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.

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.

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.

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.

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.

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.

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.

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.

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.

Molecular crosstalk between articular cartilage, meniscus, synovium, and subchondral bone in osteoarthritis.

AIMS: Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA. METHODS: We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs. RESULTS: During OA, there were 626, 97, 1,060, and 2,330 differentially expressed genes in articular cartilage, meniscus, synovium, and subchondral bone, respectively. Gene Ontology enrichment revealed that these genes were enriched in extracellular matrix and structure organization, ossification, neutrophil degranulation, and activation at different degrees. Through ligand-receptor pairing and proteome of OA synovial fluid, we predicted ligand-receptor interactions and constructed a crosstalk atlas of the whole joint. Several interactions were reproduced by transwell experiment in chondrocytes and synovial cells, including TNC-NT5E, TNC-SDC4, FN1-ITGA5, and FN1-NT5E. After lipopolysaccharide (LPS) or interleukin (IL)-1ß stimulation, the ligand expression of chondrocytes and synovial cells was upregulated, and corresponding receptors of co-culture cells were also upregulated. CONCLUSION: Each tissue displayed a different expression pattern in transcriptome, demonstrating their specific roles in OA. We highlighted tissue molecular crosstalk through ligand-receptor pairs in OA pathophysiology, and generated a crosstalk atlas. Strategies to interfere with these candidate ligands and receptors may help to discover molecular targets for future OA therapy.Cite this article: Bone Joint Res 2022;11(12):862-872.

An Improved Modeling and Numerical Analysis Method for Tooth Surface Wear of Double-Arc Harmonic Gears.

Tooth surface wear is one of the most common failure modes of harmonic gears, especially in space drive mechanisms. Due to difficulty accurately modeling its wear failure model and the complex mechanism, its dynamic behavior and wear mechanism have not been deeply investigated, and study of the double-arc tooth profile wear model is relative lacking. Therefore, an improved wear modelling and analysis method that is more in line with actual conditions for double-arc harmonic gears is here proposed. Firstly, a tooth surface wear model under mixed elastohydrodynamic lubrication (EHL) was established based on the Archard formula, which combines the Reynolds equation and double-arc tooth profile equation, and considering the meshing offset caused by elastic deformation. Then, the wear analysis method combined with mixed EHL was derived, and numerical simulation analysis of the wear characteristics in lubrication state was carried out, including wear depth calculation and wear output comparison of different tooth profiles. Furthermore, the influence of main working parameters and design parameters on the wear quantity was analyzed. The results show that wear depth for mixed EHL is significantly less than at dry contact. The double-arc tooth profile can withstand more wear cycles than the involute tooth profile, and the input torque and the number of cycles significantly affect the amount of tooth wear. This study further reveals the tooth wear mechanism for harmonic gears, and provides a theoretical basis for the structural optimization design, wear reduction, and life prolonging of harmonic gears.

Articular fibrocartilage-targeted therapy by microtubule stabilization.

The fibrocartilage presented on the joint surface was caused by cartilage injury or degeneration. There is still a lack of effective strategies for fibrocartilage. Here, we hypothesized that the fibrocartilage could be viewed as a raw material for the renewal of hyaline cartilage and proposed a previously unidentified strategy of cartilage regeneration, namely, "fibrocartilage hyalinization." Cytoskeleton remodeling plays a vital role in modifying the cellular phenotype. We identified that microtubule stabilization by docetaxel repressed cartilage fibrosis and increased the hyaline cartilage extracellular matrix. We further designed a fibrocartilage-targeted negatively charged thermosensitive hydrogel for the sustained delivery of docetaxel, which promoted fibrocartilage hyalinization in the cartilage defect model. Moreover, the mechanism of fibrocartilage hyalinization by microtubule stabilization was verified as the inhibition of Sparc (secreted protein acidic and rich in cysteine). Together, our study suggested that articular fibrocartilage-targeted therapy in situ was a promising strategy for hyaline cartilage repair.

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.

The Establishment of a Mouse Model for Degenerative Kyphoscoliosis Based on Senescence-Accelerated Mouse Prone 8.

Objective: Degenerative kyphoscoliosis (DKS) is a complex spinal deformity associated with degeneration of bones, muscles, discs, and facet joints. The aim of this study was to establish an animal model of degenerative scoliosis that recapitulates key pathological features of DKS and to validate the degenerative changes in senescence-accelerated mouse prone 8 (SAMP8) mice. Methods: Thirty male mice were divided into 2 groups: 10 bipedal C57BL/6J mice were used as the control group, and 20 bipedal SAMP8 mice were used as the experimental group. Mice were bipedalized under general anesthesia. The incidence of scoliosis and bone quality was determined using radiographs and in vivo micro-CT images 4, 8, and 12 weeks after surgery, respectively. Histomorphological studies of muscle samples were performed after sacrifice at 12 weeks after surgery. Results: On the 12th week, the incidence rates of kyphosis in C57BL/6J and SAMP8 groups were 50% and 100%, respectively. Overall, the incidence and angle of kyphosis were significantly higher in the bipedal SAMP8 group compared to the C57BL/6J group (44.7°± 6.2° vs. 84.3°± 10.3°, P<0.001). Based on 3D reconstruction of the entire spine, degeneration of the intervertebral disc was observed in bipedal SAMP8 mice, including the reduction of disc height and the formation of vertebral osteophytes. The bone volume ratio (BV/TV) was significantly suppressed in the bipedal SAMP8 group compared with the bipedal C57BL/6J group. In addition, HE staining and Mason staining of the paraspinal muscle tissue showed chronic inflammation and fibrosis in the muscles of the bipedal SAMP8 group. Conclusions: The SAMP8 mouse model can be taken as a clinically relevant model of DKS, and accelerated aging of the musculoskeletal system promotes the development of kyphosis.

High-fidelity noise-reconstructed empirical mode decomposition for mechanical multiple and weak fault extractions.

The premise to ensure the safe operation of rotating machinery is to accurately and timely capture all kinds of damages and fault signatures, whose challenging issues are the multiple and weak faults. Ensemble noise-reconstructed empirical mode decomposition (ENEMD) is a smart method of adaptively decomposing and denoising for mechanical fault diagnosis. However, the original ENEMD and its derivative methods suffer from the drawbacks of critical noise estimation on the high accuracy, leading to the powerless capability for accurate multiple and weak fault signature extraction. Thus, high-fidelity noise-reconstructed empirical mode decomposition (HNEMD) is proposed to overcome the drawbacks, whose compositions include: (1) The cepstral neighboring coefficient editing is proposed to obtain the pre-whitening signal with the actual white noise, from which the major noise can be well purified by the minimax thresholding. (2) The high order singular value decomposition (HOSVD) local reconstruction is developed to estimate the minor noise from the pre-characterizing signal, where the tensor with the reasonable singular order is constructed by the sliding window and Hankel matrix. (3) The high-fidelity noise recovered by the major noise and the minor noise is reconstructed and combined with the basic ENEMD algorithm for accurate signature extraction, especially for the multiple or/and weak fault ones. Three repeatable simulations are analyzed to illustrate the signature extraction capability and noise estimation process of this method. Moreover, the effective detections of weak and multiple faults from a hot strip finishing mill gearbox and an aerospace bearing further validate the feasibility of the proposed method.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant.

The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.

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.

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.

Upregulation of TMEM45A Promoted the Progression of Clear Cell Renal Cell Carcinoma in vitro.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive type of primary kidney cancer worldwide. Transmembrane protein 45A (TMEM45A) has been reported to be closely associated with the progression of several cancers. However, the role of TMEM45A in ccRCC remains unclear. Our study intended to explore the potential role of TMEM45A in ccRCC. METHODS: Data on the expression of TMEM45A were obtained from multiple databases, including UCSC, GEPIA2, Oncomine and TIMER. Real-world samples of ccRCC and paired normal renal tissues were used to confirm the information obtained from the databases. In addition, the prognostic value of TMEM45A was evaluated. Loss-of-function assays were performed using TMEM45A-targeting lentivirus to evaluate the biological role of TMEM45A in renal cancer cells. Gene set enrichment analysis (GSEA) was performed to investigate the potential molecular mechanisms. RESULTS: TMEM45A was significantly overexpressed in patients with ccRCC and correlated with poor overall survival and disease-free survival. In addition, the expression of TMEM45A was closely associated with various clinicopathological parameters such as histological grade and TNM stage. Knockdown of TMEM45A inhibited the proliferation and migration and promoted the apoptosis of ccRCC cells in vitro. The results of the GSEA suggested that TMEM45A was potentially involved in the promotion of epithelial-mesenchymal transition (EMT) and inflammatory response in ccRCC. CONCLUSION: TMEM45A was overexpressed and associated with poor survival and acted as a tumour promoter in ccRCC; therefore, might be a potential prognostic marker and therapeutic target.

Microtubule Stabilization Enhances the Chondrogenesis of Synovial Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are well known for their multi-directional differentiation potential and are widely applied in cartilage and bone disease. Synovial mesenchymal stem cells (SMSCs) exhibit a high proliferation rate, low immunogenicity, and greater chondrogenic differentiation potential. Microtubule (MT) plays a key role in various cellular processes. Perturbation of MT stability and their associated proteins is an underlying cause for diseases. Little is known about the role of MT stabilization in the differentiation and homeostasis of SMSCs. In this study, we demonstrated that MT stabilization via docetaxel treatment had a significant effect on enhancing the chondrogenic differentiation of SMSCs. MT stabilization inhibited the expression of Yes-associated proteins (YAP) and the formation of primary cilia in SMSCs to drive chondrogenesis. This finding suggested that MT stabilization might be a promising therapeutic target of cartilage regeneration.