Mapping theme evolution and identifying hotspots in biomarkers of systemic lupus erythematosus based on global research.

Objective: To perform a bibliometric analysis in the field of biomarkers for systemic lupus erythematosus. Methods: Publications were from Web of Science. Microsoft Excel, VOSviewer, Science Mapping Analysis software Tool, CiteSpace and Tableau were used for analysis. Results: A total of 1112 publications were identified; 1503 institutions from 69 countries contributed, with the highest outputs from China and Karolinska University Hospital. Petri had a tremendous impact. Academic collaborations were localized. Lupus and Arthritis & Rheumatology were the top two journals in terms of publications and citations. Lymphocyte, autoantibody, type I interferon, genetic polymorphisms and urinary biomarkers have been high-frequency themes. Conclusion: Global collaboration needs to be further strengthened. Immune cell, cytokine and gene-level research as a whole and noninvasive tests are the future trends.

Longitudinal study of patients with anti-SAE antibody positive dermatomyositis: a multicenter cohort study in China.

OBJECTIVES: To describe the longitudinal study and long-term prognosis of multicentre large inception cohort of patients with anti-SAE positive DM. METHODS: We retrospectively recruited patients with anti-SAE+DM in four tertiary referral centers from China between March 2005 and December 2022. Long-term survival analysis was performed in the enrolled patients. The Myositis Damage Index (MDI) and Cutaneous Disease Area and Severity Index (CDASI) were used to evaluate the degree of different organ damage and the extent of skin rashes. Longitudinal computed tomographic (CT) patterns were analyzed. Phenotypes were characterized using unsupervised cluster analysis. RESULTS: All-cause death occurred in 10.5% (4/38) of all patients, in which three patients succumbed to malignancies at 13, 18, and 36 months. Most patients had favorable long-term outcomes, 35.3% of them were in drug-free remission. Skin rashes showed significant improvement evaluated by CDASI with time. However, damage to different systems was observed in 70.6% of the surviving patients using the MDI, which mainly consisted in skin damage, accounting for 47.1%. Nine patients with anti-SAE+DM associated interstitial lung disease (ILD) underwent repeat CT showed marked radiological improvement at 6 months or being stable after 12 months. In further, different characteristics and outcomes were also showed in three clusters identified by unsupervised analysis. CONCLUSIONS: Anti-SAE+DM is characterized with lower mortality rate and the development of malignancies being the primary cause of death. Patients who survived showed notable cutaneous damage, while the ILD tends to stabilize. Clusters identified with unsupervised analysis could assist physicians in identifying higher risk of mortality.

Dual-Tuning Azole-Based Ionic Liquids for Reversible CO2 Capture from Ambient Air.

A strategy of tuning azole-based ionic liquids for reversible CO2 capture from ambient air was reported. Through tuning the basicity of anion as well as the type of cation, an ideal azole-based ionic liquid with both high CO2 capacity and excellent stability was synthesized, which exhibited a highest single-component isotherm uptake of 2.17 mmol/g at the atmospheric CO2 concentration of 0.4 mbar at 30 °C, even in the presence of water. The bound CO2 can be released by relatively mild heating of the IL-CO2 at 80 °C, which makes it promising for energy-efficient CO2 desorption and sorbent regeneration, leading to excellent reversibility. To the best of our knowledge, these azole-based ionic liquids are superior to other adsorbent materials for direct air capture due to their dual-tunable properties and high CO2 capture efficiency, offering a new prospect for efficient and reversible direct air capture technologies.

Semantic Segmentation of Remote Sensing Images Depicting Environmental Hazards in High-Speed Rail Network Based on Large-Model Pre-Classification.

With the rapid development of China's railways, ensuring the safety of the operating environment of high-speed railways faces daunting challenges. In response to safety hazards posed by light and heavy floating objects during the operation of trains, we propose a dual-branch semantic segmentation network with the fusion of large models (SAMUnet). The encoder part of this network uses a dual-branch structure, in which the backbone branch uses a residual network for feature extraction and the large-model branch leverages the results of feature extraction generated by the segment anything model (SAM). Moreover, a decoding attention module is fused with the results of prediction of the SAM in the decoder part to enhance the performance of the network. We conducted experiments on the Inria Aerial Image Labeling (IAIL), Massachusetts, and high-speed railway hazards datasets to verify the effectiveness and applicability of the proposed SAMUnet network in comparison with commonly used semantic segmentation networks. The results demonstrated its superiority in terms of both the accuracies of segmentation and feature extraction. It was able to precisely extract hazards in the environment of high-speed railways to significantly improve the accuracy of semantic segmentation.

Knocking out FAM20C in pre-osteoblasts leads to up-regulation of osteoclast differentiation to affect long bone development.

Family with sequence similarity 20 member C (FAM20C) is a Golgi casein kinase that phosphorylates extracellularly-secreted regulatory proteins involved in bone development and mineralization, but its specific role in bone development is still largely unknown. In this study, to examine the specific mechanisms that FAM20C influences bone development, we cross-bred Osx-Cre with FAM20Cflox/flox mice to establish a Osx-Cre; FAM20Cflox/flox knockout (oKO) mouse model; FAM20C was KO in pre-osteoblasts. oKO development was examined at 1-10 weeks, in which compared to control FAM20Cflox/flox, they had lower body weights and bone tissue mineralization. Furthermore, oKO had lower bone volume fractions, thickness, and trabecular numbers, along with higher degrees of trabecular separation. These mice also had decreased femoral metaphyseal cartilage proliferation layer, along with thickened hypertrophic layer and increased apoptotic cell counts. Transcriptomic analysis found that differentially-expressed genes in oKO were concentrated in the osteoclast differentiation pathway, in line with increased osteoclast presence. Additionally, up-regulation of osteoclast-related, and down-regulation of osteogenesis-related genes, were identified, in which the most up-regulated genes were signal regulatory protein ß-1 family (Sirpb1a-c) and mitogen-activated protein kinase 13. Overall, FAM20C KO in pre-osteoblasts leads to abnormal long bone development, likely due to subsequent up-regulation of osteoclast differentiation-associated genes.

Translation and Validation of the Chinese Language Version of the Control of Allergic Rhinitis and Asthma Test in Patients with Allergic Rhinitis.

Objective: Due to the escalating global prevalence of allergic rhinitis (AR) and its status as an independent risk factor for asthma, timely and effective control of AR is crucial. Achieving this often involves the accurate assessment of AR. Currently, the Control of Allergic Rhinitis and Asthma Test (CARAT) is widely used as an assessment tool, but its measurement effectiveness in Chinese AR patients remains unclear. Therefore, this study aims to evaluate the reliability and validity of the Chinese version of the CARAT10 scale (CARAT10-C) and analyze its application value in the assessment of allergic rhinitis and asthma control trials. Methods: The study enrolled 130 patients with AR from the Ear, Nose, and Throat (ENT) outpatient department of a comprehensive teaching hospital from March to May 2022 as participants. The reliability and validity of the CARAT10-C scale were assessed using Cronbach's alpha coefficient (CAC), Kaiser-Meyer-Olkin (KMO), and Bartlett's sphericity test. Additionally, the study analyzed the effectiveness of the CARAT10-C scale in its application within the Control of Allergic Rhinitis and Asthma Test (CARAT). Results: The Cronbach's alpha coefficient ranges between 0 and 1, with higher values indicating better reliability. Significant differences in exploratory factor analysis suggest good validity. The Cronbach's alpha coefficient of the CARAT10-C scale was 0.806. Exploratory factor analysis revealed that the eigenvalues of Component 1 (3.851) and Component 2 (2.193) were both greater than 1, with a cumulative variance contribution rate (CVCR) of 60.436%. Items 6-10 were primarily loaded on Component 1 (Asthma), while items 1-4 were mainly influenced by Component 2 (AR), with loading ranges of 0.508-0.874, all significant at P < .001. The composite reliability (CAC) of the CARAT10-C scale was 0.806, exceeding 0.8, indicating high reliability. Component 1 had a CAC of 0.834, and Component 2 had a CACs of 0.807, both exceeding 0.8, indicating high reliability for both components. Conclusion: The CARAT10-C scale demonstrates good reliability and validity in the preliminary assessment of AR. It holds potential value in the evaluation and management of AR in China, although the specific application effects still require further investigation.

Secretion of IFN-γ by specific T cells in HCMV infection.

One major risk for recipients undergoing allogeneic hematopoietic stem cell transplants (allo-HSCTs) is infection with the human cytomegalovirus (HCMV). For HCMV treatment, it is especially crucial to be able to differentiate between recipients who are at high risk of reactivation and those who are not. In this study, HCMV-DNA was collected from 60 HLA-A*02 allo-HSCT recipients before and after transplantation. After transplantation, the release of interferon (IFN)-γ by T cells specific to HCMV was assessed using the enzyme-linked immunospot assay (ELISPOT). The results show that the median viral load (VL) was significantly higher in the HCMV persistent-infection group compared to the non-persistent-infection group (p = 0.002), and that the late-infection rate was considerably higher in the high-VL group compared to the low-VL group (p = 0.014). The uninfected group had a considerably higher median IFN-γ spot-forming cell (SFC) count than the persistent-infection group (p = 0.001), and IFN-γ SFC counts correlated negatively and linearly with VLs (r = -0.397, p = 0.002). The immune-response groups showed significantly difference in median VL (p = 0.018), and the high immune response group had a reduced late-infection rate than the no/low immune response groups (p = 0.049). Our study showed that allo-HSCT recipients with a high VL at an early transplantation stage were at high risk for late HCMV infection. Further HCMV reactivation can be prevented by HCMV-specific T cells secreting enough IFN-γ.

Therapeutic effects and molecular mechanisms of quercetin in gynecological disorders.

Quercetin is a representative flavonoid that is widely present in fruits, herbs, and vegetables. It is also an important active core component in traditional Chinese medicines. As an important flavonoid, quercetin has various properties and exerts antioxidant, anti-inflammatory, and cardioprotective effects. The public interest in quercetin is increasing, and quercetin has been used to prevent or treat numerous of diseases, such as polycystic ovary syndrome (PCOS), cancer, autoimmune diseases and chronic cardiovascular diseases, in clinical experiments and animal studies due to its powerful antioxidant properties and minimal side effects. Quercetin exerts marked pharmacological effects on gynecological disorders; however, there have been no reviews about the potential health benefits of quercetin in the context of gynecological disorders, including PCOS, premature ovary failure (POF), endometriosis (EM), ovarian cancer (OC), cervical cancer (CC) and endometrial carcinoma (EC). Thus, this review aimed to summarize the biological effects of quercetin on gynecological disorders and its mechanisms.

The Production Splitting Method of Offshore Multilayer Combined Water Flooding Gas Wells with Gas Dissolving.

Offshore gas reservoirs are characterized by thin interlayers, high production, few wells, etc., and are often exploited by multilayer combined mining, whereas the production dynamics of multilayer gas reservoirs are very different from those of single-layer gas reservoirs. Therefore, clarifying the gas production contribution of each layer in multilayer combined gas reservoirs is an important prerequisite for analyzing the potential of gas reservoirs and realizing efficient development. In this paper, unlike the past method of evaluating the gas production contribution of each layer by using the KH attribute of the reservoir, we combined the modified B-L equation considering CO2 dissolution and the multilayer multizone seepage equation to establish a dynamic split model of the production dynamics of multilayer water-driven gas reservoirs, verified the reliability of the model through the numerical model and the results of the production well logging, quantitatively analyzed the degree of influence of each parameter on the contribution of the layered gas production, and designed the orthogonal experiments. The main controlling factors of the gas production contribution of each layer were determined. The results of the study show that (1) the main controlling factors for the gas production contribution of each layer in the early stage of WDG are, in order, permeability, thickness, outer boundary distance, porosity, CO2 content, and total gas production rate; however, the main controlling factors for the gas production contribution of each layer in the late stage of WDG are, in order, thickness, permeability, outer boundary distance, porosity, CO2 content, and total gas production rate; and the combined view shows that the permeability and thickness have the greatest influence. (2) In multilayer production, the conditions of high permeability, close gas-water boundary, poor gas content, and low CO2 content will reduce the gas production contribution of the layer with the increase of production time. (3) Compared with the results of production logging and numerical simulation, the split model can better predict the gas production of each layer, and the prediction error is no more than 10%. (4) By comparing with the numerical simulation results, the model can realize the prediction of the time of seeing water in the layer with stronger water body capability. (5) The model takes into account the effect of the CO2 content, better reflects the actual gas composition of each layer, and can improve the production prediction accuracy by up to 4%. Considering the high cost of production logging in offshore oil and gas fields, the inability of the KH method to reflect the dynamic changes of gas production in each layer, the poor application of stratified sampling to dry gas reservoirs, and other limitations, the model in this paper can be utilized to simulate the multilayer water-driven gas drive process when the energy of the water body is strong by using the geological parameters of the reservoir and the fluid parameters, and the simulation results of this model provide directions for offshore multilayer water-driven gas reservoirs to improve the recovery rate, and for plugging and regulating the water and exploiting the potential of gas wells that have seen water.

Biomimetic Design of a Dynamic M-O-V Pyramid Electron Bridge for Enhanced Nitrogen Electroreduction.

Electrochemical nitrogen reduction reaction (eNRR) offers a sustainable route for ammonia synthesis; however, current electrocatalysts are limited in achieving optimal performance within narrow potential windows. Herein, inspired by the heliotropism of sunflowers, we present a biomimetic design of Ru-VOH electrocatalyst, featuring a dynamic Ru-O-V pyramid electron bridge for eNRR within a wide potential range. In situ spectroscopy and theoretical investigations unravel the fact that the electrons are donated from Ru to V at lower overpotentials and retrieved at higher overpotentials, maintaining a delicate balance between N2 activation and proton hydrogenation. Moreover, N2 adsorption and activation were found to be enhanced by the Ru-O-V moiety. The catalyst showcases an outstanding Faradaic efficiency of 51.48% at -0.2 V (vs RHE) with an NH3 yield rate exceeding 115 µg h-1 mg-1 across the range of -0.2 to -0.4 V (vs RHE), along with impressive durability of over 100 cycles. This dynamic M-O-V pyramid electron bridge is also applicable to other metals (M = Pt, Rh, and Pd).

Circular RNA hsa_circ_0005519 contributes to acute kidney injury via sponging microRNA-98-5p.

BACKGROUND: This study intends to explore the role and molecular mechanism of hsa_circ_0005519 in acute kidney injury (AKI). METHODS: We conducted reverse transcription-qPCR for human serum to determine levels of hsa_circ_0005519 in AKI patients and healthy controls. Hsa_circ_0005519 was inhibited for expression in HK-2 cells using specific siRNAs. A number of techniques, MTT and ELISA assays, were used to analyze the potential role of hsa_circ_0005519 in cell viability, oxidative stress, and inflammation of LPS-induced HK-2 cells. RESULTS: The serum of patients with AKI exhibited a significant increase in hsa_circ_0005519 expression, compared with healthy controls. Hsa_circ_0005519 was knockdown by siRNA, and its knockdown led to cell viability increase in LPS-induced HK-2 cells. Inhibition of hsa_circ_0005519 can reverse the TNF-α, IL-6 and IL-1ß increase in LPS-induced HK-2 cells. Inhibiting hsa_circ_0005519 led to downregulation of MPO and MDA levels. MiR-98-5p was a downstream miRNA for hsa_circ_0005519. MiR-98-5p can offset the effects of hsa_circ_0005519 on LPS-induced HK-2 cells. IFG1R was a target gene for miR-98-5p. CONCLUSIONS: These findings indicate that the highly expressed hsa_circ_0005519 plays a promoting role in AKI.

Subphenotypes of self-reported symptoms and outcomes in long COVID: a prospective cohort study with latent class analysis.

OBJECTIVE: To characterise subphenotypes of self-reported symptoms and outcomes (SRSOs) in postacute sequelae of COVID-19 (PASC). DESIGN: Prospective, observational cohort study of subjects with PASC. SETTING: Academic tertiary centre from five clinical referral sources. PARTICIPANTS: Adults with COVID-19 ≥20 days before enrolment and presence of any new self-reported symptoms following COVID-19. EXPOSURES: We collected data on clinical variables and SRSOs via structured telephone interviews and performed standardised assessments with validated clinical numerical scales to capture psychological symptoms, neurocognitive functioning and cardiopulmonary function. We collected saliva and stool samples for quantification of SARS-CoV-2 RNA via quantitative PCR. OUTCOMES MEASURES: Description of PASC SRSOs burden and duration, derivation of distinct PASC subphenotypes via latent class analysis (LCA) and relationship with viral load. RESULTS: We analysed baseline data for 214 individuals with a study visit at a median of 197.5 days after COVID-19 diagnosis. Participants reported ever having a median of 9/16 symptoms (IQR 6-11) after acute COVID-19, with muscle-aches, dyspnoea and headache being the most common. Fatigue, cognitive impairment and dyspnoea were experienced for a longer time. Participants had a lower burden of active symptoms (median 3 (1-6)) than those ever experienced (p<0.001). Unsupervised LCA of symptoms revealed three clinically active PASC subphenotypes: a high burden constitutional symptoms (21.9%), a persistent loss/change of smell and taste (20.6%) and a minimal residual symptoms subphenotype (57.5%). Subphenotype assignments were strongly associated with self-assessments of global health, recovery and PASC impact on employment (p<0.001) as well as referral source for enrolment. Viral persistence (5.6% saliva and 1% stool samples positive) did not explain SRSOs or subphenotypes. CONCLUSIONS: We identified three distinct PASC subphenotypes. We highlight that although most symptoms progressively resolve, specific PASC subpopulations are impacted by either high burden of constitutional symptoms or persistent olfactory/gustatory dysfunction, requiring prospective identification and targeted preventive or therapeutic interventions.

Abnormal expression of PRKAG2-AS1 in endothelial cells induced inflammation and apoptosis by reducing PRKAG2 expression.

PRKAG2 is required for the maintenance of cellular energy balance. PRKAG2-AS1, a long non-coding RNA (lncRNA), was found within the promoter region of PRKAG2. Despite the extensive expression of PRKAG2-AS1 in endothelial cells, the precise function and mechanism of this gene in endothelial cells have yet to be elucidated. The localization of PRKAG2-AS1 was predominantly observed in the nucleus, as revealed using nuclear and cytoplasmic fractionation and fluorescence in situ hybridization. The manipulation of PRKAG2-AS1 by knockdown and overexpression within the nucleus significantly altered PRKAG2 expression in a cis-regulatory manner. The expression of PRKAG2-AS1 and its target genes, PRKAG2b and PRKAG2d, was down-regulated in endothelial cells subjected to oxLDL and Hcy-induced injury. This finding suggests that PRKAG2-AS1 may be involved in the mechanism behind endothelial injury. The suppression of PRKAG2-AS1 specifically in the nucleus led to an upregulation of inflammatory molecules such as cytokines, adhesion molecules, and chemokines in endothelial cells. Additionally, this nuclear suppression of PRKAG2-AS1 facilitated the adherence of THP1 cells to endothelial cells. We confirmed the role of nuclear knockdown PRKAG2-AS1 in the induction of apoptosis and inhibition of cell proliferation, migration, and lumen formation through flow cytometry, TUNEL test, CCK8 assay, and cell scratching. Finally, it was determined that PRKAG2-AS1 exerts direct control over the transcription of PRKAG2 by its binding to their promoters. In conclusion, downregulation of PRKAG2-AS1 suppressed the proliferation and migration, promoted inflammation and apoptosis of endothelial cells, and thus contributed to the development of atherosclerosis resulting from endothelial cell injury.

TLR9 Knockdown Alleviates Sepsis via Disruption of MyD88/NF-κB Pathway Activation.

Sepsis is a life-threatening organ dysfunction due to dysregulated host response to infection, accompanied by a high rate of mortality worldwide. During sepsis progression, toll-like receptors (TLRs) play essential roles in the aberrant inflammatory response that contributes to sepsis-related mortality. Here, we demonstrated a critical role of TLR9 in the progression of sepsis. A septic mouse model was established by cecal ligation and puncture (CLP), then administered with lentivirus encoding si-TLR9/LY294002. TLR9 protein expression and p65 nuclear translocation level/TLR9 protein positive expression/interaction between TLR9 and myeloid differentiation primary response protein 88 (MyD88) in the cecal tissues were examined by Western blot/immunohistochemistry/co-immunoprecipitation assays. Serum levels of pro-inflammatory factors [e.g., interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α)] as well as bacterial contents in the liver/spleen/mesenteric lymph nodes (MLN) were measured by ELISA and bacterial mobility assay. TLR9 expression was augmented in the cecal tissues, TLR9 and MyD88 interaction was enhanced, nuclear p65 protein level was increased, cytoplasmic p65 protein level was decreased, and the nuclear factor kappa B (NF-κB) pathway was activated in CLP-induced septic mice, while TLR9 knockout protected against CLP-induced sepsis via the MyD88/NF-κB pathway inactivation. Briefly, TLR9 inhibition-mediated protection against CLP-induced sepsis was associated with a reduction in pro-inflammatory cytokine release and a promotion of bacterial clearance via a mechanism involving the MyD88/NF-κB pathway inactivation.

MiR-136-5p in cancer: Roles, mechanisms, and chemotherapy resistance.

MicroRNAs (miRNAs) have emerged as important regulators of gene expression, and the deregulation of their activity has been linked to the onset and progression of a variety of human malignancies. Among these miRNAs, miR-136-5p has attracted significant attention due to its diverse roles in cancer biology. Mostly, miR-136-5p is downregulated in malignancies. It could inhibit viability, proliferation, migration, invasion and promote apoptosis of tumor cells. This review article provides a comprehensive overview of the current understanding of miR-136-5p in different sorts of human cancers: genital tumors, head and neck tumors, tumors from the digestive and urinary systems, skin cancers, neurologic tumors, pulmonary neoplasms and other cancers by discussing its molecular mechanisms, functional roles, and impact in chemotherapies. In conclusion, miR-136-5p could be a promising new biomarker and potential clinical therapeutic target.

Thoracic SMARCA4-deficient tumors: a clinicopathological analysis of 52 cases with SMARCA4-deficient non-small cell lung cancer and 20 cases with thoracic SMARCA4-deficient undifferentiated tumor.

Background: Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a distinct clinicopathological entity with an aggressive clinical course. Additionally, SMARCA4/BRG1 deficiency can be observed in a few patients with non-small cell lung cancer (NSCLC). We aimed to compare the clinicopathological, immunohistochemical and prognostic features of SMARCA4-deficient NSCLC (SMARCA4-dNSCLC) with those of thoracic SMARCA4-UT. Methods: Patients with BRG1-deficient tumors in the lung or thorax were enrolled in the study from the Department of Pathology of West China Hospital, Sichuan University, from January 2014 to June 2022. We retrospectively collected the clinicopathological and immunohistochemical features and outcomes of these patients. Results: Seventy-two patients had tumors in the lung or thorax with BRG1-deficient expression, including 52 patients with SMARCA4-dNSCLC and 20 patients with thoracic SMARCA4-UT. Among the patients with SMARCA4-dNSCLC, 98.1% were male, 85.7% were smokers, and 79.5% (35/44) had tumor-node-metas-tasis (TNM) III-IV tumors. Among the patients with thoracic SMARCA4-UT, all were males who smoked, and 93.75% (15/16) had TNM III-IV tumors. Pure solid architecture and necrosis were the predominant pathological features. Rhabdoid morphology was observed in some SMARCA4-dNSCLCs (10/52, 19.2%) and thoracic SMARCA4-UTs (11/20, 55%). In most patients with thoracic SMARCA4-UT, the tumors exhibited scattered weak expression or negative expression of epithelial markers, and positive expression of CD34 and Syn. Overall survival (OS) and progression-free survival (PFS) were not significantly different between patients with SMARCA4-dNSCLC and patients with thoracic SMARCA4-UT (p = 0.63 and p = 0.20, respectively). Conclusions: Thoracic SMARCA4-DTs include SMARCA4-dNSCLC and thoracic SMARCA4-UT. Both have overlapping clinicopathological features and poor prognosis. We hypothesize that thoracic SMARCA4-UT may be the undifferentiated or dedifferentiated form of SMARCA4-dNSCLC. However, further studies with larger cohorts and longer follow-up periods are needed.

Thoracic SMARCA4-deficient undifferentiated tumor: A clinicopathological and prognostic analysis of 35 cases and immunotherapy efficacy.

BACKGROUND: Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized distinct clinicopathological entity according to the fifth edition of the 2021 World Health Organization Classification (WHO) for thoracic tumors. Thoracic SMARCA4-UTs are diagnostically challenging to diagnose, especially on small biopsies. METHODS: We identified 35 thoracic SMARCA4-UTs from the Department of Pathology of West China Hospital, Sichuan University, between January 2017 and December 2022. In the present study, we summarized the clinicopathological features, prognostic significance and immunotherapy efficacy of thoracic SMARCA4-UTs. RESULTS: All 35 patients were male, and 88.6 % were smokers. The left upper lobe (25.7 %) and mediastinum (20.0 %) were the most affected sites. 17.1 % of the patients received surgical treatment. 30.4 % of the patients were stage III, and 69.6 % were stage IV. Solid architecture (100 %), rhabdoid morphology (51.4 %) and necrosis (42.9 %) were the common histological features. Immunohistochemical staining revealed CD34 and synaptophysin positivity in most patients (76.9 % and 65.2 %, respectively). Patients had unfavorable outcomes. Patients who received immunotherapy had better OS and PFS than those who did not (p = 0.007 and p = 0.02, respectively). Five patients were evaluated for immunotherapy efficacy, and four of those patients were negative expression of PD-L1. Cases 1-4 presented TIL counts ranging from 20 to 1000/HPF. Case 5 presented TIL counts of 5-10/HPF. Mutations in SMARCA4 were confirmed in cases 4 and 5, and the TMB was 5.98 and 5.03 mutations/Mb, respectively. Case 1 achieved a CR, cases 2-4 achieved a PR, and case 5 had a PD. Five patients who received immunotherapy were all alive, with OS ranging from 10.7 to 33.6 months. CONCLUSIONS: Thoracic SMARCA4-UTs exhibited an aggressive clinical course, presented solid architecture with or without necrosis and/or rhabdoid morphology, and frequently expressed CD34 and synaptophysin. Some thoracic SMARCA4-UTs appear to be associated with responsiveness to immunotherapy, suggesting the need for validation in larger series.

Higher risk of hepatotoxicity associated with cabozantinib in cancer patients.

BACKGROUND: The efficacy of cabozantinib has attracted interest in various solid tumors. The primary aim of this study was to evaluate the risk of hepatotoxicity associated with cabozantinib in the patients with cancer. METHODS: PubMed, Cochrane, and EMBASE databases were searched for published randomized controlled trials (RCTs) from inception to September 9, 2023. The mainly outcomes were all-grade and grade ≥3 elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), expressed as relative risk (RR) and 95% confidence interval (CI). All data were pooled using fixed-effect or random-effects models according to the heterogeneity of the included RCTs. RESULTS: Among the 922 records identified, 8 RCTs incorporating 2613 patients with cancer were included. For patients receiving cabozantinib, the relative risks of all-grade AST elevation (RR, 2.63; 95% CI, 2.16-3.20, P < 0.001), all-grade ALT elevation (RR, 2.89; 95% CI, 2.31-3.60, P < 0.001), grade ≥3 AST elevation (RR, 2.26; 95% CI, 1.34-3.83, P = 0.002), and grade ≥3 ALT elevation (RR, 3.40; 95% CI, 1.65-7.01, P < 0.001) were higher than those of patients who did not receive cabozantinib group. Further subgroup analysis showed that the relative risk of hepatotoxicity associated with cabozantinib was higher than that in the other TKIs (erlotinib, sunitinib, and sorafenib) and the non-TKI drug groups (everolimus, prednisone, mitoxantrone, and paclitaxel). CONCLUSIONS: Compared with other solid tumor drugs, such as everolimus, sorafenib, sunitinib, paclitaxel, mitoxantrone-prednisone et al., cabozantinib has a higher risk of hepatotoxicity.

Living, Heat-Killed Limosilactobacillus mucosae and Its Cell-Free Supernatant Differentially Regulate Colonic Serotonin Receptors and Immune Response in Experimental Colitis.

Lactobacillus species have been shown to alleviate gut inflammation and oxidative stress. However, the effect of different lactobacilli components on gut inflammation has not been well studied. This study aims to identify the differences in the effect and mechanisms of different forms and components of Limosilactobacillus mucosae (LM) treatment in the alleviation of gut inflammation using a colitis mouse model that is induced by dextran sodium sulfate (DSS). Seventy-two C57BL/6 mice were divided into six groups: control, DSS, live LM+DSS (LM+DSS), heat-killed LM+DSS (HKLM+DSS), LM cell-free supernatant + DSS (LMCS+DSS), and MRS medium + DSS (MRS+DSS). The mice were treated with different forms and components of LM for two weeks before DSS treatment. After that, the mice were sacrificed for an assessment of their levels of inflammatory cytokines, serotonin (5-HT) receptors (HTRs), and tryptophan metabolites. The results showed that, compared to other treatments, LMCS was more effective (p < 0.05) in the alleviation of DSS-induced body weight loss and led to an increase in the disease activity index score. All three forms and components of LM increased (p < 0.05) the levels of indole-3-acetic acid but reduced (p < 0.05) the levels of 5-HT in the colon. HKLM or LMCS reduced (p < 0.05) the percentages of CD3+CD8+ cytotoxic T cells but increased (p < 0.05) the percentages of CD3+CD4+ T helper cells in the spleen. LM or HKLM increased (p < 0.05) abundances of CD4+Foxp3+ regulatory T cells in the spleen. The LM and LMCS treatments reduced (p < 0.05) the expression of the pro-inflammatory cytokines Il6 and Il17a. The mice in the HKLM+DSS group had higher (p < 0.05) mRNA levels of the anti-inflammatory cytokine Il10, the cell differentiation and proliferation markers Lgr5 and Ki67, the 5-HT degradation enzyme Maoa, and HTRs (Htr1a, Htr2a, and Htr2b) in the colon. All three forms and components of LM reduced the phosphorylation of STAT3. The above findings can help to optimize the functionality of probiotics and develop new dietary strategies that aid in the maintenance of a healthy gut.

Antennal transcriptome analysis of Psyttalia incisi (silvestri) (Hymenoptera: Braconidae): identification and tissue expression profiling of candidate odorant-binding protein genes.

BACKGROUND: Olfaction plays an important role in host-seeking by parasitoids, as they can sense chemical signals using sensitive chemosensory systems. Psyttalia incisi (Silvestri) (Hymenoptera: Braconidae) is the dominant parasitoid of Bactrocera dorsalis (Hendel) in fruit-producing regions of southern China. The olfactory behavior of P. incisi has been extensively studied; however, the chemosensory mechanisms of this species are not fully understood. RESULTS: Bioinformatics analysis of 64,515 unigenes from the antennal transcriptome of both male and female adults P. incisi identified 87 candidate chemosensory genes. These included 13 odorant-binding proteins (OBPs), seven gustatory receptors (GRs), 55 odorant receptors (ORs), 10 ionotropic receptors (IRs), and two sensory neuron membrane proteins (SNMPs). Phylogenetic trees were constructed to predict evolutionary relationships between these chemosensory genes in hymenopterans. Moreover, the tissue expression profiles of 13 OBPs were analyzed by quantitative real-time PCR, revealing high expression of seven OBPs (1, 3, 6, 7, 8, 12, and 13) in the antennae. CONCLUSION: This study represents the first identification of chemosensory genes and the determination of their expression patterns in different tissues of P. incisi. These results contribute to a better understanding of the function of the chemosensory system of this parasitoid species.