In-situ activation of biomimetic single-site bioorthogonal nanozyme for tumor-specific combination therapy.

Copper-catalyzed click chemistry offers creative strategies for activation of therapeutics without disrupting biological processes. Despite tremendous efforts, current copper catalysts face fundamental challenges in achieving high efficiency, atom economy, and tissue-specific selectivity. Herein, we develop a facile "mix-and-match synthetic strategy" to fabricate a biomimetic single-site copper-bipyridine-based cerium metal-organic framework (Cu/Ce-MOF@M) for efficient and tumor cell-specific bioorthogonal catalysis. This elegant methodology achieves isolated single-Cu-site within the MOF architecture, resulting in exceptionally high catalytic performance. Cu/Ce-MOF@M favors a 32.1-fold higher catalytic activity than the widely used MOF-supported copper nanoparticles at single-particle level, as first evidenced by single-molecule fluorescence microscopy. Furthermore, with cancer cell-membrane camouflage, Cu/Ce-MOF@M demonstrates preferential tropism for its parent cells. Simultaneously, the single-site CuII species within Cu/Ce-MOF@M are reduced by upregulated glutathione in cancerous cells to CuI for catalyzing the click reaction, enabling homotypic cancer cell-activated in situ drug synthesis. Additionally, Cu/Ce-MOF@M exhibits oxidase and peroxidase mimicking activities, further enhancing catalytic cancer therapy. This study guides the reasonable design of highly active heterogeneous transition-metal catalysts for targeted bioorthogonal reactions.

Photo-induced three-component reaction for the construction of α-tertiary amino acid derivatives.

The synthesis of α-tertiary amino acids (ATAAs), which are pivotal components in natural metabolism and pharmaceutical innovation, continues to attract significant research interest. Despite substantial advancements, the pursuit of a facile, versatile, and resource-efficient methodology remains an area of active development. In this work, we introduce a visible light-triggered three-component reaction involving readily available nitrosoarenes, N-acyl pyrazoles, and allyl or (bromomethyl)benzenes under mild conditions. This approach enables the straightforward assembly of a wide array of ATAA derivatives (41 examples) in commendably high yields (up to 89%). Mechanistic investigations elucidate that the reaction proceeds through a dehydration condensation between nitrosoarenes and N-acyl pyrazoles to generate ketimine intermediates. This is followed by a light-driven halogen atom transfer (XAT) process and a radical addition, culminating in the formation of the desired products. The approach showcases excellent functional group compatibility and late-stage derivatization potential, offering new insights and avenues for the synthesis of ATAA analogs.

Deep radiomics-based prognostic prediction of oral cancer using optical coherence tomography.

BACKGROUND: This study aims to evaluate the integration of optical coherence tomography (OCT) and peripheral blood immune indicators for predicting oral cancer prognosis by artificial intelligence. METHODS: In this study, we examined patients undergoing radical oral cancer resection and explored inherent relationships among clinical data, OCT images, and peripheral immune indicators for oral cancer prognosis. We firstly built a peripheral blood immune indicator-guided deep learning feature representation method for OCT images, and further integrated a multi-view prognostic radiomics model incorporating feature selection and logistic modeling. Thus, we can assess the prognostic impact of each indicator on oral cancer by quantifying OCT features. RESULTS: We collected 289 oral mucosal samples from 68 patients, yielding 1,445 OCT images. Using our deep radiomics-based prognosis model, it achieved excellent discrimination for oral cancer prognosis with the area under the receiver operating characteristic curve (AUC) of 0.886, identifying systemic immune-inflammation index (SII) as the most informative feature for prognosis prediction. Additionally, the deep learning model also performed excellent results with 85.26% accuracy and 0.86 AUC in classifying the SII risk. CONCLUSIONS: Our study effectively merged OCT imaging with peripheral blood immune indicators to create a deep learning-based model for inflammatory risk prediction in oral cancer. Additionally, we constructed a comprehensive multi-view radiomics model that utilizes deep learning features for accurate prognosis prediction. The study highlighted the significance of the SII as a crucial indicator for evaluating patient outcomes, corroborating our clinical statistical analyses. This integration underscores the potential of combining imaging and blood indicators in clinical decision-making. TRIAL REGISTRATION: The clinical trial associated with this study was prospectively registered in the Chinese Clinical Trial Registry with the trial registration number (TRN) ChiCTR2200064861. The registration was completed on 2021.

Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer.

Although hypercoagulability is commonly associated with malignancies, whether coagulation factors directly affect tumor cell proliferation remains unclear. Herein, by performing single-cell RNA sequencing (scRNA-seq) of the prostate tumor microenvironment (TME) of mouse models of castration-resistant prostate cancer (CRPC), we report that immunosuppressive neutrophils (PMN-MDSCs) are a key extra-hepatic source of coagulation factor X (FX). FX activation within the TME enhances androgen-independent tumor growth by activating the protease-activated receptor 2 (PAR2) and the phosphorylation of ERK1/2 in tumor cells. Genetic and pharmacological inhibition of factor Xa (FXa) antagonizes the oncogenic activity of PMN-MDSCs, reduces tumor progression, and synergizes with enzalutamide therapy. Intriguingly, F10high PMN-MDSCs express the surface marker CD84 and CD84 ligation enhances F10 expression. Elevated levels of FX, CD84, and PAR2 in prostate tumors associate with worse survival in CRPC patients. This study provides evidence that FXa directly promotes cancer and highlights additional targets for PMN-MDSCs for cancer therapies.

[Guidelines for quality control of human use experience study on traditional Chinese medicine].

National Medical Products Administration released the Special provisions on the administration of registration of traditio-nal Chinese medicine(TCM) in February 2023, encouraging high-quality human use experience(HUE) study in TCM clinical practice to obtain sufficient evidence for TCM registration support. The provisions suggested that the HUE study should meet the relevant requirements and accept the drug registration verification. This paper aims to standardize the HUE study, obtain high-quality HUE data to support registration applications, and promote the standardization of research. In accordance with the relevant laws and regulations of the state and the requirements of the technical guidelines for the HUE study in the drug review center of the National Medical Products Administration, the clinical characteristics of TCM were considered, and the Clinical Evaluation Committee of Traditional Chinese Me-dicine of the Chinese Pharmaceutical Association organized and formulated the Guidelines for quality control of human use experience study on traditional Chinese medicine,including the conditions of medical institutions carrying out HUE study, researchers, sponsors, key information and requirements of pharmacy, research programs, key points of ethical review, requirements of the research implementation process, risk management, and subject protection of HUE study. After several rounds of consultation with experts, a guideline document suitable for supporting drug registration and guiding HUE study on TCM was finally formed.

Co-delivery of PROTAC and siRNA via novel liposomes for the treatment of malignant tumors.

Targeted elimination of damaged or overexpressed proteins within the tumor serves a pivotal role in regulating cellular function and restraining tumor cell growth. Researchers have been striving to identify safer and more effective methods for protein removal. Here, we propose the synergistic employment of a small molecule degrading agent (PROTAC) and siRNA to attain enhanced protein clearance efficiency and tumor therapeutic effects. Co-delivery liposomes were prepared to facilitate the efficient encapsulation of PROTAC and siRNA. Specifically, the cationic liposome significantly improved the solubility of the insoluble PROTAC (DT2216). The cationic polymer (F-PEI) achieved efficient encapsulation of the nucleic acid drug, thereby promoting endocytosis and enhancing the therapeutic impact of the drug. Both in vivo and in vitro experiments demonstrated remarkable degradation of target proteins and inhibition of tumor cells by the co-delivery system. In conclusion, the co-delivery liposomes furnished a nano-delivery system proficient in effectively encapsulating both hydrophilic and hydrophobic drugs, thereby presenting a novel strategy for targeted combination therapy in treating tumors.

TAFRO syndrome with abdominal pain as the first symptom accompanied by liver damage with hyperbilirubinemia: A case report.

Thrombocytopenia, anasarca, fever, reticulin fibrosis on bone marrow biopsy/renal dysfunction, and organomegaly (TAFRO) syndrome are infrequent conditions with diverse clinical and pathological characteristics related to multi-organ damage. There are few reports of TAFRO syndrome accompanied by liver damage with hyperbilirubinemia. We describe the case of a 61-year-old male who presented with sudden onset abdominal pain accompanied by liver damage with hyperbilirubinemia. His symptoms worsened, leading to fever, hepatic insufficiency, serous cavity effusions, thrombocytopenia, and acute renal failure. Fever and anasarca relapsed after steroid discontinuation. The patient was ultimately diagnosed with TAFRO syndrome by biopsies taken from the axillary lymph nodes. He was then administered steroids, which resolved his symptoms almost completely. Our case was notable for its atypical signs and total remission of TAFRO syndrome.

Intelligent Gesture Recognition Based on Screen Reflectance Multi-Band Spectral Features.

Human-computer interaction (HCI) with screens through gestures is a pivotal method amidst the digitalization trend. In this work, a gesture recognition method is proposed that combines multi-band spectral features with spatial characteristics of screen-reflected light. Based on the method, a red-green-blue (RGB) three-channel spectral gesture recognition system has been developed, composed of a display screen integrated with narrowband spectral receivers as the hardware setup. During system operation, emitted light from the screen is reflected by gestures and received by the narrowband spectral receivers. These receivers at various locations are tasked with capturing multiple narrowband spectra and converting them into light-intensity series. The availability of multi-narrowband spectral data integrates multidimensional features from frequency and spatial domains, enhancing classification capabilities. Based on the RGB three-channel spectral features, this work formulates an RGB multi-channel convolutional neural network long short-term memory (CNN-LSTM) gesture recognition model. It achieves accuracies of 99.93% in darkness and 99.89% in illuminated conditions. This indicates the system's capability for stable operation across different lighting conditions and accurate interaction. The intelligent gesture recognition method can be widely applied for interactive purposes on various screens such as computers and mobile phones, facilitating more convenient and precise HCI.

Three-mode ratiometric biosensor based on integrated DNA-driven magnetic beads for Clostridium perfringens detection.

A three-mode biosensor incorporated ratiometric (electrochemical/colorimetric, electrochemical/photothermal) into its design was constructed using DNA-driven magnetic beads (DMBs) as a bridge to detect C. perfringens. It further enhances the accuracy of detection results while maintaining compatibility with applications in multiple scenarios. Briefly, the G-quadruplex was combined with aptamer and immobilized onto magnetic beads through amide-bond, resulting in the integration of DMBs. The DMBs and supernatant were separated by magnetic separation when the target was present. Subsequently, the DMBs were utilized to construct the electrochemical biosensor, whereas the supernatant was used to construct colorimetric and photothermal biosensors. The limits of detection the ratiometric biosensor were ultimately reduced to 0.26 and 0.27 lg CFU g-1, respectively, in comparison to the single three-mode biosensor. Moreover, this biosensor had been applied in real-sample assays successfully. The establishment of this platform provides a new method for detecting pathogens in the fields of food safety and environmental monitoring.

Qualitative study on health self-management of patients with metabolic syndrome among bereaved population after earthquake.

The study explore the influencing factors and healthy self-management of MS patients with bereaved relatives after Wenchuan and Yushu Earthquake of their real life; explore difficulties and challenges in the process of self-management; and supply information that could not be sought in quantitative studies. Purposive sampling was used to recruit 36 MS patients who are bereavement population in two earthquakes, and those patients met the inclusion criteria for semi-structured focus group interview. The Nvivo11 software was used to collate and analyze the transcribed data. The main influencing factors of health self-management behavior for MS patients are as follows: the degree of understanding of disease prevention knowledge, emotion management induced by earthquake trauma, the source of disease-related information, access and identification are very limited; ethnic traditional culture, religious beliefs, and production activities and routines before and after the earthquake is an important factor in their healthy self-management behavior. The lack of health beliefs and self-efficacy of MS patients among bereaved families after Wenchuan and Yushu earthquake are key obstacle in their self-management. The overall level of the knowledge of patients' MS prevention, self-efficacy and self-management behaviors are still low. Some positive factors that can be changed including MS prevention knowledge, self-efficacy, social support, and family function. Some negative factors which can be improved afterwards, including negative coping style, traumatic life experiences from earthquake and smoking.

Aromatic Nitration Enhances Absorption of Biomass Burning Brown Carbon in an Oxidizing Urban Environment.

Brown carbon (BrC) from biomass burning constitutes a significant portion of light-absorbing components in the atmosphere. Although the aging of BrC surrogates from biomass burning has been studied in many laboratory settings, BrC aging behavior in real-world urban environments is not well understood. In this study, through a combination of online dynamic monitoring and offline molecular characterization, the ambient optical aging of BrC was linked to its dynamic changes in molecular composition. Enhanced light absorption by BrC was consistently observed during the periods dominated by oxygenated biomass burning organic aerosol (BBOA), in contrast to periods dominated by primary emissions or secondary formation in aqueous-phase. This enhancement was linked to the formation of nitrogen-containing compounds during the ambient aging of BBOA. Detailed molecular characterization, alongside analysis of environmental parameters, revealed that an increased atmospheric oxidizing capacity, marked by elevated levels of ozone and nighttime NO3 radicals, facilitated the formation of nitrated aromatic BrC chromophores. These chromophores were primarily responsible for the enhanced light absorption during the ambient aging of BBOA. This study elucidates the nitration processes that enhance BrC light absorption for ambient BBOA, and highlights the crucial role of meteorological conditions. Furthermore, our findings shed light on the chemical and optical aging processes of biomass burning BrC in ambient air, offering insights into its environmental behavior and effects.

BCL2 expression is enriched in advanced prostate cancer with features of lineage plasticity.

The widespread use of potent androgen receptor signaling inhibitors (ARSIs) has led to an increasing emergence of AR-independent castration-resistant prostate cancer (CRPC), typically driven by loss of AR expression, lineage plasticity, and transformation to prostate cancers (PCs) that exhibit phenotypes of neuroendocrine or basal-like cells. The anti-apoptotic protein BCL2 is upregulated in neuroendocrine cancers and may be a therapeutic target for this aggressive PC disease subset. There is an unmet clinical need, therefore, to clinically characterize BCL2 expression in metastatic CRPC (mCRPC), determine its association with AR expression, uncover its mechanisms of regulation, and evaluate BCL2 as a therapeutic target and/or biomarker with clinical utility. Here, using multiple PC biopsy cohorts and models, we demonstrate that BCL2 expression is enriched in AR-negative mCRPC, associating with shorter overall survival and resistance to ARSIs. Moreover, high BCL2 expression associates with lineage plasticity features and neuroendocrine marker positivity. We provide evidence that BCL2 expression is regulated by DNA methylation, associated with epithelial-mesenchymal transition, and increased by the neuronal transcription factor ASCL1. Finally, BCL2 inhibition had antitumor activity in some, but not all, BCL2-positive PC models, highlighting the need for combination strategies to enhance tumor cell apoptosis and enrich response.

A Comprehensive Pan-Cancer Analysis Identified that TRIB3 was Associated with Immune Cell Infiltration and Poor Prognosis.

BACKGROUND: Previous studies have demonstrated that TRIB3 plays a carcinogenic role in tumor progression. However, the exploration of TRIB3 at the pan-cancer level has not been reported. AIMS: This study aimed to conduct a comprehensive pan-cancer analysis of TRIB3. OBJECTIVE: We explored the expression pattern and functional mechanism of TRIB3 on the basis of multiple databases. METHOD: We first explored the expression level of TRIB3 in the TCGA database. Then, the receiver operation characteristic curve (ROC), Kaplan-Meier plotter, and Cox regression were used to estimate the diagnostic and prognostic value of TRIB3, respectively. We also explored the relationship between TRIB3 and the infiltration of tumor immune cells, as well as the expression of immune checkpoint molecules. Gene enrichment and protein interaction network analysis were carried out to identify possible carcinogenic molecular mechanisms and functional pathways. Finally, we compared the non-promoter region methylation of TRIB3 in normal and tumor tissues and explored potential systems with unique functions in TRIB3-mediated tumorigenesis. RESULT: The expression level of TRIB3 was elevated in multiple tumor types, and the high expression of TRIB3 was associated with poor prognosis. TRIB3 had a higher frequency of genetic changes in several tumors and showed varying trends in TRIB3 methylation levels. Additionally, high expression of TRIB3 was also associated with infiltration of cancer-related fibroblasts and different types of immune cells and was positively correlated with the expression of immune checkpoint molecules. Furthermore, gene enrichment analysis suggested that TRIB3 may play a role in the malignant progression of cancer by participating in protein post-translational modifications and activating transcription initiation factors. CONCLUSION: Our pan-cancer analysis provided the potential carcinogenic role of TRIB3 in tumors and verified a promising target for clinical immune treatment.

Cynbungenins A-K, structurally diverse steroids with cytotoxic activity from the roots of Cynanchum bungei Decne.

Chemical investigation of the acid hydrolysate of Cynanchum bungei roots led to the isolation of eleven undescribed steroids, namely cynbungenins A-K (1-11), and seven previously described analogues (12-18). The complete structures of these compounds were elucidated using the comprehensive spectroscopic analyses and reference data. Structurally, compounds 1 and 2 represent the first example of androstane-type steroids found in the Cynanchum plants, and compounds 3-6 and 12 are characterized as pregnane-type steroids with a rare 8,14-seco-steroid core. In the cytotoxic activity assay, compound 16 displayed the strongest cytotoxic effect against MCF-7, HCT-116, HeLa, and HepG2 cancer cell lines, with IC50 values of 9.98-16.42 µM, and further research indicated that it induced both apoptosis and cell cycle arrest in the G0/G1 phase in a dose-dependent manner toward HepG2 cells.

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer.

Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease. CBP/p300 bromodomain inhibition enhances response to standard of care therapeutics. Functional studies, CBP/p300 cistrome mapping, and transcriptome in CRPC revealed that CBP/p300 regulates DDR. Further mechanistic investigation showed that CBP/p300 attenuation via therapeutic targeting and genomic knockdown decreases homologous recombination (HR) factors in vitro, in vivo, and in human prostate cancer (PCa) tumors ex vivo. Similarly, CBP/p300 expression in human prostate tissue correlates with HR factors. Lastly, targeting CBP/p300 impacts HR-mediate repair and patient outcome. Collectively, these studies identify CBP/p300 as drivers of PCa tumorigenesis and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed and DDR therapies.

Isotope-Based Characterization of Soil Elemental Mercury Emissions from Historical Mercury Mining Areas: Driving Pathways and Relative Contributions.

Photo-, microbial, and abiotic dark reduction of soil mercury (Hg) may all lead to elemental mercury (Hg(0)) emissions. Utilizing lab incubations, isotope signatures of Hg(0) emitted from mining soils were characterized to quantify the interplay and contributions of various Hg reduction pathways, which have been scarcely studied. At 15 °C, microbial reduced Hg(0) showed a negative mass-dependent fractionation (MDF) (δ202Hg = -0.30 ± 0.08‰, 1SD) and near-zero mass-independent fractionation (MIF) (Δ199Hg = 0.01 ± 0.04‰, 1SD), closely resembling dark reduced Hg(0) (δ202Hg = -0.18 ± 0.05‰, Δ199Hg = -0.01 ± 0.03‰, 1SD). In comparison, photoreduced Hg(0) exhibited significant MDF and MIF (δ202Hg = -0.55 ± 0.05‰, Δ199Hg = -0.20 ± 0.07‰, 1SD). In the dark, Hg isotopic signatures remained constant over the temperature range of 15-35 °C. Nonetheless, light exposure and temperature changes together altered Hg(0) MIF signatures significantly. Isotope mixing models along with Hg(0) emission flux data highlighted photo- and microbial reduction contributing 79-88 and 12-21%, respectively, of the total Hg(0) emissions from mining soils, with negligible abiotic dark reduction. Microorganisms are the key driver of soil Hg(0) emissions by first dissolving HgS and then promoting ionic Hg formation, followed by facilitating the photo- and microbial reduction of organically bound Hg. These insights deepen our understanding of the biogeochemical processes that influence Hg(0) releases from surface soils.

A pathology foundation model for cancer diagnosis and prognosis prediction.

Histopathology image evaluation is indispensable for cancer diagnoses and subtype classification. Standard artificial intelligence methods for histopathology image analyses have focused on optimizing specialized models for each diagnostic task1,2. Although such methods have achieved some success, they often have limited generalizability to images generated by different digitization protocols or samples collected from different populations3. Here, to address this challenge, we devised the Clinical Histopathology Imaging Evaluation Foundation (CHIEF) model, a general-purpose weakly supervised machine learning framework to extract pathology imaging features for systematic cancer evaluation. CHIEF leverages two complementary pretraining methods to extract diverse pathology representations: unsupervised pretraining for tile-level feature identification and weakly supervised pretraining for whole-slide pattern recognition. We developed CHIEF using 60,530 whole-slide images spanning 19 anatomical sites. Through pretraining on 44 terabytes of high-resolution pathology imaging datasets, CHIEF extracted microscopic representations useful for cancer cell detection, tumour origin identification, molecular profile characterization and prognostic prediction. We successfully validated CHIEF using 19,491 whole-slide images from 32 independent slide sets collected from 24 hospitals and cohorts internationally. Overall, CHIEF outperformed the state-of-the-art deep learning methods by up to 36.1%, showing its ability to address domain shifts observed in samples from diverse populations and processed by different slide preparation methods. CHIEF provides a generalizable foundation for efficient digital pathology evaluation for patients with cancer.

Overlooked Trace Molecules in Organic Aerosol Revealed by Gas Chromatography-Orbitrap Mass Spectrometry.

Molecular characterization of organic aerosol (OA) is crucial for understanding its sources and atmospheric processes. However, the chemical components of OA remain not well constrained. This study used gas chromatography-Orbitrap mass spectrometry (GC-Orbitrap MS) and GC-Quadrupole MS (GC-qMS) to investigate the organic composition in PM2.5 from Xi'an, Northwest China. GC-Orbitrap MS identified 335 organic tracers, including overlooked isomers and low-concentration molecules, approximately 1.6 times more than GC-qMS. The "molecular corridor" assessment shows the superior capability of GC-Orbitrap MS in identifying an expansive range of compounds with higher volatility and oxidation states, such as furanoses/pyranoses, di/hydroxy/ketonic acids, di/poly alcohols, aldehydes/ketones, and amines/amides. Seasonal variations in OA composition reflect diverse sources: increased di/poly alcohols in winter are derived from indoor emissions, furanoses/pyranoses and heterocyclics in spring and summer might be from biogenic emissions and secondary formation, and amides in autumn are probably from biomass burning. Integrating partial least squares discriminant analysis (PLS-DA) and potential source contribution function (PSCF) models, the source similarities and differences are further elucidated, highlighting the role of local emissions and transport from southern cities. This study offers new insights into the OA composition aided by the high mass resolution and sensitivity of GC-Orbitrap MS.

AQP4 is upregulated in schizophrenia and Its inhibition attenuates MK-801-induced schizophrenia-like behaviors in mice.

BACKGROUND: The pathophysiology and molecular mechanisms of schizophrenia (SCZ) remain unclear, and the effective treatment resources are still limited. The goal of this study is to identify the expression of AQP4 in SCZ patients and explore whether AQP4 inhibition could ameliorate schizophrenia-like behaviors and its mechanisms. METHODS: Microarray datasets of PFC compared with healthy control were searched in the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were analyzed with the GEO2R online tool. The Venny online tool and metascape online software were used to identify common abnormally expressed genes and conduct cell type signature enrichment analysis. SCZ mouse models were induced with MK-801, an NMDA receptor antagonist (intraperitoneal injection, 0.1 mg/kg/day for 7 days), and C6 cell models were treated with 100 µM MK-801. RT-qPCR, Western Blotting, and immunofluorescence were employed to determine the expression of AQP4, proinflammatory cytokines, and GFAP. Open field tests and social interaction tests were performed to evaluate the schizophrenia-like behaviors. RESULTS: Bioinformatics analysis identified upregulation of AQP4 in the PFC of SCZ patients compared with healthy controls. Cell type signature enrichment analysis showed that all three DEGs lists were strongly enriched in the FAN EMBRYONIC CTX ASTROCYTE 2 category. Upregulation of AQP4 was also observed in MK-801-treated C6 cells and the PFC of MK-801-induced SCZ mouse model. Moreover, AQP4 inhibition with TGN-020 (an inhibitor of AQP4) improved anxiety-like behavior and social novelty preference defects in MK-801-treated mice. AQP4 inhibition also reduced the expression of IL-1ß, IL-6, and TNF-α in MK-801-treated C6 cells and mouse model. CONCLUSIONS: AQP4 is upregulated in the PFC of SCZ patients compared with healthy controls. AQP4 inhibition could alleviate the anxiety-like behavior and social novelty defects in MK-801-treated mice, this may be due to the role of AQP4 in the regulation of the expression of proinflammatory cytokines.

Association of gut microbiota with lactose intolerance and coeliac disease: a two-sample Mendelian randomization study.

Background and objectives: Lactose intolerance and coeliac disease are common clinical nutrient malabsorption disorders, with an unclear pathogenesis and limited therapeutic options. It is widely believed that the gut microbiota plays an important role in many digestive disorders, but its role in lactose intolerance and coeliac disease is not yet clear. This study aimed to investigate the correlation between gut microbiota and lactose intolerance and coeliac disease. Materials and methods: This study utilized the genome-wide association study database to investigate the association between gut microbiota and lactose intolerance and coeliac disease using Mendelian randomization (MR). The robustness of our findings was confirmed through subsequent analyses including Cochrane's Q statistic, MR-Egger Intercept Regression, MR-PRESSO Global Test and Leave-one-out methods. Results: By employing the inverse variance weighted method, we identified that family Veillonellaceae, genus Oxalobacter and Senegalimassilia were protective against lactose intolerance, whereas genus Anaerotruncus, Eubacterium rectale group and Ruminococcus2 were found to be risk factors for lactose intolerance. Regarding coeliac disease, class Bacilli and Gammaproteobacteria, family FamilyXIII and Veillonellaceae, genus Eisenbergiella, Lachnoclostridium, RuminococcaceaeUCG014 and Ruminococcus2 were identified as protective factors, while class Betaproteobacteria, genus Eubacterium xylanophilum group and Blautia were risk factors. Furthermore, reverse the MR analysis did not reveal any evidence of a causal relationship between lactose intolerance or coeliac disease and the bacteria identified in our study. Conclusion: This study provides novel insights into exploring the role of gut microbiota in lactose intolerance and coeliac disease; however, further experiments investigations are required to elucidate the specific underlying mechanisms.