Causal relationship between neuroticism and bone mineral density: A univariable and multivariable Mendelian randomization study.

Recent observational studies have indicated that psychiatric disorders were associated with risk of bone mineral density (BMD) reduction. But the causal relationship between neuroticism and BMD remained unclear. By using public genome-wide association study data, a 2-sample bidirectional Mendelian randomization (MR) study was performed to investigate the causal relationship between neuroticism and BMD (heel BMD, forearm BMD, femoral neck BMD, lumbar spine BMD, and total body BMD). Inverse-variance weighted, weighted median, and MR-Egger were used to assess the causal effects. Multiple sensitivity analyses were conducted to assess the potential bias of the causal estimates. Multivariable MR analysis was used to assess the direct causal effects of neuroticism on BMD with adjustment of common risk factors of BMD reduction. Univariable MR analysis indicated that genetically predicted higher neuroticism was significantly associated with an increased risk of heel BMD reduction (inverse-variance weighted ß = -0.039; se = 0.01; P = .0001; Bonferroni-corrected P = .0005) but not with other BMD (forearm BMD, femoral neck BMD, lumbar spine BMD, and total body BMD) potentially due to limited statistical power. The causal effects remained significant after accounting for the effects of body mass index, smoking, and drinking. Genetic proxy for higher neuroticism was significantly associated with an increased risk of heel BMD reduction. Further studies were warranted to elucidate the underlying biological mechanisms and explore the potential application in disease early screening and management.

Construction and application of "organ-system-centered" undergraduate nursing professional training model.

OBJECTIVE: The purpose of this study is to construct an organ system-centered undergraduate nursing professional training model and explore its application effect. METHODS: This study is divided into two steps. In the early stage, literature review and expert consultation were used to establish the training mode (curriculum and assessment standard) of nursing undergraduate specialty based on organ system reform. Secondly, a cross-sectional survey method was used to investigate the training quality of nursing students who graduated from Jinzhou Medical University from 2007 to 2017 under this model. RESULTS: A five-module curriculum system was established, including general courses, public basic courses, professional education courses, expanding elective courses and concentrated practical teaching. Under the teaching reform of organ system, the nursing graduates of Jinzhou Medical University, who are mainly employed in public hospitals, are generally not satisfied with their jobs, salaries, contents and prospects. Their overall satisfaction with their alma mater is very high; Graduates have certain independent core competence; Employers are basically satisfied with graduates. CONCLUSION: The training mode of undergraduate nursing specialty based on organ system reform basically meets the training requirements and objectives.

Network Pharmacology and Experimental Analysis to Explore the Effect and Mechanism of Modified Buyang Huanwu Decoction in the Treatment of Diabetic Nephropathy.

Purpose: Preventing and treating diabetic nephropathy (DN) are global challenges due to the complexity and diversity of its causes and manifestations. It is important to find effective medications to treat DN. Patients and Methods: Gene expression files of DN were downloaded from the GEO database to identify the differentially expressed genes. Network pharmacology and molecular docking were used to explore the possible mechanisms of modified Buyang Huanwu Decoction (mBHD) in treating DN. Biochemical, histopathological, and real-time PCR analyses were conducted in both in vivo and in vitro DN models to investigate the effects of mBHD. Results: A total of 336 active ingredients and 124 potential targets of mBHD associated with DN were identified. Among them, 8 hub genes were found to be important targets for mBHD in treating DN and were significantly correlated with the infiltration status of six immune cells. Partially, the active ingredients of mBHD demonstrated good stability in binding to CASP3 and TP53. mBHD treatment significantly reduced levels of total cholesterol, triglyceride, blood urea nitrogen, serum creatinine, and microalbumin in db/db mice. HE and Masson's staining results showed that mBHD attenuated renal injury in db/db mice. Additionally, mBHD treatment could significantly alter the expression of CASP3, CCL2, TP53, ALB, and HMOX1. Conclusion: mBHD may be involved in the treatment of DN through multiple ingredients, targets, and pathways. In addition, mBHD could alleviate renal injury in db/db mice, possibly involving CASP3, CCL2, TP53, ALB, and HMOX1.

Identification of differentially expressed genes, pathways, and immune infiltration in diabetes.

This study aimed to perform exhaustive bioinformatic analysis by using GSE29221 micro-array maps obtained from healthy controls and Type 2 Diabetes (T2DM) patients. Raw data are downloaded from the Gene Expression Omnibus database and processed by the limma package in R software to identify Differentially Expressed Genes (DEGs). Gene ontology functional analysis and Kyoto Gene Encyclopedia and Genome Pathway analysis are performed to determine the biological functions and pathways of DEGs. A protein interaction network is constructed using the STRING database and Cytoscape software to identify key genes. Finally, immune infiltration analysis is performed using the Cibersort method. This study has implications for understanding the underlying molecular mechanism of T2DM and provides potential targets for further research.

Predictive role of depressive symptoms on frailty and its components in Chinese middle-aged and older adults: a longitudinal analysis.

BACKGROUND: To investigate the cross-sectional and longitudinal associations between depressive symptoms and the prevalence of frailty and its components in a nationally representative sample of middle-aged and older Chinese adults. METHOD: The China Health and Retirement Longitudinal Study (CHARLS) provided data on 2581 (after inclusion and exclusion criteria) adults aged ≥ 45 years. Every two years, face-to-face, computer-aided personal interviews (CAPI), and structured questionnaires were used to follow up with the respondents. The Chinese version of the Center for Epidemiologic Studies-Depression Scale (CES-D) was used to evaluate depressive symptoms, and the Fried criteria were used to measure frailty. The odds ratio (OR) and 95% confidence interval (CI) for the association of exposure (depressive symptoms at baseline) with the onset of the outcome (frailty and its components) in the individuals at baseline were analyzed by binary logistic regression. RESULTS: At baseline, 11.62% of participants had frailty, and 57.92% had depressive symptoms. In the cross-sectional analysis, depressive symptoms (OR = 5.222, 95%CI 3.665-7.442) were associated with frailty. In the longitudinal analysis, after adjusting for the full set of covariates among participants free of baseline frailty, depressive symptoms were significantly associated with incident frailty during the short term (OR = 2.193, 95%CI 1.324-3.631) and the long term (OR = 1.926, 95%CI 1.021-3.632). Meanwhile, depressive symptoms were associated with an increased risk of weakness (OR = 1.990, 95%CI 1.250-3.166), slowness (OR = 1.395, 95%CI 1.044-1.865), and exhaustion (OR = 2.827, 95%CI 2.150-3.719) onset during the short-term. Depressive symptoms were associated with an increased risk of exhaustion (OR = 2.869, 95%CI 2.004-4.109) onset during the long-term. CONCLUSION: Among middle-aged and older adults, depressive symptoms could predict frailty during 2 years of follow-up and 4 years of follow-up. When considering potential confounding factors, depressive symptoms were considered a predictor of weakness, slowness, and exhaustion. Interventions aimed at preventing depressive symptoms may be beneficial in reducing frailty and its components.

Potential Predictive Value of Platelet Parameters in Preeclampsia.

Objective: Preeclampsia is a serious pregnancy complication that jeopardizes the health of both the mother and the fetus. Platelet parameters are closely linked to the severity of preeclampsia. This study aimed to assess the diagnostic potential of platelet parameters in the early second trimester for the detection of preeclampsia. Methods: A total of 840 participants from the Affiliated Hospital of Jining Medical College were included in the study, consisting of 327 healthy pregnant women, 209 with mild preeclampsia, and 304 with severe preeclampsia. General clinical data and platelet parameters for these three groups of pregnant women were collected, and differences among them were compared. In addition, univariate analysis and logistic regression were used to identify preeclampsia risk factors, and receiver operating characteristic curve analysis was conducted to assess the predictive value of platelet parameters. Results: Platelet count was not found to significantly differ between the healthy and preeclampsia groups. However, mean platelet volume, platelet distribution width (PDW), and platelet-large cell ratios (P-LCR) were observed to be significantly higher in the preeclampsia group than the healthy group. After adjusting for confounding factors (such as age, gestational week at blood sampling, systolic and diastolic blood pressure, and body mass index during the second trimester), it was determined that PDW and P-LCR could be considered effective predictors of preeclampsia. Conclusion: In clinical practice, P-LCR and PDW hold potential predictive value for preeclampsia.

Unexpected response of terrestrial carbon sink to rural depopulation in China.

China is experiencing large-scale rural-urban migration and rapid urbanization, which have had significant impact on terrestrial carbon sink. However, the impact of rural-urban migration and its accompanying urban expansion on the carbon sink is unclear. Based on multisource remote sensing product data for 2000-2020, the soil microbial respiration equation, relative contribution rate, and threshold analysis, we explored the impact of rural depopulation on the carbon sink and its threshold. The results revealed that the proportion of the rural population in China decreased from 63.91 % in 2000 to 36.11 % in 2020. Human pressure decreased by 1.82% in rural depopulation areas, which promoted vegetation restoration in rural areas (+8.45 %) and increased the carbon sink capacity. The net primary productivity (NPP) and net ecosystem productivity (NEP) of the vegetation in the rural areas increased at rates of 2.95 g C m-2 yr-1 and 2.44 g C m-2 yr-1. Strong rural depopulation enhanced the carbon sequestration potential, and the NEP was 1.5 times higher in areas with sharp rural depopulation than in areas with mild rural depopulation. In addition, the rural depopulation was accompanied by urban expansion, and there was a positive correlation between the comprehensive urbanization level (CUL) and NEP in 75.29 % of urban areas. In the urban areas, the vegetation index increased by 88.42 %, and the urban green space partially compensated for the loss of carbon sink caused by urban expansion, with a growth rate of 4.96 g C m-2 yr-1. Changes in rural population have a nonlinear impact on the NEP. When the rural population exceeds 545.686 people/km2, an increase in the rural population will have a positive impact on the NEP. Our research shows that rural depopulation offers a potential opportunity to restore natural ecosystems and thus increase the carbon sequestration capacity.

Changes in Gut Microbiota in Patients with Multiple Sclerosis Based on 16s rRNA Gene Sequencing Technology: A Review and Meta-Analysis.

BACKGROUND: This meta-analysis explores alterations in the gut microbiota of patients with Multiple Sclerosis (MS) using 16S ribosomal RNA (rRNA) gene sequencing. METHODS: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, our comprehensive review spanned major databases, including PubMed, Web of Science, Embase, Cochrane, and Ovid, targeting observational studies that implemented 16S rRNA gene sequencing on fecal specimens. The quality of these studies was meticulously evaluated using the Newcastle-Ottawa scale. RESULTS: Our search yielded 26 relevant studies conducted between 2015-2022, encompassing 2885 participants. No significant differences were observed in alpha diversity indices (Shannon, Chao1, Operational Taxonomic Units (OTU), and Simpson) between MS patients and controls in general. Nonetheless, subgroup analyses according to disease activity using the Shannon index highlighted a significant decrease in microbial diversity during MS's active phase. Similarly, an evaluation focusing on MS phenotype revealed diminished diversity in individuals with relapsing-remitting MS (RRMS). Microbial composition analysis revealed no consistent increase in pro-inflammatory Bacteroidetes or decrease in anti-inflammatory Firmicutes within the MS cohort. CONCLUSION: The gut microbiome's role in MS presents a complex panorama, where alterations in microbial composition might hold greater significance to disease mechanisms than diversity changes. The impact of clinical factors such as disease activity and phenotype are moderately significant, underscoring the need for further research to elucidate these relationships. Prospective research should employ longitudinal methodologies to elucidate the chronological interplay among gut microbiota, disease evolution, and therapeutic strategies.

Neoadjuvant therapy of sequential TACE, camrelizumab, and apatinib for single huge hepatocellular carcinoma (NEO-START): study protocol for a randomized controlled trial.

BACKGROUND: The high recurrence rate after liver resection emphasizes the urgent need for neoadjuvant therapy in hepatocellular carcinoma (HCC) to enhance the overall prognosis for patients. Immune checkpoint inhibitors, camrelizumab combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) apatinib, have emerged as a first-line treatment option for patients with unresectable HCC, yet its neoadjuvant application in combination with transarterial chemoembolization (TACE) in HCC remains unexplored. Therefore, this study aims to investigate the efficacy and safety of sequential TACE, camrelizumab, and apatinib as a neoadjuvant therapy for single, huge HCC. METHODS: This multi-center, open-label randomized phase 3 trial will be conducted at 7 tertiary hospitals. Patients with single huge (≥ 10 cm in diameter), resectable HCC will be randomly assigned in a 1:1 ratio to arm of surgery alone or arm of neoadjuvant therapy followed by surgery. In the neoadjuvant therapy group, patients will receive TACE within 1 week after randomization, followed by camrelizumab (200 mg q2w, 4 cycles), along with apatinib (250 mg qd, 2 months). Patients will receive liver resection after neoadjuvant therapy unless the disease is assessed as progressive. The primary outcome is recurrence-free survival (RFS) at 1 year. The planned sample size of 60 patients will be calculated to permit the accumulation of sufficient RFS events in 1 year to achieve 80% power for the RFS primary endpoint. DISCUSSION: Synergistic effects provided by multimodality therapy of locoregional treatment, TKI, and anti-programmed cell death 1 inhibitor significantly improved overall survival for patients with unresectable HCC. Our trial will investigate the efficacy and safety of the triple combination of TACE, camrelizumab, and apatinib as a neoadjuvant strategy for huge, resectable HCC. TRIAL REGISTRATION: www.chitr.org.cn ChiCTR2300078086. Registered on November 28, 2023. Start recruitment: 1st January 2024. Expected completion of recruitment: 15th June 2025.

Intestinal mycobiota dysbiosis associated inflammation activation in chronic schizophrenia.

The microbiome-gut-brain axis is related to schizophrenia (SCZ). The role of intestinal mycobiota in SCZ has been under investigated. We present a half-year follow-up study involving 109 chronic SCZ patients and 77 healthy controls. Intestinal mycobiota was tested by internal transcribed spacer (ITS). Untargeted liquid chromatography-mass spectrometry (LC-MS) was used to measure fecal metabolites. Symptom severity was assessed using the Positive and Negative Syndrome Scale. Enterotype analysis showed that Candida-type patients exhibited severer positive symptoms and depression factors than Saccharomyces-type patients. Candida and its top species and operational taxonomic units (OTUs) were positively correlated with depression factors (all p=0.001). Fecal metabolites analysis showed that upregulated metabolites were associated with chronic inflammation (NF-κB pathway and T helper cell differentiation), downregulated metabolites were associated with glutamate metabolism, serotonergic and dopaminergic synapse. Procrustes analysis revealed significant correlation between intestinal mycobiota and fecal metabolites (M2=0.937, p<0.001). Metabolic module analysis showed that the top module, MEturquoise (associated with Th1 and Th2 cell differentiation), was negatively correlated with SCZ (r=-0.783, p<0.0001), positively correlated with Candida, Aspergillus, Trichosporon and Talaromyces (decreased in SCZ) and negatively correlated with Saccharomyces (increased in SCZ). We also found impairments of intestinal barrier in SCZ, characterized by increased in blood D-lactate (mucosa impairment marker) and decreased in blood mucin 2 (mucosal barrier protective protein). Serum levels of TNF-α was increased and showed stable high levels during treatment. This study suggests that mycobiota dysbiosis-related chronic inflammation and an impaired intestinal mucosal barrier are associated with chronic SCZ.

Analytical performance evaluation of hemoglobin A1c on an ARKRAY HA-8160 analyzer with newly-developed mobile phase buffer.

Background: Most glycated hemoglobin A1c (HbA1c) analytical reagents used were obtained from the analyzer's manufacturer. However, clinical laboratories need more choices for HbA1c analytical reagents to overcome the limitations of dedicated reagents for special analyzers. We developed new mobile phase buffers as HbA1c diagnostic reagents and evaluated their analytical performance for the HbA1c assay. Methods: Different mobile phase buffers used as HbA1c diagnostic reagents were prepared using different concentrations of sodium salts. According to the Clinical and Laboratory Standards Institute (CLSI) recommendation guidelines, the analytical performances of the newly developed mobile phase buffers were evaluated on an ARKRAY HA-8160 Analyzer. Both quality controls and clinical blood samples were used in these experiments. To assess the quality of the newly developed mobile phase buffers, precision, accuracy, linearity, carryover, interference, bias, correlation with commercial reagents, and stability were analyzed. Results: The CVs of intra-assay precision and interassay precision of quality control and clinical.There were fewer than 1.00 % blood sample assays using the newly developed mobile phase buffer. The RDs of accuracy were less than 1.00 %. Linearity: R2 = 0.9998 in the concentration range of 4.40%-17.30 %. Carryover: 0.00 %. Reagent comparison revealed that the Pearson regression equation was Y = 0.9884x+0.05692 (R2 = 0.9977), and the Bland-Altman mean difference was -0.02650 % (CI: -0.2121 %-0.1591 %) between the two analytical reagents. Stability was also acceptable within 12 months. This mobile phase buffer showed good anti-interference ability. Conclusion: The newly developed mobile phase buffers demonstrated good analytical performance and were suitable for clinical HbA1c assays on an ARKRAY HA-8160 Analyzer.

Revisiting the current and emerging concepts of postharvest fresh fruit and vegetable pathology for next-generation antifungal technologies.

Fungal infections of fresh fruits and vegetables (FFVs) can lead to safety problems, including consumer poisoning by mycotoxins. Various strategies exist to control fungal infections of FFVs, but their effectiveness and sustainability are limited. Recently, new concepts based on the microbiome and pathobiome have emerged and offer a more holistic perspective for advancing postharvest pathogen control techniques. Understanding the role of the microbiome in FFV infections is essential for developing sustainable control strategies. This review examines current and emerging approaches to postharvest pathology. It reviews what is known about the initiation and development of infections in FFVs. As a promising concept, the pathobiome offers new insights into the basic mechanisms of microbial infections in FFVs. The underlying mechanisms uncovered by the pathobiome are being used to develop more relevant global antifungal strategies. This review will also focus on new technologies developed to target the microbiome and members of the pathobiome to control infections in FFVs and improve safety by limiting mycotoxin contamination. Specifically, this review stresses emerging technologies related to FFVs that are relevant for modifying the interaction between FFVs and the microbiome and include the use of microbial consortia, the use of genomic technology to manipulate host and microbial community genes, and the use of databases, deep learning, and artificial intelligence to identify pathobiome markers. Other approaches include programming the behavior of FFVs using synthetic biology, modifying the microbiome using sRNA technology, phages, quorum sensing, and quorum quenching strategies. Rapid adoption and commercialization of these technologies are recommended to further improve the overall safety of FFVs.

Comparative proteomics reveals that fatty acid metabolism is involved in myocardial adaptation to chronic hypoxic injury.

Congenital heart disease (CHD) is the most serious form of heart disease, and chronic hypoxia is the basic physiological process underlying CHD. Some patients with CHD do not undergo surgery, and thus, they remain susceptible to chronic hypoxia, suggesting that some protective mechanism might exist in CHD patients. However, the mechanism underlying myocardial adaptation to chronic hypoxia remains unclear. Proteomics was used to identify the differentially expressed proteins in cardiomyocytes cultured under hypoxia for different durations. Western blotting assays were used to verify protein expression. A Real-Time Cell Analyzer (RTCA) was used to analyze cell growth. In this study, 3881 proteins were identified by proteomics. Subsequent bioinformatics analysis revealed that proteins were enriched in regulating oxidoreductase activity. Functional similarity cluster analyses showed that chronic hypoxia resulted in proteins enrichment in the mitochondrial metabolic pathway. Further KEGG analyses found that the proteins involved in fatty acid metabolism, the TCA cycle and oxidative phosphorylation were markedly upregulated. Moreover, knockdown of CPT1A or ECI1, which is critical for fatty acid degradation, suppressed the growth of cardiomyocytes under chronic hypoxia. The results of our study revealed that chronic hypoxia activates fatty acid metabolism to maintain the growth of cardiomyocytes.

Using broadly targeted plant metabolomics technology combined with network pharmacology to explore the mechanism of action of the Yishen Gushu formula in the treatment of postmenopausal osteoporosis in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Yishen Gushu Formula (YSGSF) is composed of Epimedium, prepared Rehmannia, Drynaria, Eucommia, Dodder, ginseng, Astragalus, Ligusticum wallichii, Aucklandia and Panax notoginseng. It can improve bone mineral density by regulating bone metabolism. However, the mechanism of YSGSF in the treatment of Postmenopausal osteoporosis (PMOP) remains unclear. AIM OF THE STUDY: The compounds, targets, and molecular mechanisms of YSGSF in the treatment of PMOP were investigated using broad-spectrum target metabolomics from plants, combined with network pharmacology and animal studies, leading to a discussion on a novel approach to understanding YSGSF's action in PMOP treatment. MATERIALS AND METHODS: Using ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) within a comprehensive targeted metabolomics framework, the active constituents of YSGSF were identified. This, alongside network pharmacology and molecular docking, facilitated the identification of critical signaling pathways and targets pertinent to YSGSF's therapeutic effect on PMOP. Subsequently, an animal model for PMOP was developed. Following intervention grouping, rats' weight changes were recorded; serum bone metabolic factors were assessed via ELISA; bone microstructure was examined using HE staining and Micro-CT; and key signaling pathway proteins and genes were analyzed through immunohistochemistry to validate YSGSF's potential mechanism in PMOP treatment. RESULTS: A total of 84 main active components of YSGSF were identified. The key signaling pathways affected by YSGSF in the treatment of PMOP were the TNF and IL-7 signaling pathways, closely related to TNF-α, IL-1ß, c-jun and other protein targets. The results of animal experiments showed that YSGSF could downregulate the expression of TNF-a, IL-1ß and c-Jun proinflammatory factors by regulating the TNF and IL-7 signaling pathways and regulate the inflammatory response, osteocyte differentiation and apoptosis to control the development of PMOP. CONCLUSION: YSGSF activates the TNF-α and IL-7 signaling pathways in PMOP rats, reducing TNF-α and IL-1ß levels, the c-Jun inflammatory response, and osteocyte differentiation and apoptosis, thus playing a significant role in treating PMOP.

Obesity and lipid indices as predictors of depressive symptoms in middle-aged and elderly Chinese: insights from a nationwide cohort study.

BACKGROUND: Depressive symptoms are one of the most common psychiatric disorders, with a high lifetime prevalence rate among middle-aged and elderly Chinese. Obesity may be one of the risk factors for depressive symptoms, but there is currently no consensus on this view. Therefore, we investigate the relationship and predictive ability of 13 obesity- and lipid-related indices with depressive symptoms among middle-aged and elderly Chinese. METHODS: The data were obtained from The China Health and Retirement Longitudinal Study (CHARLS). Our analysis includes individuals who did not have depressive symptoms at the baseline of the CHARLS Wave 2011 study and were successfully follow-up in 2013 and 2015. Finally, 3790 participants were included in the short-term (from 2011 to 2013), and 3660 participants were included in the long-term (from 2011 to 2015). The average age of participants in short-term and long-term was 58.47 years and 57.88 years. The anthropometric indicators used in this analysis included non-invasive [e.g. waist circumference (WC), body mass index (BMI), and a body mass index (ABSI)], and invasive anthropometric indicators [e.g. lipid accumulation product (LAP), triglyceride glucose index (TyG index), and its-related indices (e.g. TyG-BMI, and TyG-WC)]. Receiver operating characteristic (ROC) analysis was used to examine the predictive ability of various indicators for depressive symptoms. The association of depressive symptoms with various indicators was calculated using binary logistic regression. RESULTS: The overall incidence of depressive symptoms was 20.79% in the short-term and 27.43% in the long-term. In males, WC [AUC = 0.452], LAP [AUC = 0.450], and TyG-WC [AUC = 0.451] were weak predictors of depressive symptoms during the short-term (P < 0.05). In females, BMI [AUC = 0.468], LAP [AUC = 0.468], and TyG index [AUC = 0.466] were weak predictors of depressive symptoms during the long-term (P < 0.05). However, ABSI cannot predict depressive symptoms in males and females during both periods (P > 0.05). CONCLUSION: The research indicates that in the middle-aged and elderly Chinese, most obesity- and lipid-related indices have statistical significance in predicting depressive symptoms, but the accuracy of these indicators in prediction is relatively low and may not be practical predictors.

Peripheral cutaneous synucleinopathy characteristics in genetic Parkinson's disease.

Background: Cutaneous phosphorylated alpha-synuclein (p-α-syn) deposition is an important biomarker of idiopathic Parkinson's disease (iPD). Recent studies have reported synucleinopathies in patients with common genetic forms of PD. Objective: This study aimed to detect p-α-syn deposition characteristic in rare genetic PD patients with CHCHD2 or RAB39B mutations. Moreover, this study also aimed to describe peripheral alpha-synuclein prion-like activity in genetic PD patients, and acquire whether the cutaneous synucleinopathy characteristics of genetic PD are consistent with central neuropathologies. Methods: We performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with CHCHD2 mutations, two patients with RAB39B mutations, 16 patients with PRKN mutations, 14 patients with LRRK2 mutations, five patients with GBA mutations, 100 iPD patients, and 20 healthy controls. We detected cutaneous synucleinopathies using immunofluorescence staining and a seeding amplification assay (SAA). A systematic literature review was also conducted, involving 64 skin biopsies and 205 autopsies of genetic PD patients with synucleinopathy. Results: P-α-syn was deposited in the peripheral cutaneous nerves of PD patients with CHCHD2, LRRK2, or GBA mutations but not in those with RAB39B or PRKN mutations. There were no significant differences in the location or rate of α-syn-positive deposits between genetic PD and iPD patients. Peripheral cutaneous synucleinopathy appears to well represent brain synucleinopathy of genetic PD, especially autosomal dominant PD (AD-PD). Cutaneous α-synuclein SAA analysis of iPD and LRRK2 and GBA mutation patients revealed prion-like activity. Conclusion: P-α-syn deposition in peripheral cutaneous nerves, detected using SAA and immunofluorescence staining, may serve as an accurate biomarker for genetic PD and iPD in the future.

The value of cardiopulmonary comorbidity in patients with acute large vessel occlusion stroke undergoing endovascular thrombectomy: a retrospective, observational cohort study.

BACKGROUND: Chronic lung and heart diseases are more likely to lead an intensive end point after stroke onset. We aimed to investigate characteristics and outcomes of endovascular thrombectomy (EVT) in patients with acute large vessel occlusion stroke (ALVOS) and identify the role of comorbid chronic cardiopulmonary diseases in ALVOS pathogenesis. METHODS: In this single-center retrospective study, 191 consecutive patients who underwent EVT due to large vessel occlusion stroke in neurological intensive care unit were included. The chronic cardiopulmonary comorbidities and several conventional stroke risk factors were assessed. The primary efficacy outcome was functional independence (defined as a mRS of 0 to 2) at day 90. The primary safety outcomes were death within 90 days and the occurrence of symptomatic intracranial hemorrhage(sICH). Univariate analysis was applied to evaluate the relationship between factors and clinical outcomes, and logistic regression model were developed to predict the prognosis of ALVOS. RESULTS: Endovascular therapy in ALVOS patients with chronic cardiopulmonary diseases, as compared with those without comorbidity, was associated with an unfavorable shift in the NHISS 24 h after EVT [8(4,15.25) versus 12(7.5,18.5), P = 0.005] and the lower percentage of patients who were functionally independent at 90 days, defined as a score on the modified Rankin scale of 0 to 2 (51.6% versus 25.4%, P = 0.000). There was no significant between-group difference in the frequency of mortality (12.1% versus 14.9%, P = 0.580) and symptomatic intracranial hemorrhage (13.7% versus 19.4%, P = 0.302) or of serious adverse events. Moreover, a prediction model showed that existence of cardiopulmonary comorbidities (OR = 0.456, 95%CI 0.209 to 0.992, P = 0.048) was independently associated with functional independence at day 90. CONCLUSIONS: EVT was safe in ALVOS patients with chronic cardiopulmonary diseases, whereas the unfavorable outcomes were achieved in such patients. Moreover, cardiopulmonary comorbidity had certain clinical predictive value for worse stroke prognosis.

Prenatal High-Sucrose Diet Induced Vascular Dysfunction of Renal Interlobar Arteries in the Offspring via PPARγ-RXRg-ROS/Akt Signaling.

SCOPE: Prenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high-sucrose diet (HS) during pregnancy causes vascular damage in renal interlobar arteries (RIA) from offspring still keeps unclear. METHODS AND RESULTS: Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Swollen mitochondria and distributed myofilaments are observed in vascular smooth muscle cells of RIA exposed to prenatal HS. Maternal HS increases phenylephrine (PE)-induced vasoconstriction in the RIA from adult offspring. NG-Nitro-l-arginine (L-Name) causes obvious vascular tension in response to PE in offspring from control group, not in HS. RNA-Seq of RIA is performed to reveal that the gene retinoid X receptor g (RXRg) is significantly decreased in the HS group, which could affect vascular function via interacting with PPARγ pathway. By preincubation of RIA with apocynin (NADPH inhibitor) or capivasertib (Akt inhibitor), the results indicate that ROS and Akt are the vital important factors to affect the vascular function of RIA exposure to prenatal HS. CONCLUSION: Maternal HS during the pregnancy increases PE-mediated vasoconstriction of RIA from adult offspring, which is mainly related to the enhanced Akt and ROS regulated by the weakened PPARγ-RXRg.

Eco-friendly multifunctional coating for polyester-cotton blended fabrics with superior flame retardancy and antibacterial properties.

Since the fire hazards of polyester-cotton blended (PTCO) fabrics and the hidden dangers of bacterial infection concerns caused by the contained cotton fiber, the design of flame retardant and antibacterial PTCO fabrics has received considerable attention. In this work, flame-retardant PTCO fabrics with satisfactory antibacterial properties were fabricated via a convenient and eco-friendly impregnation treatment involving guanidine phosphate (GP) and polyethylenimine (PEI). The prepared PTCO fabrics demonstrated excellent flame retardancy with a high limiting oxygen index value of 30.5 % and self-extinguishing capability, the damaged length was only 34 mm in the vertical flammability test. Furthermore, the peak heat release rate and the total heat release of coated PTCO fabrics were reduced significantly by 49 % and 38 %, respectively, indicating a substantial enhancement in fire safety. According to the analysis of the char residues and volatiles, GP presented great catalytic carbonization property, and PEI assisted the formation of the dense and stable carbon layer. The stable carbon layer effectively restricted mass and oxygen transfer between the PTCO fabrics and the environment. In addition, the introduction of PEI also produced more nonflammable gases to enhance the flame retardancy of the PTCO fabrics. Importantly, the GP/PEI coating barely deteriorate the physical and mechanical properties of the PTCO fabrics. The antibacterial rate of the GP/PEI-coated PTCO fabrics against Escherichia coli and Staphylococcus aureus was 99.99 %, similar to that of GP-coated fabrics, indicating the efficacy antibacterial properties of GP, and the addition of PEI did not compromise the antibacterial properties of GP. This work offers an efficient and simple approach to producing multifunctional PTCO fabrics with excellent flame retardancy and antibacterial properties, which are hopeful to expand the promising application of PTCO fabrics.

Unraveling the complexity of rapid eye movement microstates: insights from nonlinear EEG analysis.

Although rapid eye movement (REM) sleep is conventionally treated as a unified state, it comprises two distinct microstates: phasic and tonic REM. Recent research emphasizes the importance of understanding the interplay between these microstates, hypothesizing their role in transient shifts between sensory detachment and external awareness. Previous studies primarily employed linear metrics to probe cognitive states, such as oscillatory power, while in this study, we adopt Lempel-Ziv Complexity (LZC), to examine the nonlinear features of electroencephalographic (EEG) data from the REM microstates and to gain complementary insights into neural dynamics during REM sleep. Our findings demonstrate a noteworthy reduction in LZC during phasic REM compared to tonic REM states, signifying diminished EEG complexity in the former. Additionally, we noted a negative correlation between decreased LZC and delta band power, along with a positive correlation with alpha band power. This study highlights the potential of nonlinear EEG metrics, particularly LZC, in elucidating the distinct features of REM microstates. Overall, this research contributes to advancing our understanding of the complex dynamics within REM sleep and opens new avenues for exploring its implications in both clinical and nonclinical contexts.