Turn-on fluorescent aptasensing for the determination of serotonin via target-induced knot displacement at corona.

A turn-on fluorescence aptasensing approach for the highly sensitive and selective determination of 5-HT was proposed via target-induced knot displacement. 5-HT can be determined in a range from 0.5 nM to 100 nM with a limit of detection as low as 0.1 nM and a low dissociation constant of 2.3 nM.

Novel glycosidase from Paenibacillus lactis 154 hydrolyzing the 28-O-ß-D-glucopyranosyl ester bond of oleanane-type saponins.

Oleanane-type ginsenosides are a class of compounds with remarkable pharmacological activities. However, the lack of effective preparation methods for specific rare ginsenosides has hindered the exploration of their pharmacological properties. In this study, a novel glycoside hydrolase PlGH3 was cloned from Paenibacillus lactis 154 and heterologous expressed in Escherichia coli. Sequence analysis revealed that PlGH3 consists of 749 amino acids with a molecular weight of 89.5 kDa, exhibiting the characteristic features of the glycoside hydrolase 3 family. The enzymatic characterization results of PlGH3 showed that the optimal reaction pH and temperature was 8 and 50 °C by using p-nitrophenyl-ß-D-glucopyranoside as a substrate, respectively. The Km and kcat values towards ginsenoside Ro were 79.59 ± 3.42 µM and 18.52 s-1, respectively. PlGH3 exhibits a highly specific activity on hydrolyzing the 28-O-ß-D-glucopyranosyl ester bond of oleanane-type saponins. The mechanism of hydrolysis specificity was then presumably elucidated through molecular docking. Eventually, four kinds of rare oleanane-type ginsenosides (calenduloside E, pseudoginsenoside RP1, zingibroside R1, and tarasaponin VI) were successfully prepared by biotransforming total saponins extracted from Panax japonicus. This study contributes to understanding the mechanism of enzymatic hydrolysis of the GH3 family and provides a practical route for the preparation of rare oleanane-type ginsenosides through biotransformation. KEY POINTS: • The glucose at C-28 in oleanane-type saponins can be directionally hydrolyzed. • Mechanisms to interpret PlGH3 substrate specificity by molecular docking. • Case of preparation of low-sugar alternative saponins by directed hydrolysis.

Molecular basis for substrate transport of Mycobacterium tuberculosis ABC importer DppABCD.

The type I adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter DppABCD is believed to be responsible for the import of exogenous heme as an iron source into the cytoplasm of the human pathogen Mycobacterium tuberculosis (Mtb). Additionally, this system is also known to be involved in the acquisition of tri- or tetra-peptides. Here, we report the cryo-electron microscopy structures of the dual-function Mtb DppABCD transporter in three forms, namely, the apo, substrate-bound, and ATP-bound states. The apo structure reveals an unexpected and previously uncharacterized assembly mode for ABC importers, where the lipoprotein DppA, a cluster C substrate-binding protein (SBP), stands upright on the translocator DppBCD primarily through its hinge region and N-lobe. These structural data, along with biochemical studies, reveal the assembly of DppABCD complex and the detailed mechanism of DppABCD-mediated transport. Together, these findings provide a molecular roadmap for understanding the transport mechanism of a cluster C SBP and its translocator.

Identification of Y‒linked biomarkers and exploration of immune infiltration of normal-appearing gray matter in multiple sclerosis by bioinformatic analysis.

Background: The knowledge of normal‒appearing cortical gray matter (NAGM) in multiple sclerosis (MS) remains unclear. In this study, we aimed to identify diagnostic biomarkers and explore the immune infiltration characteristics of NAGM in MS through bioinformatic analysis and validation in vivo. Methods: Differentially expressed genes (DEGs) were analyzed. Subsequently, the functional pathways of the DEGs were determined. After screening the overlapping DEGs of MS with two machine learning methods, the biomarkers' efficacy and the expression levels of overlapping DEGs were calculated. Quantitative reverse transcription polymerase chain reaction (qRT‒PCR) identified the robust diagnostic biomarkers. Additionally, infiltrating immune cell populations were estimated and correlated with the biomarkers. Finally, the characteristics of immune infiltration of NAGM from MS were evaluated. Results: A total of 98 DEGs were identified. They participated in sensory transduction of the olfactory system, synaptic signaling, and immune responses. Nine overlapping genes were screened by machine learning methods. After verified by ROC curve, four genes, namely HLA‒DRB1, RPS4Y1, EIF1AY and USP9Y, were screened as candidate biomarkers. The mRNA expression of RPS4Y1 and USP9Y was significantly lower in MS patients than that in the controls. They were selected as the robust diagnostic biomarkers for male MS patients. RPS4Y1 and USP9Y were both positively correlated with memory B cells. Moreover, naive CD4+ T cells and monocytes were increased in the NAGM of MS patients compared with those in controls. Conclusions: Low expressed Y‒linked genes, RPS4Y1 and USP9Y, were identified as diagnostic biomarkers for MS in male patients. The inhomogeneity of immune cells in NAGM might exacerbate intricate interplay between the CNS and the immune system in the MS.

The opportunities and challenges of the disease-modifying immunotherapy for type 1 diabetes: A systematic review and meta-analysis.

There are multiple disease-modifying immunotherapies showing the potential of preventing or delaying the progression of type 1 diabetes (T1D). We designed and performed this systematic review and meta-analysis to gain an overview of what a role immunotherapy plays in the treatment of T1D. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to December 2023. We included clinical trials of immunotherapy conducted in patients with T1D that reported the incidence of hypoglycemia or changes from baseline in at least one of following outcomes: 2 h and 4 h mixed-meal-stimulated C-peptide area under the curve (AUC), fasting C-peptide, daily insulin dosage, glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). The results were computed as the weighted mean differences (WMDs) or odds ratios (ORs) and 95% confidence intervals (CIs) in random-effect model. In all, 34 clinical trials were included. When compared with control groups, 2 h C-peptide AUC was marginally higher in patient treated with nonantigen-based immunotherapies (WMD, 0.04nmol/L, 95% CI, 0.00-0.09 nmol/L, P=0.05), which was mainly driven by the effects of T cell-targeted therapy. A greater preservation in 4 h C-peptide AUC was observed in patients with nonantigen-based immunotherapies (WMD, 0.10nmol/L, 95% CI, 0.04-0.16 nmol/L, P=0.0007), which was mainly driven by the effects of tumor necrosis factor α (TNF-α) inhibitor and T cell-targeted therapy. After excluding small-sample trials, less daily insulin dosage was observed in patient treated with nonantigen-based immunotherapies when compared with control groups (WMD, -0.07units/kg/day, 95% CI, -0.11 to -0.03units/kg/day, P=0.0004). The use of antigen-based immunotherapies was also associated with a lower daily insulin dosage versus control groups (WMD, -0.11units/kg/day, 95% CI, -0.23 to -0.00units/kg/day, P=0.05). However, changes of HbA1c or FPG were comparable between nonantigen-based immunotherapies or antigen-based immunotherapies and control groups. The risk of hypoglycemia was not increased in patients treated with nonantigen-based immunotherapies or patients treated with antigen-based immunotherapies when compared with control groups. In conclusion, nonantigen-based immunotherapies were associated with a preservation of 2 h and 4 h C-peptide AUC in patients with T1D when compared with the controls, which was mainly driven by the effects of TNF-a inhibitor and T cell-targeted therapy. Both nonantigen-based immunotherapies and antigen-based immunotherapies tended to reduce the daily insulin dosage in patients with T1D when compared with the controls. However, they did not contribute to a substantial improvement in HbA1c or FPG. Both nonantigen-based immunotherapies and antigen-based immunotherapies were well tolerated with not increased risk of hypoglycemia in patients with T1D.

An oligopeptide permease, OppABCD, requires an iron-sulfur cluster domain for functionality.

Oligopeptide permease, OppABCD, belongs to the type I ABC transporter family. Its role is to import oligopeptides into bacteria for nutrient uptake and to modulate the host immune response. OppABCD consists of a cluster C substrate-binding protein (SBP), OppA, membrane-spanning OppB and OppC subunits, and an ATPase, OppD, that contains two nucleotide-binding domains (NBDs). Here, using cryo-electron microscopy, we determined the high-resolution structures of Mycobacterium tuberculosis OppABCD in the resting state, oligopeptide-bound pre-translocation state, AMPPNP-bound pre-catalytic intermediate state and ATP-bound catalytic intermediate state. The structures show an assembly of a cluster C SBP with its ABC translocator and a functionally required [4Fe-4S] cluster-binding domain in OppD. Moreover, the ATP-bound OppABCD structure has an outward-occluded conformation, although no substrate was observed in the transmembrane cavity. Here, we reveal an oligopeptide recognition and translocation mechanism of OppABCD, which provides a perspective on how this and other type I ABC importers facilitate bulk substrate transfer across the lipid bilayer.

Relationship between Sociodemographic and Health-Related Factors and Sedentary Time in Middle-Aged and Older Adults in Taiwan.

Background and Objectives: This study aimed to investigate the associations between sociodemographic and health-related factors and sedentary time in middle-aged and older Taiwanese adults. Materials and Methods: A total of 1031 participants (460 men, 571 women; mean age 65.0 years ± 7.8 years; range 55 to 93 years) were randomly recruited from the National Computer Assessment Telephone Interview, Taiwan, in 2013. Sedentary time, TV viewing, physical activity, and sociodemographic factors were assessed through questionnaires. Body mass index was self-reported and calculated to evaluate obesity. In 2023, the associations between sedentary time and sociodemographic and health-related factors were analyzed using Pearson's correlation, cross tabulation, and logistic regression and were stratified by gender. Results: Over 47% of participants reported spending more than 2 h watching TV, and more than 33% reported engaging in over 6 h of total sedentary activities. Men and women with insufficient physical activity had a higher probability of prolonged sedentary time than their physically active counterparts (p = 0.032 for men, p = 0.024 for women). Both men and women who spent more than 2 h watching TV daily were more likely to have high sedentary time compared to those with shorter TV viewing durations (both p < 0.001). Highly educated and unmarried women exhibited a higher likelihood of prolonged sedentary time than their less educated and married counterparts (p = 0.021 and p = 0.01, respectively). Conclusions: Sedentary time showed significant and positive associations with both insufficient physical activity and prolonged TV viewing in both genders. Additionally, significant associations were observed between sedentary time and high education and unmarried status in women. These findings emphasize the importance of implementing gender-specific approaches in future interventions and policy initiatives aimed at reducing sedentary behavior among middle-aged and older adults.

Nomogram to predict overall survival of patients receiving radical gastrectomy and incomplete peri-operative adjuvant chemotherapy for stage II/III gastric cancer: a retrospective bi-center cohort study.

BACKGROUND: To establish a nomogram to predict the probability of survival of patients with stage II/III gastric cancer (GC) who received incomplete peri-operative adjuvant chemotherapy (PAC). METHODS: The medical records of stage II/III GC patients who received curative resection and 1 to 5 cycles of PAC from two tertiary hospitals were retrospectively reviewed. Patients were randomly classified into either a training group or validation group at a ratio of 7:3. The nomogram was constructed based on various prognostic factors using Cox regression analysis in the training cohort, and was validated by the validation group. Concordance index and calibration curves were used to evaluate the discrimination and calibration of the nomogram. Additionally, decision curve analysis (DCA) was used to compare the net clinical benefits of the nomogram and eighth version of TNM staging system. RESULTS: A total of 1,070 consecutive patients were included and 749 patients were enrolled into the training group. Lower body mass index (< 18.5 kg/m2), total gastrectomy, stage III disease and fewer cycles of PAC were identified to be independent predictors for poorer survival. The area under the curve (AUC) values of receiver operating characteristics (ROC) curve predicting 5-year survival probabilities and C-index were 0.768 and 0.742, 0.700 (95%CI: 0.674-0.726) and 0.689 (95%CI: 0.646-0.732) in the training and validation groups, respectively. The calibration curves in the validation cohort showed good agreement between the prediction and observation of 1-, 3- and 5-year survival probabilities. Furthermore, DCA showed that our model has a better net benefit than that of TNM staging system. CONCLUSIONS: The findings emphasize the value of completing PAC. The nomogram which was established to predict survival probability in patients with stage II/III GC receiving radical gastrectomy and incomplete PAC had good accuracy and was verified through both internal and external validation.

Transceptor NRT1.1 and receptor-kinase QSK1 complex controls PM H+-ATPase activity under low nitrate.

NRT1.1, a nitrate transceptor, plays an important role in nitrate binding, sensing, and nitrate-dependent lateral root (LR) morphology. However, little is known about NRT1.1-mediated nitrate signaling transduction through plasma membrane (PM)-localized proteins. Through in-depth phosphoproteome profiling using membranes of Arabidopsis roots, we identified receptor kinase QSK1 and plasma membrane H+-ATPase AHA2 as potential downstream components of NRT1.1 signaling in a mild low-nitrate (LN)-dependent manner. QSK1, as a functional kinase and molecular link, physically interacts with NRT1.1 and AHA2 at LN and specifically phosphorylates AHA2 at S899. Importantly, we found that LN, not high nitrate (HN), induces formation of the NRT1.1-QSK1-AHA2 complex in order to repress the proton efflux into the apoplast by increased phosphorylation of AHA2 at S899. Loss of either NRT1.1 or QSK1 thus results in a higher T947/S899 phosphorylation ratio on AHA2, leading to enhanced pump activity and longer LRs under LN. Our results uncover a regulatory mechanism in which NRT1.1, under LN conditions, promotes coreceptor QSK1 phosphorylation and enhances the NRT1.1-QSK1 complex formation to transduce LN sensing to the PM H+-ATPase AHA2, controlling the phosphorylation ratio of activating and inhibitory phosphorylation sites on AHA2. This then results in altered proton pump activity, apoplast acidification, and regulation of NRT1.1-mediated LR growth.

A comparative analysis of the levels and drivers of regional coordinated development in the Yangtze River Economic Belt and Yellow River Basin, China.

Positioned in the era of the transformation of China's primary social contradictions, this study delves into the new connotations of regional coordinated development(RCD) from the perspective of "factors" coordination within the region and constructs an RCD evaluation system from five subsystems of regional economic coordination(REC), urban-rural coordination(URC), economic and social coordination(EASC), resource and environmental coordination(RAEC), and material and spiritual civilization coordination(MASCC). Then, the Entropy weight-TOPSIS model is used to evaluate the RCD levels of the 19 provinces located in the Yangtze River Economic Belt(YREB) and Yellow River Basin(YRB) from 2010 to 2019, and the two-way fixed-effects model is employed to illustrate the driving mechanisms of various influencing factors on the RCD in YRB and YREB. The results show that:(1)the RCD levels of YRB and YREB show a fluctuating upward trend during 2010 and 2019, however, both regions have low RCD levels, as seen by the mean RCD indices for YREB and YRB, which are only 0.433 and 0.309, respectively. (2) The RCD level of YREB is higher than that of YEB. In 2019, the "coordinated" provinces in YRB and YREB account for 37.50% and 81.82% of the total number of provinces in the basins, respectively, the "uncoordinated" and "low coordinated" provinces all located in YRB. (3) The RCD of YRB and YREB is significantly improved by REC, URC and RAEC, but not significantly positively by MASCC or EASC, and insufficient development of MASCC is the main contradiction limiting the increase in the RCD level of YRB, while the low level of EASC has become the main obstacle limiting the RCD of YREB. (4)Finally, based on the varying impact degrees and directions of different influencing factors on the RCD in YRB and YREB, the recommendations to promote RCD are proposed.

Psychometric evaluation of the Chinese version of the stressors in breast cancer scale: a translation and validation study.

OBJECTIVE: To translate the Stressors in Breast Cancer Scale (SBCS) from English to Chinese and assess its psychometric properties. METHODS: The Brislin's translation model was applied to perform forward translation, back translation, cross-cultural adaptation, Whereas the Chinese version of the SBCS was formed by conducting pre-testing. A cohort of 878 breast cancer patients participated in this methodological study. Content validity, construct validity, convergent validity, discriminant validity, and criterion-related validity were used to establish validity. Internal consistency reliability, split-half reliability, and test-retest reliability were used to establish reliability. RESULTS: The final scale contained five dimensions and 24 items, including interpersonal relationship and healthcare strains, worries and concerns about the future, physical appearance and sex strains, daily difficulties and health. The average content validity index of the scale was 0.975. The goodness-of-fit index (χ2/DF = 2.416, RMSEA = 0.057, GFI = 0.896, CFI = 0.947, IFI = 0.947, and TLI = 0.939) indicated that the model was well-fitted. The composite reliability (CR) of the dimensions ranged from 0.825 to 0.934, the average variance extracted (AVE) ranged from 0.539 to 0.712, and the correlation coefficients of each dimension with the other dimensions were less than the square root of the AVE for that dimension. The Criterion-related validity was 0.511. The Cronbach's alpha was 0.938, and the dimensions ranged from 0.779 to 0.900. Split-half reliability was 0.853, with dimensions ranging from 0.761 to 0.892. Test-retest reliability was 0.855. CONCLUSIONS: The Chinese version of the SBCS has good reliability and validity, which can be applied to the assessment of stressors in breast cancer patients in China.

Quantitative Detection of Pipeline Cracks Based on Ultrasonic Guided Waves and Convolutional Neural Network.

In this study, a quantitative detection method of pipeline cracks based on a one-dimensional convolutional neural network (1D-CNN) was developed using the time-domain signal of ultrasonic guided waves and the crack size of the pipeline as the input and output, respectively. Pipeline ultrasonic guided wave detection signals under different crack defect conditions were obtained via numerical simulations and experiments, and these signals were input as features into a multi-layer perceptron and one-dimensional convolutional neural network (1D-CNN) for training. The results revealed that the 1D-CNN performed better in the quantitative analysis of pipeline crack defects, with an error of less than 2% in the simulated and experimental data, and it could effectively evaluate the size of crack defects from the echo signals under different frequency excitations. Thus, by combining the ultrasonic guided wave detection technology and CNN, a quantitative analysis of pipeline crack defects can be effectively realized.

Weight reduction and the risk of gallbladder and biliary disease: A systematic review and meta-analysis of randomized clinical trials.

In this meta-analysis, we aim to evaluate the risk of gallbladder and biliary disease of weight management strategies and investigate the association between weight reduction and risk of gallbladder or biliary disease. Randomized controlled trials (RCTs) with a duration of at least 12 weeks that compare antiobesity medications (AOMs) with placebo or bariatric surgery with less intensive weight management strategy were concluded. Weight management strategy was associated with a significant increased risk of gallbladder or biliary disease (OR 1.361, 95% CI 1.147 to 1.614, P < 0.001, I2 = 3.5%), cholelithiasis, cholecystitis, and cholecystectomy compared with placebo or controls. The increased risk of gallbladder or biliary disease was observed both in pharmacotherapies subgroup and bariatric surgery subgroup. With regards of specific pharmacotherapies, an increased risk of gallbladder or biliary disease was observed in trials with glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatments. In addition, trials with indication of obesity and overweight treatment and trials with higher doses showed significant higher risk of gallbladder or biliary disease compared with placebo or controls. In conclusion, weight management strategy was associated with an increased risk of gallbladder or biliary disease when compared with placebo or control groups.

Clinical Experiences of Perinatal Palliative Care After a Stillbirth: A Narrative Therapy for Grief.

Narrative care for families suffering from perinatal loss is rarely provided by medical institutions in China Mainland. However, with the advancement of the Chinese narrative medicine theory and practice, the clinical significance of narrative care has been increasingly recognized. Based on the principles of Chinese narrative medicine, this narrative case study described traumatic narrative foreclosures occuring in a family suffering from stillbirth, and highlighted the multidisciplinary collaboration for practising narrative care in the process of supporting the bereaved in our hospital. Meanwhile, we advocate the establishment of a narrative care ecology by training more obsteticians and nurses with good narrative competence in purpose of helping the family experiencing perinatal losses to overcome their tramatic narrative foreclosures, increasing the chances of another successful pregnancy and childbirth as well as enhancing their quality of life.

Diversifying crop rotation increases food production, reduces net greenhouse gas emissions and improves soil health.

Global food production faces challenges in balancing the need for increased yields with environmental sustainability. This study presents a six-year field experiment in the North China Plain, demonstrating the benefits of diversifying traditional cereal monoculture (wheat-maize) with cash crops (sweet potato) and legumes (peanut and soybean). The diversified rotations increase equivalent yield by up to 38%, reduce N2O emissions by 39%, and improve the system's greenhouse gas balance by 88%. Furthermore, including legumes in crop rotations stimulates soil microbial activities, increases soil organic carbon stocks by 8%, and enhances soil health (indexed with the selected soil physiochemical and biological properties) by 45%. The large-scale adoption of diversified cropping systems in the North China Plain could increase cereal production by 32% when wheat-maize follows alternative crops in rotation and farmer income by 20% while benefiting the environment. This study provides an example of sustainable food production practices, emphasizing the significance of crop diversification for long-term agricultural resilience and soil health.

Altered expression of the Plexin-B2 system in tuberous sclerosis complex and focal cortical dysplasia IIb lesions.

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.

Prevalence of hypertension among type 2 diabetes mellitus patients in China: a systematic review and meta-analysis.

This study aimed to estimate the prevalence of hypertension in Chinese patients with type 2 diabetes mellitus (T2DM) using the results of a regional study. The studies were reviewed using PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine, Wan Fang Data and Chinese Science Citation Database. After screening articles and data extraction, Stata V.16 was used for statistical analysis. This study was registered in the Prospective Register Systematic Reviews (CRD42020170649). A total of 2126 articles were identified, and nine papers were finally included. Random-effects modelling showed that the pooled prevalence of hypertension among Chinese patients with T2DM was 54% (95% CI 47 to 61%). Subgroup analysis showed that the prevalence in men (59.8%; 95% CI 49.0 to 70.7%) was higher than that in women (40.2%; 95% CI 29.3 to 59.2%). The prevalence in North China was higher than that in East China. The prevalence in institution-based settings (56%; 95% CI 48 to 64%) was higher than that in community-based settings (51%; 95% CI 34 to 69%). Appropriate preventive measures should be undertaken, such as health education, to control and reduce the risk of hypertension in diabetic patients and reduce the burden of cardiovascular disease.

Rasd1 is involved in white matter injury through neuron-oligodendrocyte communication after subarachnoid hemorrhage.

AIMS: Rasd1 has been reported to be correlated with neurotoxicity, metabolism, and rhythm, but its effect in case of subarachnoid hemorrhage (SAH) remained unclear. White matter injury (WMI) and ferroptosis participate in the early brain injury (EBI) after SAH. In this work, we have investigated whether Rasd1 can cause ferroptosis and contribute to SAH-induced WMI. METHODS: Lentivirus for Rasd1 knockdown/overexpression was administrated by intracerebroventricular (i.c.v) injection at 7 days before SAH induction. SAH grade, brain water content, short- and long-term neurobehavior, Western blot, real-time PCR, ELISA, biochemical estimation, immunofluorescence, diffusion tensor imaging (DTI), and transmission electron microscopy (TEM) were systematically performed. Additionally, genipin, a selective uncoupling protein 2(UCP2) inhibitor, was used in primary neuron and oligodendrocyte co-cultures for further in vitro mechanistic studies. RESULTS: Rasd1 knockdown has improved the neurobehavior, glia polarization, oxidative stress, neuroinflammation, ferroptosis, and demyelination. Conversely, Rasd1 overexpression aggravated these changes by elevating the levels of reactive oxygen species (ROS), inflammatory cytokines, MDA, free iron, and NCOA4, as well as contributing to the decrease of the levels of UCP2, GPX4, ferritin, and GSH mechanistically. According to the in vitro study, Rasd1 can induce oligodendrocyte ferroptosis through inhibiting UCP2, increasing reactive oxygen species (ROS), and activating NCOA4-mediated ferritinophagy. CONCLUSIONS: It can be concluded that Rasd1 exerts a modulated role in oligodendrocytes ferroptosis in WMI following SAH.

Gut microbiota and serum metabolome reveal the mechanism by which TCM polysaccharides alleviate salpingitis in laying hens challenged by bacteria.

This paper aimed to evaluate the effect of 3 kinds of TCM polysaccharides instead of antibiotics in preventing salpingitis in laying hens. After feeding the laying hens with Lotus leaf polysaccharide, Poria polysaccharide, and Epimedium polysaccharide, mixed bacteria (E. coli and Staphylococcus aureus) were used to infect the oviduct to establish an inflammation model. Changes in antioxidant, serum immunity, anti-inflammatory, gut microbiota, and serum metabolites were evaluated. The results showed that the 3 TCM polysaccharides could increase the expression of antioxidant markers SOD, GSH, and CAT, and reduce the accumulation of MDA in the liver; the contents of IgA and IgM in serum were increased. Decreased the mRNA expression of TLR4, NFκB, TNF-α, IFN-γ, IL1ß, IL6, and IL8, and increased the mRNA expression of anti-inflammatory factor IL5 in oviduct tissue. 16sRNA high-throughput sequencing revealed that the 3 TCM polysaccharides improved the intestinal flora disturbance caused by bacterial infection, increased the abundance of beneficial bacteria such as Bacteroides and Actinobacillus, and decreased the abundance of harmful bacteria such as Romboutsia, Turicibacter, and Streptococcus. Metabolomics showed that the 3 TCM polysaccharides could increase the content of metabolites such as 3-hydroxybutyric acid and isobutyl-L-carnitine, and these results could alleviate the further development of salpingitis. In conclusion, the present study has found that using TCM polysaccharides instead of antibiotics was a feasible way to prevent bacterial salpingitis in laying hens, which might make preventing this disease no longer an issue for breeding laying hens.