The relationship between serum levels of epidermal growth factor and ß-human chorionic gonadotropin and the type and prognosis of ectopic pregnancy.

PURPOSE: This work aimed to explore the relationship between epidermal growth factor (EGF) and ß-human chorionic gonadotropin (ß-HCG) and ectopic pregnancy types and impact on prognosis. METHODS: Twenty women with normal pregnancies (NPs) were recruited as control group, and twenty women each with tubal pregnancy (TP) and cervical pregnancy (CP) were recruited. Blood samples were collected to detect EGF and ß-HCG. Data on length of hospital stay and incidence of complications were collected. The differences in serum EGF and ß-HCG levels were compared among groups and within various types of ectopic pregnancy using analysis of variance and Pearson correlation analysis. RESULTS: Serum EGF and ß-HCG were notably lower in TP and CP group vs. controls (P < 0.05). In subgroup analysis within the types of ectopic pregnancy, serum EGF levels were drastically higher in TP group vs. CP group (P < 0.05). Serum EGF levels were negatively correlated with pregnancy outcomes and incidence of complications (P < 0.05). In patients with TP and CP, serum EGF and ß-HCG recovery time and hospital stay differed drastically (P < 0.05). Serum EGF and ß-HCG levels showed optimal cutoff values identified at 2.65 µg/L and 11,745.35 IU/L, respectively. The corresponding area under the curve (AUC) values were 0.885 and 0.841. CONCLUSION: Elevated levels of EGF may be associated with the occurrence of ectopic pregnancy and may impact the type of ectopic pregnancy, pregnancy outcomes, and the incidence of complications. Further clinical research is warranted to investigate these findings.

Differences in intracranial atherosclerosis plaque between posterior circulation and anterior circulation on high-resolution magnetic resonance imaging: A systematic review and meta-analysis.

OBJECTIVE: The clinical characteristics and mechanisms of stroke caused by anterior circulation atherosclerotic plaques (ACAPs) and posterior circulation atherosclerotic plaques (PCAPs) are distinct. We aimed to compare the differences in vulnerability, morphology, and distribution between ACAPs and PCAPs based on hign-resolution magnetic resonance imaging (HR-MRI). MATERIALS AND METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang database were retrieved from inception through May 2023. Meta-analysis was performed by R 4.2.1 software. The quality of the literature was assessed by the Agency for Healthcare Research and Quality (AHRQ). Subgroup analysis was conducted to explore the heterogeneity of the pooled results. RESULTS: There were a total of 13 articles, including 1194 ACAPs and 1037 PCAPs. The pooled estimates demonstrated that the incidence of intraplaque hemorrhage in the PCAPs was higher (OR 1.72, 95%CI 1.35-2.18). The plaque length (SMD 0.23, 95%CI 0.06-0.39) and remodeling index (SMD 0.29, 95%CI 0.14-0.44) of PCAPs were larger than those in ACAPs. However, there were no evident differences in significant enhancement or stenosis degree between the two groups. CONCLUSION: There were more unstable features in PCAPs, highlighting an elevated risk of recurrent ischemic stroke in the posterior circulation. Furthermore, PCAPs were prone to developing penetrating artery disease due to their wider distribution. Nevertheless, posterior circulation arteries exhibited a greater propensity for outward remodeling, which may lead treatment team to miss the optimal intervention stage by being overlooked on angiographic detection.

Mindfulness therapy for patients with coronary heart disease: A systematic review and meta-analysis.

AIM: Coronary heart disease (CHD) is a prevalent cardiovascular disease with high mortality rates worldwide. Patients with CHD often experience adverse psychological stress related to the disease's diagnosis, treatment and recovery phases. This stress can hurt sleep quality and overall quality of life. Mindfulness-based interventions (MBIs) have been studied as a psychotherapeutic approach to alleviating the psychological stress associated with CHD. This study aimed to determine the effectives of MBIs for health outcomes in patients with CHD. METHODS: A total of eight English-language databases were searched, and eight relevant studies were included in the analysis. The included studies were assessed for literature quality, and data were extracted and analysed using Review Manager 5.3. RESULTS: A total of eight studies involving 802 participants were included in the analysis. Compared to control groups, MBIs significantly reduced anxiety, depression, perceived stress, and systolic blood pressure. However, there was no significant effect on diastolic blood pressure, quality of life or body mass index. One study reported that MBIs significantly improved sleep quality in patients with acute myocardial infarction after percutaneous coronary intervention but had no significant effect on body mass index. CONCLUSION: MBIs had significant effects on anxiety and depression in patients with CHD, reduced perceived stress and were associated with reductions in systolic blood pressure and improvements in sleep quality. However, they did not significantly affect diastolic blood pressure, quality of life or body mass index.

Modulation of Kv7 Channel Currents by Echinocystic Acid.

Modulation of KCNQ-encoded voltage-gated potassium Kv7/M channel function represents an attractive strategy to treat neuronal excitability disorders such as epilepsy, pain, and depression. The Kv7 channel group includes five subfamily members (Kv7.1-Kv7.5). Pentacyclic triterpenes display extensive pharmacological activities including antitumor, anti-inflammatory, and antidepression effects. In this study, we investigated the effects of pentacyclic triterpenes on Kv7 channels. Our results show that echinocystic acid, ursonic acid, oleanonic acid, demethylzeylasteral, corosolic acid, betulinaldehyde, acetylursolic acid, and α-boswellic acid gradually exert decreasing degrees of Kv7.2/Kv7.3 channel current inhibition. Echinocystic acid was the most potent inhibitor, with a half-maximal inhibitory concentration (IC50) of 2.5 µM. It significantly shifted the voltage-dependent activation curve in a positive direction and slowed the time constant of activation for Kv7.2/Kv7.3 channel currents. Furthermore, echinocystic acid nonselectively inhibited Kv7.1-Kv7.5 channels. Taken together, our findings indicate that echinocystic acid is a novel and potent inhibitor that could be used as a tool to further understand the pharmacological functions of neuronal Kv7 channels. SIGNIFICANCE STATEMENT: Pentacyclic triterpenes reportedly have multiple potential therapeutic uses such as anticancer, anti-inflammatory, antioxidant, and antidepression effects. In the present study, we show that echinocystic acid, ursonic acid, oleanonic acid, and demethylzeylasteral inhibit Kv7.2/Kv7.3 channels to varying degrees. Of these, echinocystic acid was the most potent Kv7.2/Kv7.3 current inhibitor and inhibited Kv7.1-Kv7.5 currents in a nonselective manner.

Inhibition of Kv7/M Channel Currents by Fangchinoline.

INTRODUCTION: Voltage-gated Kv7/M potassium channels play an essential role in the control of membrane potential and neuronal excitability. Fangchinoline, a bisbenzylisoquinoline alkaloid, displays extensive biological activities including antitumor, anti-inflammatory, and antihypertension effects. In this study, we investigated the effects of fangchinoline on Kv7/M channels. METHODS: A perforated whole-cell patch technique was used to record Kv7 currents from HEK293 cells and M-type currents from mouse dorsal root ganglion (DRG) neurons. RESULTS: Fangchinoline inhibited Kv7.2/Kv7.3 currents in a concentration-dependent manner, with an IC50 of 9.5 ± 1.2 µM. Fangchinoline significantly inhibited Kv7.1, Kv7.2, Kv7.3, Kv7.4, and Kv7.3/Kv7.5 channels without selective effects. Furthermore, fangchinoline significantly slowed the activation of Kv7.1-Kv7.5 channels and inhibited native M-channel currents of DRG neurons. CONCLUSION: Taken together, our findings indicate that fangchinoline concentration-dependently inhibited Kv7/M channel currents.

High total bilirubin-to-uric acid ratio predicts poor sleep quality after acute ischemic stroke: a prospective nested case-control study.

BACKGROUND: Sleep disorders are prevalent after stroke, resulting in high recurrence rates and mortality. But the biomarkers of sleep disorders in stroke patients remain to be elucidated. This study aimed to explore the relationship between total bilirubin-to-uric acid ratio (TUR) and sleep quality after acute ischemic stroke (AIS). METHODS: Three hundred twenty-six AIS patients were recruited and followed up 1 month after stroke in our study. Serum total bilirubin and uric acid levels were obtained within 24 h after admission. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality 1 month after stroke. We conducted receiver operating characteristic (ROC) curve analysis and screened the optimal biomarker to differentiate sleep disorders after stroke. Then the TUR was stratified according to the best cut-off value (0.036) of the ROC and further analysed by binary logistic regression analysis. Additionally, the interaction was used to explore the difference in its effect on post-stroke sleep quality in different subgroups. RESULTS: Three hundred thirty-one patients (40.2%) were considered as having poor sleep quality during the one-month follow-up. Compared to patients with good sleep, patients with poor sleep were more likely to have higher TUR (IQR), 0.05 (0.03-0.06) versus 0.03 (0.02-0.04), P < 0.001. After adjusting for confounding factors, binary regression analysis demonstrated that a high TUR (≥0.036) was independently related to post-stroke poor sleep quality (OR = 3.75, 95% CI = 2.02-6.96, P < 0.001). CONCLUSIONS: High TUR is associated with an increased risk of poor sleep quality in AIS patients, especially in females, diabetics, and patients with hyperlipidaemia.

Cardiac parameters affect prognosis in patients with non-large atherosclerotic infarction.

BACKGROUND: Although large artery atherosclerosis (LAA) is the most common type of cerebral infarction, non-LAA is not uncommon. The purpose of this paper is to investigate the prognosis of patients with non-LAA and to establish a corresponding nomogram. PATIENTS AND METHODS: Between June 2016 and June 2017, we had 1101 admissions for acute ischemic stroke (AIS). Of these, 848 were LAA and 253 were non-LAA. Patients were followed up every 3 months with a minimum of 1 year of follow-up. After excluding patients who were lost follow-up and patients who did not meet the inclusion criteria, a total of 152 non-LAA patients were included in this cohort study. After single-factor analysis and multifactor logistic regression analysis, the risk factors associated with prognosis were derived and different nomograms were developed based on these risk factors. After comparison, the best model is derived. RESULTS: Logistics regression found that the patient's National Institutes of Health Stroke Scale (NIHSS) score, ejection fraction (EF), creatine kinase-MB (CK-MB), age, neutrophil-to-lymphocyte ratio (NLR), aspartate aminotransferase (AST), and serum albumin were independently related to the patient's prognosis. We thus developed three models: model 1: single NIHSS score, AUC = 0.8534; model 2, NIHSS + cardiac parameters (CK-MB, EF), AUC = 0.9325; model 3, NIHSS + CK-MB + EF + age + AST + NLR + albumin, AUC = 0.9598. We compare the three models: model 1 vs model 2, z = - 2.85, p = 0.004; model 2 vs model 3, z = - 1.58, p = 0.122. Therefore, model 2 is considered to be the accurate and convenient model. CONCLUSIONS: Predicting the prognosis of patients with non-LAA is important, and our nomogram, built on the NIHSS and cardiac parameters, can predict the prognosis accurately and provide a powerful reference for clinical decision making.

Identification of favorable SNP alleles and candidate genes for traits related to early maturity via GWAS in upland cotton.

BACKGROUND: Early maturity is one of the most important and complex agronomic traits in upland cotton (Gossypium hirsutum L). To dissect the genetic architecture of this agronomically important trait, a population consisting of 355 upland cotton germplasm accessions was genotyped using the specific-locus amplified fragment sequencing (SLAF-seq) approach, of which a subset of 185 lines representative of the diversity among the accessions was phenotypically characterized for six early maturity traits in four environments. A genome-wide association study (GWAS) was conducted using the generalized linear model (GLM) and mixed linear model (MLM). RESULTS: A total of 81,675 SNPs in 355 upland cotton accessions were discovered using SLAF-seq and were subsequently used in GWAS. Thirteen significant associations between eight SNP loci and five early maturity traits were successfully identified using the GLM and MLM; two of the 13 associations were common between the models. By computing phenotypic effect values for the associations detected at each locus, 11 highly favorable SNP alleles were identified for five early maturity traits. Moreover, dosage pyramiding effects of the highly favorable SNP alleles and significant linear correlations between the numbers of highly favorable alleles and the phenotypic values of the target traits were identified. Most importantly, a major locus (rs13562854) on chromosome Dt3 and a potential candidate gene (CotAD_01947) for early maturity were detected. CONCLUSIONS: This study identified highly favorable SNP alleles and candidate genes associated with early maturity traits in upland cotton. The results demonstrate that GWAS is a powerful tool for dissecting complex traits and identifying candidate genes. The highly favorable SNP alleles and candidate genes for early maturity traits identified in this study should be show high potential for improvement of early maturity in future cotton breeding programs.

[Bushen Tiaojing Recipe Regulated Expressions of BMPR I[/ALK6-Smads in Mouse Oocytes Cul- ture in vitro].

Objective To observe the effects of Bushen Tiaojing Recipe (BTR) on the counts of survival preantral follicles and the bone morphogenetic protein receptor II (BMPR II )/activin receptor- like kinase 6-drosophila mothers against decapentaplegic proteins (ALK6-Smads) signal pathway in oocytes cultured in vitro, and to study its mechanism for improving the quality of oocytes. Methods Prean- tral follicles were mechanically isolated from 65 female 12-day old healthy Kunming mice, which were inoculated by normal rats' serum (as the control group) , high, medium, low dose BTR containing serums (as Shen-supplementing groups) , high dose BTR containing serum + K02288 (as the inhibitor group) , respectively. All were cultured by common method in vitro. On the 6th day the counts of survival preantral follicles were compared between each Shen-supplementing group and the control group respectively. mR- NA expressions of BMPR II, ALK6, Smad1 , Smad5, and Smad8 were detected by Real-time fluorescence quantitative PCR. The protein expressions of indices mentioned above and phospho-Smadl/5/8 (p- Smadl/5/8) were detected by cellular immunofluorescence test. Results Compared with the control group, the quantity of survival preantral follicles increased in the high dose BTR containing serum group; mRNA expressions of BMPR II, ALK6, Smad5, and Smad8 were elevated, protein expressions of indi- ces mentioned above and p-Smadl/5/8 were increased in the 3 Shen-supplementing groups (P <0. 05) ; mRNA and protein expressions of Smad1 were increased in high and medium dose BTR containing serum groups (P<0.05). Compared with the high dose BTR containing serum group, protein expressions of Smad1/5/8 were reduced in the inhibitor group (P <0.05). Conclusion BTR could elevate the quantity of survival preantral follicles cultured in vitroand improve the quality of oocytes, which might be possibly as- sociated to regulating the BMPR II/ALK6-Smads signal pathway in oocytes.

Association between Oxidative Balance Score and Severe Headache or Migraine among American Adults A Cross-Section Study.

BACKGROUND: Migraine is implicated in oxidative stress. The oxidative balance score (OBS) assesses the combined impact of diet and lifestyle on oxidative and antioxidant balance in diseases. However, the association between OBS and migraine remains underexplored. OBJECTIVE: We aimed to examine the relationship between OBS and severe headaches or migraines among American adults. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, defining severe headaches or migraine via self-reports and calculating OBS from 16 diaries and 4 lifestyle factors. Multivariable weighted logistic regression models were used to explore the OBS-migraine relationship, with stratified analysis for result validation. RESULTS: The study included 6,653 participants (average age 45.6, 52.1% male), and 19.1% reported severe headaches or migraines. There was a significant inverse association between OBS and severe headache or migraine, with an adjusted odds ratio (OR) of 0.97 (95% [confidence interval] CI: 0.96, 0.98, p < 0.001). The highest OBS tertile had an adjusted OR of 0.58 (95% CI: 0.47, 0.73) compared to the lowest. This pattern was consistent across sexes, with an adjusted OR of 0.98 (0.95, 1.00) in males and 0.97 (0.95, 1.00) in females. The adjusted OR for migraine was 0.61 (0.44, 0.87) and 0.54 (0.37, 0.79) in the highest tertile for males and females, respectively. CONCLUSION: The study highlights a significant association between OBS and severe headaches or migraines, suggesting the potential role of oxidative stress in these conditions. The findings emphasize the importance of a balanced, antioxidant-rich diet and lifestyle in managing severe headaches or migraine.

Nutritional management interventions and multi-dimensional outcomes in frail and pre-frail older adults: A systematic review and meta-analysis.

BACKGROUND: Frailty, a prevalent geriatric syndrome, presents challenges exacerbated by malnutrition. Nutritional Management Interventions (NMIs) offer hope in frailty reversal, necessitating exploration of their multi-dimensional outcomes. OBJECTIVES: Assess NMIs' impact on frail and pre-frail older adults across diverse outcomes. METHODS: A systematic review and meta-analysis of 13 studies (2012-2023) evaluated NMIs' effects on physical, dietary, psychological, and frailty aspects. Literature quality was assessed, and data analyzed with Review Manager 5.3. RESULTS: A total of 13 studies involving participants were included in the analysis. Participants numbered 968, with the intervention group averaging 77.05±0.77 years and the control group 78.75±0.8 years. Compared to control groups,NMIs significantly increased body weight (SMD = 0.26, P = 0.03) and improved gait speed (SMD = 0.18, P = 0.03). Protein intake showed significance for interventions≤12 weeks (SMD = 1.04, P < 0.001). No significant differences in energy intake (SMD = 0.20, P = 0.60), but >12 weeks NMIs reduced energy intake (SMD = -0.73, P = 0.006). No significant differences in depressive symptoms, frailty scores, BMI, TUG, Handgrip Strength, or SPPB. CONCLUSION: This meta-analysis underscores NMIs' potential benefits for frail and pre-frail older adults. Personalized, multidimensional interventions are recommended despite study limitations, emphasizing extended interventions and diverse assessments for holistic care.

Single-cell sequencing of the substantia nigra reveals microglial activation in a model of MPTP.

Background: N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to induce PD models, but the effect of MPTP on the cells and genes of PD has not been fully elucidated. Methods: Single-nucleus RNA sequencing was performed in the Substantia Nigra (SN) of MPTP mice. UMAP analysis was used for the dimensionality reduction visualization of the SN in the MPTP mice. Known marker genes highly expressed genes in each cluster were used to annotate most clusters. Specific Differentially Expressed Genes (DEGs) and PD risk genes analysis were used to find MPTP-associated cells. GO, KEGG, PPI network, GSEA and CellChat analysis were used to reveal cell type-specific functional alterations and disruption of cell-cell communication networks. Subset reconstruction and pseudotime analysis were used to reveal the activation status of the cells, and to find the transcription factors with trajectory characterized. Results: Initially, we observed specific DEGs and PD risk genes enrichment in microglia. Next, We obtained the functional phenotype changes in microglia and found that IGF, AGRN and PTN pathways were reduced in MPTP mice. Finally, we analyzed the activation state of microglia and revealed a pro-inflammatory trajectory characterized by transcription factors Nfe2l2 and Runx1. Conclusion: Our work revealed alterations in microglia function, signaling pathways and key genes in the SN of MPTP mice.

Gut-brain bidirectional determination in regulating the residual feed intake of small-sized meat ducks.

The gut-brain axis is essential in maintaining the homeostasis of neuronal system, endocrine system, and intestinal microbiota in both the afferent and efferent directions. This axis is considered to be a key mechanism that regulates feed efficiency (FE). This study aimed to investigate the regulatory mechanisms of gut-brain axis-related genes on the residual feed intake (RFI) in H-strain small-sized meat ducks. A total of 500 ducks with similar initial BW (635.2 ± 15.1 g) were selected and reared in the same experimental facility until slaughter at 42 d of age. RFI was calculated from the average daily gain (ADG), average daily feed intake (ADFI), and metabolic body weight (MBW0.75). Thirty high-RFI (H-RFI) and 30 low-RFI (L-RFI) birds were selected for further evaluation of growth performance, carcass characteristics, and blood biochemical parameter measurements. Six L-RFI and 6 H-RFI birds were then subjected to hypothalamic transcriptomic and cecal microbial sequencing analyses. Results indicated that L-RFI birds exhibited lower production performance (ADFI, FCR, and RFI) and blood biochemical indices (total cholesterol and ghrelin content) compared with H-RFI birds (P < 0.05). Gene expression differed significantly between the L-RFI and H-RFI birds, with 70 upregulated and 50 downregulated genes. The bacterial communities of L-RFI birds showed higher abundances of Bacteroides, Bifidobacterium, and Lactococcus, and lower abundances of Erysipelatoclostridium, Parasutterella, Fournierella, and Blautia compared with H-RFI birds (P < 0.05). Interactive analysis revealed bacterial communities associated with FE were significantly correlated with hypothalamic genes (P < 0.05), for example, Bacteroides was positively correlated with DGKH and LIPT2, while negatively correlated with CAPN9, GABRD, and PDE1A. Bifidobacterium showed significant correlations with ATP2A3, CALHM6, and TMEM121B. Overall, RFI was a crucial indicator of FE, regulated by interactions between brain gene expression and gut microbiota through cAMP signaling, neuroactive ligand-receptor interaction, and calcium signaling pathways. Notably, increased expression of hypothalamic genes and abundance of carbohydrate-utilization microbiota in L-RFI meat ducks improved FE by enhancing energy metabolism and volatile fatty acids absorption.

KAN0438757, a novel PFKFB3 inhibitor, prevent the progression of severe acute pancreatitis via the Nrf2/HO-1 pathway in infiltrated macrophage.

Acute pancreatitis (AP) is a non-infectious pancreatic enzyme-induced disorder, a life-threatening inflammatory condition that can cause multi-organ dysfunction, characterized by high morbidity and mortality. Several therapies have been employed to target this disorder; however, few happen to be effectively employable even in the early phase. PFKFB3(6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-3) is a critical regulator of glycolysis and is upregulated under inflammatory, mitogenic, and hypoxia conditions. Essential information on the targeting of the inflammatory pathway will present the termination of the disorder and recovery. Herein we investigated the protective function of KAN0438757, a potent inhibitor of PFKFB3, and its mechanism of impeding AP induced in mice. KAN0438757 was confirmed to activate the Nrf2/HO-1 inflammatory signaling pathways in response to caerulein induced acute pancreatitis (CAE-AP) and fatty acid ethyl ester induced severe acute pancreatitis (FAEE-SAP). Additionally, KAN0438757 alleviated the inflammatory process in infiltrated macrophage via the Nrf2/HO-1 inflammatory signaling pathway and demonstrated a significant effect on the growth of mice with induced AP. And more importantly, KAN0438757 displayed negligible toxicity in vivo. Taken together our data suggest KAN0438757 directly suppresses the inflammatory role of PFKFB3 and induces a protective role via the Nrf2/HO-1 pathway, which could prove as an excellent therapeutic platform for SAP amelioration.

Renal function affects the safety and efficacy of tirofiban in acute ischemic stroke thrombectomy patients.

BACKGROUND: Acute ischemic stroke poses a significant health threat, and thrombectomy has become a routine treatment. Tirofiban has emerged as a promising adjunct therapy to minimize reocclusion after thrombectomy. We aimed to investigate whether renal function influences the safety and efficacy of tirofiban in patients undergoing endovascular therapy. METHODS: Patients' clinical data collected from the stroke unit were analyzed. The modified Rankin scale score and symptomatic intracranial hemorrhage (sICH) were used as outcome measures. RESULTS: A total of 409 patients (mean age: 66.5 years, 292 males [71.4%]) were included. Tirofiban significantly improved 3-month functional outcomes (adjusted odds ratio [aOR] = 2.408, 95% confidence interval [CI] 1.120-5.175), reduced 3-month mortality (aOR = 0.364, 95% CI 0.155-0.856), and decreased the incidence of sICH (aOR = 0.339, 95% CI 0.149-0.767) in patients with estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m². However, no significant improvement in prognosis was observed with tirofiban in patients with eGFR < 90 mL/min/1.73 m². Interaction analysis suggested a potential influence of renal function on tirofiban efficacy. CONCLUSION: Renal function may impact the efficacy of tirofiban. Administration of tirofiban in direct thrombectomy patients with normal renal function is safe and improves prognosis. However, the prognostic benefits of tirofiban are limited in patients with impaired renal function.

The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer.

Lactylation has been recently identified as a new type of posttranslational modification occurring widely on lysine residues of both histone and nonhistone proteins. The acetyltransferase p300 is thought to mediate protein lactylation, yet the cellular concentration of the proposed lactyl-donor, lactyl-coenzyme A, is about 1,000 times lower than that of acetyl-CoA, raising the question of whether p300 is a genuine lactyltransferase. Here, we report that alanyl-tRNA synthetase 1 (AARS1) moonlights as a bona fide lactyltransferase that directly uses lactate and ATP to catalyze protein lactylation. Among the candidate substrates, we focused on the Hippo pathway, which has a well-established role in tumorigenesis. Specifically, AARS1 was found to sense intracellular lactate and translocate into the nucleus to lactylate and activate the YAP-TEAD complex; and AARS1 itself was identified as a Hippo target gene that forms a positive-feedback loop with YAP-TEAD to promote gastric cancer (GC) cell proliferation. Consistently, the expression of AARS1 was found to be upregulated in GC, and elevated AARS1 expression was found to be associated with poor prognosis for patients with GC. Collectively, this work found AARS1 with lactyltransferase activity in vitro and in vivo and revealed how the metabolite lactate is translated into a signal of cell proliferation.

Circ-Bptf Ameliorates Learning and Memory Impairments via the miR-138-5p/p62 Axis in APP/PS1 Mice.

Alzheimer's disease (AD) is a common age-associated progressive neurodegenerative disorder that is implicated in the aberrant regulation of numerous circular RNAs (circRNAs). Here, we reported that circ-Bptf, a conserved circRNA derived from the Bptf gene, showed an age-dependent decrease in the hippocampus of APP/PS1 mice. Overexpression of circ-Bptf significantly reversed dendritic spine loss and learning and memory impairment in APP/PS1 mice. Moreover, we found that circ-Bptf was predominantly localized to the cytoplasm and upregulated p62 expression by binding to miR-138-5p. Furthermore, the miR-138-5p mimics reversed the decreased expression of p62 induced by the silencing of circ-Bptf. Together, our findings suggested that circ-Bptf ameliorated learning and memory impairments via the miR-138-5p/p62 axis in APP/PS1 mice. It may act as a potential player in AD pathogenesis and therapy.

Amelioratory effects of testosterone treatment on cognitive performance deficits induced by soluble Aß1-42 oligomers injected into the hippocampus.

This study was undertaken to investigate the protective effects and potential mechanism of testosterone (T) on cognitive performance in adult male rats given bilateral intrahippocampal injections of beta amyloid 1-42 oligomers (Aß1-42) combined with gonadectomy (Aß+GDX). A series of experiments were designed to verify the optimal administration time and dose of T and to explore its potential protective mechanisms on spatial ability in Aß+GDX rats in the Morris water maze test. Aß1-42 was injected only once two weeks before testing, while T and the androgen receptor (AR) antagonist flutamide (F) were administered daily beginning 2 days before and throughout the 6 days of testing. The Aß1-42 injection and GDX individually impaired cognitive performance, and the combination of these treatments was additive, leading to even greater impairment. The serum T level peaked at 48 h after administration. T doses ranging from 0.25 to 1.00 mg corresponding to serum T levels of 4.5-21.35 ng/ml improved the spatial ability. Animals administered 0.75 mg of T corresponding to the serum T level of 15.2 ng/ml had the most significantly improved behavioral performances. However, higher T doses of 1.50 and 2.00 mg resulting in serum T levels of 34.8 and 45 ng/ml, respectively, impaired the behavioral performances. F had no effect on the serum T level and spatial ability, but it blocked the activational effect of T. These findings indicate that the effect of T on behavioral performances is partly mediated through ARs.

[Effect of Toxoplasma gondii infection on thymus cells in rats].

OBJECTIVE: To study the pathological damage of thymus and thymus cell apoptosis of male rats infected with Toxoplasma gondii. METHODS: Fifty Wistar male rats (7-8-week-old) were randomly divided into infection group (40) and control group (10). Rats in infection group were infected with 5 x 10(4) tachyzoites by intraperitoneal injection, while those in control group received same volume of PBS. On the 3rd, 6th, 9th and 12th day post infection, ten rats from infection group and two from control group were sacrificed, the thymus glands were removed. The thymus tissue sections were stained with hematoxylin and eosin (HE) for observation on histopathological changes. Single thymus cell suspensions were prepared. Cell cycle analysis was performed by flow cytometry, and proliferation index was calculated. Thymus frozen sections were stained with Hoechst 33258, and morphologic changes in apoptotic nuclei were observed under fluorescence microscope. Expression of Bcl-2 and Bax proteins were determined by using immunohistochemistry. RESULTS: Microscopic examination showed that pathological changes occurred in thymus grand on the 3rd day after infection. The space between connective tissue capsules was widened, cells in cortex and medulla cells were sparse, and more phagocytes and extravasated blood were found in thymus. On the 6th day post infection the thymus damage was aggravated, and no significant improvement was seen on day 12. On the 3rd, 6th, 9th and 12th day after infection, thymocyte proliferation index was (11.15 +/- 0.99)%, (6.17 +/- 1.02)%, (5.45 +/- 0.96)% and (6.63 +/- 1.52)%, respectively, and each of them was significantly lower than that of the control [(13.81 +/- 1.18)%] (P < 0.01). On the 3rd day after infection, the number of apoptotic cells increased, significantly increased on day 6, and there was no much difference in the number of apoptotic cells between day 6 and day 12. The immunohistochemistry results showed that on the 3rd, 6th, 9th and 12th day post-infection, the gray scale value of Bax positive cells was 88.21 +/- 4.74, 64.69 +/- 6.82, 83.62 +/- 5.79, and 101.09 +/- 6.72, respectively, and each of them was significantly lower than that of the control (128.69 +/- 8.95) (P < 0.01), while there was no significant change in the Bcl-2 protein level (P > 0.05). CONCLUSION: T. gondii causes severe pathological damage in host thymus tissue with a decrease in the proliferation index, an increase in the number of apoptotic cells, and high expression of Bax protein.

Effects of traditional Chinese exercises on the rehabilitation of patients with chronic heart failure: A meta-analysis.

Background: With the development of rehabilitation medicine, exercise therapy has gradually become one of the methods to prevent and treat cardiovascular diseases. It is widely used in clinic because it can further reduce the mortality rate, improve clinical symptoms, restore the activity ability of the body, improve the quality of life of patients and reduce the hospitalization rate. Traditional Chinese exercises have developed rapidly in recent years, which mainly include Baduanjin, Tai Ji, etc. However, meta-analyses of all types of exercises are not well characterized. Objectives: To evaluate the effect of traditional Chinese exercises (TCEs) on the rehabilitation of patients with chronic heart failure (CHF) using a meta-analysis. Methods: A systematic search of randomized controlled trials (RCTs) on TCEs for patients with CHF in 13 databases (PubMed, China National Knowledge Infrastructure, etc.). Meta-analysis was performed using Review Manager software (version 5.3) after two investigators independently screened the studies, assessed the quality of the studies, and extracted the data. Results: Meta-analysis of 21 randomized controlled trials which involved 1,665 patients with chronic heart failure showed that practicing TCEs was effective in improving patients' physiological outcomes such as VO2max [MD = 2.14, 95% CI (1.02, 3.26), P < 0.001], AT [MD = 1.61, 95% CI (1.06, 2.16), P < 0.001], and left ventricular ejection fraction [MD = 2.60, 95% CI (1.17, 4.02), P < 0.001]. Non-physiological outcomes benefited from the application of TCEs: 6-min walking distance [MD = 38.55, 95% CI (36.67, 40.42), P < 0.001], quality of life [MD = 5.52, 95% CI (3.17, 7.88), P < 0.001], and single-item TCM symptom scores in CHF patients: tiredness and fatigue [MD = 0.78, 95% CI (0.03, 1.53), P = 0.04], shortness of breath [MD = 0.44,95% CI (0.26, 0.62), P < 0.0001], facial puffiness and limb swelling [MD = 0.44,95% CI (0.12, 0.76), P = 0.007], palpitations [MD = 0.68,95% CI (0.14, 1.21), P = 0.01] were improved. Conclusions: TCEs improved several recovery indicators, heart failure-related clinical symptoms, quality of life, and physiological indicators in patients with CHF. It is worthwhile to expand the participants for practical application in clinical practice, but the existing evidence is insufficient and the heterogeneity of outcome is large. Therefore, more high-quality clinical trials are needed to support these results. Systematic review registration: PROSPERO, identifier [CRD42022383246].