation with rBPE005, rBPE275, and rBPE123. Furthermore, four apoptosis-associated genes (Caspase-3, Caspase-8, Bax, and Bcl-2) were also detected to explore the damage of the proteins to the cells. RESULTS: Expressions of all Th1- and Th2-related cytokine genes were induced with three proteins, and different cytokine expression patterns induced by each protein depend on the stimulation time and dose of protein. However, expressions of apoptosis-related genes did not change. CONCLUSION: These results showed that the secreted antigens of Brucella induced an immune reaction via the production of Th1- and Th2-type cytokines in BMDMs without exerting any damage on the cells.

Synergistic impact of plasma albumin and cognitive function on all-cause mortality in Chinese older adults: a prospective cohort study.

Background: Hypoalbuminemia and cognitive impairment (CI) each independently increase the mortality risk in older adults. However, these two geriatric syndromes can occur simultaneously. In community-dwelling older adults, is the combination of hypoalbuminemia and CI linked to a higher mortality risk than either condition alone? Objective: We aimed to investigate the association between plasma albumin, cognitive function, and their synergistic effect on mortality in Chinese community-dwelling older adults. Methods: Data from the Chinese Longitudinal Healthy Longevity Survey (2012) included 1,858 participants aged ≥65. Baseline assessments comprised albumin levels and cognitive status. All-cause mortality was confirmed through 2014-2018 surveys. Cox proportional hazards models assessed associations, and restricted cubic splines explored albumin-mortality relationship. Results: During a median follow-up of 48.85 months, 921 deaths. Albumin≥35 g/L vs < 35g/L [HR: 1.33 (95%CI, 1.10, 1.62)] and CI vs normal cognition [HR: 1.69 (95%CI, 1.43, 1.99)] independently predicted mortality. A dose-response relationship with mortality was observed for albumin quartiles (p < 0.001). Each SD increase in MMSE or albumin correlated with 22% and 15% lower mortality risk, respectively. Combined hypoproteinemia and CI increased the mortality risk by 155%, with a notably higher risk in males, those aged <85 years, and individuals living in rural areas. Interaction effects of albumin and CI on mortality were observed (p < 0.001). In the single CI group, older adults had a 61% increased risk of mortality in the hypoproteinaemia group compared with the albumin-normal group. Restricted cubic spline revealed a reverse J-shaped association, particularly for participants without CI. For individuals with CI, albumin levels were inversely associated with mortality risk. Conclusion: Hypoproteinemia and CI, individually and combined, increased all-cause mortality risk in Chinese older adults, with stronger effects observed in males, younger older adults, and those living in rural areas. These findings emphasize the importance of targeted adjustments and early nutrition programs in health prevention and clinical care for older adults.

Self-injury and suicide among people living with HIV/AIDS in China: a systematic review and meta-analysis.

BACKGROUND: The prevalence of self-injury and suicide is higher than the general population of people living with HIV/AIDS (PLWHA). However, the results reported in existing studies are highly variable in China. The purpose of this systematic review and meta-analysis was to synthesize the currently available high-quality evidence to explore the prevalence and influence factors of self-injury and suicide among PLWHA in China. METHOD: We retrieve literature written in Chinese and English through databases such as PubMed, Embase, Web of Science, Cochrane Library, SinoMed, CNKI, WanFang Database, and CQVIP from inception to 1 September 2022. Sata 16.0 software was used for analysis. RESULTS: A total of 28 studies were included with a sample size of 1,433,971 and had a satisfactory quality score of ≥ 5. The prevalence among PLWHA in China were 30% for suicidal ideation (SI), 5% for suicide attempt (SA), 8% for suicide plan (SP), 7% for attempted suicide (AS), and 3‰ for completed suicide. High stigma (OR = 2.94, 95%CI: 1.90 - 4.57), depression (OR, 3.17; 95%CI, 2.20 - 4.57), anxiety (OR, 3.06; 95%CI, 2.23 - 4.20), low self-esteem (OR, 3.82, 95%CI, 2.22 - 6.57), high HIV related stress (OR, 2.53; 95%CI, 1.36 - 4.72), and unemployment (OR, 2.50; 95%CI, 1.51 - 4.15) are risk factors for SI; high social support (OR, 0.61; 95%CI, 0.44 - 0.84) and spouse infected with HIV (OR, 0.39; 95%CI, 0.21 - 0.74) are protective factors for SI; depression (OR, 1.62; 95%CI, 1.24 - 2.13), high aggression (OR, 4.66; 95%CI, 2.59 - 8.39), and more negative life events (OR, 2.51; 95%CI, 1.47 - 4.29) are risk factors for AS; high level of education (OR, 1.31; 95%CI, 1.21 - 1.43) is risk factor for CS. CONCLUSION: Figures indicate that approximately one-third of PLWHA had suicidal ideation, and three out of 1,000 completed suicide in China. Positive events are protective factors for self-injury and suicide among PLWHA, while negative events are risk factors. This suggests that psychosocial support and risk assessment should be integrated into the care of PLWHA.