Nanogold amplified electrochemiluminescence/electrochemistry in bipolar silica nanochannel array for ultrasensitive detection of SARS-CoV-2 pseudoviruses.

The prompt and accurate point-of-care test (POCT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infected persons or virus-containing environmental samples is of great importance. The present work reports a highly integrated electrochemiluminescence/electrochemical (ECL/EC) sensor for determination of SARS-CoV-2 pseudoviruses, in which bio-recognition element (SARS-CoV-2 IgG antibody), bifunctional probe (tris (2,2'-bipyridyl) ruthenium (Ru(bpy)32+)), and amplification material (gold nanoparticles (Au NPs)) are designed into bipolar silica nanochannel array (bp-SNA). bp-SNA consisting of homogeneous two-layer mesoporous silica films bears inner silanol groups and outer amino groups, generating a solid "electrostatic nanocage" for stable confinement of Ru(bpy)32+ and Au NPs inside the nanochannels and further providing functional sites for covalent modification of SARS-CoV-2 IgG antibody. Owing to the preconcentration capacity of bp-SNA and amplified effect of Au NPs, ECL or EC signals of Ru(bpy)32+ can be remarkably promoted and thereby increase the analytical performance, which can be diminished by immunorecognization of target SARS-CoV-2 pseudoviruses on the sensing interface. The developed integrated ECL/EC sensor based on Ru@AuNPs/bp-SNA modified solid indium tin oxide electrode enables the sensitive analysis of SARS-CoV-2 pseudoviruses by ECL mode with a linear range of 50 TU mL-1-5000 TU mL-1, as well as the EC mode with a linear range of 100 TU mL-1-5000 TU mL-1. Moreover, the designed sensor showed satisfactory results in the analyses of saliva and pond water samples. When flexible electrode substate (polyethylene terephthalate) is employed, Ru@AuNPs/bp-SNA has great potential to integrate with KN95 face masks for direct detection of SARS-CoV-2 pseudoviruses produced from breathing, talking and coughing processes, which could provide an efficient platform for POCT diagnosis.

Cuproptosis associated cytoskeletal destruction contributes to podocyte injury in chronic kidney disease.

The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored ATP synthesis. Among the transcriptome sequencing data, the difference of CXCL5 was the most significant. Both high copper and ADR exposure can cause up-regulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease.

Biotransformation of Cacumen platycladi Extract by Lactiplantibacillus plantarum CCFM1348 Promotes Hair Growth in Mice.

Cacumen platycladi (CP) is a frequently used traditional Chinese medicine to treat hair loss. In this study, CP fermented by Lactiplantibacillus plantarum CCFM1348 increased the proliferation of human dermal papilla cells. In an in vivo assay, compared to nonfermented CP, postbiotics (fermented CP) and synbiotics (live bacteria with nonfermented CP) promoted hair growth in mice. The Wnt/ß-catenin signaling pathway plays crucial roles in the development of hair follicles, including growth cycle restart and maintenance. Both postbiotics and synbiotics upregulated ß-catenin, a major factor of the Wnt/ß-catenin signaling pathway. Postbiotics and synbiotics also increased the vascular endothelial growth factor expression and decreased the BAX/Bcl2 ratio in the dorsal skin of mice. These results suggest that fermented CP by L. plantarum CCFM1348 may promote hair growth through regulating the Wnt/ß-catenin signaling pathway, promoting the expression of growth factors and reducing apoptosis.

Amino Functionality Enables Aqueous Synthesis of Carboxylic Acid-Based MOFs at Room Temperature by Biomimetic Crystallization.

Enzyme immobilization within metal-organic frameworks (MOFs) is a promising solution to avoid denaturation and thereby utilize the desirable properties of enzymes outside of their native environments. The biomimetic mineralization strategy employs biomacromolecules as nucleation agents to promote the crystallization of MOFs in water at room temperature, thus overcoming pore size limitations presented by traditional postassembly encapsulation. Most biomimetic crystallization studies reported to date have employed zeolitic imidazole frameworks (ZIFs). Herein, we expand the library of MOFs suitable for biomimetic mineralization to include zinc(II) MOFs incorporating functionalized terephthalic acid linkers and study the catalytic performance of the enzyme@MOFs. Amine functionalization of terephthalic acids is shown to accelerate the formation of crystalline MOFs enabling new enzyme@MOFs to be synthesized. The structure and morphology of the enzyme@MOFs were characterized by PXRD, FTIR, and SEM-EDX, and the catalytic potential was evaluated. Increasing the linker length while retaining the amino moiety gave rise to a family of linkers; however, MOFs generated with the 2,2'-aminoterephthalic acid linker displayed the best catalytic performance. Our data also illustrate that the pH of the reaction mixture affects the crystal structure of the MOF and that this structural transformation impacts the catalytic performance of the enzyme@MOF.

Association of Biological Age Acceleration with Cardiac Morphology, Function, and Incident Heart Failure: Insights from UK Biobank Participants.

BACKGROUND: Advanced age is associated with an increased risk of adverse cardiovascular events. The relationship between biological age acceleration (BAA), cardiac size, cardiac function, and heart failure (HF) is not well-defined. METHODS: Utilizing the UK Biobank cohort, we assessed biological age using the Klemera-Doubal and PhenoAge method. BAA was quantified by residual analysis compared to chronological age. Cardiovascular magnetic resonance (CMR) imaging provided detailed insights into cardiac structure and function. We employed multivariate regression to examine links between BAA and CMR-derived cardiac phenotypes. Cox proportional hazard regression models analyses was applied to explore the causative relationship between BAA and HF. Additionally, Mendelian randomization was used to investigate the genetic underpinnings of these associations. RESULTS: A significant correlation was found between increased BAA and deleterious changes in cardiac structure, such as diminished left ventricular mass, lower overall ventricular volume, and reduced stroke volumes across ventricles and atria. Throughout a median follow-up of 13.8 years, participants with greater biological aging showed a heightened risk of HF (26% per standard deviation [SD] increase in KDM-BA acceleration, 95% confidence intervals [CI]: 23%-28%; 33% per SD increase in PhenoAge acceleration, 95% CI: 32%-35%). Mendelian randomization analysis suggests a likely causal link between BAA, vital cardiac metrics, and HF risk. CONCLUSIONS: In this cohort, accelerated biological aging may serve as a risk indicator for altered cardiac dimensions, functionality, and the onset of heart failure among middle-aged and elderly adults. It holds promise as a focal point for evaluating risk and developing targeted interventions.

Dexmedetomidine Prolongs Lidocaine Intravenous Regional Anesthesia in Rats by Blocking the Hyperpolarization-Activated Cation Current.

Purpose: Intravenous regional anesthesia (IVRA) using lidocaine provides effective localized analgesia but its duration is limited. The mechanism by which dexmedetomidine enhances lidocaine IVRA is unclear but may involve modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Materials and Methods: Lidocaine IVRA with varying dexmedetomidine concentrations was performed in the tails of Sprague-Dawley rats. Tail-flick and tail-clamping tests assessed IVRA analgesia and anesthesia efficacy and duration. Contributions of α2 adrenergic receptors and HCN channels were evaluated by incorporating an α adrenergic receptor antagonist, the HCN channel inhibitor ZD7288, and the HCN channel agonist forskolin. Furthermore, whole-cell patch clamp electrophysiology quantified the effects of dexmedetomidine on HCN channels mediating hyperpolarization-activated cation current (Ih) in isolated dorsal root ganglion neurons. Results: Dexmedetomidine dose-dependently extended lidocaine IVRA duration and analgesia, unaffected by α2 receptor blockade. The HCN channel inhibitor ZD7288 also prolonged lidocaine IVRA effects, while the HCN channel activator forskolin shortened effects. In dorsal root ganglion neurons, dexmedetomidine concentration-dependently inhibited Ih amplitude and shifted the voltage-dependence of HCN channel activation. Conclusion: Dexmedetomidine prolongs lidocaine IVRA duration by directly inhibiting HCN channel activity, independent of α2 adrenergic receptor activation. This HCN channel inhibition represents a novel mechanism underlying the anesthetic and analgesic adjuvant effects of dexmedetomidine in IVRA.

Lathyrane and premyrsinane Euphorbia diterpenes against Alzheimer's disease: Bioinspired synthesis, anti-cholinesterase and neuroprotection bioactivity.

The first systematic acylated diversification of naturally scarce premyrsinane diterpenes, together with their biosynthetic precursors lathyrane diterpene were carried out. Two new series of premyrsinane derivates (1a-32a) and lathyrane derivates (1-32) were synthesized from the naturally abundant lathyrane diterpene Euphorbia factor L3 through a bioinspired approach. The cholinesterase inhibitory and neuroprotective activities of these diterpenes were investigated to explore potential anti-Alzheimer's disease (AD) bioactive lead compounds. In general, the lathyrane diterpenes showed the better acetylcholinesterase (AChE) inhibitory activity than that of premyrsinanes. The lathyrane derivative 17 bearing a 3-dimethylaminobenzoyl moiety showed the best AChE inhibition effect with the IC50 value of 7.1 µM. Molecular docking demonstrated that 17 could bond with AChE well (-8 kal/mol). On the other hand, premyrsinanes showed a better neuroprotection profile against H2O2-induced injury in SH-SY5Y cells. Among them, the premyrsinane diterpene 16a had significant neuroprotective effect with the cell viability rate of 113.5 % at 12.5 µM (the model group with 51.2 %). The immunofluorescence, western blot and reactive oxygen species (ROS) analysis were conducted to demonstrate the mechanism of 16a. Furthermore, a preliminary SAR analysis of the two categories of diterpenes was performed to provide the insights for anti-AD drug development.

Bisphenol S enhances the cell proliferation ability of prostate cancer cells by regulating the expression of SDS.

Recent times have witnessed an increase in both incidence and mortality rates of prostate cancer. While some individuals with localized or metastatic cancer may progress slowly with a lower mortality risk, those with intermediate or high-risk cancer often face a higher likelihood of death, despite treatment. Bisphenol A (BPA) has been linked to various cancers, including prostate and breast cancer, yet the relationship between bisphenol S (BPS) and human health remains underexplored. In our study, we employed ssGSEA analysis to evaluate the BPS-associated score in a prostate cancer cohort. Additionally, differential expression analysis identified BPS-related genes within the same group. Through COX and LASSO regression analyses, we developed and validated a BPS-related risk model using ROC curve and survival analyses. A nomogram, integrating clinical characteristics with this risk model, was established for improved predictive accuracy, further substantiated by calibration curve validation. Molecular docking analysis suggested potential binding between SDS and BPS. We also conducted cell proliferation assays on C4-2 and LNCaP prostate cancer cells, revealing increased cell growth at a BPS concentration of 10-7 M, as evidenced by CCK8 and EdU assays. In summary, our findings shed light on the BPS-prostate cancer linkage, identifying BPS-associated genes, establishing a validated risk model, exploring SDS-BPS binding potential, and assessing BPS's effect on prostate cancer cell growth. These insights underscore the need for further investigation into BPS and its impact on human diseases.

Esophageal cancer screening, early detection and treatment: Current insights and future directions.

Esophageal cancer ranks among the most prevalent malignant tumors globally, primarily due to its highly aggressive nature and poor survival rates. According to the 2020 global cancer statistics, there were approximately 604000 new cases of esophageal cancer, resulting in 544000 deaths. The 5-year survival rate hovers around a mere 15%-25%. Notably, distinct variations exist in the risk factors associated with the two primary histological types, influencing their worldwide incidence and distribution. Squamous cell carcinoma displays a high incidence in specific regions, such as certain areas in China, where it meets the cost-effectiveness criteria for widespread endoscopy-based early diagnosis within the local population. Conversely, adenocarcinoma (EAC) represents the most common histological subtype of esophageal cancer in Europe and the United States. The role of early diagnosis in cases of EAC originating from Barrett's esophagus (BE) remains a subject of controversy. The effectiveness of early detection for EAC, particularly those arising from BE, continues to be a debated topic. The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses. In areas with higher incidences, such as China and Japan, early diagnosis is more common, which has led to the advancement of endoscopic methods as definitive treatments. These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality. Early screening, prompt diagnosis, and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

Association of air pollution with incidence of elderly-onset seborrheic dermatitis: A prospective cohort study in UK Biobank.

BACKGROUND: Elderly-onset seborrheic dermatitis (SD) seriously affects the quality of life. However, associations between air pollution exposures and elderly-onset SD incidence have not been elucidated. OBJECTIVES: Investigate air pollution's role in the incidence of elderly-onset SD. METHODS: We engaged a prospective cohort analysis utilizing the UK Biobank database. Exposure data for specific air pollutants (PM2.5, PM2.5-10, NOX, NO2, and PM10) spanning various years was incorporated. Through a composite air pollution score constructed from five pollutants and employing Cox proportional hazards models, the relationship between pollution and SD was delineated. RESULTS: Our examination of 193,995 participants identified 3,363 SD cases. Higher concentrations of specific pollutants, particularly in the upper quartile (Q4), were significantly linked to an elevated SD risk. Notably, PM2.5, PM10, NO2, and NOX exhibited hazard ratios of 1.11, 1.15, 1.22, and 1.15, respectively. The correlation was further solidified with a positive association between air pollution score increments and SD onset. Intriguingly, this association was accentuated in certain demographics, including younger males, the socioeconomically deprived, smokers, daily alcohol consumers, and those engaging in regular physical activity. CONCLUSIONS: Our findings revealed that air pollution exposures were associated with elderly-onset SD incidence. These results emphasize the importance of preventing environmental exposures to the risk of SD development.

Distribution and associations of anterior lens zonules lengths in patients with cataract.

PURPOSE: To investigate the characteristics and associations of anterior lens zonules lengths in cataract patients via ultrasound biomicroscope (UBM) measurement. METHODS: Patients with age-related cataracts and high myopic cataracts who planned to undergo cataract surgery were included in the study. After routine ophthalmic examinations, the UBM was performed on both eyes to get images of the anterior lens zonules, and Image J software was used to measure the lengths of the lens zonules. Axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and white-to-white (WTW) diameter of both eyes were obtained by IOL Master 700. Univariate and multivariate regression analyses were used to assess associated factors of anterior lens zonules lengths. RESULTS: Forty-nine patients with age-related cataracts and 33 patients with high myopic cataracts were enrolled. High myopic cataract patients were younger and had longer anterior lens zonules. Multivariate regression analysis showed that anterior lens zonules lengths were associated with axial lengths (temporal location: ß = 0.036, P = 0.029; nasal location: ß = 0.034, P = 0.011; superior location: ß = 0.046, P = 0.002) and ACD (inferior location: ß = 0.305, P = 0.016) in right eyes. In left eyes, anterior lens zonules lengths were associated with axial lengths (temporal location: ß = 0.028, P = 0.017; inferior location: ß = 0.026, P = 0.016; nasal location: ß = 0.033, P < 0.001) and ACD (inferior location: ß = 0.215, P = 0.030; superior location: ß = 0.290, P = 0.011). CONCLUSIONS: High myopic cataract patients have longer anterior lens zonules. AL and ACD contributed to the lengths of anterior lens zonules. Thus, for patients with long AL and deeper ACD, lens zonules measurement was crucial. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn identifier is ChiCTR2300071397.

Whole-exome sequencing combined with postoperative data identify c.1614dup (CAMKK2) as a novel candidate monogenic obesity variant.

Early-onset obesity is a rising health concern influenced by heredity. However, many monogenic obesity variants (MOVs) remain to be discovered due to differences in ethnicity and culture. Additionally, patients with known MOVs have shown limited weight loss after bariatric surgery, suggesting it can be used as a screening tool for new candidates. In this study, we performed whole-exome sequencing (WES) combined with postoperative data to detect candidate MOVs in a cohort of 62 early-onset obesity and 9 late-onset obesity patients. Our findings demonstrated that patients with early-onset obesity preferred a higher BMI and waist circumference (WC). We confirmed the efficacy of the method by identifying a mutation in known monogenic obesity gene, PCSK1, which resulted in less weight loss after surgery. 5 genes were selected for further verification, and a frameshift variant in CAMKK2 gene: NM_001270486.1, c.1614dup, (p. Gly539Argfs*3) was identified as a novel candidate MOV. This mutation influenced the improvement of metabolism after bariatric surgery. In conclusion, our data confirm the efficacy of WES combined with postoperative data in detecting novel candidate MOVs and c.1614dup (CAMKK2) might be a promising MOV, which needs further confirmation. This study enriches the human monogenic obesity mutation database and provides a scientific basis for clinically accurate diagnosis and treatment.

Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.

miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis.

Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 µg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1ß, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI.

Functional cellulose-derived epoxy cross-linked with BADGE resin to construct high-performance epoxy composites.

The development of equipped bio-based epoxy materials has been gaining much attention recently. Nevertheless, finding the balance between the structure and properties of materials remains a significant challenge. In this work, cellulose-based epoxy (PHPCEP) with "soft" and "hard" cooperative structures was designed and demonstrated to endow bisphenol A diglycidyl ether (BADGE) with excellent toughness, heat resistance, mechanical strength, glass transition temperature, thermal stability, and solvent resistance. When 5 wt% PHPCEP was incorporated into BADGE composites, the resulting materials exhibited the maximum flexural strength (121.9 MPa) and tensile strength (71.4 MPa), a high glass transition temperature (148.3 °C), and 10 wt% PHPCEP/BADGE demonstrated the highest impact strength (70.5 kJ/m2). These figures are 18.8 %, 16.1 %, 21.5 %, and 254.3 % higher than the corresponding values of neat BADGE. The results of dynamic mechanical properties and heat degradation of the cured specimens also suggest that PHPCEP/BADGE materials have superior stiffness and toughness than neat BADGE, which could be attributed to the strong interaction between PHPCEP and BADGE, delivering better thermal stability for the composites compared to the pristine resin. Considering the remarkable effect, this work provides an effective way of highly efficient utilization of abundant cellulose and a high-performance additive for composite materials.

Gallbladder microbial species and host bile acids biosynthesis linked to cholesterol gallstone comparing to pigment individuals.

Gallstones are crystalline deposits in the gallbladder that are traditionally classified as cholesterol, pigment, or mixed stones based on their composition. Microbiota and host metabolism variances among the different types of gallstones remain largely unclear. Here, the bile and gallstone microbial species spectra of 29 subjects with gallstone disease (GSD, 24 cholesterol and 5 pigment) were revealed by type IIB restriction site-associated DNA microbiome sequencing (2bRAD-M). Among them (21 subjects: 18 cholesterol and 3 pigment), plasma samples were subjected to liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics. The microbiome yielded 896 species comprising 882 bacteria, 13 fungi, and 1 archaeon. Microbial profiling revealed significant enrichment of Cutibacterium acnes and Microbacterium sp005774735 in gallstone and Agrobacterium pusense and Enterovirga sp013044135 in the bile of cholesterol GSD subjects. The metabolome revealed 2296 metabolites, in which malvidin 3-(6''-malonylglucoside), 2-Methylpropyl glucosinolate, and ergothioneine were markedly enriched in cholesterol GSD subjects. Metabolite set enrichment analysis (MSEA) demonstrated enriched bile acids biosynthesis in individuals with cholesterol GSD. Overall, the multi-omics analysis revealed that microbiota and host metabolism interaction perturbations differ depending on the disease type. Perturbed gallstone type-related microbiota may contribute to unbalanced bile acids metabolism in the gallbladder and host, representing a potential early diagnostic marker and therapeutic target for GSD.

The E3 ligase TRIM7 suppresses the tumorigenesis of gastric cancer by targeting SLC7A11.

Tripartite motif-containing protein 7 (TRIM7), as an E3 ligase, plays an important regulatory role in various physiological and pathological processes. However, the role of TRIM7 in gastric cancer (GC) is still undefined. Our study detected the expression of TRIM7 in clinical specimens and investigated the regulatory effect and molecular mechanism of TRIM7 on GC progression through in vitro and in vivo experiments. Our finding showed that TRIM7 was significantly downregulated in GC, and patients with high expression of TRIM7 showed long overall survival. Both in vitro and in vivo experiments showed that TRIM7 dramatically suppressed the malignant progression of GC. Further investigation showed that ferroptosis was the major death type mediated by TRIM7. Mechanistically, TRIM7 interacted with SLC7A11 through its B30.2/SPRY domain and promoted Lys48-linked polyubiquitination of SLC7A11, which effectively suppressing SLC7A11/GPX4 axis and inducing ferroptosis in GC cells. In vivo experiments and correlation analysis based on clinical specimens further confirmed that TRIM7 inhibited tumor growth through suppressing SLC7A11/GPX4 axis. In conclusion, our investigation demonstrated for the first time that TRIM7, as a tumor suppressor, induced ferroptosis via targeting SLC7A11 in GC, which provided a new strategy for the molecular therapy of GC by upregulating TRIM7.

ESCRT-I protein UBAP1 controls ventricular expansion and cortical neurogenesis via modulating adherens junctions of radial glial cells.

Intricate cerebral cortex formation is orchestrated by the precise behavior and division dynamics of radial glial cells (RGCs). Endocytosis functions in the recycling and remodeling of adherens junctions (AJs) in response to changes in RGC activity and function. Here, we show that conditional disruption of ubiquitin-associated protein 1 (UBAP1), a component of endosomal sorting complex required for transport (ESCRT), causes severe brain dysplasia and prenatal ventriculomegaly. UBAP1 depletion disrupts the AJs and polarity of RGCs, leading to failure of apically directed interkinetic nuclear migration. Accordingly, UBAP1 knockout or knockdown results in reduced proliferation and precocious differentiation of neural progenitor cells. Mechanistically, UBAP1 regulates the expression and surface localization of cell adhesion molecules, and ß-catenin over-expression significantly rescues the phenotypes of Ubap1 knockdown in vivo. Our study reveals a critical physiological role of the ESCRT machinery in cortical neurogenesis by regulating AJs of RGCs.

Functional analysis reveals calcium-sensing receptor gene regulating cell-cell junction in renal tubular epithelial cells.

PURPOSE: Calcium-sensing receptor (CASR) influences the expression pattern of multiple genes in renal tubular epithelial cells. The objective of this inquiry was to explore the molecular mechanisms of CASR in renal tubular epithelial cells and nephrolithiasis. METHODS: HK-2 cells were transfected with lentiviruses carrying either CASR (named CASR) or an empty vector negative control (named NC), as well as shRNA intended to target CASR (named shCASR) or its corresponding negative control (named shNC). CCK-8 assay was used to detect the effect of CASR on the proliferation of HK-2 cells. RNA-Sequencing was applied to explore potential pathways regulated by CASR in HK-2 cells. RESULTS: PCR and western blot results showed that CASR expression was significantly increased in CASR cells and was decreased in shCASR cells when compared to their corresponding negative control, respectively. CCK-8 assay revealed that CASR inhibited the proliferation of HK-2 cells. RNA-Sequencing results suggested that the shCASR HK-2 cells exhibited a significant up-regulation of 345 genes and a down-regulation of 366 genes. These differentially expressed genes (DEGs) were related to cell apoptosis and cell development. In CASR HK-2 cells, 1103 DEGs primarily functioned in mitochondrial energy metabolism, and amino acid metabolism. With the Venn diagram, 4 DEGs (Clorf116, ENPP3, IL20RB, and CLDN2) were selected as the hub genes regulated by CASR. Enrichment analysis revealed that these hub genes were involved in cell-cell junction, and epithelial cell development. CONCLUSIONS: In summary, our investigation has the potential to offer novel perspectives on CASR regulating cell-cell junction in HK-2 cells.

Virtual Reality Therapy for the Management of Chronic Spinal Pain: Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness of virtual reality (VR) therapy in adults with chronic spinal pain (CSP) is unclear. OBJECTIVE: This study was conducted to compare the effectiveness of VR therapy and other therapies in adults with CSP, especially patients with inflammation-related pain. METHODS: PubMed, Web of Science, Cochrane Library, Embase, and CINAHL databases were searched up to November 11, 2023. Randomized controlled trials (RCTs) comparing adults with CSP receiving VR therapy with those receiving other therapies were included. The trial registration platform as well as the reference lists of included studies and previous systematic reviews and meta-analyses were manually searched. Two independent reviewers performed study selection, data extraction, risk-of-bias assessment, and evaluation of the quality of the evidence. The weighted mean difference (WMD) was used as the effect size used to synthesize the outcome measure. RESULTS: In total, 16 RCTs involving 800 participants were included in this meta-analysis. The pooled data from 15 (94%) RCTs including 776 (97%) participants showed that VR therapy was superior in improving pain intensity (WMD=-1.63, 95% CI -2.11 to -1.16, P<.001, I2=90%) and reducing inflammatory markers, including C-reactive protein (WMD=-0.89, 95% CI -1.07 to -0.70, P<.001, I2=0%), tumor necrosis factor-alpha (WMD=-6.60, 95% CI -8.56 to -4.64, P<.001, I2=98%), and interleukin-6 (WMD=-2.76, 95% CI -2.98 to -2.53, P<.001, I2=0%). However, no significant differences were found in terms of the spinal range of motion (ROM), disability level, or fear of movement. In addition, 10 (63%) of the included RCTs had a high risk of bias. CONCLUSIONS: VR therapy may be an effective and safe intervention for reducing symptoms in patients with CSP, as it is shown to exert significant analgesic effects and beneficial improvements in inflammatory factor levels. However, this approach may not have significant effects on the spinal ROM, disability level, or fear of movement. Notably, the quality of the evidence from the RCTs included in this study ranged from moderate to low. Therefore, we recommend that readers interpret the results of this study with caution. TRIAL REGISTRATION: PROSPERO CRD42022382331; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=382331.