Adaptive Low-Rank Tensor Estimation Model Based Multichannel Weak Fault Detection for Bearings.

Multichannel signals contain an abundance of fault characteristic information on equipment and show greater potential for weak fault characteristics extraction and early fault detection. However, how to effectively utilize the advantages of multichannel signals with their information richness while eliminating interference components caused by strong background noise and information redundancy to achieve accurate extraction of fault characteristics is still challenging for mechanical fault diagnosis based on multichannel signals. To address this issue, an effective weak fault detection framework for multichannel signals is proposed in this paper. Firstly, the advantages of a tensor on characterizing fault information were displayed, and the low-rank property of multichannel fault signals in a tensor domain is revealed through tensor singular value decomposition. Secondly, to tackle weak fault characteristics extraction from multichannel signals under strong background noise, an adaptive threshold function is introduced, and an adaptive low-rank tensor estimation model is constructed. Thirdly, to further improve the accurate estimation of weak fault characteristics from multichannel signals, a new sparsity metric-oriented parameter optimization strategy is provided for the adaptive low-rank tensor estimation model. Finally, an effective multichannel weak fault detection framework is formed for rolling bearings. Multichannel data from the repeatable simulation, the publicly available XJTU-SY whole lifetime datasets and an accelerated fatigue test of rolling bearings are used to validate the effectiveness and practicality of the proposed method. Excellent results are obtained in multichannel weak fault detection with strong background noise, especially for early fault detection.

A novel allogeneic acellular matrix scaffold for porcine cartilage regeneration.

BACKGROUND: Cartilage defects are common sports injuries without significant treatment. Articular cartilage with inferior regenerative potential resulted in the poor formation of hyaline cartilage in defects. Acellular matrix scaffolds provide a microenvironment and biochemical properties similar to those of native tissues and are widely used for tissue regeneration. Therefore, we aimed to design a novel acellular cartilage matrix scaffold (ACS) for cartilage regeneration and hyaline-like cartilage formation. METHODS: Four types of cartilage injury models, including full-thickness cartilage defects (6.5 and 8.5 mm in diameter and 2.5 mm in depth) and osteochondral defects (6.5 and 8.5 mm in diameter and 5 mm in depth), were constructed in the trochlear groove of the right femurs of pigs (n = 32, female, 25-40 kg). The pigs were divided into 8 groups (4 in each group) based on post-surgery treatment differences. was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and histologic and immunohistochemistry tests. RESULTS: At 6 months, the ACS-implanted group exhibited better defect filling and a greater number of chondrocyte-like cells in the defect area than the blank groups. MRI and micro-CT imaging evaluations revealed that ACS implantation was an effective treatment for cartilage regeneration. The immunohistochemistry results suggested that more hyaline-like cartilage was generated in the defects of the ACS-implanted group. CONCLUSIONS: ACS implantation promoted cartilage repair in full-thickness cartilage defects and osteochondral defects with increased hyaline-like cartilage formation at the 6-month follow-up.

Multi-Pathway Microenvironment Regulation for Atherosclerosis Therapy Based on Beta-Cyclodextrin/L-Arginine/Au Nanomotors with Dual-Mode Propulsion.

Most of the current non-pharmacological treatment strategies for atherosclerosis (AS) suffer from poor penetration into the plaque and only aim at a certain factor in its formation process, resulting in limited therapeutic effect. Herein, a kind of nanomotor with dual-mode propulsion is constructed, which is sensitive to higher reactive oxygen species (ROS) at the AS site and near-infrared (NIR) laser by the covalent binding and self-assembly of ß-cyclodextrin (ß-CD) and L-arginine (LA) with immobilization of Au nanoparticles. NIR laser irradiation can be used as a driving force and to ablate inflammatory macrophages through the photothermal effect. The nitric oxide (NO) released by the nanomotors can be used as another driving force and a therapeutic agent to promote endothelial repair in the plaque site. LA can eliminate ROS in the inflammatory site, and ß-CD can promote the removal of cholesterol from foam cells. In particular, the two driving modes of nanomotors synergistically promote their aggregation and penetration in the plaque. This kind of nanomotor can regulate the microenvironment of AS in multiple ways, including combination therapy for endothelial repair, lipid clearance, and reducing ROS, which is expected to become a potential non-pharmacological strategy in the treatment of AS.

Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1.

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.

Decreased expression of HADH is related to poor prognosis and immune infiltration in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is the subtype pf kidney cancer having the highest mortality as well as the highest potential of invasion and metastasis. The expression of HADH, encoding a key enzyme in fatty acid ß-oxidation, has rarely been reported to correlate with prognosis and immune infiltration in cancers. This study aimed to explore the prognostic value of HADH in patients with KIRC. Gene expression profiles and clinical data of KIRC patients were acquired from The Cancer Genome Atlas. We compared the expression of HADH between KIRC tissues and normal tissues. Then, the relationship between HADH expression and the clinicopathological characteristics (survival, age, gender, stage, and grade) of KIRC was explored. Data from several online databases and paraffin-embedded specimens from two cohorts were used for external validation (10 cases from Meizhou People's Hospital and another 75 cases from a tissue chip, with both cohorts including KIRC samples and paired normal tissues). We also predicted the fractions of tumor-infiltrating immune cells (TIICs) in various tissues using CIBERSORT. Next, we estimated the prognostic value of differences in TIIC proportions between the high and low HADH expression groups. Finally, gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms by which HADH expression influences patient survival. The expression of HADH was significantly lower in KIRC tissue than in normal tissue. Decreased expression of HADH was significantly correlated with high histologic grade, advanced stage, and poor prognosis. The differential expression of HADH was validated at the protein level by immunohistochemistry. Multivariate Cox regression analysis indicated that HADH was an independent prognostic factor for KIRC. In addition, HADH expression was significantly associated with the accumulation of several TIICs, especially regulatory T cells. Finally, GSEA revealed that the transcriptome of the low HADH expression group was significantly enriched in genes involved in not only epithelial-mesenchymal transition and inflammatory response but also TNF-α, IL-6-JAK-STAT3, and interferon-γ signaling. In conclusion, our study demonstrated that decreased expression of HADH is related to poor prognosis and immune infiltration in KIRC; this finding may provide crucial information for the development of immunotherapies.

Up-regulation expression and prognostic significance of Syntaxin4 in kidney renal clear cell carcinoma.

BACKGROUND: Syntaxin4 (STX4) gene encodes the protein STX4, a member of soluble N-ethylmaleimide-sensitive factor attachment protein receptors protein, playing a vital role in cell invadopodium formation and invasion, which is associated with the malignant progression of various human cancers. However, the expression and prognostic significance of STX4 in kidney renal clear cell carcinoma (KIRC) remain to be investigated. METHODS: In this study, we collected the mRNA expression of STX4 in 535 KIRC patients from The Cancer Genome Atlasthrough the University of California Santa Cruz Xena database platform. Then we explored the expression of STX4 in KIRC, and the relationship with clinicopathological characteristics and prognostic value. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes function enrichment analyses were used to explore the potential mechanism of STX4 in KIRC. qRT-PCR analysis was performed toverify the above results with real world tissue specimens. RESULTS: The results indicated that STX4 was up-expressed in KIRC, and were associated with higher histological grade, advanced stage, and poorer prognosis. Moreover, elevated STX4 expression is an independent risk factor for KIRC. qRT-PCR analysis showed that STX4 was significantly elevated in 10 paired of KIRC samples compared to normal samples. Functional enrichment analysis indicated that endo/exocytosis, autophagy, mTOR signaling pathway, and NOD-like receptor signaling pathway were enriched. CONCLUSIONS: In summary, STX4 is constantly up-expressed in KIRC tissues, associated with a poor prognosis. We suggest that it can be an effective biomarker for the prognosis of KIRC and may be a novel therapeutic target in KIRC.

Risk factors for ecchymosis in patients receiving rivaroxaban for thromboprophylaxis after total knee arthroplasty: a retrospective cohort study.

WHAT IS KNOWN AND OBJECTIVE: Ecchymosis of the limb is commonly seen after total knee arthroplasty (TKA) when using anticoagulants for thromboprophylaxis, but it is unknown which factors may predispose patients to an increased risk. The aim of this study was to evaluate risk factors for ecchymosis in patients receiving rivaroxaban after TKA. METHODS: A retrospective, single-centre cohort analysis was conducted. The electronic medical records of patients admitted to the Department of Orthopedics during January 2018 to December 2019 and who received rivaroxaban 10 mg daily after TKA were reviewed for documentation of ecchymosis. Baseline demographics, laboratory values and surgical information were included for analysing their relationship with ecchymosis. RESULTS AND DISCUSSION: A total of 227 patients were included in the study. Among them, 54 patients (23.8%) developed ecchymosis, and 173 did not. The ecchymosis group had a higher proportion of patients with a body weight >60 kg [83.33% vs. 50.00%, p = 0.0004] and hypertension [61.11% vs 41.46%, p = 0.0304]. The ecchymosis group also had a higher BMI [26.04 ± 2.71 kg/m2 vs 24.52 ± 3.18 kg/m2 , p = 0.0066] mean arterial pressure (MAP) recorded from post-operation day 1 to day 3 [105.21 mmHg vs 91.52 mmHg, p = 0.0003]. However, serum albumin concentrations before surgery [3.85 g/dL vs. 4.20 g/dL, p = 0.0225] and on post-operation day 3 [3.50 g/dL vs. 3.91 g/dL, p = 0.0370] were lower in the ecchymosis group. Serum haemoglobin on post-operation day 3 was also lower [10.07 g/dL vs. 11.57 g/dL, p = 0.0459]. Five risk factors for ecchymosis were identified by binary logistic regression: mean MAP (from POD1 to POD3) (OR=2.901, 95% CI: 2.522-3.293, p < 0.001), BMI (OR=2.513, 95% CI: 1.929-3.011, p < 0.001), history of hypertension (OR=2.661, 95% CI: 1.272-4.535, p = 0.032), post-surgery serum albumin level (OR=0.848, 95% CI: 0.735-0.977, p = 0.023) and post-surgery serum haemoglobin level (OR=0.943; 95% CI: 0.898-0.990, p = 0.018). WHAT IS NEW AND CONCLUSION: The present analyses identified that BMI, history of hypertension, mean MAP (POD1 to POD3), post-surgery serum albumin level and post-surgery serum haemoglobin level were independent risk factors for rivaroxaban-related ecchymosis in patients who underwent TKA. These factors should be considered and optimized before starting rivaroxaban therapy.

Pull-In Effect of Suspended Microchannel Resonator Sensor Subjected to Electrostatic Actuation.

In this article, the pull-in instability and dynamic characteristics of electrostatically actuated suspended microchannel resonators are studied. A theoretical model is presented to describe the pull-in effect of suspended microchannel resonators by considering the electrostatic field and the internal fluid. The results indicate that the system is subjected to both the pull-in instability and the flutter. The former is induced by the applied voltage which exceeds the pull-in value while the latter occurs as the velocity of steady flow get closer to the critical velocity. The statically and dynamically stable regions are presented by thoroughly studying the two forms of instability. It is demonstrated that the steady flow can remarkably extend the dynamic stable range of pull-in while the applied voltage slightly decreases the critical velocity. It is also shown that the dc voltage and the steady flow can adjust the resonant frequency while the ac voltage can modulate the vibrational amplitude of the resonator.

Formulation and evaluation of gastroretentive floating drug delivery system of dipyridamole.

A multiple-unit floating alginate bead drug delivery system with prolonged stomach retention time was developed in this study. The floating alginate beads were prepared by ionic cross-linking method, using CaCO3 as the gas-forming agent. Over 92% of the beads remained floating after 9 h. In order to prepare sustained-release dosage forms of dipyridamole, the solid dispersion technique was applied using a blend of Eudragit L100 and Eudragit RLPO. Afterwards, the solid dispersions of dipyridamole were incorporated into the floating alginate beads. The drug release was modified by changing the ratio of Eudragit RLPO and Eudragit L100 in the solid dispersions. The in vivo results showed that the relative bioavailability of alginate beads was enhanced by approximately 2.52-fold compared with that of the commercial tablet. Therefore, our study illustrated the potential use of floating alginate beads combined with the solid dispersion technique for the delivery of acid-soluble compounds, such as dipyridamole.

Revealing the characteristics of SETD2-mutated clear cell renal cell carcinoma through tumor heterogeneity analysis.

Background: Renal cell carcinoma (RCC) is the most prevalent type of malignant kidney tumor in adults, with clear cell renal cell carcinoma (ccRCC) comprising about 75% of all cases. The SETD2 gene, which is involved in the modification of histone proteins, is often found to have alterations in ccRCC. Yet, our understanding of how these SETD2 mutations affect ccRCC characteristics and behavior within the tumor microenvironment is still not fully understood. Methods: We conducted a detailed analysis of single-cell RNA sequencing (scRNA-seq) data from ccRCC. First, the data was preprocessed using the Python package, "scanpy." High variability genes were pinpointed through Pearson's correlation coefficient. Dimensionality reduction and clustering identification were performed using Principal Component Analysis (PCA) and the Leiden algorithm. Malignant cell identification was conducted with the "InferCNV" R package, while cell trajectories and intercellular communication were depicted using the Python packages "VIA" and "cellphoneDB." We then employed the R package "Deseq2" to determine differentially expressed genes (DEGs) between groups. Using high-dimensional weighted gene correlation network analysis (hdWGCNA), co-expression modules were identified. We intersected these modules with DEGs to establish prognostic models through univariate Cox and the least absolute shrinkage and selection operator (LASSO) method. Results: We identified 69 and 53 distinctive cell clusters, respectively. These were classified further into 12 unique cell types. This analysis highlighted the presence of an abnormal tumor sub-cluster (MT + group), identified by high mitochondrial-encoded protein gene expression and an indication of unfavorable prognosis. Investigation of cellular interactions spotlighted significant interactions between the MT + group and endothelial cells, macrophaes. In addition, we developed a prognostic model based on six characteristic genes. Notably, risk scores derived from these genes correlated significantly with various clinical features. Finally, a nomogram model was established to facilitate more accurate outcome prediction, incorporating four independent risk factors. Conclusion: Our findings provide insight into the crucial transcriptomic characteristics of ccRCC associated with SETD2 mutation. We discovered that this mutation-induced subcluster could stimulate M2 polarization in macrophages, suggesting a heightened propensity for metastasis. Moreover, our prognostic model demonstrated effectiveness in forecasting overall survival for ccRCC patients, thus presenting a valuable clinical tool.

Association between milk consumption and kidney stones in U.S. adults: results from NHANES 2007-2018.

Background: Dietary strategies play a crucial role in the prevention of kidney stones. While milk is known for its rich nutritional content, its impact on kidney stone formation remains unclear. This study aimed to examine the relationship between milk consumption and the risk of kidney stones among U.S. adults. Methods: We included 24,620 participants aged 20 and older from the National Health and Nutrition Examination Survey (2007-2018). Milk consumption was defined based on each participant's response to the questionnaire item on "Past 30 day milk product consumption." Kidney stones history was self-reported by participants. The analysis employed weighted multivariate logistic regression models, followed by subgroup analyses for result validation, and explored the age-related dynamics of milk consumption's effect on kidney stone risk using a restricted cubic spline model. Results: Adjusted findings revealed that higher milk intake was associated with a decreased risk of kidney stones (odds ratio [OR] = 0.90, 95% confidence interval [CI] 0.85-0.96), notably among women (OR = 0.86, 95% CI 0.80-0.92) but not significantly in men (OR = 0.94, 95% CI 0.86-1.02). Smoothed curves across all ages showed that women consuming milk had a lower incidence of kidney stones than those who did not, particularly with regular consumption. Conclusion: This study uncovered that across all age groups, higher frequency of milk consumption in women is associated with a reduced risk of kidney stones. However, further prospective cohort studies are needed to confirm this finding.

Estimated Costs of Drug-Related Problems Prevented by Pharmacist Prescription Reviews Among Hospitalized Internal Medicine Patients.

BACKGROUND AND OBJECTIVES: Data are lacking on the estimated costs of pharmacist prescription reviews (PPRs) for hospitalized internal medicine patients. This study investigates the estimated costs of drug-related problems (DRPs) prevented by PPRs among hospitalized internal medicine patients. METHODS: We reviewed all medication orders for patients at an academic teaching hospital in China for 2 years. DRPs were categorized using the Pharmaceutical Care Network Europe classification. The severity of the potential harm of DRPs was assessed by the Harm Associated with Medication Error Classification (HAMEC) tool. The estimated cost of PPRs was calculated. RESULTS: A total of 162426 medication orders for 4314 patients were reviewed, and 1338 DRPs were identified by pharmacists who spent 2230 hours performing PPRs. Among the 1080 DRPs that were prospectively intervened upon, 703 were resolved. The HAMEC tool showed that 47.1% of DRPs were assessed as level 2, 30.4% as level 3, 20.6% as level 1, and 0.6% carried a life-threatening risk. Pharmacist interventions contributed to the prevention of DRP errors and a reduction of $339 139.44. This resulted in a mean cost saving of $482.42 per patient at an input cost of $21 495.06 over the 2 years. The benefit-cost ratio was 15.8. CONCLUSION: PPRs are beneficial for detecting potential DRPs and creating potential cost savings among hospitalized internal medicine patients.

Exploring the safety profile of tremelimumab: an analysis of the FDA adverse event reporting system.

BACKGROUND: Despite the approval of tremelimumab in 2022, there is a lack of pharmacovigilance studies investigating its safety profile in real-world settings using the FDA Adverse Event Reporting System (FAERS) database. AIM: This pharmacovigilance study aimed to comprehensively explore the adverse events (AEs) associated with tremelimumab using data mining techniques on the FAERS database. METHOD: The study utilized data from the FAERS database, covering the period from the first quarter of 2004 to the third quarter of 2022. Disproportionality analysis, the Benjamini Hochberg adjustment method and volcano plots were used to identify and evaluate AE signals associated with tremelimumab. RESULTS: The study uncovered 233 AE cases associated with tremelimumab. Among these cases, pyrexia (n = 39), biliary tract infection (n = 23), and sepsis (n = 21) were the three main AEs associated with tremelimumab use. The study also investigated the system organ classes associated with tremelimumab-related AEs. The top three classes were gastrointestinal disorders (17.9%), infections and infestations (16.6%), and general disorders and administration site infections (11.2%). Several AEs were identified that were not listed on the drug label of tremelimumab. These AEs included pyrexia, biliary tract infection, sepsis, dyspnea, infusion site infection, hiccup, appendicitis, hypotension, dehydration, localised oedema, presyncope, superficial thrombophlebitis and thrombotic microangiopathy. CONCLUSION: This pharmacovigilance study identified several potential adverse events signals related to tremelimumab including some adverse events not listed on the drug label. However, further basic and clinical research studies are needed to validate these results.

Near Infrared Responsive Gold Nanorods Attenuate Osteoarthritis Progression by Targeting TRPV1.

Osteoarthritis (OA) is the most common degenerative joint disease worldwide, with the main pathological manifestation of articular cartilage degeneration. It have been investigated that pharmacological activation of transient receptor potential vanilloid 1 (TRPV1) significantly alleviated cartilage degeneration by abolishing chondrocyte ferroptosis. In this work, in view of the thermal activated feature of TRPV1, Citrate-stabilized gold nanorods (Cit-AuNRs) is conjugated to TRPV1 monoclonal antibody (Cit-AuNRs@Anti-TRPV1) as a photothermal switch for TRPV1 activation in chondrocytes under near infrared (NIR) irradiation. The conjugation of TRPV1 monoclonal antibody barely affect the morphology and physicochemical properties of Cit-AuNRs. Under NIR irradiation, Cit-AuNRs@Anti-TRPV1 exhibited good biocompatibility and flexible photothermal responsiveness. Intra-articular injection of Cit-AuNRs@Anti-TRPV1 followed by NIR irradiation significantly activated TRPV1 and attenuated cartilage degradation by suppressing chondrocytes ferroptosis. The osteophyte formation and subchondral bone sclerosis are remarkably alleviated by NIR-inspired Cit-AuNRs@Anti-TRPV1. Furthermore, the activation of TRPV1 by Cit-AuNRs@Anti-TRPV1 evidently improved physical activities and alleviated pain of destabilization of the medial meniscus (DMM)-induced OA mice. The study reveals Cit-AuNRs@Anti-TRPV1 under NIR irradiation protects chondrocytes from ferroptosis and attenuates OA progression, providing a potential therapeutic strategy for the treatment of OA.

Effect of preparation conditions on the size and encapsulation properties of mPEG-PLGA nanoparticles simultaneously loaded with vincristine sulfate and curcumin.

This study prepared monomethoxy poly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA) nanoparticles simultaneously loaded with vincristine sulfate (Vin) and curcumin (Cur) via O/W emulsion solvent evaporation. Five independent processing parameters were systematically evaluated to enhance the entrapment of dual agents with different properties (i.e. Vin and Cur, which are the hydrophilic and hydrophobic, respectively) into mPEG-PLGA nanoparticles and to control the particle size. The approaches used to investigate the enhancement of drug entrapment efficiencies and control over the particle size included mPEG-PLGA concentration, polyvinyl alcohol (PVA) concentration, initial Vin/Cur content, dichloromethane-to-acetone volume ratio, and aqueous-to-organic phase volume ratio. The nanoparticles produced using the optimum formulation conditions had a particle size of 131.5 nm with a low polydispersity index of 0.047. The entrapment efficiencies were 63.52 ± 2.36% for Vin and 54.60 ± 2.46% for Cur (n = 3). The drug loadings were 1.06 ± 0.04% for Vin and 3.64 ± 0.16% for Cur (n = 3).

Decreased Expression of GLYATL1 Predicts Poor Prognosis in Patients with Clear Cell Renal Cell Carcinoma.

Background: GLYATL1 is a member of the glycine-N-acyltransferase family, which catalyses acyl group transfer. The role of GLYATL1 in cancer is largely unknown; therefore, the potential value of GLYATL1 in clear cell renal cell carcinoma (ccRCC) was explored. Methods: The ccRCC gene expression profiles and clinical data were obtained from the University of California Santa Cruz Xena platform. Differential expression and survival analysis were performed using R software. Samples from the TIMER public database and real-world were used for validation. The potential molecular mechanism of GLYATL1 in ccRCC was explored using gene set enrichment analysis (GSEA). Results: GLYATL1 was downregulated, indicating a poor prognosis in ccRCC. Low expression of GLYATL1 was significantly associated with advanced stage and higher histological grade ccRCC. The differential expression of GLYATL1 was validated at the protein level using clinical samples and tissue microarray. The results of GSEA showed that multiple crucial signalling pathways including fatty acid metabolism, adipogenesis, oxidative phosphorylation and epithelial-mesenchymal transition were enriched. Conclusion: This study demonstrated that GLYATL1 downregulation has an unfavourable impact on the survival of patients with ccRCC. The resulting data indicated that GLYATL1 could be a potential new target for ccRCC therapy, which may be helpful for the personalized treatment of such individuals.

Construction and validation of cuproptosis-related lncRNA prediction signature for bladder cancer and immune infiltration analysis.

Bladder cancer (BC) is a common urologic tumor with a high recurrence rate. Cuproptosis and long noncoding RNAs (lncRNAs) have demonstrated essential roles in the tumorigenesis of many malignancies. Nevertheless, the prognostic value of cuproptosis-related lncRNA (CRLs) in BC is still unclear. The public data used for this study were acquired from the Cancer Genome Atlas database. A comprehensive exploration of the expression profile, mutation, co-expression, and enrichment analyses of cuproptosis-related genes was performed. A total of 466 CRLs were identified using Pearson's correlation analysis. 16 prognostic CRLs were then retained by univariate Cox regression. Unsupervised clustering divided the patients into two clusters with diverse survival outcomes. The signature consists of 7 CRLs was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Survival curves and receiver operating characteristics showed the prognostic signature possessed good predictive value, which was validated in the testing and entire sets. The reliability and stability of our signature were further confirmed by stratified analysis. Additionally, the signature-based risk score was confirmed as an independent prognostic factor. Gene set enrichment analysis showed molecular alteration in the high-risk group was closely associated with cancer. We then developed the clinical nomogram using independent prognostic indicators. Notably, the infiltration of immune cells and expression of immune checkpoints were higher in the high-risk group, suggesting that they may benefit more from immunotherapy. In summary, the prognostic signature might effectively predict the prognosis and provide new insight into the clinical treatment of BC patients.

Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration.

Purpose: Chondrocytes (CHs) in cartilage undergo several detrimental events during the development of osteoarthritis (OA). However, the mechanism underlying CHs regeneration involved in pathogenesis is largely unknown. The aim of this study was to explore the underlying mechanism of regeneration of CHs involved in the pathological condition and the potential therapeutic strategies of cartilage repair. Methods and Materials: CHs were isolated from human cartilage in different OA stages and the high-resolution cellular architecture of human osteoarthritis was examined by applying single-cell RNA sequencing. The analysis of gene differential expression and gene set enrichment was utilized to reveal the relationship of cartilage regeneration and microtubule stabilization. Microtubule destabilizer (nocodazole) and microtubule stabilizer (docetaxel) treated-human primary CHs and rats cartilage defect model were used to investing the effects and downstream signaling pathway of microtubule stabilization on cartilage regeneration. Results: CHs subpopulations were identified on the basis of their gene markers and the data indicated an imbalance caused by an increase in the degeneration and disruption of CHs regeneration in OA samples. Interestingly, the CHs subpopulation namely CHI3L1+ CHs, was characterized by the cell regenerative capacity, stem cell potency and the activated microtubule (MT) process. Furthermore, the data indicated that MT stabilization was effective in promoting cartilage regeneration in rats with cartilage injury model by inhibiting YAP activity. Conclusion: These findings lead to a new understanding of CHs regeneration in the OA pathophysiology context and suggest that MT stabilization is a promising therapeutic target for OA and cartilage injury.

Downregulation of Crystallin Lambda 1 is a New Independent Prognostic Marker in Clear Cell Renal Cell Carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC), the most prevalent kidney cancer subtype, has a high mortality rate. Crystallin lambda 1 (CRYL1) encodes an enzyme that catalyzes the dehydrogenation of L-gulonate into dehydro-L-gulonate in uronate cycle. CRYL1 dysregulation has been linked to the progression of several cancers. This research aimed to evaluate the prognostic significance of CRYL1 expression in ccRCC prognosis. Methods: Clinical data and gene expression profiles on ccRCC were retrieved from the University of California Santa Cruz Xena platform. Differences (variations) in the expression profiles of CRYL1 in ccRCC and healthy tissues were found using RNA-sequencing data, and these findings were validated using qPCR with real-world samples. CRYL1 expression levels were also linked to clinicopathological characteristics, survival, and immune microenvironments. The potential pathway via which CRYL1 expression levels impact the prognosis of patients with ccRCC was investigated using gene set enrichment analysis (GSEA). Results: In ccRCC tissues, CRYL1 expression levels were lower compared to healthy renal tissues in TCGA cohort (n = 535, P < 0.001), which was validated in another real-world cohort (n = 14, P < 0.001). Lower CRYL1 expression levels were linked to unfavorable clinicopathological characteristics and prognoses (P < 0.001). According to multivariate Cox regression analysis (P < 0.001), CRYL1 expression levels in patients with ccRCC could serve as an independent prognostic indicator. Furthermore, a strong link between CRYL1 expression levels and immune microenvironment was observed (P < 0.001). Finally, GSEA revealed that CRYL1 expression levels (P < 0.001) were associated with fatty acid metabolism, G2M checkpoint delays, and epithelial-mesenchymal transitions in ccRCC. Conclusion: Our study found that lower levels of CRYL1 expression were linked to unfavorable clinicopathological characteristics and worse prognoses, and CRYL1 could serve as a new target for the treatment of ccRCC, which is useful for personalized medicine.