Does nature-based social prescription improve mental health outcomes? A systematic review and meta-analysis.

Background: A nature-based social prescription (NBSP) is an approach to improving mental health outcomes that involves prescribing nature-based interventions as complementary or alternative therapy to traditional ones. A variety of advantages are available from NBSP for people looking to enhance their mental well-being. The effect size of the nature-based social prescriptions (NBSPs) has not been thoroughly evaluated by systematic reviews and meta-analyses. Objectives: The current study aimed to analyze existing studies and conduct a meta-analysis to determine the overall effect size of the nature-based social prescriptions (NBSP's) outcomes on mental health. Methods: By choosing the relevant papers from among those that were available, a meta-analysis was carried out in the current study. A systematic search of electronic databases (Pub Med, Web of Science, Scopus, Cochrane Library, Embase, CINAHL, and PsychINFO) was conducted to identify relevant studies. Studies were included if they evaluated the effects of NBSP on mental health outcomes. Effect sizes were calculated using the random effects model. Results: Meta-analysis of interventions statistics shows that CBT (SMD -0.0035; 95% CI: [-0.5090; 0.5020]; Tau^2: 0.1011; Tau: 0.318), digital intervention (SMD -0.3654; 95% CI: [-0.5258; 1.2566]; Tau^2: 0.2976, Tau: 0.5455), music intervention (SMD -2.1281; 95% CI: [-0.4659; 4.7221]; Tau^2: 3.4046; Tau:1.8452), and psychological interventions (SMD -0.8529; 95% CI: [0.3051; 1.4007]; Tau^2: 0.1224; Tau: 0.3499) do not significantly impact. The other interventions [social belongingness, communication training, blue intervention, nature-based education, cognitive behavior group therapy (CBGT), social prescribing coordinator, self-help intervention, participatory, organizational intervention, inpatient services, brief diet, internet-based intervention, prenatal intervention, yoga and meditation, ergonomics training program, yoga nidra intervention, and storytelling] highlighted above are significant. Conclusion: The conclusion of the meta-analysis supports the idea that incorporating nature-based social prescription interventions into mental healthcare plans can effectively complement traditional therapies and improve mental health outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023412458, CRD42023412458.

Paternal and maternal exposures to adverse childhood experiences and spontaneous fetal loss: a nationwide cross-sectional analysis.

BACKGROUND: Adverse childhood experiences (ACEs) might be associated with maternal spontaneous fetal loss, while evidence among Chinese population is limited. This study aims to explore the associations of adverse childhood experiences (ACEs) among women and their spouses with the risk of spontaneous abortion and stillbirth. METHOD: Data were from the China Health and Retirement Longitudinal Study (CHARLS) 2014 survey. ACEs were categorized into intra-familial ACEs and extra-familial ACEs. The associations of maternal and paternal ACEs with women's history of spontaneous abortion and stillbirth were investigated by logistic regression. RESULTS: 7,742 women were included with 9.05% and 2.47% experiencing at least one spontaneous abortion or stillbirth, respectively. Women exposed to 2, 3, and ≥ 4 ACEs were at significantly higher odds of spontaneous abortion, with adjusted odds ratios (ORs) of 1.52 (95% [CI, Confidence Interval] 1.10-2.10), 1.50 (95% CI 1.07-2.09) and 1.68 (95% CI 1.21-2.32), respectively. A significant association between ≥ 4 maternal intra-familial ACEs and stillbirth (OR 2.23, 95% CI 1.12-4.42) was also revealed. Furthermore, paternal exposures to 3 and ≥ 4 overall ACEs were significantly associated with their wives' history of spontaneous abortion, with adjusted ORs of 1.81 (95% CI 1.01-3.26) and 1.83 (95% CI 1.03-3.25), respectively. CONCLUSION: Both maternal and paternal ACEs were associated with spontaneous abortion, and potential mediators might need to be considered to further explore impacts of maternal and paternal ACEs on maternal reproductive health.

A qualitative internet-based study of parental experiences of adolescents suffering from affective disorders with non-suicidal self-injury during the COVID-19 pandemic.

Objective: Non-suicidal self-injury (NSSI) behaviors of adolescents with affective disorders can directly deteriorate parents' internal experiences, and negative parental experiences can exacerbate or even worsen NSSI behaviors. This study investigates the impact of NSSI behaviors exhibited by adolescents with affective disorders on the internal experiences of parents. Specifically, our research focuses on the inner experiences of parents when their children engage in NSSI behaviors during social isolation of the COVID-19, offering insights for addressing parental mental health issues related to NSSI and developing positive parental behavioral models to optimize adolescent behavior during major public health events. Methods: Semi-structured interviews were conducted with 21 parents of adolescents with affective disorders displaying NSSI behaviors during the COVID-19 pandemic. The Colaizzi 7-step analysis was employed to refine and categorize emerging themes. Results: Our study revealed that parents of adolescents facing NSSI during the COVID-19 pandemic underwent different internal experiences, which could be classified into four themes: negative experience, high caregiving burden, lack of caregiving capacity, and resilience. Conclusion: This Internet-based research is the first to explore the internal experiences of parents of adolescents with affective disorders experiencing NSSI during the COVID-19 pandemic. It sheds light on how parents, in response to their children's NSSI behaviors, undergo resilience following negative experiences, explore more open and supportive family model. Despite these positive outcomes, parents express a need for increased knowledge about NSSI illness care and a desire for professional assistance.

Sorafenib inhibits ossification of the posterior longitudinal ligament by blocking LOXL2-mediated vascularization.

Ossification of the Posterior Longitudinal Ligament (OPLL) is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone, resulting in limited spinal mobility and nerve compression. Employing both bulk and single-cell RNA sequencing, we elucidate the molecular characteristics, cellular components, and their evolution during the OPLL process at a single-cell resolution, and validate these findings in clinical samples. This study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in vivo. Notably, our study identifies LOXL2 as a key regulator in this process. Through gain-and loss-of-function studies, we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament cells. It acts via the HIF1A pathway, promoting the secretion of downstream VEGFA and PDGF-BB. This function is not related to the enzymatic activity of LOXL2. Furthermore, we identify sorafenib, a broad-spectrum tyrosine kinase inhibitor, as an effective suppressor of LOXL2-mediated vascular morphogenesis. By disrupting the coupling between vascularization and osteogenesis, sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone mass. These findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.

Mixed exposure to haloacetaldehyde disinfection by-products exacerbates lipid aggregation in the liver of mice.

Haloacetaldehyde disinfection by-products (HAL-DBPs) are among the top three unregulated DBPs found in drinking water. The cytotoxicity and genotoxicity of HALs are much higher than that of the regulated trihalomethanes and haloacetic acids. Previous studies have mainly focused on the toxic effects of single HALs, with few examining the toxic effects of mixed exposures to HALs. The study aimed to observe the effects of mixed exposures of 1∼1000X the realistic level of HALs on the hepatotoxicity and lipid metabolism of C57BL/6J mice, based on the component and concentration of HALs detected in the finished water of Shanghai. Exposure to realistic levels of HALs led to a significant increase in phosphorated acetyl CoA carboxylase 1 (p-ACC1) in the hepatic de novo lipogenesis (DNL) pathway. Additionally, exposure to 100X realistic levels of HALs resulted in significant alterations to key enzymes of lipid ab initio synthesis, including ACC1, fatty acid synthase (FAS), and diacylglycerol acyltransferase 2 (DGAT2), as well as key proteins of lipid disposal such as carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator activated receptor α (PPARα). Exposure to 1000-fold realistic levels of HALs significantly increased hepatic and serum triglyceride levels, as well as total cholesterol, low-density lipoprotein, alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and lactate dehydrogenase levels, significantly decreased high-density lipoprotein. Meanwhile, histopathological analysis demonstrated that HALs exacerbated tissue vacuolization and inflammatory cell infiltration in mouse livers, which showed the typical phenotypes of non-alcoholic fatty liver disease (NAFLD). These results suggested that the HALs mixture is a critical risk factor for NAFLD and is significantly highly toxic to C57BL/6J mice.

Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy.

The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there is a growing demand for off-the-shelf universal cell therapies. In this study, we have generated universal CAR-engineered NKT (UCAR-NKT) cells by integrating iNKT TCR engineering and HLA gene editing on hematopoietic stem cells (HSCs), along with an ex vivo, feeder-free HSC differentiation culture. The UCAR-NKT cells are produced with high yield, purity, and robustness, and they display a stable HLA-ablated phenotype that enables resistance to host cell-mediated allorejection. These UCAR-NKT cells exhibit potent antitumor efficacy to blood cancers and solid tumors, both in vitro and in vivo, employing a multifaceted array of tumor-targeting mechanisms. These cells are further capable of altering the tumor microenvironment by selectively depleting immunosuppressive tumor-associated macrophages and myeloid-derived suppressor cells. In addition, UCAR-NKT cells demonstrate a favorable safety profile with low risks of graft-versus-host disease and cytokine release syndrome. Collectively, these preclinical studies underscore the feasibility and significant therapeutic potential of UCAR-NKT cell products and lay a foundation for their translational and clinical development.

A point-of-care testing platform for on-site identification of genetically modified crops.

Genetically modified (GM) food is still highly controversial nowadays. Due to the disparate policies and attitudes worldwide, demands for a rapid, cost-effective and user-friendly GM crop identification method are increasingly significant for import administration, market supervision, etc. However, as the most-recognized methods, nucleic acid-based identification approaches require bulky instruments, long turn-around times and trained personnel, which are only suitable in laboratories. To fulfil the urgent needs of on-site testing, we develop a point-of-care testing platform that is able to identify 12 types of GM crops in less than 40 minutes without using laboratory settings. Our system integrates sample pre-treatment modules in a microfluidic chip, performs DNA amplification via a battery-powered portable kit, and presents results via eye-recognized colorimetric change. A paraffin-based reflow method and a slip plate-based fluid switch are developed to encapsulate and release amplification primers in individual microwells on demand, thus enabling identification of varied targets simultaneously. Our system offers an efficient, affordable and convenient tool for GM crop identification, thus it will not only benefit customs and market administration bureaus, but also satisfy demands of numerous consumers.

NK-92MI Cells Engineered with Anti-claudin-6 Chimeric Antigen Receptors in Immunotherapy for Ovarian Cancer.

Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR-NK cell efficacy. Claudin-6 (CLDN6) has been reported to be overexpressed in ovarian cancer and may be an attractive target for CAR-NK cells immunotherapy. However, the feasibility of using anti-CLDN6 CAR-NK cells to treat ovarian cancer remains to be explored. Methods: CLDN6 expression in primary human ovarian cancer, normal tissues and cell lines were detected by immunohistochemistry and western blot. Two types of third-generation CAR NK-92MI cells targeting CLDN6, CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) and CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB) were constructed by lentivirus transfection, sorted by flow cytometry and verified by western blot and qPCR. OVCAR-3, SK-OV-3, A2780, Hey and PC-3 cells expressing the GFP and luciferase genes were transduced. Subcutaneous and intraperitoneal tumor models were established via NSG mice. The ability of CLDN6-CAR NK cells to kill CLDN6-positive ovarian cancer cells were evaluated in vitro and in vivo by live cell imaging and bioluminescence imaging. Results: Both CLDN6-CAR1 and CLDN6-CAR2 NK-92MI cells could specifically killed CLDN6-positive ovarian cancer cells (OVCAR-3, SK-OV-3, A2780 and Hey), rather than CLDN6 negative cell (PC-3), in vitro. CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) exhibited stronger cytotoxicity than CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB). Furthermore, CLDN6-CAR1 NK cells could effectively eliminate ovarian cancer cells in subcutaneous and intraperitoneal tumor models. More importantly, CAR-NK cells combined with immune checkpoint inhibitors, anti-PD-L1, could synergistically enhance the antitumor efficacy of CLDN6-targeted CAR-NK cells. Conclusions: These results indicate that CLDN6-CAR NK cells possess strong antitumor activity and represent a promising immunotherapeutic modality for ovarian cancer.

Molecular Cloning and Functional Analysis of Secretory Phospholipase A2 from Apostichopus japonicus.

Secretory phospholipase A2 (sPLA2) plays important roles in phospholipid metabolism, skin barrier maintenance, immune response and other processes in organisms. sPLA2 of sea cucumber A. japonicus (AjPLA2) has not yet been reported. This study successfully amplified the AjPLA2 sequence. The total cDNA of AjPLA2 is 931 bp, including a 480 bp ORF that encodes 159 amino acids. The AjPLA2 protein includes a 16-aa signal peptide, a 5-aa precursor peptide and a 138-aa mature peptide. Homologous alignment showed that AjPLA2 and the sPLA2s from starfish have the typical domains of the Group IB sPLA2. And additional amino acid sequences were found around the ß-Wing, which is different from the Group IB sPLA2. These results showed that AjPLA2 and sPLA2s from starfish all belong to a new group in the Group I sPLA2 family. AjPLA2 is widely distributed in sea cucumber tissues. The functional analysis also showed that AjPLA2 was upregulated in the intestine by feeding. When the body wall was damaged, it was significantly upregulated around the wound. And the expression levels of AjPLA2 were significantly increased in V. splendens-infected sea cucumbers. The results indicated that AjPLA2 plays roles in the sea cucumber immunologic process. Combined with the upregulation of unsaturated fatty acids (PUFAs) content in A. japonicus, it demonstrated that AjPLA2 could participate in the immune of A. japonicus by hydrolyzing phospholipid and releasing PUFAs. This study had a solid foundation for the further research of AjPLA2 gene function in vivo, development and application of AjPLA2 protein.

Simultaneous photocatalytic degradation and SERS detection of tetracycline with self-sustainable and recyclable ternary PI/TiO2/Ag flexible microfibers.

Facile and efficient photocatalysts using sunlight, as well as fast and sensitive surface-enhanced Raman spectroscopy (SERS) substrates, are urgently needed for practical degradation of tetracycline (TC). To meet these requirements, a new paradigm for PI/TiO2/Ag organic‒inorganic ternary flexible microfibers based on semiconducting titanium dioxide (TiO2), the noble metal silver (Ag) and the conjugated polymer polyimide (PI) was developed by engineering a simple method. Under sunlight, the photocatalytic characteristics of the PI/TiO2/Ag flexible microfibers containing varying amounts of Ag quantum dots (QDs) were evaluated with photocatalytic degradation of TC in aqueous solution. The results demonstrated that the amount of Ag affected the photocatalytic activity. Among the tested samples, PI/TiO2/Ag-0.07 (93.1%) exhibited a higher photocatalytic degradation rate than PI/TiO2 (25.7%), PI/TiO2/Ag-0.05 (77.7%), and PI/TiO2/Ag-0.09 (63.3%). This observation and evaluation conducted in the present work strongly indicated a charge transfer mechanism. Moreover, the PI/TiO2/Ag-0.07 flexible microfibers exhibited highly sensitive SERS detection, as demonstrated by the observation of the Raman peaks for TC even at an extremely low concentration of 10-10 moles per liter. The excellent photocatalytic performance and SERS detection capability of the PI/TiO2/Ag flexible microfibers arose from the Schottky barrier formed between Ag and TiO2 and also from the outstanding plasmonic resonance and visible light absorptivity of Ag, along with immobilization by the PI. The successful synthesis of PI/TiO2/Ag flexible microfibers holds significant promise for sensitive detection and efficient photocatalytic degradation of antibiotics.

Building a Charge Transfer Bridge between g-C3N4 and Perovskite with Molecular Engineering to Achieve Efficient Perovskite Solar Cells.

Effective defect passivation and efficient charge transfer within polycrystalline perovskite grains and corresponding boundaries are necessary to achieve highly efficient perovskite solar cells (PSCs). Herein, focusing on the boundary location of g-C3N4 during the crystallization modulation on perovskite, molecular engineering of 4-carboxyl-3-fluorophenylboronic acid (BF) on g-C3N4 was designed to obtain a novel additive named BFCN. With the help of the strong bonding ability of BF with both g-C3N4 and perovskite and favorable intramolecular charge transfer within BFCN, not only has the crystal quality of perovskite films been improved due to the effective defects passivation, but the charge transfer has also been greatly accelerated due to the formation of additional charge transfer channels on the grain boundaries. As a result, the champion BFCN-based PSCs achieve the highest photoelectric conversion efficiency (PCE) of 23.71% with good stability.

Urbanization-driven forest soil greenhouse gas emissions: Insights from the role of soil bacteria in carbon and nitrogen cycling using a metagenomic approach.

Increasing population densities and urban sprawl have induced greenhouse gas (GHG) emissions from the soil, and the soil microbiota of urban forests play a critical role in the production and consumption of GHGs, supporting green development. However, the function and potential mechanism of soil bacteria in GHG emissions from forests during urbanization processes need to be better understood. Here, we measured the fluxes of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) in Cinnamomum camphora forest soils along an urbanization gradient. 16S amplicon and metagenomic sequencing approaches were employed to examine the structure and potential functions of the soil bacterial community involved in carbon (C) and nitrogen (N) cycling. In this study, the CH4 and CO2 emissions from urban forest soils (sites U and G) were significantly greater than those from suburban soils (sites S and M). The N2O emissions in the urban center (site U) were 24.0 % (G), 13.8 % (S), and 13.5 % (M) greater than those at the other three sites. These results were related to the increasing bacterial alpha diversity, interactions, and C and N cycling gene abundances (especially those involved in denitrification) in urban forest soils. Additionally, the soil pH and metal contents (K, Ca, Mg) affected key bacterial populations (such as Methylomirabilota, Acidobacteriota, and Proteobacteria) and indicators (napA, nosZ, nrfA, nifH) involved in reducing N2O emissions. The soil heavy metal contents (Fe, Cr, Pb) were the main contributors to CH4 emissions, possibly by affecting methanogens (Desulfobacterota) and methanotrophic bacteria (Proteobacteria, Actinobacteriota, and Patescibacteria). Our study provides new insights into the benefits of conservation-minded urban planning and close-to-nature urban forest management and construction, which are conducive to mitigating GHG emissions and supporting urban sustainable development by mediating the core bacterial population.

Traditional Chinese medicine Qingre Huoxue decoction enhances wound healing in through modulation of angiogenic and inflammatory pathways.

This study investigates the therapeutic potential of Qingre Huoxue Decoction (QHD), a traditional Chinese herbal formulation, in promoting wound healing in an imiquimod-induced murine model of psoriasis. The research was driven by the need for effective wound healing strategies in psoriatic conditions, where conventional treatments often fall short. Employing a combination of in vivo and in vitro methodologies, we assessed the effects of QHD on key factors associated with wound healing. Our results showed that QHD treatment significantly reduced the expression of angiogenic proteins HIF-1α, FLT-1, and VEGF, and mitigated inflammatory responses, as evidenced by the decreased levels of pro-inflammatory cytokines and increased expression of IL-10. Furthermore, QHD enhanced the expression of genes essential for wound repair. In vitro assays with HUVECs corroborated the anti-angiogenic effects of QHD. Conclusively, the study highlights QHD's efficacy in enhancing wound healing in psoriatic conditions by modulating angiogenic and inflammatory pathways, presenting a novel therapeutic avenue in psoriasis wound management.

Sedentary behavior, physical activity, sleep duration and obesity risk: Mendelian randomization study.

BACKGROUND: Observational studies have suggested associations between sedentary behaviors (SB), physical activity (PA), sleep duration (SD), and obesity, but the causal relationships remain unclear. METHODS: We used Mendelian randomization (MR) with genetic variation as instrumental variables (IVs) to assess the causality between SB/PA/SD and obesity. Genetic variants associated with SB/PA/SD were obtained from Genome-wide association study (GWAS), and obesity data came from FinnGen. The primary MR analysis used the instrumental variable weighted (IVW) method, with sensitivity tests including Cochran Q, MR-Egger intercepts, and MR-Radial. Expression Quantitative Trait Loci (eQTL) analysis was applied to identify significant genetic associations and biological pathways in obesity-related tissues. RESULTS: The MR analysis revealed causal relationships between four SB-related lifestyle patterns and obesity. Specifically, increased genetic liability to television watching (IVW MR Odds ratio [OR] = 1.55, [95% CI]:[1.27, 1.90], p = 1.67×10-5), computer use ([OR] = 1.52, [95% CI]:[1.08, 2.13], p = 1.61×10-2), leisure screen time (LST) ([OR] = 1.62, [95% CI] = [1.43, 1.84], p = 6.49×10-14, and driving (MR [OR] = 2.79, [95% CI]:[1.25, 6.21], p = 1.23×10-2) was found to increase the risk of obesity. Our findings indicate that no causal relationships were observed between SB at work, sedentary commuting, PA, SD, and obesity. The eQTL analysis revealed strong associations between specific genes (RPS26, TTC12, CCDC92, NICN1) and SNPs (rs10876864, rs2734849, rs4765541, rs7615206) in both subcutaneous and visceral adipose tissues, which are associated with these SBs. Enrichment analysis further revealed that these genes are involved in crucial biological pathways, including cortisol synthesis, thyroid hormone synthesis, and insulin secretion. CONCLUSIONS: Our findings support a causal relationship between four specific SBs (LST, television watching, computer use, driving) and obesity. These results provide valuable insights into potential interventions to address obesity effectively, supported by genetic associations in the eQTL and enrichment analysis. Further research and public health initiatives focusing on reducing specific SBs may be warranted.

Design of MXene-Based Multiporous Nanosheet Stacking Structures Integrating Multiple Synergistic SERS Enhancements for Ultrasensitive Detection of Chloramphenicol.

Motivated by the desire for more sensitivity and stable surface-enhanced Raman scattering (SERS) substrates to trace detect chloramphenicol due to its high toxicity and ubiquity, MXene has attracted increasing attention and is encountering the high-priority task of further observably improving detection sensitivity. Herein, a universal SERS optimization strategy that incorporates NH4VO3 to induce few-layer MXenes assembling into multiporous nanosheet stacking structures was innovatively proposed. The synthesized Nb2C-based multiporous nanosheet stacking structure can achieve a low limit of detection of 10-10 M and a high enhancement factor of 2.6 × 109 for MeB molecules, whose detection sensitivity is improved by 3 orders of magnitude relative to few-layer Nb2C MXenes. Such remarkably enhanced SERS sensitivity mainly originates from the multiple synergistic contributions of the developed physical adsorption, the chemical enhancement, and the conspicuously improved electromagnetic enhancement arising from the intersecting MXenes. Furthermore, the improved SERS sensitivity endows Nb2C-based multiporous structures with the capability to achieve ultrasensitive detection of chloramphenicol with a wide linear range from 100 µg/mL to 1 ng/mL. We believe it is of great significance in conspicuously developing the SERS sensitivity of other MXenes with surficial negative charges and has a great promising perspective for the trace detection of other antibiotics in microsystems.

Quantitative Proteomic Analysis Identifying and Evaluating TRAF6 and IL-8 as Potential Diagnostic Biomarkers in Neonatal Patients with Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a common gastrointestinal complication in premature infants, resulting in high morbidity and mortality, and its early detection is crucial for accurate treatment and outcome prediction. Extensive research has demonstrated a clear correlation between NEC and extremely low birth weight, degree of preterm, formula feeding, infection, hypoxic/ischemic damage, and intestinal dysbiosis. The development of noninvasive biomarkers of NEC from stool, urine, and serum has attracted a great deal of interest because to these clinical connections and the quest for a deeper knowledge of disease pathophysiology. Therefore, this study aims to identify protein expression patterns in NEC and discover innovative diagnostic biomarkers. In this study, we recruited five patients diagnosed with NEC and paired necrotic segments of intestinal tissue with adjacent normal segments of intestine to form experimental and control groups. Quantitative proteomics tandem mass tagging (TMT) labeling technique was used to detect and quantify the proteins, and the expression levels of the candidate biomarkers in the intestinal tissues were further determined by quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, Immunofluorescence methods and enzyme-linked immunosorbent assay (ELISA). A total of 6880 proteins were identified and quantified in patients with NEC. A significant disparity in protein expression was observed between necrotic and normal segments of intestinal tissue in NEC patients. A total of 55 proteins were found to be upregulated, and 40 proteins were found to be downregulated in NEC patients when using a p-value of < 0.05, and an absolute fold change of > 1.2 for analysis. GO function enrichment analysis showed the positive regulation of significant biological processes such as mitochondrial organization, vasoconstriction, rRNA catabolism, fluid shear stress response, and glycerol ether biosynthesis processes. Enrichment analysis also revealed essential functions such as ligand-gated ion channel activity, potassium channel activity, ligand-gated cation channel activity, ligand-gated ion channel activity, and ligand-gated channel activity, including molecular functions such as ligand-gated ion channel activity and mitotic events in this comparative group. Significant changes were found in endomembrane protein complex, membrane fraction, mitochondrial membrane fraction, membrane components, membrane intrinsic components, and other localized proteins. Additional validation of intestinal tissue and serum revealed a substantial increase in TRAF6 (tumor necrosis factor receptor-associated factor 6) and IL-8(Interleukin-8, CXCL8). The quantitative proteomic TMT method can effectively detect proteins with differential expression in the intestinal tissues of NEC patients. Proteins TRAF6 and CXCL8/IL-8 are significantly upregulated in the intestinal tissues and serum samples of patients and may serve as valuable predictor factors for NEC's early diagnosis.

Contribution of platelets to disruption of the blood-brain barrier during arterial baroreflex dysfunction.

BACKGROUND: Arterial baroreflex dysfunction, like many other central nervous system disorders, involves disruption of the blood-brain barrier, but what causes such disruption in ABR dysfunction is unclear. Here we explored the potential role of platelets in this disruption. METHODS: ABR dysfunction was induced in rats using sinoaortic denervation, and the effects on integrity of the blood-brain barrier were explored based on leakage of Evans blue or FITC-dextran, while the effects on expression of CD40L in platelets and of key proteins in microvascular endothelial cells were explored using immunohistochemistry, western blotting and enzyme-linked immunosorbent assay. Similar experiments were carried out in rat brain microvascular endothelial cell line, which we exposed to platelets taken from rats with ABR dysfunction. RESULTS: Sinoaortic denervation permeabilized the blood-brain barrier and downregulated zonula occludens-1 and occludin in rat brain, while upregulating expression of CD40L on the surface of platelets and stimulating platelet aggregation. Similar effects of permeabilization and downregulation were observed in healthy rats that received platelets from animals with ABR dysfunction, and in rat brain microvascular endothelial cells, but only in the presence of lipopolysaccharide. These effects were associated with activation of NF-κB signaling and upregulation of matrix metalloprotease-9. These effects of platelets from animals with ABR dysfunction were partially blocked by neutralizing antibody against CD40L or the platelet inhibitor clopidogrel. CONCLUSION: During ABR dysfunction, platelets may disrupt the blood-brain barrier when CD40L on their surface activates NF-kB signaling within cerebral microvascular endothelial cells, leading to upregulation of matrix metalloprotease-9. Our findings imply that targeting CD40L may be effective against cerebral diseases involving ABR dysfunction.

Senescence-related genes analysis in breast cancer reveals the immune microenvironment and implications for immunotherapy.

Despite the advent of precision therapy for breast cancer (BRCA) treatment, some individuals are still unable to benefit from it and have poor survival prospects as a result of the disease's high heterogeneity. Cell senescence plays a crucial role in the tumorigenesis, progression, and immune regulation of cancer and has a major impact on the tumor microenvironment. To find new treatment strategies, we aimed to investigate the potential significance of cell senescence in BRCA prognosis and immunotherapy. We created a 9-gene senescence-related signature. We evaluated the predictive power and the role of signatures in the immune microenvironment and infiltration. In vitro tests were used to validate the expression and function of the distinctive critical gene ACTC1. Our risk signature allows BRCA patients to receive a Predictive Risk Signature (PRS), which may be used to further categorize a patient's response to immunotherapy. Compared to conventional clinicopathological characteristics, PRS showed strong predictive efficacy and precise survival prediction. Moreover, PRS subgroups were examined for altered pathways, mutational patterns, and possibly useful medicines. Our research offers suggestions for incorporating senescence-based molecular classification into risk assessment and ICI therapy decision-making.

Metabolomics reveal root differential metabolites of different root-type alfalfa under drought stress.

Introduction: Alfalfa (Medicago sativa L.) is the favored premium feed ingredient in animal husbandry production which is in serious jeopardy due to soil moisture shortages. It is largely unknown how different root types of alfalfa respond to arid-induced stress in terms of metabolites and phytohormones. Methods: Therefore, rhizomatous rooted M. sativa 'Qingshui' (or QS), tap-rooted M. sativa 'Longdong' (or LD), and creeping rooted M. varia 'Gannong No. 4' (or GN) were investigated to identify metabolites and phytohormones responses to drought conditions. Results: We found 164, 270, and 68 significantly upregulated differential metabolites were categorized into 35, 38, and 34 metabolic pathways in QS, LD, and GN within aridity stress, respectively. Amino acids, organic acids, sugars, and alkaloids were the four categories of primary differential metabolites detected, which include 6-gingerol, salicylic acid (SA), indole-3-acetic acid (IAA), gibberellin A4 (GA4), abscisic acid (ABA), trans-cinnamic acid, sucrose, L-phenylalanine, L-tyrosine, succinic acid, and nicotinic acid and so on, turns out these metabolites are essential for the resistance of three root-type alfalfa to aridity coercing. Discussion: The plant hormone signal transduction (PST) pathway was dramatically enriched after drought stress. IAA and ABA were significantly accumulated in the metabolites, indicating that they play vital roles in the response of three root types of alfalfa to water stress, and QS and LD exhibit stronger tolerance than GN under drought stress.

I2/CF3CO2Ag-mediated iodolactonization of various allenoic acids to access versatile 6- to 9-membered ring vinylic iodolactones.

Medium-sized lactones are important structural units, but their synthesis remains a great challenge. Herein, we report I2/CF3CO2Ag-mediated iodolactonization of allenoic acids to synthesize various 6- to 9-membered ring vinylic iodolactones in 16-89% yield. This protocol not only develops a new cyclization strategy of allenoic acids, but also provides highly functionalized medium-sized lactones containing alkene and halogen groups.