Temporal dynamics of immune cell patterns in bladder cancer patients receiving Bacillus Calmette-Guérin therapy.

BACKGROUND: Bacillus Calmette-Guérin (BCG) is capable of enhancing the infiltration of immune cells into the tumour. However the temporal dynamics of immune cell patterns in patients receiving BCG instillation remains unclear. METHODS: Ninety-six patients who underwent intravesical BCG therapy, comprising 46 responders and 50 non-responders, were retrospectively enroled to explore the evolving immune landscape. This study involved a detailed examination of sequential samples collected before, during, and after BCG treatment to assess BCG's influence on the immune microenvironment, employing techniques such as immunohistochemistry, fluorescent multiplex immunohistochemistry, and mass spectrometry techniques. RESULTS: Our study found that initial BCG instillation leads to enhanced immune cell infiltration, correlating with treatment efficacy, with responders exhibiting more pronounced increases. Non-responders experience a rise in immune cell infiltration and PD-L1 expression during the first instillation, which returns to baseline after treatment. In non-responders, BCG re-challenge fail to further increase immune cell infiltration into the tumour or improve patient outcomes. Strikingly, proteomics data revealed that GBP1 expression was induced by BCG treatment in non-responders. CONCLUSIONS: Our findings demonstrated the induction of tumour PD-L1 expression by BCG in non-responders, and therefore provide insights for the combination of BCG and anti-PD1/anti-PD-L1 therapy.

Is chemotherapy beneficial? A retrospective study of chemotherapy in patients with invasive intraductal papillary-mucinous carcinoma.

Background and aim: Whether chemotherapy can improve the prognosis of invasive intraductal papillary-mucinous carcinoma (IPMC) still remains unclear. The aim of this study is to observe the difference in survival time of patients with invasive IPMC receiving or not receiving chemotherapy. Methods: 117 patients with invasive IPMC were included in The Surveillance, Epidemiology, and End Results (SEER) database. These patients were subsequently divided into two subgroups according to whether they received chemotherapy or not: the non-chemotherapy group (patients who did not receivechemotherapy, N = 58), the chemotherapy group (patients who received chemotherapy, N = 59). The overall survival (OS) and cancer specific survival (CSS) of two treatment groups were evaluated. Results: Before adjusting for pathology grade, the Kaplan-Meier analysis showed that the difference of survival time is not significant between non-chemotherapy group and chemotherapy group (P > 0.05), but the land-mark analysis showed that short-term death risk of the chemotherapy group is significantly lower than non-chemotherapy group (P < 0.05). After adjust the pathology grade, survival time of the chemotherapy group is significantly longer than non-chemotherapy group (P < 0.05). Univariate and multivariate Cox regression showed that chemotherapy was an independent prognostic protective factor for invasive IPMC (P < 0.05). Land-mark analysis showed that short-term death risk of the chemotherapy group is significantly lower than non-chemotherapy group in N1-N2 subgroup (P < 0.05). Conclusion: Chemotherapy is an independent protective factor IPMC, especially reducing the risk of short-term death for IPMC patients with lymph node metastasis.

Altered Brain Structure in Hemifacial Spasm Patients: A Multimodal Brain Structure Study.

Objective: Hemifacial spasm (HFS) is a clinical neurosurgical disease, which brain structural alterations caused by HFS remain a topic of debate. We evaluated changes in brain microstructure associated with HFS and observed their relevance to clinical characteristics. Methods: We enrolled 72 participants. T1-weighted structural and diffusion tensor images were collected from all participants using 3.0T magnetic resonance equipment. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to identify changes in gray matter volume (GMV) and disruptions in white matter (WM) integrity. The severity of the spasms was graded using the Cohn scale. Results: VBM analysis revealed that the GMV was significantly reduced in the left Thalamus and increased GMV in the right Cerebellum IV-V of the HFS group. TBSS analysis showed that FA in the left superior longitudinal fasciculus (SLF) of the HFS group was significantly increased. GMV in the thalamus showed a negative correlation with disease duration and Cohn grade, while FA in the left SLF had a positive correlation with both the disease duration and Cohn grade. Conclusion: We identified regions with altered GMV in HFS patients. Additionally, we determined that FA in the left SLF might serve as a significant neural indicator of HFS.

Application value of individualized tube voltage, contrast injection, and adaptive statistical iterative reconstruction V algorithm based on body mass index in renal computed tomography angiography for radiation and iodinated contrast dose reduction.

OBJECTIVES: To explore the application value of body mass index (BMI)-based kilovoltage peak (kVp) selection and contrast injection protocol combined with different adaptive statistical iterative reconstruction V (ASIR-V) strengths in renal computed tomography angiography (CTA) in reducing radiation and contrast medium (CM) doses. METHODS: One-hundred renal CTA patients were prospectively enrolled and were divided into individualized kVp group (group A, n = 50) and conventional 100 kVp group (group B, n = 50), both with automatic tube current modulation and CM of Iohexol at 350 mgI/mL concentration. Group A: 70 kVp, noise index (NI) of 18 and CM dose rate of 17 mgI/kg/s for 10 s for BMI <25 kg/m2 patients; 80 kVp, NI = 17, and CM dose rate of 19 mgI/kg/s for 10 s for 25 kg/m2≤BMI≤30 kg/m2 patients. Group B: 100 kVp, 50 mL of CM at the flow rate of 4.5 mL/s. The objective image quality, effective radiation dose, CM dose, injection rate, and image quality were compared between the 2 groups. RESULTS: There was no significant difference in patient characteristics between the 2 groups (P > .05). Compared to group B, group A significantly reduced effective radiation dose by 28.4%, CM dose by 27.2%, and injection rate by 22.7% (all P < .001). The 2 groups had similar SD values in erector spine (P > .05). Group A had significantly higher CT values, SNR, and CNR values of the renal arteries than group B (all P < .001). The 2 radiologists had excellent agreement (Kappa value > 0.8) in the subjective scores of renal CTA images and showed no statistically significant difference between the 2 groups (4.57 ± 0.42 vs 4.41 ± 0.49) (P > .05). CONCLUSIONS: BMI-based scan and reconstruction protocol in renal CTA significantly reduces radiation and contrast doses while maintaining diagnostic image quality. ADVANCES IN KNOWLEDGE: (i) BMI-based individualized tube voltage selection and contrast injection protocol in renal CTA reduces both radiation and contrast doses over conventional protocol. (ii) The combination of lower kVp and higher weight ASIR-V maybe used to improve image quality in terms of contrast enhancement and image noise under lower radiation and contrast dose conditions. (iii) Renal CTA of normal size (BMI ≤ 30 kg/m2) patients acquired at low radiation dosage and low iodine contrast dose through the combination of low tube voltage and ASIR-V algorithm achieves excellent diagnostic image quality with a good inter-rater agreement.

Association between adverse childhood experiences and obesity, and sex differences: A systematic review and meta-analysis.

BACKGROUND: Obesity is one of the most common health problems worldwide. Although studies have reported associations between adverse childhood experiences (ACEs) and obesity, specific subtype associations and sex differences are unclear. OBJECTIVE: To systematically evaluate the association between ACEs and adult obesity risk and sex differences. METHODS: Five databases, PubMed, Web of Science, Cochrane Library, Embase, and PsycINFO, were searched with a June 10, 2024 deadline. Included studies investigated the association between at least one ACE and obesity. Two researchers independently assessed the risk of bias using the Newcastle-Ottawa Scale (NOS) and its adaptations and extracted relevant characteristics and outcomes. Statistical analyses were performed using STATA 17.0, including random effects models, heterogeneity tests, sensitivity analyses, publication bias assessments, Meta-regression analyses, and subgroup analyses. Dose-response analyses revealed potential trends between different levels of abuse and risk of obesity. RESULTS: The meta-analysis included 46 studies and showed a notable increased risk of obesity in adults experiencing ACEs (OR: 1.48, 95% CI: 1.38-1.59). Subgroup analyses showed significantly increased risk in Europe and North America, with significant increases observed in both developed and developing countries. Prospective, retrospective, and cross-sectional studies showed strong associations. Different types of ACEs (physical, sexual, psychological, and non-physical, psychological, or sexual abuse) were linked to a higher obesity risk. Sex difference analyses showed that females faced a greater risk when experiencing physical (OR: 1.606), sexual (OR: 1.581), and non-physical, psychological, or sexual (OR: 1.319) abuse; males exhibited increased risk only with non-physical, psychological, or sexual abuse (OR: 1.240). Dose-response analyses indicated that a higher number of ACEs was associated with an increased risk of obesity in adults. CONCLUSIONS: ACEs significantly increase the risk of adult obesity, with consistent findings across geographic regions, levels of economic development, and types of study design. Sex difference analysis indicates that females are particularly affected. Future research should prioritize including studies from underrepresented geographic areas to enhance understanding of the global impact of ACEs on obesity risk. Additionally, strengthening child protection and intervention efforts is crucial to mitigate the adverse effects of ACEs on adult health.

Key platelet genes play important roles in predicting the prognosis of sepsis.

Sepsis is a life-threatening organ malfunction induced by an imbalanced immunological reaction to infection in the host. Many studies have utilized traditional RNA sequencing (RNA-seq) data to identify important biological targets to predict sepsis prognosis. However, alterations in core cells and functional status cannot be effectively detected in sepsis patients. The goal of this study was to identify key cells through single-cell RNA-seq (scRNA-seq), and combine bulk RNA-seq data and multiple algorithm analysis to construct a stable prognostic model for sepsis. The scRNA-seq and bulk RNA-seq data from sepsis patients were collected from the Gene Expression Omnibus (GEO) database. The R package "Seurat" was used to process the scRNA-seq data. Cell communication was investigated using the R package "CellChat". The pseudo-time of the cells was calculated using the R package "monocle". The R package "limma" was used to identify differentially expressed genes (DEGs) between the sepsis group and the control group. Weighted gene correlation network analysis (WGCNA) was used to identify critical modules. Eight kinds of machine learning and 90 algorithm combinations were used to construct the prognostic model for sepsis. Quantitative real-time PCR (qRT‒PCR) was performed to determine the expression of key genes in the cecal ligation and puncture (CLP)-induced sepsis mouse model. The immunological status and related properties of DEGs were then investigated in the high- and low-risk groups delineated by the model. By combining the scRNA-seq data from nine samples, 13 clusters and 9 cell types were identified. CellChat analysis revealed that the number and strength of interactions between platelets and a variety of cells increased. We identified key platelet genes from the scRNA-seq data and combined these genes and the results of differential analysis and WGCNA of the bulk RNA-seq data. After univariate Cox regression analysis, we calculated the Cindex of the model constructed by the combination of 90 algorithms, and we finally determined the "CoxBoost + Lasso" combination. Multivariate Cox regression was used to construct the final prognostic model. The qRT-PCR results revealed significant differences in five key prognostic genes between the CLP and sham groups. The data was classified into high- and low-risk groups based on the model score. The high-risk group had a poorer survival rate and less immune infiltration. We identified the importance of platelets in sepsis patients through scRNA-seq, and established prognostic models with key genes that were identified via scRNA-seq combined with bulk RNA-seq analysis. The results of this model were closely associated with patient survival rates and immunological status and this model is useful for the prognostic management of sepsis.

Lake water storage changes and their cause analysis in Mongolia.

Lake is an important water resources in Mongolia, which has undergone a large variation in past decades. However, it is still challenging to monitor long-term changes in lake water storage (LWS) due to the lack of lake level monitoring and long-term satellite altimetry data for Mongolian lakes. According to the Advanced Land Observing Satellite Digital Elevation Model (ALOS DEM) and the Joint Research Centre (JRC) dataset, we estimated the LWS changes of 55 Mongolian lakes (> 10 km2) from 1991 to 2020. The results showed that the LWS increased by 40.24 km3 from 1991 to 1997, especially for northwestern Mongolia with 31.47 km3. However, the LWS decreased by 32.44 km3 from 1998 to 2010, and the lakes in the northwestern and southern decreased by 20.24 km3 (62%) and 7.38 km3 (23%), respectively, and then the LWS continued to decrease by 10.22 km3 from 2011 to 2020. The precipitation was the primary cause of lake change, which could explain 45.13% of LWS change based on Generalized Linear Model, followed by temperature (26.33%) and irrigated area (16.72%). Analyzing the changing characteristic and driving mechanisms of LWS can provide a scientific basis for local water resources management and planning.

A pathological complete response to capecitabine plus oxaliplatin regimen combined with tislelizumab in advanced gastric cancer with liver metastases: A case report.

A 66-year-old female patient presenting with dysphagia was diagnosed with stage IV unresectable gastric cancer (cTxN+M1). Multiple liver metastases were identified. The patient subsequently underwent five courses of chemotherapy and immunotherapy, including the capecitabine plus oxaliplatin (XELOX) regimen combined with tislelizumab. After fifth course treatment, it was confirmed that the liver metastases had completely disappeared and the primary tumor had significantly reduced in size. Consequently, a laparoscopy was performed, revealing a retraction-like response in the primary tumor and no obvious metastases in the abdominal cavity. Subsequently, a radical total gastrectomy was carried out through open abdominal surgery. Pathological analysis showed no remaining cancer or lymph node metastases, and the tumor regression was classified as grade 0. The patient has been now receiving additional chemotherapy and immunotherapy to manage any potential residual metastases. This case illustrated the rare and significant impact of combining chemotherapy with tislelizumab, transitioning the treatment approach from palliative to curative. It highlighted the critical role of immunotherapy in managing advanced gastric cancer with liver metastases.

Berberine extends healthspan and delays neurodegenerative diseases in Caenorhabditis elegans through ROS-dependent PMK-1/SKN-1 activation.

Oxidative stress, or the chronic generation of reactive oxygen species (ROS), is thought to contribute to the progression of aging and aging related diseases. However, low degree of ROS generation has repeatedly been shown to be associated with beneficial outcomes via activation of protective signaling pathways. Berberine, a natural alkaloid isolated from Rhizomacoptidis, has a long history of medicinal use in both Ayurvedic and traditional Chinese medicine, which possesses anti-cancer, anti-inflammatory and anti-neurodegenerative properties. In this study, we utilize Caenorhabditis elegans to examine the mechanisms by which berberine influences healthspan and neurodegenerative diseases. We find that 10 µM berberine significantly extends healthy lifespan in wild type C. elegans. We further show that berberine generates ROS, which is followed by activation of PMK-1/SKN-1 to extend healthspan. Intriguingly, berberine also delays neurodegenerative diseases such as Alzheimer's and polyglutamine diseases in a PMK-1/SKN-1dependent manner. Our work suggests that berberine may be a viable candidate for the prevention and treatment of aging and aging related diseases.

ChanLingGao alleviates intestinal mucosal barrier damage and suppresses the onset and progression of Colorectal cancer in AOM/DSS murine model.

BACKGROUND: The occurrence of Colorectal Cancer (CRC) is influenced by various factors, including host susceptibility, immune imbalance, and environmental triggers. Numerous studies have underscored the critical role of chronic intestinal inflammation and dysbiosis in the development of CRC. Traditional Chinese Medicine (TCM) holds unique advantages in regulating the intricate process of and comprehensive treatment for systemic disease. Previous investigations by our team have confirmed the anti-cancer properties of the TCM compound ChanLingGao (CLG), including inhibiting cancer cell migration, and alleviating bone cancer pain. However, the mechanisms underlying its efficacy in alleviating chronic intestinal inflammation, modulating the gut microbiota, and protecting the intestinal mucosal barrier remain largely unknown. PURPOSE: This study aims to explore the inhibitory effects of CLG on CRC tumors in mice and its potential mechanisms. METHODS: A chronic inflammation-related CRC mouse model was established using AOM/DSS. The study examined the mechanisms of intestinal inflammation and tumor cell proliferation through intestinal histological morphology. High-throughput sequencing was employed to analyze changes in gut microbiota diversity and intestinal mucosal barrier integrity in CRC mice. Based on network pharmacology target prediction and Wnt/ß-catenin signaling pathway analysis, the study analyzed and discussed the potential mechanisms of CLG on CRC. RESULTS: CLG significantly ameliorated weight loss and increased survival rates in CRC mice, while suppressing tumor growth in the intestinal tract. Post-CLG treatment improved intestinal inflammation in CRC mice, with a significant reduction in inflammatory factors IL-6, IL-23 and LCN2, and inhibition of tumor cell proliferation markers Proliferating Cell Nuclear Antigen (PCNA), Recombinant Ki-67 Protein (Ki-67), and CCND1. 16sV3-V4 region microbiota sequencing results indicated that CLG improved dysbiosis, and significantly increased the abundance of Akkermansia bacteria, further promoting the expression of MUC-2 protein and mucin secretion. Additionally, CLG prevented the disruption of intestinal epithelial cell junction proteins Occludin, Claudin-1, ZO-1, and E-cadherin, restored the number of goblet cells, and preserved the integrity of the intestinal mucosal barrier. Further experiments suggested that CLG inhibited abnormal activation of the Wnt/ß-catenin pathway, and its potential mechanism in maintaining mucosal barrier integrity might be related to blocking Wnt/ß-catenin pathway. CONCLUSIONS: This study demonstrates that CLG can inhibit CRC tumor growth by regulating the gut microbiota structure, reducing intestinal inflammation, improving intestinal mucosal barrier function, and inhibiting the complex process of cancer cell proliferation. This provides new clinical insights into the "membrane-oriented" treatment of CRC with CLG.

IG-Net: An Instrument-guided real-time semantic segmentation framework for prostate dissection during surgery for low rectal cancer.

BACKGROUND AND OBJECTIVE: Accurate prostate dissection is crucial in transanal surgery for patients with low rectal cancer. Improper dissection can lead to adverse events such as urethral injury, severely affecting the patient's postoperative recovery. However, unclear boundaries, irregular shape of the prostate, and obstructive factors such as smoke present significant challenges for surgeons. METHODS: Our innovative contribution lies in the introduction of a novel video semantic segmentation framework, IG-Net, which incorporates prior surgical instrument features for real-time and precise prostate segmentation. Specifically, we designed an instrument-guided module that calculates the surgeon's region of attention based on instrument features, performs local segmentation, and integrates it with global segmentation to enhance performance. Additionally, we proposed a keyframe selection module that calculates the temporal correlations between consecutive frames based on instrument features. This module adaptively selects non-keyframe for feature fusion segmentation, reducing noise and optimizing speed. RESULTS: To evaluate the performance of IG-Net, we constructed the most extensive dataset known to date, comprising 106 video clips and 6153 images. The experimental results reveal that this method achieves favorable performance, with 72.70% IoU, 82.02% Dice, and 35 FPS. CONCLUSIONS: For the task of prostate segmentation based on surgical videos, our proposed IG-Net surpasses all previous methods across multiple metrics. IG-Net balances segmentation accuracy and speed, demonstrating strong robustness against adverse factors.

Pan-immune-inflammation value as a prognostic biomarker for colon cancer and its variation by primary tumor location.

BACKGROUND: A growing body of research indicates significant differences between left-sided colon cancers (LCC) and right-sided colon cancers (RCC). Pan-immune-inflammation value (PIV) is a systemic immune response marker that can predict the prognosis of patients with colon cancer. However, the specific distinction between PIV of LCC and RCC remains unclear. AIM: To investigate the prognostic and clinical significance of PIV in LCC and RCC patients. METHODS: This multicenter retrospective cohort study included 1510 patients with colon cancer, comprising 801 with LCC and 709 with RCC. We used generalized lifting regression analysis to evaluate the relative impact of PIV on disease-free survival (DFS) in these patients. Kaplan-Meier analysis, as well as univariate and multivariate analyses, were used to examine the risk factors for DFS. The correlation between PIV and the clinical characteristics was statistically analyzed in these patients. RESULTS: A total of 1510 patients {872 female patients (58%); median age 63 years [interquartile ranges (IQR): 54-71]; patients with LCC 801 (53%); median follow-up 44.17 months (IQR 29.67-62.32)} were identified. PIV was significantly higher in patients with RCC [median (IQR): 214.34 (121.78-386.72) vs 175.87 (111.92-286.84), P < 0.001]. After propensity score matching, no difference in PIV was observed between patients with LCC and RCC [median (IQR): 182.42 (111.88-297.65) vs 189.45 (109.44-316.02); P = 0.987]. PIV thresholds for DFS were 227.84 in LCC and 145.99 in RCC. High PIV (> 227.84) was associated with worse DFS in LCC [PIV-high: Adjusted hazard ratio (aHR) = 2.39; 95% confidence interval: 1.70-3.38; P < 0.001] but not in RCC (PIV-high: aHR = 0.72; 95% confidence interval: 0.48-1.08; P = 0.114). CONCLUSION: These findings suggest that PIV may predict recurrence in patients with LCC but not RCC, underscoring the importance of tumor location when using PIV as a colon cancer biomarker.

Latent profiles of multi-dimensional sleep characteristics and association with overweight/obesity in Chinese preschool children.

OBJECTIVES: To examine the association between latent profiles of multi-dimensional sleep characteristics and overweight/obesity (OWO) in Chinese preschool children. STUDY DESIGN: The cross-sectional analysis included 3204 preschool children recruited from 24 kindergartens in Shanghai. Parents reported children's demographics and sleep characteristics, including sleep duration, timing and disturbances. Latent profile analysis (LPA) was used to identify sleep subtypes. Logistic regression models were used to evaluate the associations between sleep characteristics/subtypes and OWO. RESULTS: Short sleep duration, late bedtime, long social jetlag and sleep disturbances were significantly associated with increased OWO. However, when considering the interplay of sleep duration and timing, there was no significant association between sleep duration and OWO for children sleeping later than 22:00. Three sleep subtypes were identified based on children's sleep duration, timing and disturbances: "Average Sleepers" (n = 2107, 65.8 %), "Good Sleepers" (n = 481, 15.0 %), and "Poor Sleepers" (n = 616, 19.2 %). "Good Sleepers" had reduced odds of being OWO (AOR, 0.72; 95 % CI, 0.56-0.93) compared to "Average Sleepers", while "Poor Sleepers" showed an increased risk of OWO (AOR, 1.36; 95 % CI, 1.11-1.67). CONCLUSIONS: These findings highlight that improving multiple sleep characteristics simultaneously is a promising option to prevent and intervene childhood obesity.

Advance in the application of 4-dimensional flow MRI in atrial fibrillation.

Atrial fibrillation (AF) is the most prevalent arrhythmia in world-wild places and is associated with the development of severe secondary complications such as heart failure and stroke. Emerging evidence shows that the modified hemodynamic environment associated with AF can cause altered flow patterns in left atrial and even systemic blood associated with left atrial appendage thrombosis. Recent advances in magnetic resonance imaging (MRI) allow for the comprehensive visualization and quantification of in vivo aortic flow pattern dynamics. In particular, the technique of 4- dimensional flow MRI (4D flow MRI) offers the opportunity to derive advanced hemodynamic measures such as velocity, vortex, endothelial cell activation potential, and kinetic energy. This review introduces 4D flow MRI for blood flow visualization and quantification of hemodynamic metrics in the setting of AF, with a focus on AF and associated secondary complications.

Nonlocal photonic quantum gates over 7.0 km.

Quantum networks provide a prospective paradigm to connect separated quantum nodes, which relies on the distribution of long-distance entanglement and active feedforward control of qubits between remote nodes. Such approaches can be utilized to construct nonlocal quantum gates, forming building blocks for distributed quantum computing and other novel quantum applications. However, these gates have only been realized within single nodes or between nodes separated by a few tens of meters, limiting the ability to harness computing resources in large-scale quantum networks. Here, we demonstrate nonlocal photonic quantum gates between two nodes spatially separated by 7.0 km using stationary qubits based on multiplexed quantum memories, flying qubits at telecom wavelengths, and active feedforward control based on field-deployed fibers. Furthermore, we illustrate quantum parallelism by implementing the Deutsch-Jozsa algorithm and the quantum phase estimation algorithm between the two remote nodes. These results represent a proof-of-principle demonstration of quantum gates over metropolitan-scale distances and lay the foundation for the construction of large-scale distributed quantum networks relying on existing fiber channels.

Paving the Way for Pass Disturb-Free Vertical NAND Storage via a Dedicated and String-Compatible Pass Gate.

In this work, we propose a dual-port cell design to address the pass disturbance in vertical NAND storage, which can pass signals through a dedicated and string-compatible pass gate. We demonstrate that (i) the pass disturb-free feature originates from weakening of the depolarization field by the pass bias at the high-VTH (HVT) state and the screening of the applied field by the channel at the low-VTH (LVT) state; (ii) combined simulations and experimental demonstrations of dual-port design verify the disturb-free operation in a NAND string, overcoming a key challenge in single-port designs; (iii) the proposed design can be incorporated into a highly scaled vertical NAND FeFET string, and the pass gate can be incorporated into the existing three-dimensional (3D) NAND with the negligible overhead of the pass gate interconnection through a global bottom pass gate contact in the substrate.

IL-27 attenuated macrophage injury and inflammation induced by Mycobacterium tuberculosis by activating autophagy.

Interleukin-27 (IL-27) is a cytokine that is reported to be highly expressed in the peripheral blood of patients with pulmonary tuberculosis (PTB). IL-27-mediated signaling pathways, which exhibit anti- Mycobacterium tuberculosis (Mtb) properties, have also been demonstrated in macrophages infected with Mtb. However, the exact mechanism remains unclear. This study aimed to clarify the potential molecular mechanisms through which IL-27 enhances macrophage resistance to Mtb infection. Both normal and PTB patients provided bronchoalveolar lavage fluid (BALF). Peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals and stimulated with 50 ng/mL macrophage-colony stimulating factor (M-CSF) to obtain monocyte-derived macrophages (MDMs). Using 100 ng/mL phorbol 12-myristate 13-acetate (PMA), THP-1 cells were induced to differentiate into THP-1-derived macrophage-like cells (TDMs). Both MDMs and TDMs were subsequently infected with the Mtb strain H37Rv and treated with 50 ng/mL IL-27 prior to infection. The damage and inflammation of macrophages were examined using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Patients with PTB had elevated levels of IL-27 in their BALF. Preconditioning with IL-27 was shown to reduce H37Rv-induced MDMs and TDMs apoptosis while also decreasing the levels of Cleaved Caspase-3, Bax and the proinflammatory cytokines TNF-α, IL-1ß, and IL-6, promoting the expression of Bcl-2 and the anti-inflammatory factors IL-10 and IL-4. Silencing of the IL-27 receptor IL-27Ra increased macrophage damage and inflammation triggered by H37Rv. Mechanistically, IL-27 activates autophagy by inhibiting TLR4/NF-κB signaling and activating the PI3K/AKT signaling pathway, thereby inhibiting H37Rv-induced macrophage apoptosis and the inflammatory response. Our study suggests that IL-27 alleviates H37Rv-induced macrophage injury and the inflammatory response by activating autophagy and that IL-27 may be a new target for the treatment of PTB.

The prevalence of alexithymia in schizophrenia: A systematic review and meta-analysis.

OBJECTIVES: This study aims to systematically evaluate the prevalence of alexithymia in patients with schizophrenia. METHODS: Computer searches were conducted in PubMed, PsycInfo, Web of Science, The Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and China Biology Medicine (CBM) electronic databases to collect studies that utilized the TAS-20 scale as a measurement tool with clearly defined diagnostic criteria to determine the prevalence of alexithymia in patients with schizophrenia, from the inception of the databases to December 29, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies, followed by meta-analysis using Stata 16.0 software. RESULTS: A total of 17 studies with 5628 participants were included. The results of the meta-analysis showed that the prevalence of alexithymia in patients with schizophrenia was 35 % (95 % CI: 32-38 %). Subgroup analysis indicated that male gender, smoking, Asian ethnicity, case-control design and divorce were associated with higher rates of alexithymia (all P<0.05). CONCLUSION: The prevalence of alexithymia in patients with schizophrenia is relatively high (35 %). However, due to limitations in the quality and quantity of included studies, further high-quality literature is needed to confirm the above conclusion.

Unraveling the Oxygen Vacancy-Performance Relationship in Perovskite Oxides at Atomic Precision via Precise Synthesis.

Understanding the fundamental effect of the oxygen vacancy atomic structure in perovskite oxides on catalytic properties remains challenging due to diverse facets, surface sites, defects, etc. in traditional powder catalysts and the inherent structural complexity. Through quantitative synthesis of tetrahedral (LaCoO2.5-T), pyramidal (LaCoO2.5-P), and octahedral (LaCoO3) epitaxial thin films as model catalysts, we demonstrate the reactivity orders of active-site geometrical configurations in oxygen-deficient perovskites during the CO oxidation model reaction: CoO4 tetrahedron > CoO6 octahedron > CoO5 pyramid. Ambient-pressure Co L-edge and O K-edge XAS spectra clarify the dynamic evolutions of active-site electronic structures during realistic catalytic processes and highlight the important roles of defect geometrical structures. In addition, in situ XAS and resonant inelastic X-ray scattering spectra and density functional theory calculations directly reveal the nature of high reactivity for CoO4 sites and that the derived shallow-acceptor defect levels in the band structure facilitate the adsorption and activation of reactive gases, resulting in more than 23-fold enhancement for catalytic reaction rates than CoO5 sites.

Neutral mononuclear indium(III) photosensitizers for CO2 photoreduction.

Herein, neutral mononuclear indium(III) complexes (In-1-In-3) containing 2,6-di(1H-pyrrol-2-yl)pyridine and substituted dipyridylpyrrole pincer ligand were employed as photosensitizers (PS) in photocatalytic CO2 reduction. In-2 exhibits good photo-activity and selectivity, which is superior to the classic PS Ru(bpy)32+. The amount of CO generation is 28.4 µmol with a CO selectivity of 93% when using In-2 as a PS and CoPc as a catalyst in CH3CN media.