Prediction of anhedonia in patients with first-episode schizophrenia using a Wavelet-ALFF-based Support vector regression model.

Anhedonia is one of the core features of the negative symptoms of schizophrenia and can be extremely burdensome. Our study applied resting-state functional magnetic resonance imaging (fMRI)-based support vector regression (SVR) to predict anhedonia in patients with first-episode schizophrenia (FES) and analysed the correlation between the wavelet-based amplitude low-frequency fluctuation (wavelet-ALFF) of the main brain region and anhedonia. We recruited 31 patients with FES and 33 healthy controls (HCs) from the Affiliated Brain Hospital of Guangzhou Medical University. All subjects completed the Temporal Experience of Pleasure Scale (TEPS) and received resting-state fMRI (rs-fMRI). We used the wavelet-ALFF method and SVR to analyse the data. Patients with FES had lower consummatory pleasure scores than healthy subjects (t = -2.71, P<0.01). FES displays variable wavelet-ALFF in a wide range of cerebral cortices (P<0.05, GFR corrected). The SVR analysis showed that wavelet-ALFF, based primarily on the right putamen (r = 0.40, P<0.05) and right superior occipital gyrus (r = -0.39, P<0.05), was effective in predicting consummatory pleasure scores with an accuracy of 56.43 %. Our study shows that abnormal spontaneous neural activity in FES may be related to the state of consummatory anhedonia in FES. Wavelet-ALFF changes in the right putamen and superior occipital gyrus may be a biological feature of FES with anhedonia and could serve as a potential biological marker of FES with anhedonia.

Triptonide induces apoptosis and inhibits the proliferation of ovarian cancer cells by activating the p38/p53 pathway and autophagy.

Ovarian cancer is a common malignant tumor in women, and 70 % of ovarian cancer patients are diagnosed at an advanced stage. Drug chemotherapy is an important method for treating ovarian cancer, but recurrence and chemotherapy resistance often lead to treatment failure. In this study, we screened 10 extracts of Tripterygium wilfordii, a traditional Chinese herb, and found that triptonide had potent anti-ovarian cancer activity and an IC50 of only 3.803 nM against A2780 cell lines. In addition, we determined that triptonide had a better antitumor effect on A2780 cell lines than platinum chemotherapeutic agents in vitro and that triptonide had no significant side effects in vivo. We found that triptonide induced apoptosis in ovarian cancer cells through activation of the p38/p53 pathway and it also induced cell cycle arrest at the S phase. In addition, we demonstrated that triptonide could activate lethal autophagy, which led to growth inhibition and cell death in ovarian cancer cells, resulting in an anti-ovarian cancer effect. Triptonide exerts its anti-ovarian cancer effect through activation of the p38/p53 pathway and induction of autophagy to promote apoptosis, which provides a new candidate drug and strategy for the treatment of ovarian cancer.

The predictive value of the hs-CRP/HDL-C ratio, an inflammation-lipid composite marker, for cardiovascular disease in middle-aged and elderly people: evidence from a large national cohort study.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is associated with inflammation and abnormal lipid metabolism. However, a single inflammatory index or a single lipid index cannot accurately predict the prognosis of CVD independently because it is prone to be affected by various confounding factors. METHODS: This population-based cohort study included 6,554 participants from the China Health and Retirement Longitudinal Study (CHARLS) to investigate correlations. In the present study, the occurrence of CVD events such as stroke and heart disease was evaluated by considering self-reported diagnoses at the beginning of the study and during wave 4, and a restricted cubic spline model was used to investigate potential nonlinear relationships in addition to multivariate logistic regression models. Stratified analyses were performed to examine how sociodemographic characteristics may influence the results. RESULTS: Seven years of follow-up (2011-2018) revealed that 786 people (11.99%) developed CVD. According to the adjusted model, the high-sensitivity C-reactive protein (hs-CRP)-to-high-density lipoprotein cholesterol (HDL-C) ratio is a contributing factor to CVD risk (OR 1.31, 95% CI 1.05-1.64). In addition, a nonlinear relationship was observed between the hs-CRP/HDL-C ratio and the occurrence of new CVD, stroke, or cardiac issues (Poverall <0.05, Pnonlinear <0.05). Moreover, noteworthy associations between the hs-CRP/HDL-C ratio and age were detected in the stratified analysis (P = 0.048), indicating that younger participants had more negative effects of a high hs-CRP/HDL-C ratio. CONCLUSIONS: According to the present cohort study, a high hs-CRP/HDL-C ratio is a significant risk factor for CVD, new stroke, and heart problems. Early intervention in patients with increased hs-CRP/HDL-C ratios may further reduce the incidence of CVD, in addition to focusing on independent lipid markers or independent inflammatory markers.

Prevalence and Risk Factors of Non-Alcoholic Fatty Liver Disease (NAFLD) in Non-Obese Patients with Schizophrenia: A Retrospective Study.

Background: To assess the prevalence and risk factors of NAFLD in non-obese patients with schizophrenia in a public psychiatric hospital in China. Methods: A total of 1,305 adult inpatients with schizophrenia in 2019 were included in this retrospective study. Body mass index (BMI) ≥ 25 kg/m2 was considered obese, and BMI < 25 kg/m2 was considered non-obese. We obtained the data from electronic records of the Affiliated Brain Hospital of Guangzhou Medical University. Results: A total of 1,045 non-obese patients and 260 obese patients were included in this study. The prevalence of NAFLD in non-obese patients was 25.0%, and it was much lower that in the obese patients (25.0% vs 64.6%, p < 0.001). Among the non-obese patients, there were significant differences in age, BMI, alanine aminotransferase (ALT), metabolic indices, and the prevalence of diabetes and hypertension between patients with NAFLD and patients without NAFLD. According to the results of binary logistic regression analysis, age, BMI, ALT, triglyceride (TG) and diabetes were significantly related to NAFLD among non-obese patients with schizophrenia. In contrast, HDL-C was was negatively associated with NAFLD among non-obese patients. Conclusion: This study suggested that NAFLD was common in patients with schizophrenia, even in non-obese patients with schizophrenia. In non-obese patients with schizophrenia, age, BMI, ALT, TG and diabetes are significantly associated with NAFLD. Moreover, HDL-C level was an independent protective factor against NAFLD. Given the adverse outcomes of NAFLD, it is necessary to increase awareness of NAFLD in patients with schizophrenia, especially in non-obese patients with schizophrenia.

Diagnostic status and epidemiological characteristics of community-acquired bacterial meningitis in children from 2019 to 2020: a multicenter retrospective study.

Community-acquired bacterial meningitis (CABM) is the main cause of morbidity and mortality in children. The epidemiology of CABM is regional and highly dynamic. To clarify the diagnostic status and epidemiological characteristics of children with CABM in this region, and pay attention to the disease burden, so as to provide evidence for the prevention and treatment of CABM. By retrospective case analysis, the clinical data of 918 CABM cases in children aged 0-14 years in Zhejiang Province from January, 2019 to December, 2020 were collected. The etiological diagnosis rate of CABM in children was 23.1%, the annual incidence rate 4.42-6.15/100,000, the annual mortality rate 0.06-0.09/100,000,the cure and improvement rate 94.4%, and the case fatality rate 1.4%. The total incidence of neuroimaging abnormalities was 20.6%. The median length of stay for CABM children was 20(16) days, with an average cost of 21,531(24,835) yuan. In addition, the incidence rate was decreased with age. Escherichia coli(E.coli) and group B Streptococcus agalactiae(GBS) were the principal pathogens in CABM infant<3 months(43.3%, 34.1%), and Streptococcus pneumoniae(S. pneumoniae) was the most common pathogen in children ≥ 3 months(33.9%). In conclusion, the annual incidence and mortality of CABM in children aged 0-14 years in Zhejiang Province are at intermediate and low level. The distribution of CABM incidence and pathogen spectrum are different in age; the incidence of abnormal neuroimaging is high; and the economic burden is heavy.

LncRNA STAT3-AS regulates endometrial receptivity via the STAT3 signaling pathway.

Endometrial receptivity is critical for the successful establishment of pregnancy in ruminants. Interferon tau (IFNT) plays a key role in promoting embryo attachment by activating the Janus kinase/signal transducer and activator of transcription pathway, which induces the expression of a series of interferon-stimulated genes (ISGs). In our previous study, sequencing analysis of goat endometrial epithelial cells (gEECs) treated with 20 ng/mL IFNT revealed a differentially expressed long non-coding RNA located on the STAT3 antisense chain, which we designated STAT3-AS. The aim of this study was to investigate the role and mechanism of STAT3-AS in establishing endometrial receptivity in goats. The results showed that STAT3-AS was expressed in both the nucleus and cytoplasm of gEECs, and its expression increased significantly in the uterus on day 15 of pregnancy. STAT3-AS expression was upregulated in gEECs treated with IFNT alone or in combination with progesterone and estradiol. Knockdown of STAT3-AS using specific short interfering RNA significantly inhibited the expression of classical ISGs such as interferon-stimulated gene 15 and 2',5'-oligodenylate synthetase 2, as well as uterine endometrial receptivity-related genes including homeobox gene A11, integrin beta 3, and vascular endothelial growth factor. Moreover, gEEC proliferation and the STAT3 pathway were suppressed in the absence of STAT3-AS. However, pretreatment with the STAT3 activator RO8191 restored the effect of silencing STAT3-AS on endometrial receptivity. Overall, these results suggest that STAT3-AS is an important regulator of endometrial receptivity in goats and that it regulates endometrial receptivity through the STAT3 pathway.

Tailored pharmacist-led intervention to improve adherence to Iron supplementation in premature infants: a randomized controlled trial in China.

Introduction: Prematurity is due to a number of factors, especially genetics. This study was designed to evaluate the impact of a pharmacist-led patient-centered medication therapy management trial on iron deficiency and medication adherence among premature infants receiving iron supplementation at a tertiary hospital in Shaoxing, China. Methods: In this randomised controlled trial, eighty-one premature infants, with or without genetic factors, born at 26 to 30 weeks and 6 days gestational age, will be recruited and randomised to an intervention group or a control group. The intervention group will receive a pharmacist-driven discharge counseling on iron supplements from recruitment, until 12 months. The control group will receive care as usual. The main outcomes were haemoglobin (g/L), serum iron (µg/L), medication adherence estimation and differentiation scale, the satisfaction with information about medicines scale, beliefs about medicines questionnaire and the Bayley scales for infant development. Results: A total of 81 patients were enrolled in the study. After intervention, results for the haemoglobin and serum iron differed significantly between the control group and the intervention group (101.36 vs. 113.55, P < 0.0001 and 51.13 vs. 101.36, P = 0.004). Additionally, there was a substantial difference between the intervention group and the control group in terms of patient medication adherence estimation and differentiation scale (27 vs. 34, P = 0.0002). the intervention group had better mental development index and psychomotor development index, compared with the control group (91.03 vs. 87.29, P = 0.035 and 95.05 vs. 90.00, P = 0.022). Discussion: In premature infants with iron deficiency, our pharmacist-led team significantly improved clinical outcomes and medication adherence.

Continuous electroproduction of formate via CO2 reduction on local symmetry-broken single-atom catalysts.

Atomic-level coordination engineering is an efficient strategy for tuning the catalytic performance of single-atom catalysts (SACs). However, their rational design has so far been plagued by the lack of a universal correlation between the coordination symmetry and catalytic properties. Herein, we synthesised planar-symmetry-broken CuN3 (PSB-CuN3) SACs through microwave heating for electrocatalytic CO2 reduction. Remarkably, the as-prepared catalysts exhibited a selectivity of 94.3% towards formate at -0.73 V vs. RHE, surpassing the symmetrical CuN4 catalyst (72.4% at -0.93 V vs. RHE). In a flow cell equipped with a PSB-CuN3 electrode, over 90% formate selectivity was maintained at an average current density of 94.4 mA cm-2 during 100 h operation. By combining definitive structural identification with operando X-ray spectroscopy and theoretical calculations, we revealed that the intrinsic local symmetry breaking from planar D4h configuration induces an unconventional dsp hybridisation, and thus a strong correlation between the catalytic activity and microenvironment of metal centre (i.e., coordination number and distortion), with high preference for formate production in CuN3 moiety. The finding opens an avenue for designing efficient SACs with specific local symmetries for selective electrocatalysis.

Cryoprotective Effect of NADES on Frozen-Thawed Mirror Carp Surimi in Terms of Oxidative Denaturation, Structural Properties, and Thermal Stability of Myofibrillar Proteins.

Quality degradation due to the formation and growth of ice crystals caused by temperature fluctuations during storage, transportation, or retailing is a common problem in frozen surimi. While commercial antifreeze is used as an ingredient in frozen surimi, its high sweetness does not meet the contemporary consumer demand for low sugar and low calories. Therefore, the development of new green antifreeze agents to achieve an enhanced frozen-thawed stability of surimi has received more attention. The aim of this study was to develop a cryoprotectant (a mixture of citric acid and trehalose) to enhance the frozen-thawed stability of surimi by inhibiting the oxidative denaturation and structural changes of frozen-thawed mirror carp (Cyprinus carpio L.) surimi myofibrillar protein (MP). The results showed that the amounts of free amine, sulfhydryl, α-helix, intrinsic fluorescence intensity, and thermal stability in the control significantly decreased after five F-T cycles, while the Schiff base fluorescence intensity, amounts of disulfide bonds and surface hydrophobicity significantly increased (p < 0.05). Compared to sucrose + sorbitol (SS), the natural deep eutectic solvents (NADES) effectively inhibited protein oxidation. After five F-T cycles, the α-helix content and Ca2+-ATPase activity of the NADES samples were 4.32% and 80.0%, respectively, higher, and the carbonyl content was 17.4% lower than those of the control. These observations indicate that NADES could inhibit oxidative denaturation and enhance the structural stability of MP.

Activation of ULK1 to trigger FUNDC1-mediated mitophagy in heart failure: Effect of Ginsenoside Rg3 intervention.

BACKGROUND: Although the development of therapies for heart failure (HF) continues apace, clinical outcomes are often far from ideal. Unc51-like-kinase 1 (ULK1)-mediated mitophagy prevents pathological cardiac remodeling and heart failure (HF). Molecularly ULK1-targeted agent to enhance mitophagy is scanty. HYPOTHESIS/PURPOSE: This study aimed to investigate whether Ginsenoside Rg3 (Rg3) can activate ULK1 to trigger FUNDC1-mediated mitophagy for protecting heart failure. METHODS: Molecular docking and surface plasmon resonance were used to detect the ULK1 binding behavior of Rg3. Established HF model in rats and transcriptome sequencing were used to evaluate the therapeutic effect and regulatory mechanism of Rg3. Loss-of-function approaches in vivo and in vitro were performed to determine the role of ULK1 in Rg3-elicited myocardial protection against HF. FUNDC1 recombinant plasmid of site mutation was applied to elucidate more in-depth mechanisms. RESULTS: Structurally, a good binding mode was unveiled between ULK1 and Rg3. In vivo, Rg3 improved cardiac dysfunction, adverse remodeling, and mitochondrial damage in HF rats. Furthermore, Rg3 promoted Ulk1-triggered mitophagy both in vivo and in vitro, manifested by the impetus of downstream Fundc1-Lc3 interaction. Of note, the protective effects conferred by Rg3 against mitophagy defects, pathological remodeling, and cardiac dysfunction were compromised by Ulk1 gene silencing both in vivo and in vitro. Mechanistically, Rg3 activated mitophagy by inducing ULK1-mediated phosphorylation of FUNDC1 at the Ser17 site, not the Ser13 site. CONCLUSION: Together these observations demonstrated that Rg3 acts as a ULK1 activator for the precise treatment of HF, which binds to ULK1 to activate FUNDC1-mediated mitophagy.