[Intensive Citrus Cultivation Suppresses Soil Phosphorus Cycling Microbial Activity].

Soil microbes are key drivers in regulating the phosphorus cycle. Elucidating the microbial mineralization process of soil phosphorus-solubilizing bacteria is of great significance for improving nutrient uptake and yield of crops. This study investigated the mechanism by which citrus cultivation affects the soil microbial acquisition strategy for phosphorus by measuring the abundance of the phoD gene, microbial community diversity and structure, and soil phosphorus fractions in the soils of citrus orchards and adjacent natural forests. The results showed that citrus cultivation could lead to a decrease in soil pH and an accumulation of available phosphorus in the soil, with a content as high as 112 mg·kg-1, which was significantly higher than that of natural forests (3.7 mg·kg-1). Citrus cultivation also affected the soil phosphorus fractions, with citrus soil having higher levels of soluble phosphorus (CaCl2-P), citrate-extractable phosphorus (Citrate-P), and mineral-bound phosphorus (HCl-P). The phosphorus fractions of natural forest soils were significantly lower than those of citrus soils, whereas the phoD gene abundance and alkaline phosphatase activity were significantly higher in natural forest soils than in citrus soils. High-throughput sequencing results showed that the Shannon diversity index of phosphate-solubilizing bacteria in citrus soils was 4.61, which was significantly lower than that of natural forests (5.35). The microbial community structure in natural forests was also different from that of citrus soils. In addition, the microbial community composition of phosphate-solubilizing bacteria in citrus soils was also different from that of natural forests, with the relative abundance of Proteobacteria being lower in natural forest soils than in citrus soils. Therefore, citrus cultivation led to a shift of soil microbial acquisition strategy for phosphorus, with external phosphorus addition being the main strategy in citrus soils, whereas microbial mineralization of organic phosphorus was the main strategy in natural forest soils to meet their growth requirements.

Unveiling the Pivotal Role of dx2-y2 Electronic States in Nickel-based Hydroxide Electrocatalysts for Methanol Oxidation.

The anodic methanol oxidation reaction (MOR) plays a crucial role in coupling with the cathodic hydrogen evolution reaction (HER) and enables the sustainable production of the high-valued formate. Nickel-based hydroxide (Ni(OH)2) as MOR electrocatalyst has attracted enormous attention. However, the key factor determining the intrinsic catalytic activity remains unknown, which significantly hinders the further development of Ni(OH)2 electrocatalyst. Here, we found that the dx2-y2 electronic state within antibonding bands plays a decisive role in the whole MOR process. The onset potential depends on the deprotonation ability (Ni2+ to Ni3+), which was closely related to the band center of dx2-y2 orbital. The closer of dx2-y2 orbital to the Fermi level showed the stronger the deprotonation ability. Meanwhile, in the high potential region, the broadening of dx2-y2 orbital would facilitate the electron transfer from methanol to catalysts (Ni3+ to Ni2+), further enhancing the catalytic properties. Our work for the first time clarifies the intrinsic relationship between dx2-y2 electronic state and the MOR activities, which adds a new layer of understanding to the methanol electrooxidation research scene.

Association of periodontitis with gastrointestinal tract disorders: A bidirectional Mendelian randomization study.

BACKGROUND: The bidirectional link of periodontitis (PD) and gastrointestinal tract (GIT) disorders has been investigated in previous epidemiological studies; however, the conclusions still remain controversial. The aim of this study was to comprehensively explore the bidirectional causal effect between PD and various GIT diseases. METHODS: Based on summary-level data of genome-wide association studies (GWASs), a two-sample bidirectional Mendelian randomization (MR) study was undertaken. Single-nucleotide polymorphisms (SNPs) associated with PD or GIT disorders (chronic gastritis [CG], gastric ulcer [GU], duodenal ulcer [DU], gastroesophageal reflux disease [GERD], irritable bowel syndrome [IBS], and diverticular disease of the intestine [DI]) in GWASs were applied as exposure. The primary method employed was the inverse-variance weighted (IVW) method, and several sensitivity analyses were performed to investigate potential pleiotropy. RESULTS: With regard to the investigation of the causality between PD and GIT disorders, the IVW method revealed that there is a causal impact of PD on GU (odds ratio [OR] 1.088; 95% confidence interval [CI], 1.036-1.141; adjusted p = 0.004) and DI (OR 0.938; 95% CI, 0.911-0.965; adjusted p = 0.000). However, no significant genetic liability was observed for the causal effect of PD on CG, DU, GERD, and IBS. Furthermore, the primary analysis did not demonstrate a causal effect of GIT disorders on PD. CONCLUSION: This MR study suggests that PD may be associated with an increased risk of GU and a reduced risk of DI, with possibly limited clinical relevance. Further studies are needed to support the conclusions of this MR study.

Cistanche phenylethanoid glycosides induce apoptosis and pyroptosis in T-cell lymphoma.

Cistanche deserticola, known for its extensive history in Traditional Chinese Medicine (TCM), is valued for its therapeutic properties. Recent studies have identified its anticancer capabilities, yet the mechanisms underlying these properties remain to be fully elucidated. In this study, we determined that a mixture of four cistanche-derived phenylethanoid glycosides (CPhGs), echinacoside, acteoside, 2-acetylacteoside, and cistanoside A, which are among the main bioactive compounds in C. deserticola, eliminated T-cell lymphoma (TCL) cells by inducing apoptosis and pyroptosis in vitro and attenuated tumor growth in vivo in a xenograft mouse model. At the molecular level, these CPhGs elevated P53 by inhibiting the SIRT2-MDM2/P300 and PI3K/AKT carcinogenic axes and activating PTEN-Bax tumor-suppressing signaling. Moreover, CPhGs activated noncanonical and alternative pathways to trigger pyroptosis. Interestingly, CPhGs did not activate canonical NLRP3-caspase-1 pyroptotic signaling pathway; instead, CPhGs suppressed the inflammasome factor NLRP3 and the maturation of IL-1ß. Treatment with a caspase-1/4 inhibitor and silencing of Gasdermin D (GSDMD) or Gasdermin E (GSDME) partially rescued CPhG-induced cell death. Conversely, forced expression of NLRP3 restored cell proliferation. In summary, our results indicate that CPhGs modulate multiple signaling pathways to achieve their anticancer properties and perform dual roles in pyroptosis and NLRP3-driven proliferation. This study offers experimental support for the potential application of CPhGs in the treatment of TCL.

Metagenomic Next-Generation Sequencing Contributes to the Early Diagnosis of Mixed Infections in Central Nervous System.

Central nervous system (CNS) infections represent a challenge due to the complexities associated with their diagnosis and treatment, resulting in a high incidence rate and mortality. Here, we presented a case of CNS mixed infection involving Candida and human cytomegalovirus (HCMV), successfully diagnosed through macrogenomic next-generation sequencing (mNGS) in China. A comprehensive review and discussion of previously reported cases were also provided. Our study emphasizes the critical role of early pathogen identification facilitated by mNGS, underscoring its significance. Notably, the integration of mNGS with traditional methods significantly enhances the diagnostic accuracy of CNS infections. This integrated approach has the potential to provide valuable insights for clinical practice, facilitating early diagnosis, allowing for treatment adjustments, and ultimately, improving the prognosis for patients with CNS infections.

Association of Preoperative Immune Checkpoint Inhibitor Therapy With Cardiopulmonary Instability and Organ Injury After High-Risk Surgery.

OBJECTIVES: To assess the relationship between prior exposure to immune checkpoint inhibitors (ICIs) and the risk of postoperative complications in cancer patients. DESIGN: Single-center retrospective cohort study. INTERVENTIONS: The main exposure was treatment with an FDA-approved ICI within 6 months before surgery. MEASUREMENTS AND MAIN RESULTS: Exposure to ICIs and covariates was determined from the electronic health record. The primary outcome was a composite of postoperative complications, including prolonged pressor or oxygen dependence, kidney injury, or myocardial injury. Secondary outcomes included each subcomponent of the primary outcome. Of 7674 subjects with cancer admitted to the ICU after surgery, 247 were exposed to one or more ICIs in the 6 months before surgery. After propensity score matching, 197 ICI-exposed subjects were matched to 777 nonexposed. The composite outcome occurred in 70 of 197 (35.5%) ICI-exposed subjects and 251 of 777 (32.3%) nonexposed. There was no difference between exposed and nonexposed groups in the primary composite outcome (odds ratio [OR], 1.12; 95% CI, 0.80-1.58) by conditional logistic regression. Risk of the secondary outcome of prolonged pressor dependence was significantly higher in ICI-exposed subjects (OR, 1.64; 95% CI, 1.01-2.67). Risks of oxygen dependence (OR, 1.13; 95% CI, 0.75-1.73), kidney injury (OR, 1.15; 95% CI, 0.77-1.71), and myocardial injury (OR, 1.76; 95% CI, 1.00-3.10) were not significantly different. There was no difference between groups in the time to hospital discharge alive (p = 0.62). CONCLUSIONS: Exposure to ICIs within 6 months before high-risk surgery was not associated with the composite outcome of cardiopulmonary instability or organ injury in patients with cancer. The potential for an association with the secondary outcomes of cardiac instability and injury is worthy of future study.

[The role of ROS/JNK/caspase 3 axis in apoptosis induction by menthol-favored electronic cigarette liquid in human periodontal ligament stem cells].

PURPOSE: To explore the cytotoxic effect of a menthol-favored E-liquid on human periodontal ligament stem cells (hPDLSCs), as well as the underlying mechanism of electronic cigarette (E-cig)-induced cell apoptosis. METHODS: PDLSCs were isolated and cultured from periodontal ligament tissues of healthy premolars extracted for orthodontic reasons. Cells in passage 3 were used to detect the surface markers of stem cells by flow cytometry. Then the cells were exposed to different doses of menthol-favored E-liquid (at 59 mg/L nicotine concentration) in the culture median (the final nicotine concentrations were 0.1 µg/mL, 1.0 µg/mL, 10 µg/mL, 50 µg/mL, 0.1 mg/mL, 0.2 mg/mL and 0.5 mg/mL, respectively) for different period of times (24, 48 and 72 h). The cell viability was analyzed by CCK-8 assay. Cell apoptosis was evaluated by flow cytometry (7-AAD and Annexin V staining) and TUNEL assay. Reactive oxygen species (ROS) production was detected with fluorescence probe DCFH-DA by confocal microscopy and flow cytometry. The protein expression levels associated with ROS/JNK/caspase 3 axis(p-JNK, JNK, c-Jun, p-c-Jun, Bcl-2, Bax and cleaved-caspase 3) were analyzed by Western blot. Immunocytofluorescense staining was applied to evaluate the expression level of p-JNK. After addition of NAC, a ROS scavenger, and MAPK/JNK specific blocker SP600125, their effects on E-cig-induced cell apoptosis were evaluated. Statistical analysis was performed with Graph Pad 5.0 software package. RESULTS: Human PDLSCs were successfully isolated and cultured and flow cytometry assay showed the mesenchymal stem cell surface biomarkers (CD73, CD90 and CD105) were positively expressed. CCK8 assay indicated cell viability was significantly(P＜0.001) different among all concentration groups at various time points (24, 48 or 72 h), and the difference in apoptosis rate among all concentration groups was also statistically significant (P＜0.001). After exposure to E-liquid with nicotine concentration ≥50 µg/mL, cell viability was significantly reduced, and the proportion of apoptotic cells and the cellular ROS level was significantly increased in a dose-dependent manner as compared with the control group(0.0 mg/mL). Western blot assay showed E-cig exposure could promote MAPK/JNK phosphorylation in a dose-dependent and time-dependent manner. Either NAC or SP600125 could partially rescue the E-cig-induced cell apoptosis via reversing up-regulation of p-JNK and cleaved caspase 3. CONCLUSIONS: ROS/JNK/caspase 3 axis is involved in menthol-favored E-liquid-induced apoptosis of hPDLSCs.

Associations between maternal serum neonicotinoid pesticide exposure during pregnancy and newborn telomere length: Effect modification by sampling season.

BACKGROUND: An increasing amount of evidence suggests that telomere length (TL) at birth can predict lifespan and is associated with chronic diseases later in life, but newborn TL may be affected by environmental pollutants. Neonicotinoids (NEOs) are widely used worldwide, and despite an increasing number of studies showing that they may have adverse effects on birth in mammals and even humans, few studies have examined the effect of NEO exposure on newborn TLs. OBJECTIVE: To investigate the effects of prenatal exposure to NEOs and the interactions between NEOs and sampling season on newborn TL. METHODS: We conducted a prospective cohort study of 500 mother-newborn pairs from the Guangxi Zhuang Birth Cohort. Ultraperformance liquid chromatographymass spectrometry was used to detect ten NEOs in maternal serum, and fluorescence quantitative PCR was used to estimate the newborn TL. A generalized linear model (GLM) was used to evaluate the relationships between individual NEO exposures and TLs , and quantile g-computation (Qgcomp) model and Bayesian kernel machine regression (BKMR) model were used to evaluate the combined effect of mixtures of components. RESULTS: The results of the GLM showed that compared with maternal TMX levels < LOD, maternal TMX levels < median were negatively correlated with newborn TL (-6.93%, 95% CI%: -11.92%, -1.66%), and the decrease in newborn TL was more pronounced in girls (-9.60%, 95% CI: -16.84%, -1.72%). Moreover, different kinds of maternal NEO exposure had different effects on newborn TL in different sampling seasons, and the effect was statistically significant in all seasons except in autumn. Mixed exposure analysis revealed a potential positive trend between NEOs and newborn TL, but the association was not statistically significant. CONCLUSION: Prenatal exposure to TMX may shorten newborn TL, and this effect is more pronounced among female newborns. Furthermore, the relationship between NEO exposure and TL may be modified by the sampling season.

Association between left ventricular remodeling and lipid profiles in obese children: an observational study.

Objective: Childhood obesity has become a prominent issue in the society, which can lead to left ventricular remodeling and severe cardiovascular complications in adulthood. It is beneficial to identify the causes of left ventricular remodeling so that targeted measures can be taken to prevent the cardiovascular disease. Therefore, this study aimed to explore the relationship between left ventricular remodeling and changes in blood lipid indexes in obese children. Methods: This study was conducted on 40 healthy non-obese children and 140 obese children diagnosed in the pediatric health department of our hospital. Clinical data collected from the two groups were compared. Echocardiography was performed to examine left ventricular configuration and cardiac function. Multiple linear regression analysis was conducted to assess the independent effects of blood lipid levels on echocardiographic parameters. Blood lipid indicators among different left ventricular structural patterns which were classified according to left ventricular mass indexes and relative wall thickness were compared. Results: Obese children exhibited significantly increased height, weight, body mass index (BMI), body fat percentage (BFP), blood pressure, triglycerides, total cholesterol, left ventricular internal diameter (LVIDd), interventricular septum (IVSd), left ventricular posterior wall diastolic thickness (LVPWd), myocardial mass (LVM) and relative wall thickness (RWT), as well as lower high-density lipoprotein cholesterol (HDL-C) and left ventricular ejection fraction (LVEF) compared to the non-obese children (P < 0.05). Multiple linear correlation analysis showed LVM had a significantly positive correlation with BMI (r = 3.21, P = 0.002) and SBP (r = 2.61, P = 0.01); LVMI had a significantly negative correlation with HDL-C (r = -2.45, P = 0.015); RWT had a significantly positive correlation with SBP (r = 2.50, P = 0.013) but a significantly negative correlation with HDL-C (r = -2.35, P = 0.02). Furthermore, there were significant differences in HDL-C values among children with different ventricular configurations (P < 0.05), with the lowest HDL-C value recorded in the concentric hypertrophy group. Conclusion: Obese children will develop left ventricular remodeling. The left ventricular configuration indexes are most significantly associated with serum HDL-C. Lower HDL-C level contributes to severer left ventricular hypertrophy, indicating a concentric hypertrophy pattern.

24-h central pressure is a valuable predictor for left ventricular hypertrophy in non-dialysis patients with chronic kidney disease.

The current research on the relationship between 24-h central pressure and 24-h brachial pressure with left ventricular hypertrophy (LVH) is characterised by limited sample size and inconsistent findings. Furthermore, the association has never been explored in chronic kidney disease (CKD). A multicentre, cross-sectional study among non-dialysis patients with CKD was conducted. All participants underwent brachial and central ambulatory blood pressure monitoring using MobilO-Graph PWA, while trained cardiologists performed echocardiography. In this study, 2117 non-dialysis patients with CKD were examined. 24-h central systolic blood pressure with c2 calibration (24-h c2SBP) demonstrated a stronger association with left ventricular mass index and LVH compared with 24-h brachial systolic blood pressure (24-h bSBP) in the univariate and multivariate regression analyses. The multivariate net reclassification index (NRI) analysis revealed that 24-h c2SBP exhibited greater discriminatory power over 24-h bSBP (NRI = 0.310, 95% CI [0.192-0.429], P < 0.001). Applying 130/135 mmHg as the threshold for 24-h bSBP/c2SBP to cross-classify, the patients were divided into concordant normotension (1509 individuals), isolated brachial hypertension (155 individuals), isolated central hypertension (11 individuals), and concordant hypertension (442 individuals). With concordant normotension as the reference, the multivariable-adjusted ORs were 0.954 (95% CI, 0.534-1.640; P = 0.870) for isolated brachial hypertension and 2.585 (95%CI, 1.841-3.633; P < 0.001) for concordant hypertension. Among non-dialysis patients with CKD, 24-h c2SBP exhibits greater efficacy in identifying the presence of LVH compared with 24-h bSBP. The presence of LVH was greater in cases of concordant hypertension compared with cases of isolated brachial hypertension and concordant normotension.

Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion.

The dysfunction of matriptase, a membrane-anchored protease, is highly related to the progression of skin and breast cancers. Epidermal growth factor (EGF)-induced matriptase activation and cancer invasion are known but with obscure mechanisms. Here, we demonstrate a vesicular-trafficking-mediated interplay between matriptase and EGF signaling in cancer promotion. We found that EGF induces matriptase to undergo endocytosis together with the EGF receptor, followed by acid-induced activation in endosomes. Activated matriptase is then secreted extracellularly on exosomes to catalyze hepatocyte growth factor precursor (pro-HGF) cleavage, resulting in autocrine HGF/c-Met signaling. Matriptase-induced HGF/c-Met signaling represents the second signal wave of EGF, which promotes cancer cell scattering, migration, and invasion. These findings demonstrate a role of vesicular trafficking in efficient activation and secretion of membrane matriptase and a reciprocal regulation of matriptase and EGF signaling in cancer promotion, providing insights into the physiological functions of vesicular trafficking and the molecular pathological mechanisms of skin and breast cancers.

Genetic regulation and targeted reversal of lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.

Vascular inflammation critically regulates endothelial cell (EC) pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulation of lysosomal activity and cholesterol metabolism have known inflammatory roles in disease, but their relevance to PAH is unclear. In human pulmonary arterial ECs and in PAH, we found that inflammatory cytokine induction of the nuclear receptor coactivator 7 (NCOA7) both preserved lysosomal acidification and served as a homeostatic brake to constrain EC immunoactivation. Conversely, NCOA7 deficiency promoted lysosomal dysfunction and proinflammatory oxysterol/bile acid generation that, in turn, contributed to EC pathophenotypes. In vivo, mice deficient for Ncoa7 or exposed to the inflammatory bile acid 7α-hydroxy-3-oxo-4-cholestenoic acid (7HOCA) displayed worsened PAH. Emphasizing this mechanism in human PAH, an unbiased, metabolome-wide association study (N=2,756) identified a plasma signature of the same NCOA7-dependent oxysterols/bile acids associated with PAH mortality (P<1.1x10-6). Supporting a genetic predisposition to NCOA7 deficiency, in genome-edited, stem cell-derived ECs, the common variant intronic SNP rs11154337 in NCOA7 regulated NCOA7 expression, lysosomal activity, oxysterol/bile acid production, and EC immunoactivation. Correspondingly, SNP rs11154337 was associated with PAH severity via six-minute walk distance and mortality in discovery (N=93, P=0.0250; HR=0.44, 95% CI [0.21-0.90]) and validation (N=630, P=2x10-4; HR=0.49, 95% CI [0.34-0.71]) cohorts. Finally, utilizing computational modeling of small molecule binding to NCOA7, we predicted and synthesized a novel activator of NCOA7 that prevented EC immunoactivation and reversed indices of rodent PAH. In summary, we have established a genetic and metabolic paradigm and a novel therapeutic agent that links lysosomal biology as well as oxysterol and bile acid processes to EC inflammation and PAH pathobiology. This paradigm carries broad implications for diagnostic and therapeutic development in PAH and in other conditions dependent upon acquired and innate immune regulation of vascular disease.

Neoadjuvant Immune Checkpoint Inhibitors in hepatocellular carcinoma: a meta-analysis and systematic review.

Background: Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy's efficacy and safety in the context of HCC. Methods: A systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276). Results: This meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety. Discussion: Neoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support.

Neutrophil hitchhiking: Riding the drug delivery wave to treat diseases.

Neutrophils are a crucial component of the innate immune system and play a pivotal role in various physiological processes. From a physical perspective, hitchhiking is considered a phenomenon of efficient transportation. The combination of neutrophils and hitchhikers has given rise to effective delivery systems both in vivo and in vitro, thus neutrophils hitchhiking become a novel approach to disease treatment. This article provides an overview of the innovative and feasible application of neutrophils as drug carriers. It explores the mechanisms underlying neutrophil function, elucidates the mechanism of drug delivery mediated by neutrophil-hitchhiking, and discusses the potential applications of this strategy in the treatment of cancer, immune diseases, inflammatory diseases, and other medical conditions.

Association between RMTg Neuropeptide Genes and Negative Effect during Alcohol Withdrawal in Mice.

Alcohol use disorders (AUDs) frequently co-occur with negative mood disorders, such as anxiety and depression, exacerbating relapse through dopaminergic dysfunction. Stress-related neuropeptides play a crucial role in AUD pathophysiology by modulating dopamine (DA) function. The rostromedial tegmental nucleus (RMTg), which inhibits midbrain dopamine neurons and signals aversion, has been shown to increase ethanol consumption and negative emotional states during abstinence. Despite some stress-related neuropeptides acting through the RMTg to affect addiction behaviors, their specific roles in alcohol-induced contexts remain underexplored. This study utilized an intermittent voluntary drinking model in mice to induce negative effect behavior 24 h into ethanol (EtOH) abstinence (post-EtOH). It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors. We observed that adult male C57BL/6J mice displayed evident anxiety, anhedonia, and depression-like symptoms at 24 h post-EtOH. The laser-capture microdissection technique, coupled with or without retrograde tracing, was used to harvest total ventral tegmental area (VTA)-projecting neurons or the intact RMTg area. The findings revealed that post-EtOH consistently reduced Pnoc and Orx levels while elevating Crf levels in these neuronal populations. Notably, RMTg Pnoc and Npy levels counteracted ethanol consumption and depression severity, while Crf levels were indicative of the mice's anxiety levels. Together, these results underscore the potential role of stress-related neuropeptides in the RMTg in regulating the negative emotions related to AUDs, offering novel insights for future research.

Endothelial cell-derived extracellular vesicles expressing surface VCAM1 promote sepsis-related acute lung injury by targeting and reprogramming monocytes.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common life-threatening syndrome with no effective pharmacotherapy. Sepsis-related ARDS is the main type of ARDS and is more fatal than other types. Extracellular vesicles (EVs) are considered novel mediators in the development of inflammatory diseases. Our previous research suggested that endothelial cell-derived EVs (EC-EVs) play a crucial role in ALI/ARDS development, but the mechanism remains largely unknown. Here, we demonstrated that the number of circulating EC-EVs was increased in sepsis, exacerbating lung injury by targeting monocytes and reprogramming them towards proinflammatory macrophages. Bioinformatics analysis and further mechanistic studies revealed that vascular cell adhesion molecule 1 (VCAM1), overexpressed on EC-EVs during sepsis, activated the NF-κB pathway by interacting with integrin subunit alpha 4 (ITGA4) on the monocyte surface, rather than the tissue resident macrophage surface, thereby regulating monocyte differentiation. This effect could be attenuated by decreasing VCAM1 levels in EC-EVs or blocking ITGA4 on monocytes. Furthermore, the number of VCAM1+ EC-EVs was significantly increased in patients with sepsis-related ARDS. These findings not only shed light on a previously unidentified mechanism underling sepsis-related ALI/ARDS, but also provide potential novel targets and strategies for its precise treatment.

ADHD and family life: A cross-sectional study of ADHD prevalence among pupils in China and factors associated with parental depression.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is increasingly recognized as a major problem for children and their families in China. However, its influence on parental mental health has been seldom explored. OBJECTIVE: To examine the prevalence of attention deficit hyperactivity disorder in a community sample of children aged 6-13 years, and the extent to which it impacts parental mental health. METHOD: Cross-sectional study of primary school pupils (number = 2497) in Deyang, Sichuan Province, South-West China. We used standardized instruments to identify children with ADHD symptoms and parent depression. RESULTS: The prevalence of ADHD was 9.8%. Factors associated with the likelihood of ADHD, included family environment(P = 0.003), time spent with children(P = 0.01), parenting style(P = 0.01), and parental relationship, pupils self-harm and lower academic ability (P = 0.001). After controlling for other factors, having a child with ADHD increased the likelihood of parents' depression (OR = 4.35, CI = 2.68~7.07), additional factors included parent relationship. CONCLUSIONS: ADHD may be a common disorder among Chinese children, the symptoms of which may increase the likelihood of parent depression. There is a need for greater detection of ADHD in schools, acknowledgement of the challenges the disorder creates for academic success and family wellbeing, and psychoeducational tools for supporting parents of children with ADHD.

Effects of transcranial direct current stimulation on cognitive function in older adults with and without mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Noninvasive brain stimulation (NIBS) has shown benefits for cognitive function in older adults. However, the effects of transcranial direct current stimulation (tDCS) on cognitive function in older adults are inconsistent across studies, and the evidence for tDCS has limitations. We aim to explore whether tDCS can improve cognitive function and different cognitive domains (i.e., learning and memory and executive function) in adults aged 65 and older with and without mild cognitive impairment and to further analyze the influencing factors of tDCS. METHODS: Five English databases (PubMed, Cochrane Library, EMBASE, Web of Science, the cumulative Index to Nursing and Allied Health Literature [CINAHL]) and four Chinese databases were searched from inception to 14 October 2023. Literature screening, data extraction, and quality assessment were completed independently by two reviewers. All statistical analyses were conducted using RevMan software (version 5.3). Standardized mean difference (SMD) along with a 95% confidence interval (CI) were used to express the effect size of the outcomes, and a random-effect model was also used. RESULTS: A total of 10 RCTs and 1761 participants were included in the meta-analysis, and the risk of bias in those studies was relatively low. A significant effect favoring tDCS on immediate postintervention cognitive function (SMD=0.16, Z=2.36, P=0.02) was found. However, the effects on immediate postintervention learning and memory (SMD=0.20, Z=2.00, P=0.05) and executive function (SMD=0.10, Z=1.22, P=0.22), and 1-month postintervention cognitive function (SMD=0.12, Z=1.50, P=0.13), learning and memory (SMD=0.17, Z=1.39, P=0.16) and executive function (SMD=0.08, Z=0.67, P=0.51) were not statistically significant. CONCLUSION: TDCS can significantly improve the immediate postintervention cognitive function of healthy older adults and MCI elderly individuals. Additional longitudinal extensive sample studies are required to clarify the specific effects of tDCS on different cognitive domains, and the optimal tDCS parameters need to be explored to guide clinical practice.

Amniotic Fluid Proteomics Analysis and In Vitro Validation to Identify Potential Biomarkers of Preterm Birth.

This study aimed to investigate the regulation of amniotic fibroblast (AFC) function by vitamin K-dependent protein Z (PROZ) during preterm birth (PTB) and its potential role in adverse pregnancy outcomes. Proteomic samples were collected from amniotic fluid in the second trimester, and AFC were isolated from the amniotic membrane and cultured in vitro. The expression of extracellular and intracellular PROZ in AFC was modulated, and their biological properties and functions were evaluated. Clinical analysis revealed a significant upregulation of PROZ expression in amniotic fluid from preterm pregnant women. In vitro experiments demonstrated that PROZ stimulated AFC migration, enhanced their proliferative capacity, and reduced collagen secretion. Overexpression of PROZ further enhanced cell migration and proliferation, while knockdown of PROZ had the opposite effect. PROZ plays a crucial role in promoting the proliferation and migration of amniotic membrane fibroblasts. Increased PROZ expression in amniotic fluid is associated with the occurrence of PTB. These findings shed light on the potential involvement of PROZ in adverse pregnancy outcomes and provide a basis for further research on its regulatory mechanisms during PTB.

Micro-computed tomographic evaluation of the shaping ability of three nickel-titanium rotary systems in the middle mesial canal of mandibular first molars: an ex vivo study based on 3D printed tooth replicas.

BACKGROUND: The preparation of the middle mesial (MM) canal of mandibular molars represents a challenge because it is often curved, narrow, and close to the root concave. The purpose of this study was to evaluate the ex vivo shaping ability of 3 nickel-titanium (NiTi) rotary systems in the MM canal using 3D printed resin tooth replicas. METHODS: A permanent mandibular first molar with a MM canal was acquired from a pool of extracted teeth and reproduced by a 3D printer. The resin tooth replicas (n = 18) were equally assigned to 3 groups for the evaluation of the shaping abilities of 3 NiTi rotary systems (OneShape [OS], Twisted Files [TF], and ProTaper Gold [PTG]) according to the manufacturer's recommendations. The tooth replicas were scanned by micro-computed tomography (micro-CT) twice before and after instrumentation of the mesiobuccal (MB), mesiolingual (ML), and MM root canals. After 3D reconstruction, the canal straightening, change of root canal volume and surface area, the mesial and distal canal wall thickness and canal transportation at the levels of 1, 2, and 3 mm below furcation were assessed. One-way variance analysis and Turkey's post hoc test were used for comparisons of the means among different groups, and paired-t test was used to compare the mesial and distal sides of the mesial roots. RESULTS: As compared with OS and TF, the use of PTG in preparation of MM canals resulted in significantly more straightening of canal curvature (p < 0.05), greater post-instrumentation canal volume and surface area, and thinner mesial and distal remaining canal wall thickness at 1, 2 and 3 mm below furcation (all p < 0.05). Regarding the root canal transportation in the mesiodistal direction, there was no significant difference among the 3 instruments (all p > 0.05) after the preparation of the MB and ML canals. However, in the MM canal, more pronounced transportation was detected in the PTG group at 2 mm below furcation, and in the TF group at 3 mm below furcation as compared with the other 2 systems (both p < 0.05). CONCLUSIONS: 3D printed tooth replicas have the advantages of consistency and can be an ideal model to evaluate the shaping ability of different instruments in the MM canal. OS and TF files performed similarly and both are appropriate for shaping the MM canal, while PTG may cause excessive and uneven resin removal, especially near the furcation, and may lead to root fragility and procedural errors.