Low dose methotrexate impaired T cell transmigration through down-regulating CXCR4 expression in rheumatoid arthritis (RA).

BACKGROUND: CXC chemokine CXCL12 is involved in the pathological development of rheumatoid arthritis (RA) through abnormal migration of peripheral immune cells in the joint. Although low dose methotrexate (MTX) is clinically used to treat RA patients, CXCL12 signaling responses to MTX-mediated treatments is still not well understood. METHODS: In this study, we examined the expression of CXCR4 (cognatic receptor for CXCL12) in peripheral T cells from RA patients and arthritis mice models received from low dose MTX therapies. The effects of low dose MTX on CXCR4 were further determined via both in vitro CD3+ T cells and Cxcr4 conditional knockout (CKO) arthritis mice models. RESULTS: Our clinical data shows that low dose MTX treatment was clinically associated with down-regulated expression of chemokine receptor CXCR4 on patient peripheral T cells. In vitro, low dose MTX significantly decreased cell transmigration through down-regulated CXCR4's expression in CD3+ T cells. Consistently, CD3+ T cells treated with low dose MTX demonstrated an increased genomic hypermethylation across the promoter region of Cxcr4 gene. Furthermore, our preclinical studies showed that low dose MTX-mediated downregulation of CXCR4 significantly improved the pathological development in mouse arthritis models. Conditional disruption of the Cxcr4 gene in peripheral immune cells potentially alleviated inflammation of joints and lung tissue in the arthritis mice, though genetic modification itself overall did not change their clinical scores of arthritis, except for a significant improvement on day 45 in CXCR4 CKO arthritis mice models during the recovery phase. CONCLUSION: Our findings suggest that the effect of low dose MTX treatment could serve to eliminate inflammation in RA patients through impairment of immune cell transmigration mediated by CXCR4.

Tract-specific magnetization transfer ratio provides insights into the severity of degenerative cervical myelopathy.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: This study's goal is to report whether Magnetization Transfer Ratio (MTR) can evaluate the severity of white matter (WM) injury in degenerative cervical myelopathy (DCM). SETTING: Laureate Institute of Brain Research, USA; Department of Neurosurgery, University of Oklahoma Health Sciences Center, USA. METHODS: 27 DCM patients were aged-matched with 20 healthy controls (HC) and categorized into treatment groups based on modified Japanese Orthopedic Association (mJOA) severity (11 mild and 16 moderate/severe). Regional and tract MTRs were extracted from the two vertebral levels containing maximum compression within magnetization transfer images. MTR differences between groups were assessed using a one-way ANOVA or Kruskal-Wallis test. The association between MTR and mJOA measures was evaluated using Spearman's correlation. RESULTS: Significant decreases in MTR were found between HC and moderate/severe groups in the overall (p = 0.0065) and ventral (p = 0.0009) WM regions; and ventral corticospinal (p = 0.0101), ventral reticulospinal (p = 0.0084), spinal lemniscus (p = 0.0079), and fasciculus cuneatus (p = 0.0219) tracts. The spinal lemniscus MTR also significantly decreased between HC and mild groups (p = 0.038). Ventral reticulospinal tract MTR correlated with upper (r = 0.439; p = 0.022) and lower (r = 0.386; p = 0.047) limb motor mJOA scores. CONCLUSIONS: Significant tract-based MTR changes and correlations align with known DCM symptoms, are demonstrated to be lost at the regional level, and display the inhomogeneous compressive damage occurring within DCM spinal cords.

Utilizing ultrasonography to determine the minimal transverse diameter of the subglottic airway for informed selection of reinforced cuffed endotracheal tube models in children.

OBJECTIVE: We explored the use of ultrasonography in determining the minimal transverse diameter of the subglottic airway (MTDSA) for the purpose of choosing an appropriate model of reinforced cuffed endotracheal tube. METHODS: A total of 110 pediatric patients who received general anesthesia and tracheal intubation for selective surgeries at the hospital from February 2019 to February 2022 were chosen. They were then randomly assigned to three groups: 39 in the MTDSA group, 35 in the age formula group, and 36 in the height formula group. We assessed how accurately the appropriate endotracheal tube model was predicted in each group and compared their predictive performance. RESULTS: The age range of the enrolled pediatric patients was 3-6 years old. The ultrasonic measurement method demonstrated a prediction accuracy of 87.18%, while the age formula method and height formula method exhibited lower accuracy rates of 54.29% and 47.22%, respectively. Notably, the ultrasonic measurement method outperformed the other two methods significantly (P < 0.05). In the MTDSA group, 2 patients had their catheters changed during anesthesia, and the proportion of patients who changed their catheters was 5.13%. In the MTDSA group, 6 catheters were replaced, and the frequency of catheter replacement was 15.38%. In contrast, these percentages were much higher in the age formula group, at 31.43% and 45.71%, and in the height formula group, at 36.11% and 52.78%. The latter two groups had significantly higher values than the MTDSA group (P < 0.05). Regarding complications such as hoarseness, laryngeal edema, aspiration, and laryngospasm, the MTDSA group experienced a notably lower total incidence of 7.69% compared to the 37.14% in the age formula group and 41.67% in the height formula group, demonstrating statistical significance (P < 0.05). CONCLUSION: The ultrasonic measurement technique employed in MTDSA exhibits impressive precision when it comes to forecasting the specific model of a reinforced cuffed endotracheal tube for pediatric patients. This enhanced accuracy contributes significantly to minimizing the need for tube replacements during anesthesia and the associated complications. It holds immense importance in assisting clinicians in selecting the most appropriate pediatric endotracheal tube model for anesthesia induction.

Self-flickering bioinspired actuator with autonomous motion and structural color switching.

Color-tunable actuators with motion and color-changing functions have attracted considerable attention in recent years, yet it remains a challenge to achieve the autonomous regulation of motion and color. Inspired by Apatura ilia butterfly with dynamic structural color and Pelargonium carnosum plant with moisture responsive bilayer structure, an automatic color-tunable actuator is developed by integrating photonic crystals layer and hygroscopic layer. Taking advantage of the asymmetric hygroscopicity between two layers and the angle-dependent structural color of photonic crystals, this actuator can continuously self-flicker in humid environment by visual switching in structural color due to automated cyclic motion. The actuator is assembled into the self-flapping biomimetic butterfly with switchable color and the self-reporting information array with dynamic visual display, demonstrating its autoregulatory motion and color. This work provides a new strategy for developing automatic color-tunable actuator and suggests its potential in the intelligent robot and optical display.

Multi-scale Hierarchical Organic Photocatalytic Platform for Self-Suspending Sacrificial Hydrogen Production from Seawater.

The widespread application of photocatalysis for converting solar energy and seawater into hydrogen is generally hindered by limited catalyst activity and the lack of sustainable large-scale platforms. Here, a multi-scale hierarchical organic photocatalytic platform was developed, combining a photosensitive molecular heterojunction with a molecular-scale gradient energy level alignment and micro-nanoscale hierarchical pore structures. The ternary system facilitates efficient charge transfer and enhances photocatalytic activity compared to conventional donor-acceptor pairs. Meanwhile, the super-wetted hierarchical interfaces of the platform endow it with the ability to repeatedly capture light and self-suspend below the water surface, which simultaneously improves the light utilization efficiency, and reduces the adverse effects of salt deposition. Under a Xe lamp illumination, the hydrogen evolution rate of this organic platform utilizing a sacrificial agent can reach 165.8 mmol h-1 m-2, exceeding that of mostly inorganic systems as reported. And upon constructing a scalable system, the platform produced 80.6 ml m-2 of hydrogen from seawater within five hours at noon. More importantly, the outcomes suggest an innovative multi-scale approach that bridges disciplines, advancing the frontier of sustainable seawater hydrogen production driven by solar energy.

Facile In Situ Building of Sulfonated SiO2 Coating on Porous Skeletons of Lithium-Ion Battery Separators.

Polyolefin separators with worse porous structures and compatibilities mismatch the internal environment and deteriorate lithium-ion battery (LIB) combination properties. In this study, a sulfonated SiO2 (SSD) composited polypropylene separator (PP@SSD) is prepared to homogenize pore sizes and in situ-built SSD coatings on porous skeletons. Imported SSD uniformizes pore sizes owing to centralized interface distributions within casting films. Meanwhile, abundant cavitations enable the in situ SSD coating to facilely fix onto porous skeleton surfaces during separator fabrications, which feature simple techniques, low cost, environmental friendliness, and the capability for continuous fabrications. A sturdy SSD coating on the porous skeleton confines thermal shrinkages and offers a superior safety guarantee for LIBs. The abundant sulfonic acid groups of SSD endow PP@SSD with excellent electrolyte affinity, which lowers Li+ transfer barriers and optimizes interfacial compatibility. Therefore, assembled LIBs give the optimal C-rate capacity and cycling stability, holding a capacity retention of 82.7% after the 400th cycle at 0.5 C.

Cell Death: Mechanisms and Potential Targets in Breast Cancer Therapy.

Breast cancer (BC) has become the most life-threatening cancer to women worldwide, with multiple subtypes, poor prognosis, and rising mortality. The molecular heterogeneity of BC limits the efficacy and represents challenges for existing therapies, mainly due to the unpredictable clinical response, the reason for which probably lies in the interactions and alterations of diverse cell death pathways. However, most studies and drugs have focused on a single type of cell death, while the therapeutic opportunities related to other cell death pathways are often neglected. Therefore, it is critical to identify the predominant type of cell death, the transition to different cell death patterns during treatment, and the underlying regulatory mechanisms in BC. In this review, we summarize the characteristics of various forms of cell death, including PANoptosis (pyroptosis, apoptosis, necroptosis), autophagy, ferroptosis, and cuproptosis, and discuss their triggers and signaling cascades in BC, which may provide a reference for future pathogenesis research and allow for the development of novel targeted therapeutics in BC.

CO2 Geostorage and Enhanced Oil Recovery: Challenges in Controlling Foam/Emulsion Generation and Propagation.

CO2 injection in subterranean reservoirs for storage, oil recovery, or both is challenging because of its very high mobility. Using a CO2 foam or emulsion is a way to remedy this problem by increasing CO2's apparent viscosity. However, the generation of the foam and its propagation in porous media present several issues that have to be overcome for this process to be economically realistic in practice. For example, it may take time, i.e., a number of pore volumes to be injected, before the foam is created. It is the objective of this Article to investigate these issues thoroughly and to identify the mechanisms underlying them by looking at the effects of various parameters. It is found that surfactant adsorption on the surface of the rock is an important factor involved in the delay of foam formation, but this may not explain all of the results. The nature and morphology of the porous medium may be, in some cases, the dominant factors for foam generation and propagation. From an understanding of the origin of the encountered problem, relevant mitigation strategies are envisioned and evaluated. It is found, for example, that when appropriately formulated and injected with the proper process, foam or emulsion generation is strongly accelerated, which very significantly shortens the delay for achieving CO2 storage.

Clinical study on improving the diagnostic accuracy of adult elbow joint cartilage injury by multisequence magnetic resonance imaging.

BACKGROUND: Due to frequent and high-risk sports activities, the elbow joint is susceptible to injury, especially to cartilage tissue, which can cause pain, limited movement and even loss of joint function. AIM: To evaluate magnetic resonance imaging (MRI) multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury. METHODS: A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study. We analyzed the accuracy of conventional MRI sequences (T1-weighted imaging, T2-weighted imaging, proton density weighted imaging, and T2 star weighted image) and Three-Dimensional Coronary Imaging by Spiral Scanning (3D-CISS) in the diagnosis of elbow cartilage injury. Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy. RESULTS: The diagnostic accuracy of 3D-CISS sequence was 89.34% ± 4.98%, the sensitivity was 90%, and the specificity was 88.33%, which showed the best performance among all sequences (P < 0.05). The combined application of the whole sequence had the highest accuracy in all sequence combinations, the accuracy of mild injury was 91.30%, the accuracy of moderate injury was 96.15%, and the accuracy of severe injury was 93.33% (P < 0.05). Compared with arthroscopy, the combination of all MRI sequences had the highest consistency of 91.67%, and the kappa value reached 0.890 (P < 0.001). CONCLUSION: Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults. Multisequence MRI is recommended to ensure the best diagnosis and treatment.

Perovskite-silicon tandem solar cells with bilayer interface passivation.

Two-terminal monolithic perovskite-silicon tandem solar cells demonstrate huge advantages in power conversion efficiency (PCE) compared to their respective single-junction counterparts1,2. However, suppressing interfacial recombination at the wide-bandgap perovskite/electron transport layer interface, without compromising its superior charge transport performance, remains a significant challenge for perovskite-silicon tandem cells3,4. By exploiting the nanoscale discretely distributed LiF ultrathin layer followed by an additional deposition of diammonium diiodide molecule, we have devised a bilayer intertwined passivation strategy that combines efficient electron extraction with further suppression of nonradiative recombination. We constructed perovskite-silicon tandem devices on double-side textured Czochralski (CZ)-based silicon heterojunction cell, which featured a mildly-textured front surface and a heavily-textured rear surface, leading to simultaneously enhanced photocurrent and uncompromised rear passivation. The resulting perovskite-silicon tandem achieved an independently certified stabilized PCE of 33.89%, accompanied by an impressive fill factor (FF) of 83.0% and an open-circuit voltage (Voc) of nearly 1.97 volts. To our knowledge, this represents the first reported certified efficiency of a two-junction tandem solar cell exceeding the single-junction Shockley-Queisser limit of 33.7%.

Temozolomide and the PARP Inhibitor Niraparib Enhance Expression of Natural Killer Group 2D Ligand ULBP1 and Gamma-Delta T Cell Cytotoxicity in Glioblastoma.

Glioblastoma (GBM) is an immunologically cold tumor, but several immunotherapy-based strategies show promise, including the administration of ex vivo expanded and activated cytotoxic gamma delta T cells. Cytotoxicity is partially mediated through interactions with natural killer group 2D ligands (NKG2DL) on tumor cells. We sought to determine whether the addition of the blood-brain barrier penetrant PARP inhibitor niraparib to the standard of care DNA alkylator temozolomide (TMZ) could upregulate NKG2DL, thereby improving immune cell recognition. Changes in viability were consistent with prior publications as there was a growth inhibitory effect of the combination of TMZ and niraparib. However, decreases in viability did not always correlate with changes in NKG2DL mRNA. ULBP1/Mult-1 mRNA was increased with the combination therapy in comparison to either drug alone in two of the three cell types tested, even though viability was consistently decreased. mRNA expression correlated with protein levels and ULBP1/MULT-1 cell surface protein was significantly increased with TMZ and niraparib treatment in four of the five cell types tested. Gamma delta T cell-mediated cytotoxicity at a 10:1 effector-to-target ratio was significantly increased upon pretreatment of cells derived from a GBM PDX with TMZ and niraparib in comparison to the control or either drug alone. Together, these data demonstrate that the combination of PARP inhibition, DNA alkylation, and gamma delta T cell therapy has the potential for the treatment of GBM.

Decoding sunitinib resistance in ccRCC: Metabolic-reprogramming-induced ABAT and GABAergic system shifts.

Sunitinib, a primary treatment for clear cell renal cell carcinoma (ccRCC), frequently encounters the challenge of resistance development. Metabolic reprogramming, a characteristic change in ccRCC, is likely linked to this resistance. Our research revealed a notable decrease in the expression of the key metabolic gene ABAT in ccRCC, which contributed to diminished sensitivity to sunitinib. Downregulation of ABAT led to an increase in the intracellular level of gamma-aminobutyric acid (GABA), triggering abnormal activation of the G-protein-coupled receptor GABA-B. This activation resulted in increased transactivation of the tyrosine kinase receptors SYK and LYN, thereby reducing the antitumor and antiangiogenic properties of sunitinib. However, the application of SYK and LYN inhibitors successfully inhibited this effect. The transactivation of SYK and LYN caused resistance to the antiangiogenic effects of sunitinib through the upregulation of PGF protein levels. Furthermore, the combined application of an LYN inhibitor with sunitinib has been shown to enhance therapeutic efficacy.

The ocean losing its breath under the heatwaves.

The world's oceans are under threat from the prevalence of heatwaves caused by climate change. Despite this, there is a lack of understanding regarding their impact on seawater oxygen levels - a crucial element in sustaining biological survival. Here, we find that heatwaves can trigger low-oxygen extreme events, thereby amplifying the signal of deoxygenation. By utilizing in situ observations and state-of-the-art climate model simulations, we provide a global assessment of the relationship between the two types of extreme events in the surface ocean (0-10 m). Our results show compelling evidence of a remarkable surge in the co-occurrence of marine heatwaves and low-oxygen extreme events. Hotspots of these concurrent stressors are identified in the study, indicating that this intensification is more pronounced in high-biomass regions than in those with relatively low biomass. The rise in the compound events is primarily attributable to long-term warming primarily induced by anthropogenic forcing, in tandem with natural internal variability modulating their spatial distribution. Our findings suggest the ocean is losing its breath under the influence of heatwaves, potentially experiencing more severe damage than previously anticipated.

Research status and hotspots of tight junctions and colorectal cancer: A bibliometric and visualization analysis.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. Over the past two decades, numerous researchers have provided important evidence regarding the role of tight junction (TJ) proteins in the occurrence and progression of CRC. The causal relationship between the presence of specific TJ proteins and the development of CRC has also been confirmed. Despite the large number of publications in this field, a bibliometric study to review the current state of research and highlight the research trends and hotspots in this field has not yet been performed. AIM: To analyze research on TJs and CRC, summarize the field's history and current status, and predict future research directions. METHODS: We searched the Science Citation Index Expanded database for all literature on CRC and TJs from 2001-2023. We used bibliometrics to analyze the data of these papers, such as the authors, countries, institutions, and references. Co-authorship, co-citation, and co-occurrence analyses were the main methods of analysis. CiteSpace and VOSviewer were used to visualize the results. RESULTS: A total of 205 studies were ultimately identified. The number of publications on this topic has steadily increased since 2007. China and the United States have made the largest contributions to this field. Anticancer Research was the most prolific journal, publishing 8 articles, while the journal Oncogene had the highest average citation rate (68.33). Professor Dhawan P was the most prolific and cited author in this field. Co-occurrence analysis of keywords revealed that "tight junction protein expression", "colorectal cancer", "intestinal microbiota", and "inflammatory bowel disease" had the highest frequency of occurrence, revealing the research hotspots and trends in this field. CONCLUSION: This bibliometric analysis evaluated the scope and trends of TJ proteins in CRC, providing valuable research perspectives and future directions for studying the connection between the two. It is recommended to focus on emerging research hotspots, such as the correlations among intestinal microbiota, inflammatory bowel disease, TJ protein expression, and CRC.

A thermo-sensitive hydrogel with prominent hemostatic effect prevents tumor recurrence via anti-anoikis-resistance.

Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell-cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H2O2) catalyzed by intracellular GOx into oxygen (O2), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery.

Wetting Behavior-Induced Interfacial transmission of Energy and Signal: Materials, Mechanisms, and Applications.

Wetting behaviors can significantly affect the transport of energy and signal (E&S) through vapor, solid, and liquid interfaces, which has prompted increased interest in interfacial science and technology. E&S transmission can be achieved using electricity, light, and heat, which often accompany and interact with each other. Over the past decade, their distinctive transport phenomena during wetting processes have made significant contributions to various domains. However, few studies have analyzed the intricate relationship between wetting behavior and E&S transport. This review summarizes and discusses the mechanisms of electrical, light, and heat transmission at wetting interfaces to elucidate their respective scientific issues, technical characteristics, challenges, commonalities, and potential for technological convergence. The materials, structures, and devices involved in E&S transportation are also analyzed. Particularly, harnessing synergistic advantages in practical applications and constructing advanced, multifunctional, and highly efficient smart systems based on wetted interfaces is the aim to provide strategies.

High nitrite accumulation in hydrogenotrophic denitrification at low temperature: Transcriptional regulation and microbial community succession.

High Pressure Hydrogenotrophic Denitrification (HPHD) provided a promising alternative for efficient and clean nitrate removal. In particular, the denitrification rates at low temperature could be compensated by elevated H2 partial pressure. However, nitrite reduction was strongly inhibited while nitrate reduction was barely affected at low temperature. In this study, the nitrate reduction gradually recovered under long-term low temperature stress, while nitrite accumulation increased from 0.1 to 41.0 mg N/L. The activities of the electron transport system (ETS), nitrate reductase (NAR), and nitrite reductase (NIR) decreased by 45.8 %, 27.3 %, and 39.3 %, respectively, as the temperature dropped from 30 °C to 15 °C. Real time quantitative PCR analysis revealed that the denitrifying gene expression rather than gene abundance regulated nitrogen biotransformation. The substantial nitrite accumulation was attributed to the significant up-regulation by 54.7 % of narG gene expression and down-regulation by 73.7 % of nirS gene expression in hydrogenotrophic denitrifiers. In addition, the nirS-gene-bearing denitrifiers were more sensitive to low temperature compared to those bearing nirK gene. The dominant populations shifted from the genera Paracoccus to Hydrogenophaga under long-term low temperature stress. Overall, this study revealed the microbial mechanism of high nitrite accumulation in hydrogenotrophic denitrification at low temperature.

Intestinal epithelial Cldn-7 regulates intestinal inflammation by altering the gut microbiota.

BACKGROUND AND AIM: Tight junctions maintain gut homeostasis by forming a physical barrier that protects the gut from invasion by microbiota. Cldn-7 is an important component involved in this protection, but the relationship between Cldn-7, intestinal inflammation, and gut microbiota has not been clarified. Here, we hypothesize that Cldn-7 depletion affects intestinal inflammation by altering the gut microbiota. METHODS: Based on the induced intestinal condition of Cldn-7 knockout mice (Cldn7fl/fl;villin-CreaERT2), we established the intestinal flora depletion model and colitis model by antibiotic drinking and feeding with dextran sodium sulfate (DSS). The environment of Cldn-7 gene deletion mice was changed by co-housing experiment. AB-PAS staining and Muc2 were used to detect the effect of co-housing and Cldn-7 deficiency on the mucus layer after flora depletion. qRT-PCR was used to detect the expression of intestinal inflammatory factors and AMPs in mice. Feces were collected and proportions of microbiota were analyzed by 16 S rRNA amplicon sequencing. RESULTS: Mice in the co-housing experiment had altered intestinal microbiota, including diversity, composition, and functional prediction, compared to controls. Intestinal inflammation was restored to some extent following altered intestinal microbiota. The intestinal inflammation caused by Cldn-7 deficiency and susceptibility to DSS could be reduced after antibiotic administration compared to controls, in terms of phenotype, pathological changes, inflammatory factors, mucus barrier, and expression of AMPs. CONCLUSIONS: In analyses of intestinal tissues, colitis induction, and gut microbiota in mice with intestinal disruption of Cldn-7, we found this protein to prevent intestinal inflammation by regulating the gut microbiota. Cldn-7might therefore be an important mediator of host-microbiome interactions. Our research has revealed that Cldn-7 plays an indispensable role in maintaining intestinal homeostasis by regulating the gut microbiota and impacting intestinal inflammation. These findings provide new insights into the pathogenesis of ulcerative colitis.

Modulating tumor-associated macrophage polarization by anti-maRCO mAb exerts anti-osteosarcoma effects through regulating osteosarcoma cell proliferation, migration and apoptosis.

PURPOSE: Osteosarcoma is a primary bone tumor lacking optimal clinical treatment options. Tumor-associated macrophages in the tumor microenvironment are closely associated with tumor development and metastasis. Studies have identified the macrophage receptor with collagenous structure (MARCO) as a specific receptor expressed in macrophages. This study aimed to investigate whether anti-MARCO mAb treatment can induce macrophage polarization in the tumor microenvironment and elicit anti-tumor effects. METHODS: THP-1 cells were treated with 20 ng/mL phorbol 12-myristate 13-acetate and 80 ng/mL interleukin-4 for 48 h to induce macrophage polarization to alternatively activated macrophages (M2). Enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, flow cytometry, and bioinformatic analyses were performed to evaluate macrophage polarization. The co-culture groups included a blank group, an M2 macrophage and U2OS co-culture group, and an anti-MARCO mAb-treated M2 macrophage group. Cell viability assays, cell scratch tests, apoptosis, and cell cycle analyses were performed to determine the effects of anti-MARCO mAb-treated macrophages on osteosarcoma cells. RESULTS: It was demonstrated that anti-MARCO mAb can drive macrophages toward classically activated macrophage (M1) polarization. Anti-MARCO mAb promoted the secretion of pro-inflammatory factors by macrophages, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta, interleukin-6 and interleukin-23. Studies on in vitro co-culture models have revealed that macrophages treated with anti-MARCO mAb can suppress the growth and migration of osteosarcoma cells, induce cell apoptosis, and inhibit cell cycle progression of osteosarcoma cells through M1 polarization of macrophages in vitro. CONCLUSION: Anti-MARCO mAb treatment exerts anti-osteosarcoma effects by affecting macrophage polarization toward M1 macrophages, offering a potential new therapeutic approach for treating osteosarcoma.

Semaglutide for the prevention of atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is reported to have cardiac benefits, but its effects on preventing atrial fibrillation (AF) remain inconclusive. This study aimed to investigate whether semaglutide can prevent AF occurrence in patients with type 2 diabetes mellitus (T2DM), obesity, or overweight. METHODS: We searched MEDLINE, EMBASE, the Cochrane CENTRAL database, and clinicaltrials.gov from inception to December 29, 2023. Randomized controlled trials of semaglutide in patients with T2DM, obesity, or overweight were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for the overall population and subgroups. RESULTS: Twenty-one trials comprising 25957 patients were included. In the overall pooled analysis, semaglutide decreased AF occurrence compared to control drugs (RR 0.70, 95 % CI 0.52-0.95). This result was consistent in trials using other antihyperglycemic medications as controls (RR 0.43, 95 % CI 0.21-0.89), but not in placebo-controlled trials (RR 0.77, 95 % CI 0.56-1.07). The outcome was favorable for patients with T2DM (RR 0.71, 95 % CI 0.52-0.97), but not for patients with overweight or obesity (RR 0.56, 95 % CI 0.18-1.73). Results varied by type of semaglutide, with oral semaglutide showing an RR of 0.49 (95 % CI 0.25-0.97) and subcutaneous semaglutide showing an RR of 0.77 (95 % CI 0.55-1.07). CONCLUSION: Semaglutide was associated with a reduced risk of AF occurrence in the overall analysis. Favorable outcomes were observed in subsets using other antihyperglycemic medications as controls, in patients with T2DM, and with oral semaglutide.