Production of succinate with two CO2 fixation reactions from fatty acids in Cupriavidus necator H16.

BACKGROUND: Biotransformation of CO2 into high-value-added carbon-based products is a promising process for reducing greenhouse gas emissions. To realize the green transformation of CO2, we use fatty acids as carbon source to drive CO2 fixation to produce succinate through a portion of the 3-hydroxypropionate (3HP) cycle in Cupriavidus necator H16. RESULTS: This work can achieve the production of a single succinate molecule from one acetyl-CoA molecule and two CO2 molecules. It was verified using an isotope labeling experiment utilizing NaH13CO3. This implies that 50% of the carbon atoms present in succinate are derived from CO2, resulting in a twofold increase in efficiency compared to prior methods of succinate biosynthesis that relied on the carboxylation of phosphoenolpyruvate or pyruvate. Meanwhile, using fatty acid as a carbon source has a higher theoretical yield than other feedstocks and also avoids carbon loss during acetyl-CoA and succinate production. To further optimize succinate production, different approaches including the optimization of ATP and NADPH supply, optimization of metabolic burden, and optimization of carbon sources were used. The resulting strain was capable of producing succinate to a level of 3.6 g/L, an increase of 159% from the starting strain. CONCLUSIONS: This investigation established a new method for the production of succinate by the implementation of two CO2 fixation reactions and demonstrated the feasibility of ATP, NADPH, and metabolic burden regulation strategies in biological carbon fixation.

The global burden of disease attributable to high body mass index in 204 countries and territories: Findings from 1990 to 2019 and predictions to 2035.

AIM: Our study aims to provide an updated estimate of age- and sex-specific deaths and disability-adjusted life years (DALYs) associated with high body mass index (BMI) from 1990 to 2019 at the global, regional and national levels, and to forecast the global burden of disease attributed to high BMI from 2020 to 2035. METHODS: We used the data for the number of deaths, DALYs, age-standardized rate (per 100 000 population), percentage change and population attributable fraction from the Global Burden of Disease Study 2019 (GBD 2019) to examine the disease burden attributable to high BMI. We further applied an autoregressive integrated moving average (ARIMA) model to predict the disease burden for the period 2020-2035. RESULTS: From 1990 to 2019, the deaths and DALYs attributable to high BMI increased by 148% and 155.86% for men, and by 111.67% and 121.78% for women, respectively. In 2019, high BMI directly accounted for 8.52% [95% uncertainty intervals (UI) 0.05, 0.12] of all-cause deaths and 5.89% (95% UI 0.04, 0.08) of global DALYs. The highest death rates were observed in men aged 65-69 and women aged 75-79. The highest DALY rates were observed in the age group of 60-64 for both sexes. In 2019, the highest age-standardized deaths and DALY rates were observed in the Central Asia region [163.15 (95% UI 107.72, 223.58) per 100 000 people] and the Oceania region [4643.33 (95% UI 2835.66, 6902.6) per 100 000 people], respectively. Fiji [319.08 (95% UI 213.77, 444.96) per 100 000 people] and Kiribati [10 000.58 (95% UI 6266.55, 14159.2) per 100 000 people] had the highest age-standardized deaths and DALY rates, respectively. In 2019, the highest age-standardized rates of high BMI-related deaths and DALYs were observed in the middle-high socio-demographic index quintile and in the middle socio-demographic index quintile. The age-standardized deaths and DALY rates attributable to high BMI are projected to increase in both sexes from 2020 to 2035. The death rates are projected to rise from 62.79 to 64.31 per 100 000 people, while the DALY rates are projected to rise from 1946 to 2099.54 per 100 000 people. CONCLUSIONS: High BMIs significantly contribute to the global disease burden. The projected rise in deaths and DALY rates attributable to high BMI by 2035 highlights the critical need to address the impact of obesity on public health. Our study provides policymakers with up-to-date and comprehensive information.

Chirality-Induced Magnet-Free Spin Generation in a Semiconductor.

Electrical generation and transduction of polarized electron spins in semiconductors (SCs) are of central interest in spintronics and quantum information science. While spin generation in SCs is frequently realized via electrical injection from a ferromagnet (FM), there are significant advantages in nonmagnetic pathways of creating spin polarization. One such pathway exploits the interplay of electron spin with chirality in electronic structures or real space. Here, utilizing chirality-induced spin selectivity (CISS), the efficient creation of spin accumulation in n-doped GaAs via electric current injection from a normal metal (Au) electrode through a self-assembled monolayer (SAM) of chiral molecules (α-helix l-polyalanine, AHPA-L), is demonstrated. The resulting spin polarization is detected as a Hanle effect in the n-GaAs, which is found to obey a distinct universal scaling with temperature and bias current consistent with chirality-induced spin accumulation. The experiment constitutes a definitive observation of CISS in a fully nonmagnetic device structure and demonstration of its ability to generate spin accumulation in a conventional SC. The results thus place key constraints on the physical mechanism of CISS and present a new scheme for magnet-free SC spintronics.

Design of Linear-Polymer-Coated Graphene Nanosheets with π-Conjugated Structure and Multi-Active-Center for Long-Lifespan and High-Rate Li-Storage Performance.

Organic material holds immense potential for Li-ion batteries (LIBs) due to their eco-friendly nature, high structural designability, abundant sources, and high theoretical capacity. However, the limited redox-active sites, low electronic conductivity, sluggish ionic diffusion, and high solubility hinder their practical application. Here, we reported the use of a linear polymer called poly(naphthalenetetracarboxylic dianhydride-pyrene-4,5,9,10-tetraone)-coated graphene nanosheets (NPT/rGO) as a cathode material for LIBs. The NPT polymer has a rotation angle of approximately 63° between each plane, which helps in exposing the active sites and preventing structural pulverization during cycling. The highly conjugated skeleton of the polymer, along with graphene, forms a synergistic effect through a π-π interaction. This combination enhances the conductivity and restricts solubility. Additionally, the linear structure of NPT and the two-dimensional rGO substrates work together to enhance charge transfer and ion diffusion rates, resulting in faster reaction kinetics. Consequently, NPT/rGO exhibits excellent electrochemical performance in terms of high capacity, superior cyclic stability, and good rate capability for LIBs. Moreover, through the combination of experimental investigations and theoretical simulations, a multiple electron reaction mechanism, an efficient Li-ion storage behavior, and a reversible dynamic evolution have been revealed. This study introduces a rational molecular design approach to enhance the electrochemical performance of polyimide derivatives, thereby contributing to the advancement of cutting-edge organic electrode materials for LIBs.

Design, Fabrication, and Characterization of a Planar Three-Electrode Trigger Switch Based on Flexible Printed Circuit Process.

An exploding foil initiator system (EFIs) is essential in modern weaponry for its safety and reliability. As the main component of EFIs, the performance of the switch is critical to EFIs. In this study, a planar three-electrode trigger switch was designed and fabricated using the Flexible Printed Circuits (FPC) process. Subsequently, the performance of the FPC switch was tested. The results show that the self-breakdown voltage of the FPC switch is stable. In addition, an FPF switch with a 0.6 mm main electrode gap demonstrated consistency, with delay times below 31.75 ns, and a jitter ranging from 1.7 ns to 10.94 ns at 900 V to 1200 V, evidencing the FPC switches' reliability and uniform performance across various voltages. Compared to the Micro-Electro-Mechanical Systems (MEMS) switches of similar dimensions, the FPC switches achieved a faster high-current attainment with less inductance, showing a 5% reduction in loop inductance. The repetitive testing results demonstrate that the FPC switch maintains consistent output performance, with stable peak currents, peak current time, and delay time over 50 action cycles, highlighting its repeatability. The FPC switch was assembled with an EFI chip and capacitor into an integrated system, which was subsequently able to successfully detonate HNS-IV at 1000 V/0.22 µF, proving the FPC switch's potential in low inductance applications.

A Micro Bridge-Wing-Thickened Low-Energy Exploding Foil Initiator Chip.

To enhance the energy efficiency of exploding foil initiator systems (EFIs) and mitigate energy loss due to ablation in the bridge-wing regions, a low-energy bridge-wing-thickened EFI chip was designed and fabricated. Computational analysis revealed that increasing the thickness of the bridge flanks significantly reduces ablation within the bridge region during the electrical explosion. The refinement of the design led to the adoption of a bridge flank thickness of 19 µm, with the bridge area dimensions specified as 0.25 mm × 0.25 mm × 4 µm. This bridge-wing-thickened EFI chip was produced by employing micro-electro-mechanical systems (MEMS) technology and underwent rigorous performance evaluations. The empirical results closely matched the computational predictions, thereby corroborating the precision of the proposed model in simulating the temperature distribution seen during the explosion process. Notably, this enhanced EFI design achieves a flyer velocity of 3800 m/s at a condition of 900 V/0.22 µF, signifying a significant advancement in EFI system efficiency and performance.

APTAnet: an atom-level peptide-TCR interaction affinity prediction model.

The prediction of affinity between TCRs and peptides is crucial for the further development of TIL (Tumor-Infiltrating Lymphocytes) immunotherapy. Inspired by the broader research of drug-protein interaction (DPI), we propose an atom-level peptide-TCR interaction (PTI) affinity prediction model APTAnet using natural language processing methods. APTAnet model achieved an average ROC-AUC and PR-AUC of 0.893 and 0.877, respectively, in ten-fold cross-validation on 25,675 pairs of PTI data. Furthermore, experimental results on an independent test set from the McPAS database showed that APTAnet outperformed the current mainstream models. Finally, through the validation on 11 cases of real tumor patient data, we found that the APTAnet model can effectively identify tumor peptides and screen tumor-specific TCRs.

Characteristics and Risk Factors for Pediatric Sepsis.

OBJECTIVE: Sepsis is considered a major cause of health loss in children and had high mortality and morbidity. Currently, there is no reliable model for predicting the prognosis of pediatric patients with sepsis. This study aimed to analyze the clinical characteristics of sepsis in children and assess the risk factors associated with poor prognosis in pediatric sepsis patients to identify timely interventions and improve their outcomes. METHODS: This study analyzed the clinical indicators and laboratory results of septic patients hospitalized in the Pediatric Intensive Care Unit of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, from January 1, 2019, to December 31, 2021. Risk factors for sepsis were identified by logistic regression analyses. RESULTS: A total of 355 children with sepsis were enrolled, with 333 children (93.8%) in the good prognosis group, and 22 children (6.2%) in the poor prognosis group. Among them, there were 255 patients (71.8%) in the sepsis group, and 100 patients (28.2%) in the severe sepsis group. The length of hospital stay in the poor prognosis group was longer than that in the good prognosis group (P<0.01). The levels of interleukin 1ß (IL-1ß) in the poor prognosis group were higher than those in the good prognosis group (P>0.05), and the platelet (PLT), albumin (ALB), and hemoglobin (Hb) levels were lower in the poor prognosis group (P<0.01). The IL-8 levels in the severe sepsis group were higher than those in the sepsis group (P<0.05). Multiple logistic regression analysis suggested that lower Hb levels, ALB levels, peak PLT counts, and higher IL-1ß levels were independent risk factors for poor prognosis in children with sepsis. CONCLUSION: Lower Hb, ALB, and PLT counts and elevated IL-1ß are independent risk factors for poor prognosis in children with sepsis.

[Reversal Effect of NVP-BEZ235 on Doxorubicin-Resistance in Burkitt Lymphoma RAJI Cell Line].

OBJECTIVE: To study the reversal effect of NVP-BEZ235 on doxorubicin resistance in Burkitt lymphoma RAJI cell line. METHODS: The doxorubicin-resistant cell line was induced by treating RAJI cells with a concentration gradient of doxorubicin. The levels of Pgp, p-AKT, and p-mTOR in cells were detected by Western blot. Cell viability was detected by MTT assay. IC50 was computed by SPSS. RESULTS: The doxorubicin-resistant Burkitt lymphoma cell line, RAJI/DOX, was established successfully. The expression of Pgp and the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line were both higher than those in RAJI cell line. NVP-BEZ235 downregulated the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line. NVP-BEZ235 inhibited the proliferation of RAJI/DOX cell line, and the effect was obvious when it was cooperated with doxorubicin. CONCLUSION: The constitutive activation of PI3K/AKT/mTOR pathway of RAJI/DOX cell line was more serious than RAJI cell line. NVP-BEZ235 reversed doxorubicin resistance of RAJI/DOX cell line by inhibiting the PI3K/AKT/mTOR signal pathway.

Discovery of novel diaryl substituted isoquinolin-1(2H)-one derivatives as hypoxia-inducible factor-1 signaling inhibitors for the treatment of rheumatoid arthritis.

Since synovial hypoxic microenvironment significantly promotes the pathological progress of rheumatoid arthritis (RA), hypoxia-inducible factor 1 (HIF-1) has been emerged as a promising target for the development of novel therapeutic agents for RA treatment. In this study, we designed and synthesized a series of diaryl substituted isoquinolin-1(2H)-one derivatives as HIF-1 signaling inhibitors using scaffold-hopping strategy. By modifying the substituents on N-atom and 6-position of isoquinolin-1-one, we discovered compound 17q with the most potent activities against HIF-1 (IC50 = 0.55 µM) in a hypoxia-reactive element (HRE) luciferase reporter assay. Further pharmacological studies revealed that 17q concentration-dependently blocked hypoxia-induced HIF-1α protein accumulation, reduced inflammation response, inhibited cellular invasiveness and promoted VHL-dependent HIF-1α degradation in human RA synovial cell line. Moreover, 17q improved the pathological injury of ankle joints, decreased angiogenesis and attenuated inflammation response in the adjuvant-induced arthritis (AIA) rat model, indicating the promising therapeutic potential of compound 17q as an effective HIF-1 inhibitor for RA therapy.

Optimization strategies for CO2 biological fixation.

Global sustainable development faces a significant challenge in effectively utilizing CO2. Meanwhile, CO2 biological fixation offers a promising solution. CO2 has the highest oxidation state (+4 valence state), whereas typical multi­carbon chemicals have lower valence states. The Gibbs free energy (ΔG) changes of CO2 reductive reactions are generally positive and this renders it necessary to input different forms of energy. Although biological carbon fixation processes are friendly to operate, the thermodynamic obstacles must be overcome. To make this reaction occur favorably and efficiently, diverse strategies to enhance CO2 biological fixation efficiency have been proposed by numerous researchers. This article reviews recent advances in optimizing CO2 biological fixation and intends to provide new insights into achieving efficient biological utilization of CO2. It first outlines the thermodynamic characteristics of diverse carbon fixation reactions and proposes optimization directions for CO2 biological fixation. A comprehensive overview of the catalytic mechanisms, optimization strategies, and challenges encountered by common carbon-fixing enzymes is then provided. Subsequently, potential routes for improving the efficiency of biological carbon fixation are discussed, including the ATP supply, reducing power supply, energy supply, reactor design, and carbon enrichment system modules. In addition, effective artificial carbon fixation pathways were summarized and analyzed. Finally, prospects are made for the research direction of continuously improving the efficiency of biological carbon fixation.

Global burden of diseases attributable to intimate partner violence: findings from the Global Burden of Disease Study 2019.

PURPOSE: Our study aims to evaluate the global burden of disease attributable to IPV from 1990 to 2019 at global, regional, national, and socio-demographic index (SDI) levels. Our research question is: What is the global burden of disease attributable to intimate partner violence (IPV) from 1990 to 2019, and how does it vary at global, regional, national, and socio-demographic index (SDI) levels? METHODS: Data parameters for the number of deaths, disability-adjusted life years (DALYs), and age-standardized rate were obtained from the Global Burden of Disease Study 2019. We calculated the percentage change and population attributable fraction with 95% uncertainty intervals. RESULTS: IPV directly accounted for 0.14% [95% UI 0.09%, 0.21%] and 0.32% [95% UI 0.17%, 0.49%] of global all-cause deaths and DALYs in 2019, respectively. The age-standardized deaths and DALYs rates of IPV increased by 12.83% and 4.00% respectively from 1990 to 2019. Women aged 35-39 and 30-34 had the highest deaths and DALYs rate respectively. The highest age-standardized rates of IPV-related deaths and DALYs were observed in Southern Sub-Saharan. Both of deaths and DALYs were high in low-socio-demographic Index (SDI) quintile in 2019. CONCLUSIONS: A higher level of deaths and DALYs attributable to IPV were reported in younger women, in the early 2000s, in Southern Sub-Saharan regions and in low SDI regions. Our study provides policymakers with up-to-date and comprehensive information.

Synergistic antitumor activity between HER2 antibody-drug conjugate and chemotherapy for treating advanced colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer associated with a poor prognosis. Effective targeted therapy alone or in combination for treating advanced CRC remains to be a major clinical challenge. Here, we propose the therapeutic efficacy and molecular mechanism underlying RC48, a FDA-approved anti-HER2 antibody conjugate via a cleavable linker to the microtubule inhibitor monomethyl auristatin E (MMAE), either alone or in combination with gemcitabine (GEM) in various models of HER2-positive advanced CRC. Our findings demonstrated that HER2 was widely expressed and located on the plasma membrane of CRC patient specimens, PDX xenograft tumors and cell lines. It confirmed that RC48 alone significantly targeted and eradicated HER2 positive CRC tumor in these models. Moreover, we screened a panel of FDA-approved first-line chemotherapy drugs in vitro. We found that GEM exhibited stronger antiproliferative activity compared to the other first-line anti-cancer agents. Furthermore, combination therapy of RC48 and GEM significantly showed synergetic antitumor activity in vitro and in vivo. To gain further mechanistic insights into the combination therapy, we performed RNA-seq analysis. The results revealed that combination treatment of RC48 and GEM regulated multiple signaling pathways, such as PI3K-AKT, MAPK, p53, Foxo, apoptosis, cell cycle and cell senescence, etc., to exert its antitumor activity in CRC cells. Collectively, these preclinical findings demonstrated that RC48 alone or combinational therapy exerted promising antitumor activity, and meriting the preclinical framework for combinational therapy of anti-HER2 drug conjugate drug and chemotherapy drugs for HER2-positive patients with advanced CRC.

[Mechanism about LMP1 of EB Virus Promoting Plasma Blast Differentiation of DLBCL Cell via mTORC1].

OBJECTIVE: To investigate possible mechanism on protien LMP1 expressed by EBV inducing plasmablast differentiation of DLBCL cell via the mTORC1 pathway. METHODS: The expression levels of LMP1 protein, CD38 and the phosphorylation levels of p70S6K in EBV+ and EBV- DLBCL cell lines were detected by Western blot. Cell lines overexpressing LMP1 gene stablely were constructed and LMP1 gene was silenced by RNAi. The expression of LMP1 gene was verified by RT-qPCR. The expression levels of LMP1 and CD38 and the phosphorylation levels of p70S6K in each group were detected by Western blot. RESULTS: Compared with EBV-DLBCL cells, the expression of LMP1 was detected on EBV +DLBCL cells (P =0.0008), EBV +DLBCL cells had higher phosphorylation levels of p70S6K (P =0.0072) and expression levels of CD38(P =0.0091). Compared with vector group, the cells of LMP1OE group had higher expression levels of LMP1 and CD38 (P =0.0353; P <0.0001), meanwhile molecular p70S6K was phosphorylated much more(P =0.0065); expression of LMP1 mRNA was verified(P <0.0001). Compared with si-NC group, expression level of LMP1 protein(P =0.0129) was not detected and phosphorylated p70S6K disappeared of LMP1KO group (P =0.0228); meanwhile, expression of CD38 decreased,although there was no significant difference (P =0.2377). CONCLUSION: LMP1 promotes DLBCL cells plasmablast differentiation via activating mTORC1 signal pathway.

Carboxylated Pocoa polysaccharides inhibited oxidative damage and inflammation of HK-2 cells induced by calcium oxalate nanoparticles.

The inhibitory effects of Chinese medicine Pocoa (PCPs) with different carboxyl group (-COOH) contents on oxidative damage and inflammatory response of renal epithelial cells and the influence of -COOH content in polysaccharides were investigated. HK-2 cell damage model was established by nanocalcium oxalate crystals (nanoCOM), and then PCPs with -COOH contents of 2.56% (PCP0), 7.48% (PCP1), 12.07% (PCP2), and 17.18% (PCP3) were used to protect the cells. PCPs could inhibit the damage of nanoCOM to HK-2 cells, increase cell viability, restore cytoskeleton and morphology, and improve lysosomal integrity. PCPs can reduce the oxidative stress response of nanoCOM to cells, inhibit the opening of mPTP and cell necrotic apoptosis, reduce the level of Ca2+ ions in cells, the production of ATP and MDA, and increase SOD expression. PCPs can also reduce the cellular inflammatory response caused by oxidative damage, and reduce the expression of nitric oxide (NO), inflammatory factors TNF-α, IL-6, IL-1ß and MCP-1, as well as the content of inflammasome NLRP3. After protection, PCPs can inhibit the endocytosis of nanoCOM crystals by cells. With the increase in -COOH content in PCPs, its ability to inhibit nanoCOM cell damage, reduce oxidative stress, reduce inflammatory response, and inhibit crystal endocytosis increases, that is, PCP3 with the highest -COOH content, shows the best biological activity. Inhibiting cell damage and inflammation and reducing a large amount of endocytosis of crystals by cells are beneficial to inhibit the formation of kidney stones.

Recent Progress of Natural and Recombinant Phycobiliproteins as Fluorescent Probes.

Phycobiliproteins (PBPs) are natural water-soluble pigment proteins, which constitute light-collecting antennae, and function in algae photosynthesis, existing in cyanobacteria, red algae, and cryptomonads. They are special pigment-protein complexes in algae with a unique structure and function. According to their spectral properties, PBPs can be mainly divided into three types: allophycocyanin, phycocyanin, and PE. At present, there are two main sources of PBPs: one is natural PBPs extracted from algae and the other way is recombinant PBPs which are produced in engineered microorganisms. The covalent connection between PBP and streptavidin was realized by gene fusion. The bridge cascade reaction not only improved the sensitivity of PBP as a fluorescent probe but also saved the preparation time of the probe, which expands the application range of PBPs as fluorescent probes. In addition to its function as a light-collecting antenna in photosynthesis, PBPs also have the functions of biological detection, ion detection, and fluorescence imaging. Notably, increasing studies have designed novel PBP-based far-red fluorescent proteins, which enable the tracking of gene expression and cell fate.

Interaction effect of midday napping duration and depressive symptoms on subjective memory impairment among older people in China: evidence from the China health and retirement longitudinal study database.

BACKGROUND: Subjective memory impairment (SMI) is common in older people. The aim of this study was to investigate the factors influencing SMI among older people in China, with specific focus on the interaction effect of midday napping duration and depressive symptoms on the risk of SMI. METHODS: Using a dataset representative of the Chinese population from a longitudinal study of health and retirement in China, subjects with SMI were screened using the question "how do you feel about your memory now?" and the Mini-Mental State Examination. A logistic regression model was applied to explore the factors affecting SMI. Additive and multiplicative models were used to analyze the interaction effect of midday napping duration and depressive symptoms on the risk of SMI. RESULTS: We enrolled 8,254 subjects included and the incidence of SMI was 63.9%. Depressive symptoms, nap time, and physical activity were influencing factors of SMI. Midday napping duration and depressive symptoms had positive additive interaction effects on the risk of SMI. When extended-length naps and depressive symptoms coexisted, the risk of SMI was 1.06 times greater than that for either alone (RERI, relative excess risk due to interaction = 0.27, 95% CI = 0.07-0.43; AP, attributable proportion = 0.14, 95% CI = 0.01-0.23; S, synergy index = 1.06, 95% CI = 0.57-1.62). When short naps and depressive symptoms coexisted, the risk of SMI was 1.2 times higher than that for either alone (RERI = 0.12, 95% CI=-0.14-0.39; AP = 0.13, 95% CI=-0.07-0.22; S = 1.20, 95% CI = 0.79-1.82). LIMITATIONS: Since this was a cross-sectional study, the cause-and-effect relationships between the associated variables cannot be inferred. CONCLUSIONS: The interaction effect that exists between nap time and depressive symptoms in older people is important for the identification and early intervention of people at risk for SMI.

Correlation study of brain-derived neurotrophic factor, EEG γ activity and cognitive function in first-episode schizophrenia.

BACKGROUND: Schizophrenia is characterised by neurotrophic, neuroelectrophysiological and cognitive dysfunction. However, there exists a paucity of research examining the association between serum brain-derived neurotrophic factor (BDNF) concentration, resting electroencephalogram (EEG) gamma activity, and cognitive impairment in individuals diagnosed with schizophrenia. METHODS: In this study, 87 first-episode schizophrenia patients and 75 healthy controls were assessed. Measurements were conducted to determine the levels of BDNF, resting EEG γ-activity at left and right frontal pole EEG electrodes respectively (FP1/FP2) leads, and cognitive function as assessed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia MATRICS Consensus Cognitive Battery (MCCB). Comparisons were made between the patient group and the control group, revealing lower BDNF levels, lower T-scores for 7 MCCB cognitive items, and higher EEG γ-activity among patients when compared to controls. RESULTS: According to the correlation analysis, there were significant associations observed in the patient group. BDNF levels were found to be correlated with EEG γ activity as well as T-scores of speed of processing (SoP), verbal learning (VeL), and reasoning problem-solving (RPS). Moreover, EEG γ activity showed an association with both the total score of the Positive and Negative Syndrome Scale (PANSS) and T-score of SoP. These findings suggest a potential relationship between BDNF levels, EEG γ activity, cognitive domains, and clinical symptoms in individuals with first-episode schizophrenia. CONCLUSIONS: In conclusion, our findings demonstrate the coexistence of neurobiochemical and electrophysiological abnormalities alongside cognitive dysfunction during the early stages of schizophrenia. These findings provide valuable insights into the mechanism of cognitive impairment in schizophrenia. By highlighting the simultaneous occurrence of these factors, our study contributes to a better understanding of the complex nature of schizophrenia and emphasizes the importance of studying its cognitive aspects.

Prevalence of common mental disorders among medical students in China: a systematic review and meta-analysis.

Background: The prevalence of mental distress is common for medical students in China due to factors such as the long duration of schooling, stressful doctor-patient relationship, numerous patient population, and limited medical resources. However, previous studies have failed to provide a comprehensive prevalence of these mental disorders in this population. This meta-analysis aimed to estimate the prevalence of common mental disorders (CMDs), including depression, anxiety, and suicidal behaviors, among medical students in China. Methods: We conducted a systematic search for empirical studies on the prevalence of depression, anxiety, suicide attempt, suicide ideation, and suicide plan in Chinese medical students published from January 2000 to December 2020. All data were collected pre-COVID-19. The prevalence and heterogeneity estimations were computed by using a random-effects model and univariate meta-regression analyses. Results: A total of 197 studies conducted in 23 provinces in China were included in the final meta-analysis. The prevalence data of depression, anxiety, suicide attempt, suicide ideation, and suicide plan were extracted from 129, 80, 21, 53, and 14 studies, respectively. The overall pooled crude prevalence for depression was 29% [38,309/132,343; 95% confidence interval (CI): 26%-32%]; anxiety, 18% (19,479/105,397; 95% CI: 15%-20%); suicide ideation, 13% (15,546/119,069; 95% CI: 11%-15%); suicide attempt, 3% (1,730/69,786; 95% CI: 1%-4%); and suicide plan, 4% (1,188/27,025; 95% CI: 3%-6%). Conclusion: This meta-analysis demonstrated the high prevalence of CMDs among Chinese medical students. Further research is needed to identify targeted strategies to improve the mental health of this population.

Altered intestinal barrier contributes to cognitive impairment in old mice with constipation after sevoflurane anesthesia.

Background: Elderly patients have a high risk of developing postoperative cognitive dysfunction (POCD). Gastrointestinal disorders, such as constipation, in the elderly population may be involved in the pathogenesis of neurological disorders by promoting inflammatory responses due to a 'leaky gut'. General anesthetic sevoflurane may impair gastrointestinal function in elderly patients to trigger neurological complications following surgery. Therefore, we hypothesized that elderly individuals with gastrointestinal dysfunction may be more vulnerable to sevoflurane and consequently develop POCD. Methods: Aged mice were randomly divided into four groups: control (CTRL), CTRL+sevoflurane (Sev), slow transit constipation (STC), and STC + Sev. Mice in the STC and STC + Sev groups were intra-gastrically administrated loperamide (3 mg/kg, twice a day for 7 days) to induce a slow transit constipation (STC) model determined with fecal water content and the time of first white fecal pellet, whereas mice in the other groups received the similar volume of saline. One week later, mice in the CTRL+Sev group and STC + Sev group received 2% sevoflurane for 2 h. The gut permeability evaluated with 4-kDa fluorescein isothiocyanate (FITC)-dextran, serum cytokines, microglia density, TLR4/NF-κB signaling expression, and POCD-like behavioral changes were determined accordingly. Results: The loperamide-induced STC mice had decreased fecal water content and prolonged time of first white fecal pellet. Sevoflurane exposure caused significantly increased gut permeability and serum cytokines, as well as the activation of microglia and the TLR4/NF-κB signaling pathway in the prefrontal cortex of the aged STC mice. Sevoflurane also caused cognitive impairment and emotional phenotype abnormality in aged STC mice. Conclusion: Aged STC mice were more vulnerable to sevoflurane anesthesia and consequently developed POCD-like behavioral changes. Our data suggest that gastrointestinal disorders including constipation may contribute to the development of POCD.