Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel.

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences  is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

The Clinical Characteristics and Manifestation of Anxious Depression Among Patients With Major Depressive Disorders-Results From a Taiwan Multicenter Study.

OBJECTIVE: Anxious depression is a prevalent characteristic observed in Asian psychiatric patients diagnosed with major depressive disorder (MDD). This study aims to investigate the prevalence and clinical presentation of anxious depression in Taiwanese individuals diagnosed with MDD. METHODS: We recruited psychiatric outpatients aged over 18 who had been diagnosed with MDD through clinical interviews. This recruitment took place at five hospitals located in northern Taiwan. We gathered baseline clinical and demographic information from the participants. Anxious depression was identified using a threshold of an anxiety/somatization factor score ≥7 on the 21-item Hamilton Rating Scale for Depression (HAM-D). RESULTS: In our study of 399 patients (84.21% female), 64.16% met the criteria for anxious depression. They tended to be older, married, less educated, with more children, and an older age of onset. Anxious depression patients had higher HAM-D and Clinical Global Impression-Severity scale score, more panic disorder (without agoraphobia), and exhibited symptoms like agitation, irritability, concentration difficulties, psychological and somatic anxiety, somatic complaints, hypochondriasis, weight loss, and increased insight. Surprisingly, their suicide rates did not significantly differ from non-anxious depression patients. This highlights the importance of recognizing and addressing these unique characteristics. CONCLUSION: Our study findings unveiled that the prevalence of anxious depression among Taiwanese outpatients diagnosed with MDD was lower compared to inpatients but substantially higher than the reported rates in European countries and the United States. Furthermore, patients with anxious depression exhibited a greater occurrence of somatic symptoms.

The effects of temperament type on infusion extravasation in newborns.

Infusion extravasation has an increased incidence in newborns, which can result in various adverse outcomes. This study aimed to investigate the effects of different types of temperament on infusion extravasation in newborns. A total of 209 newborns aged 4-7 days who were treated with infusion therapy were assessed for temperament type using the neonatal behavioral assessment scale score (NBAS). The 2009 Infusion Nurses Society clinical grading criteria for extravasation were used, and the clinical data of the newborns, such as gestational age and body weight, were collected. Out of 209 newborns assessed, 107 developed infusion extravasations, with an incidence rate of 51.2%. Newborns with intermediate temperament type were more prone to develop infusion extravasation. Newborns with low body weight, amniotic fluid aspiration syndrome, or meconium aspiration syndrome were prone to develop infusion extravasation. Body weight, temperament type of consolability, temperament type of peak of excitement, diseases, general temperament type, and NBAS total scores of the neonates were independent risk factors for infusion extravasation. Thus, different types of temperament can have an impact on neonatal extravasation.

Effects of acetylcysteine on micro-inflammation and pulmonary ventilation in chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a serious complication of chronic obstructive pulmonary disease, often characterized by increased morbidity and mortality. In traditional Chinese medicine, AECOPD is linked to phlegm-heat and blood-stasis, presenting symptoms like thick sputum, fever, and chest pain. It has been shown that acetylcysteine inhalation in conjunction with conventional therapy significantly reduced inflammatory markers and improved lung function parameters in patients with AECOPD, suggesting that acetylcysteine may be an important adjunctive therapy for patients with phlegm-heat-blood stasis type AECOPD. AIM: To investigate the effect of acetylcysteine on microinflammation and lung ventilation in patients with phlegm-heat and blood-stasis-type AECOPD. METHODS: One hundred patients with phlegm-heat and blood-stasis-type AECOPD were randomly assigned to two groups. The treatment group received acetylcysteine inhalation (10% solution, 5 mL, twice daily) along with conventional therapy, whereas the control group received only conventional therapy. The treatment duration was 14 d. Inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor-alpha) in the serum and sputum as well as lung function parameters (forced expiratory volume in one second, forced vital capacity, and peak expiratory flow) were assessed pre- and post-treatment. Acetylcysteine inhalation led to significant reductions in inflammatory markers and improvements in lung function parameters compared to those in the control group (P < 0.05). This suggests that acetylcysteine could serve as an effective adjunct therapy for patients with phlegm-heat and blood-stasis-type AECOPD. RESULTS: Acetylcysteine inhalation significantly reduced inflammatory markers in the serum and sputum and improved lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD compared with the control group. These differences were statistically significant (P < 0.05). The study concluded that acetylcysteine inhalation had a positive effect on microinflammation and lung ventilation function in patients with this type of AECOPD, suggesting its potential as an adjuvant therapy for such cases. CONCLUSION: Acetylcysteine inhalation demonstrated significant improvements in reducing inflammatory markers in the serum and sputum, as well as enhancing lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD. These findings suggest that acetylcysteine could serve as a valuable adjuvant therapy for individuals with this specific type of AECOPD, offering benefits for managing microinflammation and optimizing lung function.

Associations of body mass index, waist circumference and the weight-adjusted waist index with daily living ability impairment in older Chinese people: A cross-sectional study of the Chinese Longitudinal Healthy Longevity Survey.

AIM: To investigate the associations of body mass index (BMI), waist circumference (WC) and the weight-adjusted waist index (WWI) with the impairment of activities of daily living (ADL) in older Chinese people. METHODS: A total of 13 260 participants aged 65 years and older from the 2018 Chinese Longitudinal Healthy Longevity Survey were included in this cross-sectional study. BMI, WC and the WWI were calculated from measurements of height, weight and WC. Binary logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Non-linear correlations were investigated using restricted cubic spline curves. RESULTS: In multivariate logistic regression fully adjusted for confounding variables, our analyses revealed significant associations between WC and WWI and ADL impairment, with adjusted ORs (95% CI) of 1.01 (1.00, 1.01) and 1.08 (1.03, 1.12), respectively. Meanwhile, participants with a high WWI had a higher risk of ADL impairment compared with those with a low WWI, with an adjusted OR (95% CI) of 1.12 (1.02, 1.23). Subgroup analyses showed that only the association between WWI and ADL impairment did not differ in any of the different populations. In addition, we found that BMI, WC and WWI were non-linearly associated with ADL impairment. CONCLUSIONS: There are significant associations between WC and WWI and ADL impairment in older Chinese people. The findings show the ability of the WWI to serve as a comprehensive and effective indicator of obesity in older Chinese people and emphasize the importance of assessing WWI in screening and preventing ADL impairment in older people.

The construction of machine learning-based predictive models for high-quality embryo formation in poor ovarian response patients with progestin-primed ovarian stimulation.

OBJECTIVE: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. METHODS: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. RESULTS: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884). CONCLUSION: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

Association of Perinatal Cardiovascular Features with Angiotensin System Expressions in Maternal Preeclampsia.

We hypothesized and investigated whether prenatal exposure to preeclampsia (PE) would simultaneously affect perinatal cardiovascular features and angiotensin system expressions. This prospective study was composed of mother-neonate dyads with (n = 49) and without maternal preeclampsia (n = 48) in a single tertiary medical center. The neonates exposed to PE had significantly larger relative sizes for the left and right coronary arteries and a higher cord plasma level of aminopeptidase-N, which positively correlated with the maternal diastolic blood pressures and determined the relative sizes of the left and right coronary arteries, whereas the encoding aminopeptidase-N (ANPEP) mRNA level in the PE cord blood leukocytes was significantly decreased, positively correlated with the neonatal systolic blood pressures (SBPs), and negatively correlated with the cord plasma-induced endothelial vascular cell adhesion molecule-1 mRNA levels. The PE cord plasma significantly induced higher endothelial mRNA levels of angiotensin II type 1 receptor (AT1R) and AT4R, whereas in the umbilical arteries, the protein expressions of AT2R and AT4R were significantly decreased in the PE group. The endothelial AT1R mRNA level positively determined the maternal SBPs, and the AT4R mRNA level positively determined the neonatal chamber size and cardiac output. In conclusion, PE may influence perinatal angiotensin system and cardiovascular manifestations of neonates across placentae. Intriguing correlations between these two warrant further mechanistic investigation.

Role of the V2R-ßarrestin-Gßγ complex in promoting G protein translocation to endosomes.

Classically, G protein-coupled receptors (GPCRs) promote signaling at the plasma membrane through activation of heterotrimeric Gαßγ proteins, followed by the recruitment of GPCR kinases and ßarrestin (ßarr) to initiate receptor desensitization and internalization. However, studies demonstrated that some GPCRs continue to signal from internalized compartments, with distinct cellular responses. Both ßarr and Gßγ contribute to such non-canonical endosomal G protein signaling, but their specific roles and contributions remain poorly understood. Here, we demonstrate that the vasopressin V2 receptor (V2R)-ßarr complex scaffolds Gßγ at the plasma membrane through a direct interaction with ßarr, enabling its transport to endosomes. Gßγ subsequently potentiates Gαs endosomal translocation, presumably to regenerate an endosomal pool of heterotrimeric Gs. This work shines light on the mechanism underlying G protein subunits translocation from the plasma membrane to the endosomes and provides a basis for understanding the role of ßarr in mediating sustained G protein signaling.

Effectiveness of exercise training on arterial stiffness and blood pressure among postmenopausal women: a systematic review and meta-analysis.

BACKGROUND: The acute and long-term benefits of exercise training on cardiovascular health have been well established. The systematic review and meta-analysis aimed to systematically assess the effectiveness of exercise training on arterial stiffness and blood pressure among postmenopausal women with elevated blood pressure. METHODS: A comprehensive search was conducted on PubMed, Embase, Web of Science, ProQuest, Cochrane Library, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov website from inception to September 30, 2023, to identify the randomized controlled trials (RCTs), which evaluated the effectiveness of exercise training on arterial stiffness and blood pressure in postmenopausal women. Standardized mean differences (SMD), weighted mean differences (WMD), and 95% confidence intervals (95% CIs) were calculated using random/fixed effects models. Quality assessment was performed using the modified Jadad scale and the Cochrane Risk of Bias Tool. Sensitivity analysis and subgroup analysis were conducted based on drug dosage, treatment duration, and age of administration to further explore potential heterogeneity. Funnel plots were performed to assess publication bias and Begg's regression test was carried out for funnel plot asymmetry. RESULTS: Twenty-two RCTs involving 1978 participants were included in the quantitative analysis. The mean quality of eligible studies was 4.2 out of 7 based on the modified Jadad scale. The results indicated that exercise training had a significant effect on reducing brachial-ankle pulse wave velocity [MD = - 0.69, 95%CI (- 1.11, - 0.27), P = 0.001], decreasing augmentation index (AIx) [MD = - 6.00, 95%CI (- 6.39, - 5.61), P < 0.00001] and AIx normalized to a heart rate of 75 beats per minute (AIx@75%) [MD = - 7.01, 95%CI - 7.91 to - 6.12, P < 0.00001], lowering systolic blood pressure [MD = - 6.19, 95%CI - 9.24 to - 3.15, P < 0.0001], diastolic blood pressure [MD = - 3.57, 95%CI (- 6.10, - 1.03), P = 0.006) and pulse pressure [MD = - 8.52, 95%CI (- 16.27, - 0.76), P = 0.03]. Subgroup analysis revealed that baseline blood pressure levels had a large impact on the effect of exercise training. CONCLUSIONS: The systematic review and meta-analysis suggested that exercise training may ameliorate arterial stiffness and reduce blood pressure in postmenopausal women with elevated blood pressure. However, the optimal mode of exercise training that improves arterial stiffness and blood pressure in this population requires further investigation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021211268.

Fangchinoline Inhibits African Swine Fever Virus Replication by Suppressing the AKT/mTOR/NF-κB Signaling Pathway in Porcine Alveolar Macrophages.

African swine fever (ASF), caused by the African swine fever virus (ASFV), is one of the most important infectious diseases that cause high morbidity and mortality in pigs and substantial economic losses to the pork industry of affected countries due to the lack of effective vaccines. The need to develop alternative robust antiviral countermeasures, especially anti-ASFV agents, is of the utmost urgency. This study shows that fangchinoline (FAN), a bisbenzylisoquinoline alkaloid found in the roots of Stephania tetrandra of the family Menispermaceae, significantly inhibits ASFV replication in porcine alveolar macrophages (PAMs) at micromolar concentrations (IC50 = 1.66 µM). Mechanistically, the infection of ASFV triggers the AKT/mTOR/NF-κB signaling pathway. FAN significantly inhibits ASFV-induced activation of such pathways, thereby suppressing viral replication. Such a mechanism was confirmed using an AKT inhibitor MK2206 as it inhibited AKT phosphorylation and ASFV replication in PAMs. Altogether, the results suggest that the AKT/mTOR pathway could potentially serve as a treatment strategy for combating ASFV infection and that FAN could potentially emerge as an effective novel antiviral agent against ASFV infections and deserves further in vivo antiviral evaluations.

Development of a diagnostic nomogram for alpha-fetoprotein-negative hepatocellular carcinoma based on serological biomarkers.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Serum biomarkers play an important role in the early diagnosis and prognosis of HCC. Because a certain percentage of HCC patients are negative for alpha-fetoprotein (AFP), the diagnosis of AFP-negative HCC is essential to improve the detection rate of HCC. AIM: To establish an effective model for diagnosing AFP-negative HCC based on serum tumour biomarkers. METHODS: A total of 180 HCC patients were enrolled in this study. The expression levels of GP73, des-γ-carboxyprothrombin (DCP), CK18-M65, and CK18-M30 were detected by a fully automated chemiluminescence analyser. The variables were selected by logistic regression analysis. Several models were constructed using stepwise backward logistic regression. The performance of the models was compared using the C statistic, integrated discrimination improvement, net reclassification improvement, and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). RESULTS: The results showed that the expression levels of GP73, DCP, CK18-M65, and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls (P < 0.001). Multivariate logistic regression analysis revealed that GP73, DCP, and CK18-M65 were independent factors for diagnosing AFP-negative HCC. By comparing the diagnostic performance of multiple models, we included GP73 and CK18-M65 as the model variables, and the model had good discrimination ability (area under the curve = 0.946) and good goodness of fit. The DCA curves indicated the good clinical utility of the nomogram. CONCLUSION: Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative HCC. The diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.

Leisure-time physical activity and the incidence of atrial fibrillation in senior adults: a prospective cohort study.

OBJECTIVE: Whether physical activity could reduce the risk of atrial fibrillation (AF) remains unclear. This study was to investigate the relationship of leisure-time physical activity (LTPA) with AF incidence among Chinese older adults. METHODS: A total of 3253 participants aged ≥60 years from the Guangzhou Heart Study were successfully followed between March 2018 and September 2019. LTPA was assessed using a modified Global Physical Activity Questionnaire. AF was ascertained by 12-lead electrocardiograms, 24-hour single-lead Holter and clinical examination. The Cox proportional hazards model was used to the estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for confounders, and the population-attributable fraction (PAF) was estimated. RESULTS: A total of 76 (2.34%) new-onset cases of AF were identified during a median of 31.13 months of follow-up. After adjustment for confounders, subjects who had LTPA at least 10.0 metabolic equivalent (MET)-hours/week had a 55% lower risk of developing AF (HR: 0.45, 95%CI: 0.25-0.81), and at least 20 MET-hours/week reduced the risk by 45% (HR: 0.55, 95%CI: 0.34-0.92). At least 11% (PAF: 11%, 95%CI: 0%-20%) or 14% (PAF: 14%, 95%CI: 0%-26%) of AF cases could be avoided, respectively, if the subjects do LTPA at least 10 MET-hours/week or 20 MET-hours/week. A significant exposure-response trend was also observed between LTPA and AF risk (Plinear-trend = 0.002). For a specific LTPA, doing housework was associated with a 43% reduced risk, while engaging in ball games was associated with an increased risk. CONCLUSION: This prospective cohort study indicated that a higher LTPA volume was associated with a lower AF risk in Chinese older adults.

Fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration in patients with acute bipyridine herbicide poisoning.

OBJECTIVE: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning. METHODS: A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed. RESULTS: Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1ß (MIP-1ß) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1ß were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal. CONCLUSION: Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.

COVID-19 is associated with changes in brain function and structure: A multimodal meta-analysis of neuroimaging studies.

The actual role of coronavirus disease 2019 (COVID-19) in brain damage has been increasingly reported, necessitating a meta-analysis to collate and summarize the inconsistent findings from functional imaging and voxel-based morphometry (VBM) studies. A comprehensive voxel-wise meta-analysis of the whole brain was conducted to identify alterations in functional activity and gray matter volume (GMV) between COVID-19 patients and healthy controls (HCs) by using Seed-based d Mapping software. We included 15 functional imaging studies (484 patients with COVID-19, 534 HCs) and 9 VBM studies (449 patients with COVID-19, 388 HCs) in the analysis. Overall, patients with COVID-19 exhibited decreased functional activity in the right superior temporal gyrus (STG) (extending to the right middle and inferior temporal gyrus, insula, and temporal pole [TP]), left insula, right orbitofrontal cortex (OFC) (extending to the right olfactory cortex), and left cerebellum compared to HCs. For VBM, patients with COVID-19, relative to HCs, showed decreased GMV in the bilateral anterior cingulate cortex/medial prefrontal cortex (extending to the bilateral OFC), and left cerebellum, and increased GMV in the bilateral amygdala (extending to the bilateral hippocampus, STG, TP, MTG, and right striatum). Moreover, overlapping analysis revealed that patients with COVID-19 exhibited both decreased functional activity and increased GMV in the right TP (extending to the right STG). The multimodal meta-analysis suggests that brain changes of function and structure in the temporal lobe, OFC and cerebellum, and functional or structural alterations in the insula and the limbic system in COVID-19. These findings contribute to a better understanding of the pathophysiology of brain alterations in COVID-19. SIGNIFICANCE STATEMENT: This first large-scale multimodal meta-analysis collates existing neuroimaging studies and provides voxel-wise functional and structural whole-brain abnormalities in COVID-19. Findings of this meta-analysis provide valuable insights into the dynamic brain changes (from infection to recovery) and offer further explanations for the pathophysiological basis of brain alterations in COVID-19.

First identified Toxoplasma gondii Type I in market-sold ducks in Fujian province, China: a significant for public health.

Toxoplasma gondii (T. gondii) is an intracellular protozoan that can cause toxoplasmosis in all warm-blooded hosts. This study focused on the prevalence and genetic characterize of T. gondii in ducks from Fujian province, China. Genomic DNA was extracted from duck tissue samples (heart, liver, lung, and muscle). To assess the genetic diversity of the T. gondii isolates, it was determined by using multilocus polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. A total of 586 ducks from 5 cities in Fujian province were tested, and 35 (6.0%) of which were found to be positive for the T. gondii B1 gene. Further genotyping of these positive samples at 10 genetic markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) using PCR-RFLP revealed that one tissue samples (heart samples from Fuzhou ducks) were identified as Type I (ToxoDB#10). This study is the first report on the prevalence and genetic characterization of T. gondii in ducks in Fujian province, and Type I (ToxoDB#10) is found in ducks in China for the first time. The findings document the genetic characterization of T. gondii in free-range ducks from Fujian Province, thereby enriching the understanding of T. gondii genetic diversity in China. Moreover, these results provide essential data support for further prospective studies and underscores the "One Health" concept, emphasizing the integral link among human, animal, and environmental health.

Gut proinflammatory bacteria is associated with abnormal functional connectivity of hippocampus in unmedicated patients with major depressive disorder.

Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal-amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.

Fat loss and muscle gain: The possible role of striatal dopaminergic tone in determining the efficacy of physical exercise.

The effectiveness of exercise for obesity is contentious due to individual response variability. Owing to the roles of dopamine in motor functions, metabolism, and appetite, this study aimed to identify striatal dopamine as a predictor of variability in exercise response, specifically in terms of fat loss and muscle gain. Healthy non-exercising males completed an 8-week program, exercising 1 h, 4 days a week. Striatal dopaminergic tone was assessed by measuring dopamine transporter availability using technetium-99 m labelled tropane derivative, [99mTc]TRODAT-1 (TRODAT), single-photon emission computed tomography, and body composition (fat and muscles mass) was analysed using bioelectrical impedance. Lower baseline dopamine levels were associated with greater fat mass loss (r = 0.58, p = 0.006), percentage fat mass loss (r = 0.53, p = 0.013), and increase in muscle mass (ß = -0.53, p = 0.035, after taking age and smoking status as covariates). These findings enhance our understanding of obesity neurobiology and exercise response variability, necessitating further research for targeted interventions based on dopaminergic profiles.

Establishment of diagnostic model and identification of diagnostic markers between liver cancer and cirrhosis based on multi-chip and machine learning.

OBJECTIVE: Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC. METHODS: Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm. RESULTS: The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways. CONCLUSION: In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.

Liver X receptor inverse agonist SR9243 attenuates rheumatoid arthritis via modulating glycolytic metabolism of macrophages.

Liver X receptors (LXRs) which link lipid metabolism and inflammation, were overexpressed in experimental rheumatoid arthritis (RA) rats as observed in our previous studies, while suppression of LXRα by silybin ameliorates arthritis and abnormal lipid metabolism. However, the role of LXRs in RA remains undefined. In this study, we investigated the inhibition role of LXRs in the polarization and activation of M1 macrophage by using a special LXRs inverse agonist SR9243, which led to ameliorating the progression of adjuvant-induced arthritis (AIA) in rats. Mechanistically, SR9243 disrupted the LPS/IFN-γ-induced Warburg effect in M1 macrophages, while glycolysis inhibitor 2-DG attenuated the inhibition effect of SR9243 on M1 polarization and the cytokines expression of M1 macrophages including iNOS, TNF-α, and IL-6 in vitro. Furthermore, SR9243 downregulated key glycolytic enzymes, including LDH-A, HK2, G6PD, GLUT1, and HIF-1α in M1 macrophages, which is mediated by increased phosphorylation of AMPK (Thr172) and reduced downstream phosphorylation of mTOR (Ser2448). Importantly, gene silencing of LXRs compromises the inhibition effect of SR9243 on M1 macrophage polarization and activation. Collectively, for the first time, our findings suggest that the LXR inverse agonist SR9243 mitigates adjuvant-induced rheumatoid arthritis and protects against bone erosion by inhibiting M1 macrophage polarization and activation through modulation of glycolytic metabolism via the AMPK/mTOR/HIF-1α pathway.