Cluster-Cluster Co-Nucleation Induced Defective Polyoxometalate-Based Metal-Organic Frameworks for Efficient Tandem Catalysis.

The construction of defective sites is one of the effective strategies to create high-activity Metal-Organic frameworks (MOFs) catalysts. However, traditional synthesis methods usually suffer from cumbersome synthesis steps and disordered defect structures. Herein, a cluster-cluster co-nucleation (CCCN) strategy is presented that involves the in situ introduction of size-matched functional polyoxometalates (H6P2W18O62, {P2W18}) to intervene the nucleation process of cluster-based MOFs (UiO-66), achieving one-step inducement of exposed defective sites without redundant post-processing. POM-induced UiO-66 ({P2W18}-0.1@UiO-66) exhibits a classical reo topology for well-defined cluster defects. Moreover, the defective sites and the interaction between POM and skeletal cluster nodes are directly observed by Integrated Differential Phase Contrast in Scanning Transmission Electron Microscopy (iDPC-STEM). Owing to the molecular-level proximity between defective sites and POM in the same nano-reaction space, {P2W18}-0.1@UiO-66 exhibits efficient tandem catalysis in the preparation of γ-valerolactone (γ-GVL) from laevulinic acid (LA) by the combination of Lewis and Brønsted acids with 11 times higher performance than defective UiO-66 formed by conventional coordination modulation strategy. The CCCN strategy is applicable to different POM and has the potential to be extended to other cluster-based MOFs, which will pave a new way for the construction of functional MOFs with multi-centered synergistic catalysis.

Comparison of outcomes between stent retriever combined with contact aspiration versus contact aspiration alone in patients without hyperdense artery sign/susceptibility vessel sign.

PURPOSE: To examine the relationship between hyperdense artery sign/susceptibility vessel sign (HAS/SVS) and thrombus composition, and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior-circulation large vessel occlusion (LVO). MATERIALS AND METHODS: From January 2018 to June 2021, 103 consecutive acute anterior-circulation LVO patients (75 [63.1%] male; median age, 66 years) who underwent thrombectomy, and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was respectively assessed in noncontrast computed tomography (NCCT) and susceptibility-weighted imaging (SWI). Association of first-line thrombectomy techniques [stent retriever combined with contact aspiration (SR+CA) versus contact aspiration (CA)] with outcomes was assessed by the HAS/SVS status. RESULTS: Among the included patients, 55 (53.4%) were HAS/SVS(-), and 69 (67.0%) chose first-line SR+CA. Higher relative densities of fibrin/platelets (0.56 vs. 0.51, p<0.001) and lower relative densities of erythrocytes (0.32 vs. 0.42, p<0.001) were observed in HAS/SVS(-) than HAS/SVS(+) patients. First-line SR+CA was associated with reduced odds of distal embolization (aOR, 0.18; 95% CI, 0.04-0.83; p=0.027) and a more favorable 90-day functional outcome (aOR, 5.29; 95% CI, 1.06-26.34; p=0.042) in HAS/SVS(-) patients, and a longer recanalization time (53 min vs. 25 min, p=0.025) and higher risk of subarachnoid hemorrhage (24.2% vs. 0%, p=0.044) in HAS/SVS(+) patients. CONCLUSIONS: HAS/SVS(-) may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR+CA may have a possible better performance than CA in acute LVO patients without HAS/SVS.

Legionella effector LnaB is a phosphoryl-AMPylase that impairs phosphosignalling.

AMPylation is a posttranslational modification that generally modifies amino acid side chains of proteins with adenosine monophosphate (AMP)1,2. Here we report that with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity toward the phosphoryl group of phosphoribose on PRR42-Ub that is generated by the SidE family effectors and deubiquitinases DupA/B in an E1/E2-independent ubiquitination process3-7. The product of LnaB is further hydrolyzed by an ADP-ribosyl hydrolase, MavL, to be Ub, thereby preventing accumulation of PRR42-Ub and ADPRR42-Ub and protecting the canonical ubiquitination in host cells. LnaB represents a large family of AMPylases adopting a common structural fold, which is distinct from those of the previously known AMPylases, in bacterial pathogens of more than 20 species. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity toward phosphorylated residues and produces unique ADPylation modification in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family kinases8,9, which dampens the host downstream phosphorylation signaling. Structural studies revealed the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study presents an unprecedented regulation and molecular mechanism in bacterial pathogenesis and protein phosphorylation.

Tuning the Electronic Structures of Anchor Sites to Achieve Zero-Valence Single-Atom Catalysts for Advanced Hydrogenation.

Single-atom catalysts (SACs) have recently become highly attractive for selective hydrogenation reactions owing to their remarkably high selectivity. However, compared to their nanoparticle counterparts, atomically dispersed metal atoms in SACs often show inferior activity and are prone to aggregate under reaction conditions. Here, by theoretical calculations, we show that tuning the local electronic structures of metal anchor sites on g-C3N4 by doping B atoms (BCN) with relatively lower electronegativity allows achieving zero-valence Pd SACs with reinforced metal-support orbital hybridizations for high stability and upshifted Pd 4d orbitals for high activity in H2 activation. The precise synthesis of Pd SACs on BCN supports with varied B contents substantiated the theoretical prediction. A zero-valence Pd1/BCN SAC was achieved on a BCN support with a relatively low B content. It exhibited much higher stability in a H2 reducing environment, and more strikingly, a hydrogenation activity, approximately 10 and 34 times greater than those high-valence Pd1/g-C3N4 and Pd1/BCN with a high B content, respectively.

CsWRKY11 cooperates with CsNPR1 to regulate SA-triggered leaf de-greening and reactive oxygen species burst in cucumber.

Salicylic acid (SA) is a multi-functional phytohormone, regulating diverse processes of plant growth and development, especially triggering plant immune responses and initiating leaf senescence. However, the early SA signaling events remain elusive in most plant species apart from Arabidopsis, and even less is known about the multi-facet mechanism underlying SA-regulated processes. Here, we report the identification of a novel regulatory module in cucumber, CsNPR1-CsWRKY11, which mediates the regulation of SA-promoted leaf senescence and ROS burst. Our analyses demonstrate that under SA treatment, CsNPR1 recruits CsWRKY11 to bind to the promoter of CsWRKY11 to activate its expression, thus amplifying the primary SA signal. Then, CsWRKY11 cooperates with CsNPR1 to directly regulate the expression of both chlorophyll degradation and ROS biosynthesis related genes, thereby inducing leaf de-greening and ROS burst. Our study provides a solid line of evidence that CsNPR1 and CsWRKY11 constitute a key module in SA signaling pathway in cucumber, and gains an insight into the interconnected regulation of SA-triggered processes.

Chemical constituents from the Saposhnikovia divaricata and their antiproliferative activity.

Nine compounds were isolated and identified from ethanolic extracts of Saposhnikovia divaricata, including one new alkaloid (1), one new pentacyclic triterpenoid (9), and seven known alkaloids (2-8). Structural elucidation of compounds 1 and 9 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. All compounds were evaluated for antiproliferative activity against two cancer cell lines (LN229, A549) in vitro. Compounds (1-9) showed no significant antiproliferative activity.

ZMapp reduces diffusion of Ebola viral particles in fresh human cervicovaginal mucus.

Vaginal transmission from semen of male Ebola virus (EBOV) survivors has been implicated as a potential origin of Ebola virus disease (EVD) outbreaks. While EBOV in semen must traverse cervicovaginal mucus (CVM) to reach target cells, the behaviour of EBOV in CVM is poorly understood. CVM contains substantial quantities of IgG, and arrays of IgG bound to a virion can develop multiple Fc-mucin bonds, immobilizing the IgG/virion complex in mucus. Here, we measured the real-time mobility of fluorescent Ebola virus-like-particles (VLP) in 50 CVM specimens from 17 women, with and without ZMapp, a cocktail of 3 monoclonal IgGs against EBOV. ZMapp-mediated effective trapping of Ebola VLPs in CVM from a subset of women across the menstrual cycle, primarily those with Lactobacillus crispatus dominant microbiota. Our work underscores the influence of the vaginal microbiome on IgG-mucin crosslinking against EBOV and identifies bottlenecks in the sexual transmission of EBOV.

PEG-crosslinked O-carboxymethyl chitosan films with degradability and antibacterial activity for food packaging.

This study developed a kind of PEG-crosslinked O-carboxymethyl chitosan (O-CMC-PEG) with various PEG content for food packaging. The crosslinking agent of isocyanate-terminated PEG was firstly synthesized by a simple condensation reaction between PEG and excess diisocyanate, then the crosslink between O-carboxymethyl chitosan (O-CMC) and crosslinking agent occurred under mild conditions to produce O-CMC-PEG with a crosslinked structure linked by urea bonds. FT-IR and 1H NMR techniques were utilized to confirm the chemical structures of the crosslinking agent and O-CMC-PEGs. Extensive research was conducted to investigate the impact of the PEG content (or crosslinking degree) on the physicochemical characteristics of the casted O-CMC-PEG films. The results illuminated that crosslinking and components compatibility could improve their tensile features and water vapor barrier performance, while high PEG content played the inverse effects due to the microphase separation between PEG and O-CMC segments. The in vitro degradation rate and water sensitivity primarily depended on the crosslinking degree in comparison with the PEG content. Furthermore, caused by the remaining -NH2 groups of O-CMC, the films demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus. When the PEG content was 6% (medium crosslinking degree), the prepared O-CMC-PEG-6% film possessed optimal tensile features, high water resistance, appropriate degradation rate, low water vapor transmission rate and fine broad-spectrum antibacterial capacity, manifesting a great potential for application in food packaging to extend the shelf life.

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

Proline Metabolism in Response to Climate Extremes in Hairgrass.

Hairgrass (Deschampsia caespitosa), a widely distributed grass species considered promising in the ecological restoration of degraded grassland in the Qinghai-Xizang Plateau, is likely to be subjected to frequent drought and waterlogging stress due to ongoing climate change, further aggravating the degradation of grassland in this region. However, whether it would acclimate to water stresses resulting from extreme climates remains unknown. Proline accumulation is a crucial metabolic response of plants to challenging environmental conditions. This study aims to investigate the changes in proline accumulation and key enzymes in hairgrass shoot and root tissues in response to distinct climate extremes including moderate drought, moderate waterlogging, and dry-wet variations over 28 days using a completely randomized block design. The proline accumulation, contribution of the glutamate and ornithine pathways, and key enzyme activities related to proline metabolism in shoot and root tissues were examined. The results showed that water stress led to proline accumulation in both shoot and root tissues of hairgrass, highlighting the importance of this osmoprotectant in mitigating the effects of environmental challenges. The differential accumulation of proline in shoots compared to roots suggests a strategic allocation of resources by the plant to cope with osmotic stress. Enzymatic activities related to proline metabolism, such as Δ1-pyrroline-5-carboxylate synthetase, ornithine aminotransferase, Δ1-pyrroline-5-carboxylate reductase, Δ1-pyrroline-5-carboxylate dehydrogenase, and proline dehydrogenase, further emphasize the dynamic regulation of proline levels in hairgrass under water stress conditions. These findings support the potential for enhancing the stress resistance of hairgrass through the genetic manipulation of proline biosynthesis and catabolism pathways.

Synthesis of Bio-Base Fluorescence Carbon Dots for Selective Detection of Tartrazine and Sunset Yellow in Food Samples.

A green, economical and simple method for the preparation of water-soluble, high-fluorescent carbon quantum dots (CQDs) has been developed via hydrothermal process using pomelo peels as carbon source. The synthesized CQDs were characterized by transmission electron microscopy (TEM), X-ray diffraction(XRD), Fourier transform infrared spectroscopy (FTIR), UV - vis absorption spectra and fluorescence spectrophotometer. The results reveal that the as-prepared C-dots were spherical shape with an average diameter of 2.64 nm and emit bright blue photoluminescence (PL) with a quantum yield of approximately 3.63%. The surface of the C-dots was rich in hydroxyl groups and presented various merits including excellent photostability, low toxicity, and satisfactory solubility. Additionally, we found that two widely used synthetic food colorants, tartrazine and sunset yellow, could result in a strong fluorescence quenching of the C-dots, The possible mechanisms are caused by different ratios of inner filter and static quenching effects. According to this property, This study attempts to establish an analytical method for the determination of tartrazine and sunset yellow using carbon quantum dots as fluorescent probe. A linear relationship was found in the range of 0-100 µM tartrazine and sunset yellow with the detection limit(3σ/k) of 0.65 nM and 1.7 nM. The relative standard deviation (RSD) was 3.5% (tartrazine) and 3.0% (sunset yellow).This observation was further successfully applied for the determination of tartrazine and sunset yellow in food samples collected from local markets, and the recovery rates of the two ranges from 79% to 117.8 and 81 -103.5%, respectively. suggesting its great potential toward food routine analysis.

A xanthan gum and carbomer-codispersed divalent manganese ion-loaded tannic acid nanoparticle adjuvanted inactivated pseudorabies virus vaccine induces balanced humoral and cellular immune responses.

Adjuvants including aluminum adjuvant (Alum) and oil-water emulsion have been widely used in inactivated pseudorabies virus (PRV) vaccines to improve their performance, however, they are not sufficient to protect from PRV infection because of the weak immune response and poor Th1-type immune response. Divalent manganese ion (Mn2+) has been reported to increase the cellular immune response significantly. In this work, a xanthan gum and carbomer-dispersed Mn2+-loaded tannic acid-polyethylene glycol (TPMnXC) nanoparticle colloid is developed and used as an adjuvant to improve the performance of the inactivated PRV vaccine. The good in vitro and in vivo biocompatibility of the developed TPMnXC colloid has been confirmed by the cell viability assay, erythrocyte hemolysis, blood routine analysis, and histological analysis of mouse organs and injection site. The TPMnXC-adjuvanted inactivated PRV vaccine (TPMnXC@PRV) significantly promotes higher and more balanced immune responses indicating with an increased specific total IgG antibody and IgG2a/IgG1 ratio, efficient splenocytes proliferation, and elevated Th1- and Th2-type cytokine secretion than those of control groups. Wild PRV challenge experiment is performed using mice as a model animal, achieving a protection rate of up to 86.67 %, which is much higher than those observed from the commercial Alum. This work not only demonstrates the high potentiality of TPMnXC in practical applications but also provides a new way to develop the Mn2+-loaded nanoadjuvant for veterinary vaccines.

Three new triterpenoids from the fruit of Eleutherococcus senticosus (Rupr.) Harms.

A phytochemical investigation on the 70% EtOH extract of the fruit of Acanthpanax senticosus resulted in the isolation of three new triterpenoids, Falcatane C (1), Acasentrioid F (2), Acasentrioid G (3) together with twenty-seven known ones (4-30). Structural elucidation of all the compounds was performed by spectral methods such as 1D or 2D (1H-1H COSY, HSQC, and HMBC), NMR spectroscopy, and high-resolution mass spectrometry. Moreover, all compounds were evaluated for their effects on H2O2-induced neurotoxicity in human neuroblastoma SH-SY5Ycells. Compounds 13 and 15 showed significant neuroprotective impact at a specific concentration, and compounds 1, 3, 5, 9, 11, 13-15, 17, 20-21, 23-25, 27, 29-30 showed moderate neuroprotective effect. The current study suggests that triterpenes in Eleutherococcus senticosus (Rupr.) Harms may play an essential role in the neuroprotective properties.

FibroScan-aspartate transaminase: A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) with hepatic histological NAFLD activity score ≥ 4 and fibrosis stage F ≥ 2 is regarded as "at risk" non-alcoholic steatohepatitis (NASH). Based on an international consensus, NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), respectively; hence, we introduced the term "high-risk MASH". Diagnostic values of seven non-invasive models, including FibroScan-aspartate transaminase (FAST), fibrosis-4 (FIB-4), aspartate transaminase to platelet ratio index (APRI), etc. for high-risk MASH have rarely been studied and compared in MASLD. AIM: To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH. METHODS: A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital, between January 2012 and December 2020. After screening for MASLD and the exclusion criteria, 279 patients were included and categorized into high-risk and non-high-risk MASH groups. Utilizing threshold values of each model, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV), were calculated. Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve (AUROC). RESULTS: MASLD diagnostic criteria were met by 99.4% patients with NAFLD. The MASLD population was analyzed in two cohorts: Overall population (279 patients) and the subgroup (117 patients) who underwent liver transient elastography (FibroScan). In the overall population, FIB-4 showed better diagnostic efficacy and higher PPV, with sensitivity, specificity, PPV, NPV, and AUROC of 26.9%, 95.2%, 73.5%, 72.2%, and 0.75. APRI, Forns index, and aspartate transaminase to alanine transaminase ratio (ARR) showed moderate diagnostic efficacy, whereas S index and gamma-glutamyl transpeptidase to platelet ratio (GPR) were relatively weaker. In the subgroup, FAST had the highest diagnostic efficacy, its sensitivity, specificity, PPV, NPV, and AUROC were 44.2%, 92.3%, 82.1%, 67.4%, and 0.82. The FIB-4 AUROC was 0.76. S index and GPR exhibited almost no diagnostic value for high-risk MASH. CONCLUSION: FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI, Forns index, ARR, S index, and GPR; FAST is superior to FIB-4.

Tissue-specific O-GlcNAcylation profiling identifies substrates in translational machinery in Drosophila mushroom body contributing to olfactory learning.

O-GlcNAcylation is a dynamic post-translational modification that diversifies the proteome. Its dysregulation is associated with neurological disorders that impair cognitive function, and yet identification of phenotype-relevant candidate substrates in a brain-region specific manner remains unfeasible. By combining an O-GlcNAc binding activity derived from Clostridium perfringens OGA (CpOGA) with TurboID proximity labeling in Drosophila, we developed an O-GlcNAcylation profiling tool that translates O-GlcNAc modification into biotin conjugation for tissue-specific candidate substrates enrichment. We mapped the O-GlcNAc interactome in major brain regions of Drosophila and found that components of the translational machinery, particularly ribosomal subunits, were abundantly O-GlcNAcylated in the mushroom body of Drosophila brain. Hypo-O-GlcNAcylation induced by ectopic expression of active CpOGA in the mushroom body decreased local translational activity, leading to olfactory learning deficits that could be rescued by dMyc overexpression-induced increase of protein synthesis. Our study provides a useful tool for future dissection of tissue-specific functions of O-GlcNAcylation in Drosophila, and suggests a possibility that O-GlcNAcylation impacts cognitive function via regulating regional translational activity in the brain.

Newly synthesized proteins often receive further chemical modifications that change their structure and role in the cell. O-GlcNAcylation, for instance, consists in a certain type of sugar molecule being added onto dedicated protein segments. It is required for the central nervous system to develop and work properly; in fact, several neurological disorders such as Alzheimer's, Parkinson's or Huntington's disease are linked to disruptions in O-GlcNAcylation. However, scientists are currently lacking approaches that would allow them to reliably identify which proteins require O-GlcNAcylation in specific regions of the brain to ensure proper cognitive health. To address this gap, Yu et al. developed a profiling tool that allowed them to probe O-GlcNAcylation protein targets in different tissues of fruit flies. Their approach relies on genetically manipulating the animals so that a certain brain area overproduces two enzymes that work in tandem; the first binds specifically to O-GlcNAcylated proteins, which allows the second to add a small 'biotin' tag to them. Tagged proteins can then be captured and identified. Using this tool helped Yu et al. map out which proteins go through O-GlcNAcylation in various brain regions. This revealed, for example, that in the mushroom body ­ the 'learning center' of the fly brain ­ O-GlcNAcylation occurred predominantly in the protein-building machinery. To investigate the role of O-GlcNAcylation in protein synthesis and learning, Yu et al. used an approach that allowed them to decrease the levels of O-GlcNAcylation in the mushroom body. This resulted in reduced local protein production and the flies performing poorly in olfactory learning tasks. However, artificially increasing protein synthesis reversed these deficits. Overall, the work by Yu et al. provides a useful tool for studying the tissue-specific effects of O-GlcNAcylation in fruit flies, and its role in learning. Further studies should explore how this process may be linked to cognitive function by altering protein synthesis in the brain.

Psychological Stress Analysis to Evaluate the Effects of Transcranial Magnetic Stimulation on Mood Regulation and Quality of Life in Patients with Bipolar Disorder.

OBJECTIVE: To explore the impact of transcranial magnetic stimulation on emotion regulation and quality of life in patients with bipolar disorder (BD) and to evaluate the effectiveness of the mental stress analyzer. METHODS: Patients with BD admitted to our hospital from August 2022 to August 2023 were retrospectively selected. For the present study, 60 patients who received drug therapy served as the control group, and the other 60 patients who received repeated transcranial stimulation on this basis served as the observation group. The heart rate variability (HRV) of the two groups of patients was detected by a mental stress analyzer/HRV analysis system. Hamilton Depression Rating Scale (HAMD), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) were used to evaluate the mental state of the two groups of patients. The quality of life of the two groups was assessed using the Comprehensive Quality of Life Questionnaire 74 (GQOLI-74). Clinical effectiveness global rating scale-illness severity (CGI-SI) was used to evaluate the clinical symptoms of the two groups of patients, and the incidence of adverse reactions was calculated. RESULTS: In comparison to the control group, the high-frequency power (HF) of the patients demonstrated an elevation in the observation group, and the low-frequency power (LF) and LF/HF were significantly reduced (p < 0.05). The standard deviation of NN intervals (SDNN), standard deviation of all five-minute NN intervals (SDANN), root mean square of successive differences (rMSSD), and percent RR intervals with a difference in duration higher than 50 ms (PNN50) of patients in the observation group showed a notable increase compared to the control group (p < 0.05). Compared with the control group, the HAMD, SAS, and SDS scores of the patients in the observation group demonstrated a substantial decline relative to the control group (p < 0.05). In contrast to the control group, there was a significant increase in the overall clinical effectiveness rate among patients in the observation group, and the incidence of adverse reactions was significantly reduced (p < 0.05). CONCLUSIONS: Repetitive transcranial magnetic stimulation (rTMS) has significant clinical effects in treating BD and can effectively improve patients' anxiety, suppress emotions, and regulate patients' emotions. At the same time, rTMS has high safety and little impact on the balance of patients' autonomic nervous function, reduces the incidence of adverse reactions, accelerates the patient's recovery process, and is suitable for clinical promotion.

Association of cytokines levels, psychopathology and cognition among CR-TRS patients with metabolic syndrome.

Clozapine-resistant treatment-refractory schizophrenia (CR-TRS) patients face significant clinical challenges. While links between metabolic syndrome (MetS) and inflammatory cytokines in schizophrenia have been established, the relationship between MetS and cytokine levels in CR-TRS patients remains unexplored. This study aimed to investigate the relationship between cytokines levels, clinical symptoms and cognitive impairments in CR-TRS patients, both with and without MetS. The study included 69 CR-TRS patients (31with MetS and 38 without MetS) and 84 healthy controls. The levels of IL-2, IL-6, TNF-α and routine biochemical parameters were measured. Psychopathological symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. We found that CR-TRS patients with MetS displayed lower cognitive function scores compared to those without MetS, even when accounting for potential confounders. TNF-α levels were significantly higher in CRTRS patients with MetS compared to those without MetS, demonstrating substantial pathophysiological potential for CR-TRS patients with MetS via receiver operating characteristic curve (ROC). In CR-TRS patients without MetS, IL-2 independently contributed to the total score and general psychopathology subscore of PANSS. Additionally, IL-6 exhibited an independent contribution to the positive subscore of PANSS. In terms of cognition function, IL-6 independently contributed to the delayed memory of RBANS in CR-TRS patients without MetS. TNF-α could potentially serve as a predictive marker for distinguishing between CR-TRS patients with/without MetS, while IL-2 and IL-6 could independently contribute to psychopathological symptoms or cognitive function in CRTRS patients without MetS. Our study provided insights into the potential interplay between cytokines, clinical symptoms and cognitive impairments in CR-TRS patients with/without MetS.

Identification of potential biomarkers of gout through weighted gene correlation network analysis.

Background: Although hyperuricemia is not always associated with acute gouty arthritis, uric acid is a significant risk factor for gout. Therefore, we investigated the specific mechanism of uric acid activity. Methods: Using the gout-associated transcriptome dataset GSE160170, we conducted differential expression analysis to identify differentially expressed genes (DEGs). Moreover, we discovered highly linked gene modules using weighted gene coexpression network analysis (WGCNA) and evaluated their intersection. Subsequently, we screened for relevant biomarkers using the cytoHubba and Mcode algorithms in the STRING database, investigated their connection to immune cells and constructed a competitive endogenous RNA (ceRNA) network to identify upstream miRNAs and lncRNAs. We also collected PBMCs from acute gouty arthritis patients and healthy individuals and constructed a THP-1 cell gout inflammatory model, RT-qPCR and western blotting (WB) were used to detect the expression of C-X-C motif ligand 8 (CXCL8), C-X-C motif ligand 2 (CXCL2), and C-X-C motif ligand 1 (CXCL1). Finally, we predicted relevant drug targets through hub genes, hoping to find better treatments. Results: According to differential expression analysis, there were 76 upregulated and 28 downregulated mRNAs in GSE160170. Additionally, WGCNA showed that the turquoise module was most strongly correlated with primary gout; 86 hub genes were eventually obtained upon intersection. IL1ß, IL6, CXCL8, CXCL1, and CXCL2 are the principal hub genes of the protein-protein interaction (PPI) network. Using RT-qPCR and WB, we found that there were significant differences in the expression levels of CXCL8, CXCL1, and CXCL2 between the gouty group and the healthy group, and we also predicted 10 chemicals related to these proteins. Conclusion: In this study, we screened and validated essential genes using a variety of bioinformatics tools to generate novel ideas for the diagnosis and treatment of gout.

Two novel HLA class II alleles, HLA-DRB1*09:57 and HLA-DRB1*09:58 in Chinese individuals.

Compared with HLA-DRB1*09:01:02:05, the alleles HLA-DRB1*09:57 and HLA-DRB1*09:58 each show one nucleotide change, respectively.

Two new sesterterpenoids from Atractylodes japonica Koidz. ex Kitam.

Two new sesterterpenoids, atractylodes japonica terpenoid acid I (1) and atractylodes japonica terpenoid aldehyde I (2), were isolated from the rhizomes of Atractylodes japonica Koidz. ex Kitam together with ten known compounds (3-12). Their structures were elucidated on the basis of comprehensive spectroscopic analysis (1D/2D NMR, HRESIMS and IR). In addition, all of these isolated compounds were evaluated for their cytotoxic activities against human gastric cancer cell MGC-803 and human hepatocellular cancer cell HepG-2. Most of them exhibited moderate to weak inhibitory effects with IC50 values in the range of 25.15-88.85 µM except for 9-12.