Nonlinear association between atherogenic index of plasma and type 2 diabetes mellitus in overweight and obesity patients: evidence from Chinese medical examination data.

BACKGROUND: The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM). However, the association between the AIP and T2DM in overweight and obese populations has been infrequently studied. Therefore, this study aimed to explore this association in overweight and obese individuals with T2DM. METHODS: This cross-sectional analysis utilized data from 40,633 participants with a body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were categorized into groups of overweight and obese individuals with and without diabetes according to the T2DM criteria. The AIP, our dependent variable, was calculated using the formula log10 [(TG mol/L)/HDL-C (mol/L)]. We investigated the association between the AIP and T2DM in overweight and obese individuals using multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and threshold effect analysis. Additionally, mediation analysis evaluated the role of inflammatory cells in AIP-related T2DM. RESULTS: Overweight and obese patients with T2DM exhibited higher AIP levels than those without diabetes. After adjusting for confounders, our results indicated a significant association between the AIP and the risk of T2DM in overweight and obese individuals (odds ratio (OR) = 5.17, 95% confidence interval (CI) 4.69-5.69). Notably, participants with a high baseline AIP (Q4 group) had a significantly greater risk of T2DM than those in the Q1 group, with an OR of 3.18 (95% CI 2.94-3.45). Subgroup analysis revealed that the association between the AIP and T2DM decreased with increasing age (interaction P < 0.001). In overweight and obese populations, the association between AIP and T2DM risk displayed a J-shaped nonlinear pattern, with AIP > - 0.07 indicating a significant increase in T2DM risk. Various inflammatory cells, including neutrophils, leukocytes, and monocytes, mediated 4.66%, 4.16%, and 1.93% of the associations, respectively. CONCLUSION: In overweight and obese individuals, the AIP was independently associated with T2DM, exhibiting a nonlinear association. Additionally, the association between the AIP and T2DM decreased with advancing age. Multiple types of inflammatory cells mediate this association.

Erythroid-intrinsic activation of TLR8 impairs erythropoiesis in inherited anemia.

Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19+/- HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Identifying popular, rejected and neglected children in Chinese preschool: An exploratory study on the educational application of spatial positioning data.

Amidst the rapid advancement of Internet of Things (IoT) technology and the burgeoning field of Multimodal Learning Analytics (MMLA), this study employs spatial positioning technology as a case study to investigate the potential of multimodal data in assessing children's social development. This study combines the spatial positioning data of preschool children collected during free play sessions in natural educational settings and the spatial metrics constructed based on observational studies to establish and validate a sociometric status Decision Tree classification model. The findings suggest that the model can overall accurately identify children with three distinct sociometric statuses, albeit with some variability in efficacy across different sociometric groups and age groups. Notably, the model demonstrates a high hitting rate in identifying the potentially neglected children, providing valuable support for educators in understanding and fostering children's developmental needs. This study also highlights the advantages of emerging technology and multimodal data application in child development assessment.

Targeting lipid peroxidation-associated ferroptosis suppresses lung carcinoma progression by regulating cell cycle arrest.

Lung carcinoma is a frequently encountered cancerous growth that affects the respiratory tract and has a high occurrence rate globally. In light of the ongoing worldwide health emergency, the significance of efficient therapeutic agents and strategies is of utmost importance. A meticulous control of the cell cycle is crucial for comprehending the pathophysiology and molecular causes of lung cancer, as well as for the formulation of efficacious therapeutic medicines. The mechanism by which cells synchronize cell cycle with cell survival and death is still not fully understood. In this study, we demonstrate that the halting of the cell cycle has a strong inhibitory impact on ferroptosis, a specific type of controlled cell death triggered by excessive lipid peroxidation at the membranes of cells. Ferroptosis is halted through the mechanism of cell cycle arrest, which involves the deposition of intracellular lipids mediated by diacylglycerol acyltransferase (DGAT). Excessive amounts of polyunsaturated fatty acids (PUFAs) are stored as triacylglycerols (TAGs) within inactive cells. As a result, inhibiting DGAT causes a rearrangement of PUFAs from TAGs to phospholipids and makes arrested cells more susceptible to ferroptosis. We demonstrate that certain lung cancer cells that are resistant to antimitotic drugs and have a slow-cycling behavior exhibit an increase in lipid droplets. Furthermore, we find that the growth of tumors resistant to 5-fluorouracil, lorlatinib, and docetaxel can be effectively suppressed by a combination treatment involving the use of ferroptosis inducers and DGAT inhibitors, which induces ferroptosis. Collectively, these findings demonstrate the involvement of cell cycle arrest in conferring resistance to ferroptosis and propose a potential therapeutic approach for addressing the challenge of slow-cycling malignancies that exhibit resistance to ferroptosis.

Association between liver fat level and risk of hypertension: evidence from a Chinese health examination dataset.

BACKGROUND: Hypertension development is predominantly influenced by inflammation, excessive fat deposition, and metabolic irregularities. Among these factors, liver fat accumulation is a critical metabolic disorder. However, the quantification of liver fat levels and its associated risk for hypertension incidence remain ambiguous. This project is designed to explore the association between liver fat levels and the risk of hypertension in a healthy population. METHODS: This cross-sectional study involved 4955 participants from the Health Management Center at Henan Provincial People's Hospital who were surveyed between February 2020 and February 2023. Participants were categorized into four groups based on liver fat quartiles. Subgroup analyses, restricted cubic spline regression models, and logistic regression were utilized to assess the association between liver fat levels and hypertension risk. The relationships between liver fat levels and inflammatory markers were examined using multiple linear regression models. Additionally, a mediation analysis was conducted to explore the role of inflammatory factors in the relationship between liver fat and hypertension risk. RESULTS: Participants with hypertension exhibited greater liver fat levels than did those without hypertension. An increased risk of hypertension was associated with elevated liver fat levels, even after adjusting for other covariates [Q4 vs. Q1 in model II: odds ratio (OR = 1.28), 95% confidence interval (CI) = 1.04-1.59, P = 0.022; P for trend = 0.039]. A nonlinear relationship was observed between liver fat level and hypertension risk, with a notable increase in hypertension risk occurring at liver fat levels greater than 8.65%. Additionally, a positive correlation was found between inflammatory markers and liver fat levels. A mediation effect of 4.76% was noted, linking hypertension risk and liver fat levels through neutrophils. CONCLUSION: Liver fat levels exceeding 8.65% significantly elevated the risk of hypertension. Inflammatory factors serve as crucial mediators of the relationship between liver fat and hypertension.

Esophageal squamous cell carcinoma metastases to kidney and renal hilar lymph nodes through epithelial-mesenchymal transition: a case report and literature review.

BACKGROUND: Esophageal cancer (EC) metastasized to the kidney is extremely rare clinically. Here, we present a case of metachronous renal metastasis of esophageal squamous cell carcinoma (ESCC) through epithelial-mesenchymal transition (EMT). CASE PRESENTATION: A 60-year-old patient, male, complained of left waist pain for 5 days, 11 months after radical esophagectomy. Laboratory tests revealed haematuria. Both CT and PET-CT scan showed retroperitoneal lymph nodes and left renal masses. Subsequently the patient received a left nephrectomy and lymph nodes resection, and squamous cell carcinoma of kidney and renal hilar lymph nodes was diagnosed, combined with morphology, medical history and immunophenotype, it was presumed to be metastasis of ESCC through the EMT pathway. CONCLUSIONS: The renal metastasis of squamous cell carcinoma should be considered in patients with history of EC, although this is very rare. Histopathological examination combined with immunochemical detection is helpful in differential diagnosis.

A meta-analysis of the effects of ketamine on suicidal ideation in depression patients.

The treatment of suicidal ideation in patients with depression has been a major problem faced by psychiatric and emergency departments, and reasonable drug selection is particularly important. Ketamine has been shown to reduce suicidal ideation rapidly, but the strength of the effect is unclear and there is little evidence-based medical evidence to support this. We systematically searched all articles published on PubMed, Cochrane Library, Web of Science, CNKI and EMBASE. Stata 15 and R 4.1.3 were used for meta-analysis, and odds ratios were calculated in fixed effects or random effects models based on the heterogeneity test results. Our search resulted in 505 articles; we analyzed 14 studies, which included 1,380 participants. The 14 studies included 10 randomized controlled trial (RCT) studies and 4 single-arm studies. Our study suggests that, ketamine has a significant therapeutic effect on suicidal ideation throughout the treatment cycle. We performed network meta-analyses(NMA) and pairwise meta-analyses to compare the efficacy of ketamine in the reduction of suicidal ideation. There was a significant reduction in suicidal ideation within the first day after treatment (NMA ketamine day1 RR = 10.02, 95%CI = 4.24 to 23.68). In repeated treatment, the degree of recovery of suicidal ideation after the last dose was significantly greater than that after the first dose (RR = 0.56, 95%CI = 0.51 to 0.62). Recovery of suicidal ideation was also significantly better in the treatment end point than in the placebo group at the same time point (NMA ketamine day26 RR = 4.29, 95%CI = 1.41 to 13.08). This is the first network meta-analysis to demonstrate the role of ketamine in the alleviation of suicidal ideation. Our network meta-analysis also compared the effects of different drugs at different time points, which was not done in previous studies. This is of great reference significance for future drug research andrational drug use.

One-step of ionic liquid-assisted stabilization and dispersion: Exfoliated graphene and its applications in stimuli-responsive conductive hydrogels based on chitosan.

Conductive hydrogels, as novel flexible biosensors, have demonstrated significant potential in areas such as soft robotics, electronic devices, and wearable technology. Graphene is a promising conductive material, but its dispersibility in aqueous solutions exists difficulties. Here, we discover that untreated graphene, after exfoliation by different ionic liquids, can disperse well in aqueous solutions. We investigate the impact of four ionic liquids with varying alkyl chain lengths ([Bmim]Cl, [Omim]Cl, [Dmim]Cl, [Hmim]Cl) on the dispersibility of grapheme, and a dual physically cross-linked network hydrogel structure is designed using acrylamide (AM), acrylic acid (AA), methyl methacrylate octadecyl ester (SMA), ionic liquid@graphene (ILs@GN), and chitosan (CS). Notably, SMA, CS, AA and AM act as dynamic cross-linking points through hydrophobic interactions and hydrogen bonding, playing a crucial role in energy dissipation. The resulting hydrogel exhibits outstanding stretchability (2250 %), remarkable toughness (1.53 MJ/m3) in tensile deformation performance, high compressive strength (1.13 MPa), rapid electrical responsiveness (response time âˆ¼ 50 ms), high electrical conductivity (12.11 mS/cm), and excellent strain sensing capability (GF = 12.31, strain = 1000 %). These advantages make our composite hydrogel demonstrate high stability in extensive deformations, offering repeatability in pressure and strain and making it a promising candidate for multifunctional sensors and flexible electrodes.

Construction of mechanically robust and recyclable catalytic hydrogel based on hydroxypropyl cellulose-supported by montmorillonite/ionic liquid with different anions for pollutants(4-NP, MB, CR, Rhb) degradation.

Dye wastewater poses a serious threat to the environment and human health, necessitating sustainable degradation methods. In this study, Na-based Montmorillonite (MMT) was exfoliated using different ionic liquids ([C16MIM][Cl], [C16MIM][BF4], [C16MIM][PF6]), and silver nanoparticles (Ag NPs) were green-synthesized using hydroxypropyl cellulose (HPC). The HPC significantly enhanced the dispersion of MMT in the hydrogel. By introducing lauryl methacrylate (LMA), a hydrophobic associative network was constructed in PAM/LMA/HPC/MMT@ILs&Ag NPs hydrogel. This hydrogel demonstrated outstanding mechanical properties, with a stress of 833.21 kPa, strain of 3300 %, and toughness of 14.36 MJ/m3. It also exhibited excellent catalytic activity, with a rate constant of 0.83 min-1 for 4-nitrophenol degradation at 28 °C. The effects of temperature and catalyst concentration on the catalytic reaction were systematically investigated. This study presents a simple green synthesis approach for Ag NPs using HPC, achieving superior mechanical performance and stable MMT dispersion in aqueous solutions.

Establishment and validation of multiclassification prediction models for pulmonary nodules based on machine learning.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. This study aimed to establish novel multiclassification prediction models based on machine learning (ML) to predict the probability of malignancy in pulmonary nodules (PNs) and to compare with three published models. METHODS: Nine hundred fourteen patients with PNs were collected from four medical institutions (A, B, C and D), which were organized into tables containing clinical features, radiologic features and laboratory test features. Patients were divided into benign lesion (BL), precursor lesion (PL) and malignant lesion (ML) groups according to pathological diagnosis. Approximately 80% of patients in A (total/male: 632/269, age: 57.73 ± 11.06) were randomly selected as a training set; the remaining 20% were used as an internal test set; and the patients in B (total/male: 94/53, age: 60.04 ± 11.22), C (total/male: 94/47, age: 59.30 ± 9.86) and D (total/male: 94/61, age: 62.0 ± 11.09) were used as an external validation set. Logical regression (LR), decision tree (DT), random forest (RF) and support vector machine (SVM) were used to establish prediction models. Finally, the Mayo model, Peking University People's Hospital (PKUPH) model and Brock model were externally validated in our patients. RESULTS: The AUC values of RF model for MLs, PLs and BLs were 0.80 (95% CI: 0.73-0.88), 0.90 (95% CI: 0.82-0.99) and 0.75 (95% CI: 0.67-0.88), respectively. The weighted average AUC value of the RF model for the external validation set was 0.71 (95% CI: 0.67-0.73), and its AUC values for MLs, PLs and BLs were 0.71 (95% CI: 0.68-0.79), 0.98 (95% CI: 0.88-1.07) and 0.68 (95% CI: 0.61-0.74), respectively. The AUC values of the Mayo model, PKUPH model and Brock model were 0.68 (95% CI: 0.62-0.74), 0.64 (95% CI: 0.58-0.70) and 0.57 (95% CI: 0.49-0.65), respectively. CONCLUSIONS: The RF model performed best, and its predictive performance was better than that of the three published models, which may provide a new noninvasive method for the risk assessment of PNs.

Synthesis of 2,3-Dialkyl-5-hydroxybenzofurans via a One-pot, Three-step Reaction Sequence of 2-Monosubstituted 1,3-Diketones and 1,4-Benzoquinones.

An economical one-pot, three-step reaction sequence of readily available 2-monosubstituted 1,3-diketones and 1,4-benzoquinones has been explored for the facile access of 2,3-dialkyl-5-hydroxybenzofurans. By using cheap K2CO3 and conc. HCl as the reaction promoters, the reaction occurs smoothly via sequential Michael addition, aromatization, retro-Claisen, deacylation, hemiketalization, and dehydration processes under mild conditions in a practical manner. Additionally, an interesting phenomenon was observed during the derivatization studies, where the dihydroquinoline was converted into tetrahydroquinoline and quinoline products, respectively, via a disproportionation process.

Course and predictors of supportive care needs among colorectal cancer survivors with ostomies: a longitudinal study.

PURPOSE: Although there is a growing emphasis on supportive care for cancer patients, those with colorectal cancer (CRC) who have ostomies require special attention in terms of their physical, psychological, spiritual, and social needs. However, there has been a lack of significant progress in meeting the supportive care needs of CRC survivors with ostomies. To bridge this gap, we conducted a prospective longitudinal study to track the trends in supportive care needs among CRC survivors with ostomies and identify any predictors over 6-month period. METHODS: A prospective longitudinal study was conducted at the wound and stoma clinic of Dalian University Affiliated Xinhua Hospital, focusing on CRC survivors with ostomies. A total of 143 participants completed self-report questionnaires on the 34-item Short-Form Supportive Care Needs Survey (SCNS-SF34-C (Mandarin)) and stoma complications at the first, third, and sixth month after surgery. ANOVA with repeated measure was utilized to assess the course of supportive care needs, with Generalized Estimating Equation (GEE) applied to identify predictors of SCNS. RESULTS: The supportive care needs and five dimensions scores were statistically significant at three time points (P < 0.05). The ratings of patients at the first, third, and sixth month after surgery revealed a decreasing trend in the scores for patient care and support, psychological needs, physical and daily living needs, and health system and information needs. However, the score for sexual needs showed an increased tendency. Higher levels supportive care needs were generally connected with a short duration after ostomy, high income level, resident medical insurance, spouse caregiver, other chronic disease, and stoma complications. CONCLUSIONS: Survivors' supportive care needs showed a dynamic trend over 6 months after surgery. Through three rounds, the primary needs were health system and information needs. It is recommended to integrate interdisciplinary health professionals and establish a comprehensive support and care system to effectively meet the diverse needs at different stages. Priority should be given to individuals with ostomies during the first and third month after surgery, particularly those with higher income levels, employee medical insurance, spouse caregivers, other chronic diseases, and stoma complications.

Targeting BIRC5 as a therapeutic approach to overcome ASXL1-associated decitabine resistance.

Hypomethylating agents (HMAs) are widely employed in the treatment of myeloid malignancies. However, unresponsive or resistant to HMAs occurs in approximately 50 % of patients. ASXL1, one of the most commonly mutated genes across the full spectrum of myeloid malignancies, has been reported to predict a lower overall response rate to HMAs, suggesting an essential need to develop effective therapeutic strategies for the patients with HMA failure. Here, we investigated the impact of ASXL1 on cellular responsiveness to decitabine treatment. ASXL1 deficiency increased resistance to decitabine treatment in AML cell lines and mouse bone marrow cells. Transcriptome sequencing revealed significant alterations in genes regulating cell cycle, apoptosis, and histone modification in ASXL1 deficient cells that resistant to decitabine. BIRC5 was identified as a potential target for overcoming decitabine resistance in ASXL1 deficient cells. Furthermore, our experimental evidence demonstrated that the small-molecule inhibitor of BIRC5 (YM-155) synergistically sensitized ASXL1 deficient cells to decitabine treatment. This study sheds light on the molecular mechanisms underlying the ASXL1-associated HMA resistance and proposes a promising therapeutic strategy for improving treatment outcomes in affected individuals.

High Dietary Folic Acid Supplementation Reduced the Composition of Fatty Acids and Amino Acids in Fortified Eggs.

AIMS: The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs. METHODS: A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were fed a basal diet supplemented with 0, 5, 10, or 15 mg/kg FA in a premix for a duration of 6 weeks. RESULTS: Supplementation of FA could significantly (p < 0.05) enhance the FA content in egg yolks, particularly when 10 mg/kg was used, as it had the most effective enrichment effect. Compared to the control group, the Glu content in the 10 and 15 mg/kg FA groups showed a significant (p < 0.05) decrease. Additionally, the contents of Asp, Ile, Tyr, Phe, Cys, and Met in the 15 mg/kg FA group were significantly (p < 0.05) lower compared to the other groups. Adding FA did not have significant effects on the levels of vitamin A and vitamin E in egg yolk, but the vitamin D content in the 5 and 10 mg/kg FA groups showed a significant (p < 0.05) increase. Furthermore, the addition of FA did not have a significant effect on the levels of Cu, Fe, Mn, Se, and Zn in egg yolk. The dietary FA did not have a significant effect on the total saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) content in egg yolk. However, the total monounsaturated fatty acid (MUFA) content in the 5 and 10 mg/kg groups significantly (p < 0.05) increased. These changes in nutritional content might be attributed to the increased very low-density lipoprotein (VLDL) protein content. The significant decrease in solute carrier family 1 Member 1 (SLC1A1), solute carrier family 1 Member 2 (SLC1A2), and solute carrier family 1 Member 3 (SLC1A3) gene expression compared to the control group appeared to be the reason for the decrease in amino acid content in egg yolk within the dietary FA group. CONCLUSION: The findings suggest that the appropriate addition of FA can enhance the levels of MUFA and vitamin D in egg yolks, thereby improving their nutritional value. Excessive intake of FA can decrease the effectiveness of enriching FA in egg yolk and impact the enrichment of certain amino acids. The yolk of eggs produced by adding 10 mg/kg of FA to the feed contains the optimal amount of nutrients. This study informs consumers purchasing FA-fortified eggs.

The synergism of Lactobacillaceae, inulin, polyglucose, and aerobic exercise ameliorates hyperglycemia by modulating the gut microbiota community and the metabolic profiles in db/db mice.

This study aimed to assess the impact of Lactobacillaceae (L or H represents a low or high dose), inulin (I), and polydextrose (P) combined with aerobic exercise (A) on the composition of the gut microbiota and metabolic profiles in db/db mice. After a 12-week intervention, LIP, LIPA, and HIPA groups exhibited significant improvements in hyperglycemia, glucose tolerance, insulin resistance, inflammatory response, and short-chain fatty acid (SCFA) and blood lipid levels compared to type 2 diabetes mice (MC). After treatment, the gut microbiota composition shifted favorably in the treatment groups which significantly increased the abundance of beneficial bacteria, such as Bacteroides, Blautia, Akkermansia, and Faecalibaculum, and significantly decreased the abundance of Proteus. Metabolomics analysis showed that compared to the MC group, the contents of 5-hydroxyindoleacetic acid, 3-hydroxysebacic acid, adenosine monophosphate (AMP), xanthine and hypoxanthine were significantly decreased, while 3-ketosphinganine, sphinganine, and sphingosine were significantly increased in the LIP and LIPA groups, respectively. Additionally, LIP and LIPA not only improved sphingolipid metabolism and purine metabolism pathways but also activated AMP-activated protein kinase to promote ß-oxidation by increasing the levels of SCFAs. Faecalibaculum, Blautia, Bacteroides, and Akkermansia exhibited positive correlations with sphingosine, 3-ketosphinganine, and sphinganine, and exhibited negative correlations with hypoxanthine, xanthine and AMP. Faecalibaculum, Blautia, Bacteroides, and Akkermansia may have the potential to improve sphingolipid metabolism and purine metabolism pathways. These findings suggest that the synergism of Lactobacillaceae, inulin, polydextrose, and aerobic exercise provides a promising strategy for the prevention and management of type 2 diabetes.

The Lifetime of Hydroxyl Radical in Realistic Fuel Cell Catalyst Layer.

The lifetime of hydroxyl radicals (⋅OH) in the fuel cell catalyst layer remains uncertain, which hampers the comprehension of radical-induced degradation mechanisms and the development of longevity strategies for proton-exchange membrane fuel cells (PEMFCs). In this study, we have precisely determined that the lifetime of ⋅OH radicals can extend up to several seconds in realistic fuel cell catalyst layers. This finding reveals that ⋅OH radicals are capable of carrying out long-range attacks spanning at least a few centimeters during PEMFCs operation. Such insights hold great potential for enhancing our understanding of radical-mediated fuel cell degradation processes and promoting the development of durable fuel cell devices.

The expression of ProBDNF and its high affinity receptor P75NTR in the neurons of emotion-related brain regions of post-stroke depression rats.

OBJECTIVE: To investigate the expression of the precursor of brain-derived neurotrophic factor (proBDNF) and its high-affinity receptor p75NTR in neurons of emotion-related brain areas (prefrontal cortex, hippocampus, and amygdala) in rats with post-stroke depression (PSD), and to explore the expression levels of proBDNF and p75NTR in neurons of emotion-related brain areas by injecting tissue plasminogen activator (t-PA) into the lateral ventricle of PSD rats, this significantly improved the stress-induced depression-like behavior,thus further validating the above results. METHODS: Rats were randomly divided into four groups: a normal control group (n = 8), a depression group (n = 8), a stroke group (n = 8), and a PSD group (n = 8). The rat model of stroke was established by thread embolism, and the PSD animal model was induced by chronic unpredictable mild stress (CUMS) and solitary feeding. Behavioral tests were conducted, including weight measurement, open field tests, and sucrose preference tests. Immunofluorescence double labeling was used to detect the expression of proBDNF and p75NTR in neurons of emotion-related brain regions in the PSD rat model. Four weeks after CUMS treatment, the PSD group was selected. Rats were infused with t-PA (3 µg dissolved in 6 µL saline, Boehringer Ingelheim), proBDNF (3 µg dissolved in 6 µL saline, Abcam), or equal-volume NS once per day for 7 consecutive days using the syringe pump connecting to injection needles. After 7 days of continuous administration, animal behavior was assessed through scoring, and the expression of proBDNF and p75NTR in the emotion-related brain regions of the PSD rat model was detected using immunofluorescence double labeling. RESULTS: Compared with the normal control group and the stroke group, the body weight, sucrose water consumption, and vertical movement distance in the PSD group were significantly lower (P < 0.05). In contrast, when compared with the proBDNF injection group and saline injection group, the weight, sucrose water consumption, field horizontal movement, and vertical movement distance of the t-PA injection group significantly increased after PSD lateral ventricle intubation.Double immunofluorescence revealed a higher neuronal expression of proBDNF as well as p75NTR in the prefrontal cortex and hippocampus of PSD rats compared to control animals (P < 0.05). In the amygdala, the expression levels of proBDNF and P75NTR were significantly reduced in the PSD group compared to the control group (P < 0.05). The results of the expression levels of proBDNF and P75NTR in the emotion-related brain regions of PSD rats injected with t-PA showed that proBDNF and P75NTR was significantly reduced in the prefrontal cortex, hippocampus, and amygdala of PSD rats compared to those of the NS and proBDNF groups (P < 0.05). CONCLUSIONS: The increased expression of the brain-derived neurotrophic factor precursor proBDNF and its receptor p75NTR in neurons of emotion-related brain regions may play an important role in the pathogenesis of PSD.t-PA reduced the expression of proBDNF and its receptor p75NTR in neurons emotion-related brain regions and significantly improved the stress-induced depression-like behavior. Therefore, it is reasonable to assume that exogenous injection of t-PA may alleviate the depressive symptoms of PSD patients.Reducing the expression of proBDNF by injecting t-PA may provide a novel therapeutic approach for the treatment of stress-related mood disorders.

Hydrogen Spillover Accelerates Electrocatalytic Semi-hydrogenation of Acetylene in Membrane Electrode Assembly Reactor.

Electrocatalytic acetylene semi-hydrogenation (EASH) offers a promising and environmentally friendly pathway for the production of C2H4, a widely used petrochemical feedstock. While the economic feasibility of this route has been demonstrated in three-electrode systems, its viability in practical device remains unverified. In this study, we designed a highly efficient electrocatalyst based on a PdCu alloy system utilizing the hydrogen spillover mechanism. The catalyst achieved an operational current density of 600 mA cm-2 in a zero-gap membrane electrode assembly (MEA) reactor, with the C2H4 selectivity exceeding 85%. This data confirms the economic feasibility of EASH in real-world applications. Furthermore, through in situ Raman spectroscopy and theoretical calculations, we elucidated the catalytic mechanism involving interfacial hydrogen spillover. Our findings underscore the economic viability and potential of EASH as a greener and scalable approach for C2H4 production, thus advancing the field of electrocatalysis in sustainable chemical synthesis.

Glia-derived adenosine in the ventral hippocampus drives pain-related anxiodepression in a mouse model resembling trigeminal neuralgia.

Glial activation and dysregulation of adenosine triphosphate (ATP)/adenosine are involved in the neuropathology of several neuropsychiatric illnesses. The ventral hippocampus (vHPC) has attracted considerable attention in relation to its role in emotional regulation. However, it is not yet clear how vHPC glia and their derived adenosine regulate the anxiodepressive-like consequences of chronic pain. Here, we report that chronic cheek pain elevates vHPC extracellular ATP/adenosine in a mouse model resembling trigeminal neuralgia (rTN), which mediates pain-related anxiodepression, through a mechanism that involves synergistic effects of astrocytes and microglia. We found that rTN resulted in robust activation of astrocytes and microglia in the CA1 area of the vHPC (vCA1). Genetic or pharmacological inhibition of astrocytes and connexin 43, a hemichannel mainly distributed in astrocytes, completely attenuated rTN-induced extracellular ATP/adenosine elevation and anxiodepressive-like behaviors. Moreover, inhibiting microglia and CD39, an enzyme primarily expressed in microglia that degrades ATP into adenosine, significantly suppressed the increase in extracellular adenosine and anxiodepressive-like behaviors. Blockade of the adenosine A2A receptor (A2AR) alleviated rTN-induced anxiodepressive-like behaviors. Furthermore, interleukin (IL)-17A, a pro-inflammatory cytokine probably released by activated microglia, markedly increased intracellular calcium in vCA1 astrocytes and triggered ATP/adenosine release. The astrocytic metabolic inhibitor fluorocitrate and the CD39 inhibitor ARL 67156, attenuated IL-17A-induced increases in extracellular ATP and adenosine, respectively. In addition, astrocytes, microglia, CD39, and A2AR inhibitors all reversed rTN-induced hyperexcitability of pyramidal neurons in the vCA1. Taken together, these findings suggest that activation of astrocytes and microglia in the vCA1 increases extracellular adenosine, which leads to pain-related anxiodepression via A2AR activation. Approaches targeting astrocytes, microglia, and adenosine signaling may serve as novel therapies for pain-related anxiety and depression.