Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism.

BACKGROUND: The anti-aging protein Klotho plays a protective role in kidney disease, but its potential as a biomarker for chronic kidney disease (CKD) is controversial. Additionally, the main pathways through which Klotho exerts its effects on CKD remain unclear. Therefore, we used bioinformatics and clinical data analysis to determine its role in CKD. RESULTS: We analyzed the transcriptomic and clinical data from the Nephroseq v5 database and found that the Klotho gene was mainly expressed in the tubulointerstitium, and its expression was significantly positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with blood urea nitrogen (BUN) in CKD. We further found that Klotho gene expression was mainly negatively associated with inflammatory response and positively associated with lipid metabolism in CKD tubulointerstitium by analyzing two large sample-size CKD tubulointerstitial transcriptome datasets. By analyzing 10-year clinical data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016, we also found that Klotho negatively correlated with inflammatory biomarkers and triglyceride and positively correlated with eGFR in the CKD population. Mediation analysis showed that Klotho could improve renal function in the general population by modulating the inflammatory response and lipid metabolism, while in the CKD population, it primarily manifested by mediating the inflammatory response. Restricted cubic spline (RCS) analysis showed that the optimal concentration range for Klotho to exert its biological function was around 1000 pg/ml. Kaplan-Meier curves showed that lower cumulative hazards of all-cause mortality in participants with higher levels of Klotho. We also demonstrated that Klotho could reduce cellular inflammatory response and improve cellular lipid metabolism by establishing an in vitro model similar to CKD. CONCLUSIONS: Our results suggest that Klotho exerts protection in CKD, which may be mainly related to the regulation of inflammatory response and lipid metabolism, and it can serve as a potential biomarker for CKD.

Northeast Pacific warm blobs sustained via extratropical atmospheric teleconnections.

Large-scale marine heatwaves in the Northeast Pacific (NEP), identified here and previously as 'warm blobs', have devastating impacts on regional ecosystems. An anomalous atmospheric ridge over the NEP is known to be crucial for maintaining these warm blobs, also causing abnormally cold temperatures over North America during the cold season. Previous studies linked this ridge to teleconnections from tropical sea surface temperature anomalies. However, it was unclear whether teleconnections from the extratropics could also contribute to the ridge. Here we show that planetary wave trains, triggered by increased rainfall and latent heat release over the Mediterranean Sea accompanied by decreased rainfall over the North Atlantic, can transport wave energy to the NEP, guided by the westerly jet, and induce a quasi-barotropic ridge there. Our findings provide insights into extratropical teleconnections sustaining the NEP ridge, offering a source of potential predictability for the warm blobs and temperature fluctuations over North America.

Predictive modeling of antidepressant efficacy based on cognitive neuropsychological theory.

BACKGROUND: We aimed to develop a clinical predictive model based on the cognitive neuropsychological (CNP) theory and machine-learning to examine SSRI efficacy in the treatment of MDD. METHODS: Baseline assessments including clinical symptoms (HAMD, HAMA, BDI, and TEPS scores), negative biases (NEO-PI-R-N and NCPBQ scores), sociodemographic characteristics (social support and SES), and a 5-min eye-opening resting-state EEG were completed by 69 participants with first-episode major depressive disorder (MDD) and 36 healthy controls. The clinical symptoms and negative bias were again assessed after an 8-week treatment of depression with selective serotonin reuptake inhibitors (SSRIs). A multi-modality machine-learning model was developed to predict the effectiveness of SSRI antidepressants. RESULTS: At baseline, we observed significant differences between MDD patients and healthy controls in terms of social support, clinical symptoms, and negative bias characteristics (p < 0.001). A negative association was found (p < 0.05) between neuroticism and alpha asymmetry in both the central and central-parietal areas, as well as between negative cognitive processing bias and alpha asymmetry in the parietal region. Compared to responders, non-responders exhibited less negative cognitive processing bias and greater alpha asymmetry in both central and central-parietal regions. Importantly, we developed a multi-modality machine-learning model with 83 % specificity using the above salient features. CONCLUSIONS: Research results support the CNP theory of depression treatment. To some extent, the multimodal clinical model constructed based on the CNP theory effectively predicted the efficacy of this treatment in this population. LIMITATIONS: Small sample and only focus on the mechanisms of delayed-onset SSRI treatment.

Transformation risk and associated survival outcome of marginal zone lymphoma: A nationwide study.

Histological transformation into an aggressive B-cell lymphoma indicates a poor survival outcome for patients with indolent marginal zone lymphoma (MZL), which has been less studied. Large-scale data with long-term follow-up to investigate MZL transformation is limited. Here, by reporting a US-Nationwide cohort of 30,619 MZL patients diagnosed between 2000 and 2019, we found that transformation occurred in 2.08% (N = 624) of MZL cases, with the transformation incidence of 3.1 per 1,000 person-years. Advanced Ann Arbor stage, nodal MZL (NMZL) and splenic MZL (SMZL) were associated with an elevated risk of transformation. Certain subtype-specific characteristics, such as non-gastric extra-nodal MZL (vs. gastric, HR, 1.51, 95%CI 1.13-2.04; p = 0.006), and receiving splenectomy for SMZL (HR, 2.04, 95%CI 1.28-3.26; p = 0.003), also indicated a higher risk of transformation. Besides, transformation independently increased the overall mortality risk (HR, 1.38, 95%CI 1.24-1.53, p < 0.001), especially the higher lymphoma-caused mortality risk (HR, 3.21, 95%CI 2.81-3.67, p < 0.001). Transformation was also associated with a higher percentage of lymphoma-caused deaths. The post-transformation prognostic analyses demonstrated that female gender and age ≥ 65 years independently affected patients' mortalities. These findings, based on the largest cohort to date, contribute to a better understanding of transformed MZL, and provide valuable reference points for guidelines and patient counseling.

Riverine fluxes of different species of phosphorus in the Pearl River estuary.

Phosphorus is the most limiting nutrient in coastal waters of China, particularly in the Pearl River (PR) estuary. Rivers have different P forms including dissolved inorganic phosphorus (DIP), dissolved organic phosphorus (DOP), particulate inorganic phosphorus (PIP), and particulate organic phosphorus (POP). Their input to coastal seas has been overlooked. We hypothesize that DIP is a small fraction of total phosphorus (TP). We investigated these P forms and estimated their fluxes in PR eight outlets during 2015-2019. DIP on average is only a 30.90 % fraction of TP with PIP, POP and DOP accounting for 22.43, 31.56 and 15.37 %, respectively. The average annual fluxes of TP, DIP, DOP, PIP and POP were 12.58×, 3.34×, 1.68×, 3.19× and 4.26 × 106 mol/month, respectively, which are regulated by runoff and suspended particulate matter (SPM). The finding reveals the importance of other P forms for phytoplankton in the Pearl River estuary and their bio-availability deserves further study.

Potential neuropsychological mechanism involved in the transition from suicide ideation to action - a resting-state fMRI study implicating the insula.

BACKGROUND: Understanding the neural mechanism underlying the transition from suicidal ideation to action is crucial but remains unclear. To explore this mechanism, we combined resting-state functional connectivity (rsFC) and computational modeling to investigate differences between those who attempted suicide(SA) and those who hold only high levels of suicidal ideation(HSI). METHODS: A total of 120 MDD patients were categorized into SA group (n=47) and HSI group (n=73). All participants completed a resting-state functional MRI scan, with three subregions of the insula and the dorsal anterior cingulate cortex (dACC) being chosen as the region of interest (ROI) in seed-to-voxel analyses. Additionally, 86 participants completed the balloon analogue risk task (BART), and a five-parameter Bayesian modeling of BART was estimated. RESULTS: In the SA group, the FC between the ventral anterior insula (vAI) and the superior/middle frontal gyrus (vAI-SFG, vAI-MFG), as well as the FC between posterior insula (pI) and MFG (pI-MFG), were lower than those in HSI group. The correlation analysis showed a negative correlation between the FC of vAI-SFG and psychological pain avoidance in SA group, whereas a positive correlation in HSI group. Furthermore, the FC of vAI-MFG displayed a negative correlation with loss aversion in SA group, while a positive correlation was found with psychological pain avoidance in HSI group. CONCLUSION: In current study, two distinct neural mechanisms were identified in the insula which involving in the progression from suicidal ideation to action. Dysfunction in vAI FCs may gradually stabilize as individuals experience heightened psychological pain, and a shift from positive to negative correlation patterns of vAI-MFC may indicate a transition from state to trait impairment. Additionally, the dysfunction in PI FC may lead to a lowered threshold for suicide by blunting the perception of physical harm.

Angioimmunoblastic T-cell lymphoma: Novel recurrent mutations and prognostic biomarkers by cell-free DNA profiling.

Molecular and clinical stratification of patients with angioimmunoblastic T-cell lymphoma (AITL) is unsatisfactory, which hinders the development of personalized therapies. This study aimed to identify molecular biomarkers for AITL based on peripheral cell-free DNA (cfDNA) that could be used to predict prognosis and guide treatment non-invasively. A customized panel containing 46 genes was used to study pretreatment cfDNA and paired tumour tissues in 64 Chinese AITL patients from three clinical centres, and gene mutations in cfDNA and tumour tissue were assessed for concordance (34 paired samples). Then, the association of gene mutations and prognosis was analysed, and a functional enrichment analysis was performed. The sequencing results showed good consistency between cfDNA samples and paired tissue samples. KDM5A, STAT1, FANCM, ERBB4, PIK3R5 and NSD1 were identified as novel recurrent mutations. Mutations in FANCM or combinations of RHOA, KDM5A and FAT1 were associated with poor prognosis. Additionally, functional analysis revealed that RHOAG17 might serve as a predictive biomarker of PD-1 blockade respondence. Our findings confirmed the role of cfDNA as a liquid biopsy in AITL, and revealed novel molecular determinants that can stratify patients and guide treatment options.

Klotho reduces the risk of osteoporosis in postmenopausal women: a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Osteoporosis (OP) is one of the diseases that endanger the health of the elderly population. Klotho protein is a hormone with anti-aging effects. A few studies have discussed the relationship between Klotho and OP. However, there is still a lack of research on larger populations. This study aims to evaluate the association between OP and Klotho in American postmenopausal women. METHODS: This is a retrospective study. We searched the National Health and Nutrition Examination Survey (NHANES) database and collected data of 3 survey cycles, finally involving 871 postmenopausal women over 50 years old in the present study. All participants took dual-energy X-ray absorptiometry examination and serum Klotho testing at the time of investigation. After adjusting the possible confounding variables, a multivariate regression model was employed to estimate the relationship between OP and Klotho proteins. Besides, the P for trend and restricted cubic spline (RCS) were applied to examine the threshold effect and calculate the inflection point. RESULTS: Factors influencing the occurrence of OP included age, ethnicity, body mass index and Klotho levels. Multivariate regression analysis indicated that the serum Klotho concentration was lower in OP patients than that in participants without OP (OR[log2Klotho] = 0.568, P = 0.027). The C-index of the prediction model built was 0.765, indicating good prediction performance. After adjusting the above-mentioned four variables, P values for trend showed significant differences between groups. RCSs revealed that when the Klotho concentration reached 824.09 pg/ml, the risk of OP decreased drastically. CONCLUSION: Based on the analysis of the data collected from the NHANES database, we propose a correlation between Klotho and postmenopausal OP. A higher serum Klotho level is related to a lower incidence of OP. The findings of the present study can provide guidance for research on diagnosis and risk assessment of OP.

Antibody responses to COVID-19 vaccination in people with obesity: A systematic review and meta-analysis.

COVID-19 vaccine is critical in preventing SARS-CoV-2 infection and transmission. However, obesity's effect on immune responses to COVID-19 vaccines is still unknown. We performed a meta-analysis of the literature and compared antibody responses with COVID-19 vaccines among persons with and without obesity. We used Pubmed, Embase, Web of Science, and Cochrane Library to identify all related studies up to April 2022. The Stata.14 software was used to analyze the selected data. Eleven studies were included in the present meta-analysis. Five of them provided absolute values of antibody titers in the obese group and non-obese group. Overall, we found that the obese population was significantly associated with lower antibody titers (standardized mean difference [SMD] = -0.228, 95% CI [-0.437, -0.019], P < 0.001) after COVID-19 vaccination. Significant heterogeneity was present in most pooled analyses but was reduced after subgroup analyses. No publication bias was observed in the present analysis. The Trim and Fill method did not change the results in the primary analysis. The present meta-analysis suggested that obesity was significantly associated with decreased antibody responses to SARS-CoV-2 vaccines. Future studies should be performed to unravel the mechanism of response to the COVID-19 vaccine in obese individuals.

Which Predictor, SctO2 or SstO2, Is more Sensitive for Postoperative Cognitive Dysfunction in Spine Surgery: A Prospective Observational Study?

OBJECTIVE: Patients undergoing spinal surgery in the prone position may experience venous stasis, often resulting in edema in dependent areas of the body, including the head, and increased postoperative cognitive dysfunction (POCD). Not only does POCD present challenges for post-operative care and recovery, it can also cause permanent damage to the patient's brain and increase mortality and social costs. We aimed to clarify the incidence of POCD in patients with hypertension after prone spine surgery and to further determine the association between intraoperative somatic tissue oxygen saturation (SstO2)/cerebral tissue oxygen saturation (SctO2) and POCD. METHODS: Patients with hypertension scheduled for open prone spine surgery from January 2020 to April 2021 were included in this single-center, prospective, observational study. SctO2 and SstO2 were monitored by near-infrared spectroscopy continuously throughout the surgery. The primary outcome was POCD assessed using the Mini-Mental Status Examination (MMSE). The association of SstO2 and SctO2 with POCD was evaluated with unadjusted analyses and multivariable logistic regression. RESULTS: One hundred and one of 112 identified patients were included, 28 (27.8%) of whom developed POCD. None of the investigated SctO2 indices were predictive of POCD. However, the patients with POCD had greater decreases in intraoperative absolute SstO2 and relative SstO2 than the patients without POCD (P = 0.037, P = 0.036). Moreover, three SstO2 indices were associated with POCD, including a greater absolute SstO2 decrease (P = 0.021), a greater relative SstO2 decrease (P = 0.032), and a drop below 90% of the baseline SstO2 (P = 0.002), independent of ASA III status, preoperative platelets and postoperative sepsis. In addition, there was no correlation between intraoperative SctO2 and intraoperative SstO2 or between their respective absolute declines. CONCLUSION: Twenty-eight (27.7%) of 101 patients developed POCD in patients with hypertension undergoing prone spine surgery, and intraoperative SstO2 is associated with POCD, whereas SctO2 shows no association with POCD. This study may initially provide a valuable new approach to the prevention of POCD in this population.

Understanding guilt-related interpersonal dysfunction in obsessive-compulsive personality disorder through computational modeling of two social interaction tasks.

BACKGROUND: Obsessive-compulsive personality disorder (OCPD) is a high-prevalence personality disorder characterized by subtle but stable interpersonal dysfunction. There have been only limited studies addressing the behavioral patterns and cognitive features of OCPD in interpersonal contexts. The purpose of this study was to investigate how behaviors differ between OCPD individuals and healthy controls (HCs) in the context of guilt-related interpersonal responses. METHOD: A total of 113 participants were recruited, including 46 who were identified as having OCPD and 67 HCs. Guilt-related interpersonal responses were manipulated and measured with two social interactive tasks: the Guilt Aversion Task, to assess how anticipatory guilt motivates cooperation; and the Guilt Compensation Task, to assess how experienced guilt induces compensation behaviors. The guilt aversion model and Fehr-Schmidt inequity aversion model were adopted to analyze decision-making in the Guilt Aversion Task and the Guilt Compensation Task, respectively. RESULTS: Computational model-based results demonstrated that, compared with HCs, the OCPD group exhibited less guilt aversion when making cooperative decisions as well as less guilt-induced compensation after harming others. CONCLUSION: Our findings indicate that individuals with OCPD tend to be less affected by guilt than HCs. These impairments in guilt-related responses may prevent adjustments in behaviors toward compliance with social norms and thus result in interpersonal dysfunctions.

Causal association between obesity and hypothyroidism: a two-sample bidirectional Mendelian randomization study.

Introduction: Previous observational studies have reported a positive correlation between obesity and susceptibility to hypothyroidism; however, there is limited evidence from alternative methodologies to establish a causal link. Methods: We investigated the causal relationship between obesity and hypothyroidism using a two-sample bidirectional Mendelian randomization (MR) analysis. Single-nucleotide polymorphisms (SNPs) associated with obesity-related traits were extracted from a published genome-wide association study (GWAS) of European individuals. Summarized diagnostic data of hypothyroidism were obtained from the UK Biobank. Primary analyses were conducted using the inverse variance-weighted (IVW) method with a random-effects model as well as three complementary approaches. Sensitivity analyses were performed to ascertain the correlation between obesity and hypothyroidism. Results: MR analyses of the IVW method and the analyses of hypothyroidism/myxedema indicated that body mass index (BMI) and waist circumference (WC) were significantly associated with higher odds and risk of hypothyroidism. Reverse MR analysis demonstrated that a genetic predisposition to hypothyroidism was associated with an increased risk of elevated BMI and WC, which was not observed between WC adjusted for BMI (WCadjBMI) and hypothyroidism. Discussion: Our current study indicates that obesity is a risk factor for hypothyroidism, suggesting that individuals with higher BMI/WC have an increased risk of developing hypothyroidism and indicating the importance of weight loss in reducing the risk of hypothyroidism.

Association of Glucose-Lowering Drugs With Outcomes in Patients With Diabetes Before Hospitalization for COVID-19: A Systematic Review and Network Meta-analysis.

Importance: Patients with COVID-19 have a high prevalence of diabetes, and diabetes and blood glucose control are determinants of intensive care unit admission and mortality. Objective: To evaluate the association between COVID-19-related adverse outcomes and 8 antihyperglycemic drugs in patients with diabetes who were subsequently diagnosed and hospitalized with COVID-19. Data Sources: Data were retrieved and collected in PubMed, Embase, Cochrane Central Register, Web of Science, and ClinicalTrials.gov from database inception to September 5, 2022. Study Selection: For this systematic review and network meta-analysis, randomized clinical trials and observational studies conducted among patients with diabetes while receiving glucose-lowering therapies for at least 14 days before the confirmation of COVID-19 infection were included after blinded review by 2 independent reviewers and consultations of disagreement by a third independent reviewer. Of 1802 studies initially identified, 31 observational studies met the criteria for further analysis. Data Extraction and Synthesis: This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Bayesian network meta-analyses were performed with random effects. Main Outcomes and Measures: A composite adverse outcome, including the need for intensive care unit admission, invasive and noninvasive mechanical ventilation, or in-hospital death. Results: Thirty-one distinct observational studies (3 689 010 patients with diabetes hospitalized for COVID-19) were included. The sodium-glucose cotransporter-2 inhibitors (SGLT-2is) were associated with relatively lower risks of adverse outcomes compared with insulin (log of odds ratio [logOR], 0.91; 95% credible interval [CrI], 0.57-1.26), dipeptidyl peptidase-4 inhibitors (logOR, 0.61; 95% CrI, 0.28-0.93), secretagogues (logOR, 0.37; 95% CrI, 0.02-0.72), and glucosidase inhibitors (logOR, 0.50; 95% CrI, 0.00-1.01). Based on the surface under the cumulative ranking curves value, SGLT-2is were associated with the lowest probability for adverse outcomes (6%), followed by glucagon-like peptide-1 receptor agonists (25%) and metformin (28%). A sensitivity analysis revealed that the study was reliable. Conclusions and Relevance: These findings suggest that the use of an SGLT-2i before COVID-19 infection is associated with lower COVID-19-related adverse outcomes. In addition to SGLT-2is, glucagon-like peptide-1 receptor agonists and metformin were also associated with relatively low risk of adverse outcomes.

Decision-making biases in suicide attempters with major depressive disorder: A computational modeling study using the balloon analog risk task (BART).

BACKGROUND: In the last decade, suicidality has been increasingly theorized as a distinct phenomenon from major depressive disorder (MDD), with unique psychological and neural mechanisms, rather than being mostly a severe symptom of MDD. Although decision-making biases have been widely reported in suicide attempters with MDD, little is known regarding what components of these biases can be distinguished from depressiveness itself. METHODS: Ninety-three patients with current MDD (40 with suicide attempts [SA group] and 53 without suicide attempts [NS group]) and 65 healthy controls (HCs) completed psychometric assessments and the balloon analog risk task (BART). To analyze and compare decision-making components among the three groups, we applied a five-parameter Bayesian computational modeling. RESULTS: Psychological assessments showed that the SA group had greater suicidal ideation and psychological pain avoidance than the NS group. Computational modeling showed that both MDD groups had higher risk preference and lower ability to learn and adapt from within-task observations than HCs, without differences between the SA and NS patient groups. The SA group also had higher loss aversion than the NS and HC groups, which had similar loss aversion. CONCLUSIONS: Our BART and computational modeling findings suggest that psychological pain avoidance and loss aversion may be important suicide risk factor that are distinguishable from depression illness itself.

Coal Wall Spalling Mechanism and Grouting Reinforcement Technology of Large Mining Height Working Face.

To control the problem of coal wall spalling in large mining height working faces subject to mining, considering the Duanwang Mine 150505 fully mechanized working face, the mechanism of coal wall spalling in working faces was investigated by theoretical analysis, numerical simulation and field experiment. Based on analysis of coal wall spalling in the working face, a new grouting material was developed. The stress and plastic zone changes affecting the coal wall, before and after grouting in the working face, were analyzed using numerical simulation and surrounding rock grouting reinforcement technology was proposed for application around the new grouting material. The results showed that: (1) serious spalling of the 150505 working face was caused by the large mining height, fault influence and low roof strength, and (2) the new nano-composite low temperature polymer materials used have characteristics of rapid reaction, low polymerization temperature, adjustable setting time, high strength and environmental protection. Based on analysis of the working face coal wall spalling problem, grouting reinforcement technology based on new materials was proposed. Industrial tests were carried out on the working face. Field monitoring showed that the stability of the working face coal wall was significantly enhanced and that rib spalling was significantly improved after comprehensive anti-rib-spalling grouting measures were adopted. These results provide a basis for rib spalling control of working faces under similar conditions.

CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) responds poorly to standard chemotherapy or targeted therapy; hence, exploration for novel therapeutic targets is urgently needed. CEP192 protein is indispensable for centrosome amplification, which has been extensively characterized in both hematological malignancies and solid tumors. Here, we combined bioinformatics and experimental approaches to assess the potential of CEP192 as a prognostic and therapeutic target in HCC. CEP192 expression increased with tumor stage and was associated with poor clinicopathologic features, frequent recurrence, and higher mortality. Upon single-cell RNA sequencing, CEP192 was found to be involved in the proliferation and self-renewal of hepatic progenitor-like cells. This observation was further evidenced using CEP192 silencing, which prevented tumor cell proliferation and self-renewal by arresting cells in the G0/G1 phase of the cell cycle. Notably, CEP192 was highly correlated with multiple tumor-associated cytokine ligand-receptor axes, including IL11-IL11RA, IL6-IL6R, and IL13-IL13RA1, which could promote interactions between hepatic progenitor-like cells, PLVAP+ endothelial cells, tumor-associated macrophages, and CD4+ T cells. Consequently, CEP192 expression was closely associated with an immunosuppressive tumor microenvironment and low immunophenoscores, making it a potential predictor of response to immune checkpoint inhibitors. Taken together, our results unravel a novel onco-immunological role of CEP192 in establishing the immunosuppressive tumor microenvironment and provide a novel biomarker, as well as a potential target for therapeutic intervention of HCC.

Hypothalamic Kisspeptin Neurons Regulates Energy Metabolism and Reproduction Under Chronic Stress.

Background: Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, affecting energy homeostasis and reproduction. The aim of this study was to investigate whether stress affected energy metabolism and reproduction through the glucocorticoid receptor on Kisspeptin neurons in the hypothalamus. Methods: Four groups included control group, chronic restraint stress group, Kisspeptin specific glucocorticoid receptor knock out group (KGRKO) and KGRKO+stress group. Body weight, food intake, estrous cycle of female mice, serum sex hormone levels, serum corticosterone and prolactin, Kisspeptin expression in the hypothalamus were measured. Results: The restraint stress group showed a significant weight loss compared with the control group. KGRKO+restraint stress group had a reduced weight loss, suggesting that restraint stress might partially affect the energy metabolism through GR on Kisspeptin neurons. In terms of reproductive function, the restraint stress group and the KGRKO+restraint stress group showed missing pre-estrus period or prolonged estrous cycles. Serum LH and FSH in KGRKO + restraint stress group decreased significantly compared with KGRKO group. However, no significant difference in the level of serum testosterone was observed. After restraint stress, the levels of serum cortisol and prolactin in male and female mice were significantly higher than the control group, and the hypothalamus Kiss1 gene mRNA expression and Kisspeptin protein expression were significantly decreased. Conclusion: Chronic restraint stress induced weight loss and negative changes in reproduction, which were partially mediated by glucocorticoid receptor on Kisspeptin neurons in the hypothalamus.

Associations between metabolic syndrome and female stress urinary incontinence: a meta-analysis.

INTRODUCTION AND HYPOTHESIS: The objective was to identify the associations between metabolic syndrome (MS) and stress urinary incontinence (SUI) in women and to provide an evidence base for clinical practice. METHODS: A meta-analysis of cohort, case-control, and cross-sectional studies about the association between MS and SUI was performed using databases including PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBMdisc), Wanfang Database (WanFang Data), and VIP database (VIP). The time limit was from the commencement of each database to 1 November 2020. Two researchers independently screened literature, extracted data, and assessed the risk of bias. RevMan 5.3 software was used for statistical analysis. The dichotomous variables were presented as the risk ratio (odds ratio, OR) and 95% CI as the effect indicators. RESULTS: Six studies were included in the meta-analysis, with a total sample size of 3,678 cases. The results showed that the risk for SUI in women with MS was three times those without MS (OR = 3.41, 95% CI 2.01, 5.77, p <0.00001), and the difference was statistically significant. The results of subgroup analysis showed that MS was significantly associated with SUI in the subgroups of pre- and postmenopausal women (OR = 2.46, 95% CI 1.63, 3.73, p < 0.00001), and in the subgroups of other types of women (OR = 3.41, 95% CI 2.01, 5.77, p = 0.0003), and the differences were statistically significant. CONCLUSIONS: Metabolic syndrome is associated with SUI in women and increases its risk.

Acrolein, an endogenous aldehyde induces Alzheimer's disease-like pathologies in mice: A new sporadic AD animal model.

Alzheimer's disease (AD) is a common neurodegenerative disease that mainly affects elderly people. However, the translational research of AD is frustrating, suggesting that the development of new AD animal models is crucial. By gavage administration of acrolein, we constructed a simple sporadic AD animal model which showed classic pathologies of AD in 1 month. The AD-like phenotypes and pathological changes were as followed. 1) olfactory dysfunctions, cognitive impairments and psychological symptoms in C57BL/6 mice; 2) increased levels of Aß1-42 and Tau phosphorylation (S396/T231) in cortex and hippocampus; 3) astrocytes and microglia proliferation; 4) reduced levels of postsynaptic density 95(PSD95) and Synapsin1, as well as the density of dendritic spines in the CA1 and DG neurons of the hippocampus; 5) high-frequency stimulation failed to induce the long-term potentiation (LTP) in the hippocampus after exposure to acrolein for 4 weeks; 6) decreased blood oxygen level-dependent (BOLD) signal in the olfactory bulb and induced high T2 signals in the hippocampus, which matched to the clinical observation in the brain of AD patients, and 7) activated RhoA/ROCK2/ p-cofilin-associated pathway in hippocampus of acrolein-treated mice, which may be the causes of synaptic damage and neuroinflammation in acrolein mice model. Taken together, the acrolein-induced sporadic AD mouse model closely reflects the pathological features of AD, which will be useful for the research on the mechanism of AD onset and the development of anti-AD drugs.