Effects of Inertial Flywheel Training vs. Accentuated Eccentric Loading Training on Strength, Power, and Speed in Well-Trained Male College Sprinters.

This study aimed to evaluate and compare the effects of inertial flywheel training and accentuated eccentric loading training on the neuromuscular performance of well-trained male college sprinters. Fourteen sprinters were recruited and randomly assigned to either the flywheel training (FWT, n = 7) group or the accentuated eccentric loading training (AELT, n = 7) group. The FWT group completed four sets of 2 + 7 repetitions of flywheel squats, whereas the AELT group performed four sets of seven repetitions of barbell squats (concentric/eccentric: 80%/120% 1RM). Both groups underwent an eight-week squat training program, with two sessions per week. A two-way repeated ANOVA analysis was used to find differences between the two groups and between the two testing times (pre-test vs. post-test). The results indicated significant improvements in all measured variables for the FWT group: 1RM (5.0%, ES = 1.28), CMJ (13.3%, ES = 5.42), SJ (6.0%, ES = 2.94), EUR (6.5%, ES = 4.42), SLJ (2.9%, ES = 1.77), and 30 m sprint (-3.4%, ES = -2.80); and for the AELT group: 1RM (6.3%, ES = 2.53), CMJ (7.4%, ES = 3.44), SJ (6.4%, ES = 2.21), SLJ (2.2%, ES = 1.20), and 30 m sprint (-3.0%, ES = -1.84), with the exception of EUR (0.9%, ES = 0.63, p = 0.134), showing no significant difference. In addition, no significant interaction effects between group and time were observed for 1RM back squat, SJ, SLJ, and 30 m sprint (p > 0.05). Conversely, a significant interaction effect between group and time was observed for both CMJ and EUR (p < 0.001); post hoc analysis revealed that the improvements in CMJ and EUR were significantly greater in the FWT group compared to the AELT group (p < 0.001). These findings indicate that both FWT and AELT are effective at enhancing lower-body strength, power, and speed in well-trained male college sprinters, with FWT being particularly more effective in promoting elastic energy storage and the full utilization of the stretch-shortening cycle.

A Bruton tyrosine kinase inhibitor-resistance gene signature predicts prognosis and identifies TRIP13 as a potential therapeutic target in diffuse large B-cell lymphoma.

Bruton tyrosine kinase inhibitor (BTKi) combined with rituximab-based chemotherapy benefits diffuse large B-cell lymphoma (DLBCL) patients. However, drug resistance is the major cause of relapse and death of DLBCL. In this study, we conducted a comprehensive analysis BTKi-resistance related genes (BRRGs) and established a 10-gene (CARD16, TRIP13, PSRC1, CASP1, PLBD1, CARD6, CAPG, CACNA1A, CDH15, and NDUFA4) signature for early identifying high-risk DLBCL patients. The resistance scores based on the BRRGs signature were associated with prognosis. Furthermore, we developed a nomogram incorporating the BRRGs signature, which demonstrated excellent performance in predicting the prognosis of DLBCL patients. Notably, tumor immune microenvironment, biological pathways, and chemotherapy sensitivity were different between high- and low-resistance score groups. Additionally, we identified TRIP13 as a key gene in our model. TRIP13 was found to be overexpressed in DLBCL and BTKi-resistant DLBCL cell lines, knocking down TRIP13 suppresses cell proliferation, promotes cell apoptosis, and enhances the apoptosis effect of BTKi on DLBCL cells by regulating the Wnt/ß-catenin pathway. In conclusion, our study presents a novel BRRGs signature that could serve as a promising prognostic marker in DLBCL, and TRIP13 might be a potential therapeutic target for resistant DLBCL.

Peripheral ulcerative keratitis secondary to tuberculosis: A case report and literature review.

RATIONALE: Compared with intraocular tuberculosis, ocular tuberculosis with ocular surface involvement is rare. Corneal involvement in ocular tuberculosis may include interstitial keratitis or peripheral ulcerative keratitis. We report a case of peripheral ulcerative keratitis directly caused by tuberculosis. PATIENT CONCERNS: A 20-year-old man complained of vision loss and pain in the left eye that had lasted for 1 week. A slit lamp examination of the left eye showed a corneal epithelial defect, interstitial corneal edema, and a white irregular infiltrative lesion and ulcer (with the dimension of 2 × 2.5 mm) in the inferior temporal region. DIAGNOSES: The corneal ulcer was scraped, and the Mycobacterium tuberculosis deoxyribonucleic acid polymerase chain reaction was positive. INTERVENTIONS AND OUTCOMES: After a month of oral antituberculosis treatment, the corneal ulcer resolved, and the intraocular inflammation improved. LESSONS: Peripheral ulcerative keratitis secondary to tuberculosis can be directly caused by M tuberculosis.

Optimal Electrocatalyst Design Strategies for Acidic Oxygen Evolution.

Hydrogen, a clean resource with high energy density, is one of the most promising alternatives to fossil. Proton exchange membrane water electrolyzers are beneficial for hydrogen production because of their high current density, facile operation, and high gas purity. However, the large-scale application of electrochemical water splitting to acidic electrolytes is severely limited by the sluggish kinetics of the anodic reaction and the inadequate development of corrosion- and highly oxidation-resistant anode catalysts. Therefore, anode catalysts with excellent performance and long-term durability must be developed for anodic oxygen evolution reactions (OER) in acidic media. This review comprehensively outlines three commonly employed strategies, namely, defect, phase, and structure engineering, to address the challenges within the acidic OER, while also identifying their existing limitations. Accordingly, the correlation between material design strategies and catalytic performance is discussed in terms of their contribution to high activity and long-term stability. In addition, various nanostructures that can effectively enhance the catalyst performance at the mesoscale are summarized from the perspective of engineering technology, thus providing suitable strategies for catalyst design that satisfy industrial requirements. Finally, the challenges and future outlook in the area of acidic OER are presented.

Melanin-Like Nanomedicine Functions as a Novel RPE Ferroptosis Inhibitor to Ameliorate Retinal Degeneration and Visual Impairment in Dry Age-Related Macular Degeneration.

Ferrous ion accumulation and lethal oxidative stress mediate irreversible retinal pigment epithelial (RPE) cell ferroptosis and subsequent photoreceptor degeneration, a potential key pathogenic factor in the onset of dry age-related macular degeneration (dAMD), causing irreversible vision loss in the global elderly population. However, currently, no effective interventional treatment strategy exists in clinical practice. Herein, lesion site-targeted melanin-like nanoparticles, named ConA-MelNPs, are designed as a novel ferroptosis inhibitor for retinal degenerative diseases. ConA-MelNPs possessed chelating iron ion characteristics, alleviating severe mitochondrial damage caused by oxidative stress and protecting RPE cells from ferroptosis induced by sodium iodate (NaIO3). In a preclinical dAMD mouse model, a single intravitreal injection of ConA-MelNPs yielded significant responses in electroretinograms and visually-driven optomotor responses in visually impaired mice, resisting the challenge posed by secondary NaIO3-induced injuries, with the long-term sustainability of its therapeutic effect. Mechanistically, ConA-MelNPs achieve a therapeutic effect by interrupting the detrimental cascade involving "RPE cell ferroptosis, lethal oxidative stress, and microglial proinflammatory activation," affording the restoration of retinal homeostasis. The synthesized ConA-MelNPs demonstrated good biosafety, with no detected ophthalmic or systemic side effects. Collectively, ConA-MelNPs are proposed as a promising therapeutic option for atrophic retinal diseases such as dAMD.

Demethylation C-C coupling reaction facilitated by the repulsive Coulomb force between two cations.

Carbon chain elongation (CCE) is normally carried out using either chemical catalysts or bioenzymes. Herein we demonstrate a catalyst-free approach to promote demethylation C-C coupling reactions for advanced CCE constructed with functional groups under ambient conditions. Accelerated by the electric field, two organic cations containing a methyl group (e.g., ketones, acids, and aldehydes) approach each other with such proximity that the energy of the repulsive Coulomb interaction between these two cations exceeds the bond energy of the methyl group. This results in the elimination of a methyl cation and the coupling of the residual carbonyl carbon groups. As confirmed by high-resolution mass spectrometry and isotope-labeling experiments, the C-C coupling reactions (yields up to 76.5%) were commonly observed in the gas phase or liquid phase, for which the mechanism was further studied using molecular dynamics simulations and stationary-point calculations, revealing deep insights and perspectives of chemistry.

Analogous Chain Selenite Chlorides Ba2M(SeO3)2Cl2 (M = Cu2+, Ni2+, Co2+, Mn2+) and Pb2Cu(SeO3)2Cl2 with Tunable Spin S: Syntheses and Characterizations.

A series of analogous chain selenite chlorides Ba2M(SeO3)2Cl2 (M = Cu 1, Ni 2, Co 3, Mn 4) and Pb2Cu(SeO3)2Cl2 5 with tunable spin S from S = 1/2 to S = 5/2 have been hydrothermally synthesized and characterized. These analogues crystallized in the orthorhombic Pnnm space group (monoclinic P21/n space group for 5) all containing M2+-SeO3-M2+ spin chains, which are further separated by the Ba2+ ions (Pb2+ for 5). The magnetic susceptibility results of 1, 2, and 5 show broad maxima around 80.0, 18.9, and 78.0 K, respectively, indicating good one-dimensional (1D) magnetism. Meanwhile, no long-range order (LRO) is observed down to 2 K for both 1 and 5, while the isostructural compounds 2, 3, and 4 exhibit LRO at 3.4 K, 10.8 K, and 5.7 K, respectively, which are further confirmed by the heat capacity and electron spin resonance results, as well as the observed spin-flop transitions in the M-H curves measured at 2 K below TN. The magnetizations of 1-5 at 7 T are still far from saturation. In addition, thermal stability and FT-IR and UV-vis-NIR spectroscopy of 1-5 are reported.

Comparing the Effect of Isoinertial Flywheel Training and Traditional Resistance Training on Maximal Strength and Muscle Power in Healthy People: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis aimed to analyze whether isoinertial flywheel training (FWT) is superior to traditional resistance training (TRT) in enhancing maximal strength and muscle power in healthy individuals. METHODS: Electronic searches were conducted in the Web of Science, PubMed, Cochrane Library, SPORTDiscus, and Scopus databases up to 21 April 2024. Outcomes were analyzed as continuous variables using either a random or fixed effects model to calculate the standardized mean difference (SMD) and 95% confidence intervals (CI). RESULTS: A total of sixteen articles, involving 341 subjects, met the inclusion criteria and were included in the statistical analyses. The pooled results indicate no statistically significant differences between FWT and TRT in developing maximal strength in healthy individuals (SMD = 0.24, 95% CI [-0.26, 0.74], p = 0.35). Additionally, the pooled outcomes showed a small-sized effect in muscle power with FWT (SMD = 0.47, 95% CI [0.10, 0.84]), which was significantly higher than that with TRT (p = 0.01) in healthy individuals. Subgroup analysis revealed that when the total number of FWT sessions is between 12 and 18 (1-3 times per week), it significantly improves muscle power (SMD = 0.61, 95% CI [0.12, 1.09]). Significant effects favoring FWT for muscle power were observed in both well-trained (SMD = 0.58, 95% CI [0.04, 1.13]) and untrained individuals (SMD = 1.40, 95% CI [0.23, 2.57]). In terms of exercise, performing flywheel training with squat and lunge exercises significantly enhances muscle power (SMD = 0.43; 95% CI: 0.02-0.84, and p = 0.04). Interestingly, FWT was superior to weight stack resistance training (SMD = 0.61, 95% CI [0.21, 1.00]) in enhancing muscle power, while no significant differences were found compared to barbell free weights training (SMD = 0.36, 95% CI [-0.22, 0.94]). CONCLUSIONS: This meta-analysis confirms the superiority of FWT compared to TRT in promoting muscle power in both healthy untrained and well-trained individuals. Squats and lunges for FWT are more suitable for improving lower limb explosive power. It is recommended that coaches and trainers implement FWT for six weeks, 2-3 times per week, with at least a 48 h interval between each session. Although FWT is not superior to free weights training, it is advisable to include FWT in sport periodization to diversify the training stimuli for healthy individuals.

Process Manufacturing Intelligence Empowered by Industrial Metaverse: A Survey.

The intelligent goal of process manufacturing is to achieve high efficiency and greening of the entire production. Whereas the information system it used is functionally independent, resulting to knowledge gaps between each level. Decision-making still requires lots of knowledge workers making manually. The industrial metaverse is a necessary means to bridge the knowledge gaps by sharing and collaborative decision-making. Considering the safety and stability requirements of the process manufacturing, this article conducts a thorough survey on the process manufacturing intelligence empowered by industrial metaverse. First, it analyzes the current status and challenges of process manufacturing intelligence, and then summarizes the latest developments about key enabling technologies of industrial metaverse, such as interconnection technologies, artificial intelligence, cloud-edge computing, digital twin (DT), immersive interaction, and blockchain technology. On this basis, taking into account the characteristics of process manufacturing, a construction approach and architecture for the process industrial metaverse is proposed: a virtual-real fused industrial metaverse construction method that combines DTs with physical avatar, which can effectively ensure the safety of metaverse's application in industrial scenarios. Finally, we conducted preliminary exploration and research, to prove the feasibility of proposed method.

Anti-IL-17 Inhibits PINK1/Parkin Autophagy and M1 Macrophage Polarization in Rheumatic Heart Disease.

Rheumatic heart disease (RHD) is an important and preventable cause of cardiovascular death and disability, but the lack of clarity about its exact mechanisms makes it more difficult to find alternative methods or prevention and treatment. We previously demonstrated that increased IL-17 expression plays a crucial role in the development of RHD-related valvular inflammatory injury. Macrophage autophagy/polarization may be a pro-survival strategy in the initiation and resolution of the inflammatory process. This study investigated the mechanism by which IL-17 regulates autophagy/polarization activation in macrophages. A RHD rat model was generated, and the effects of anti-IL-17 and 3-methyladenine (3-MA) were analyzed. The molecular mechanisms underlying IL-17-induced macrophage autophagy/polarization were investigated via in vitro experiments. In our established RHD rat model, the activation of the macrophage PINK1/Parkin autophagic pathway in valve tissue was accompanied by M1 macrophage infiltration, and anti-IL-17 treatment inhibited autophagy and reversed macrophage inflammatory infiltration, thereby attenuating endothelial-mesenchymal transition (EndMT) in the valve tissue. The efficacy of 3-MA treatment was similar to that of anti-IL-17 treatment. Furthermore, in THP-1 cells, the pharmacological promotion of autophagy by IL-17 induced M1-type polarization, whereas the inhibition of autophagy by 3-MA reversed this process. Mechanistically, silencing PINK1 in THP-1 blocked autophagic flux. Moreover, IL-17-induced M1-polarized macrophages promoted EndMT in HUVECs. This study revealed that IL-17 plays an important role in EndMT in RHD via the PINK1/Parkin autophagic pathway and macrophage polarization, providing a potential therapeutic target.

Manipulating the Spin State of Spinel Octahedral Sites via a π-π Type Orbital Coupling to Boost Water Oxidation.

Spin state is often regarded as the crucial valve to release the reactivity of energy-related catalysts, yet it is also challenging to precisely manipulate, especially for the active center ions occupied at the specific geometric sites. Herein, a π-π type orbital coupling of 3d (Co)-2p (O)-4f (Ce) was employed to regulate the spin state of octahedral cobalt sites (CoOh) in the composite of Co3O4/CeO2. More specifically, the equivalent high-spin ratio of CoOh can reach to 54.7 % via tuning the CeO2 content, thereby triggering the average eg filling (1.094) close to the theoretical optimum value. The corresponding catalyst exhibits a superior water oxidation performance with an overpotential of 251 mV at 10 mA cm-2, rivaling most cobalt-based oxides state-of-the-art. The π-π type coupling corroborated by the matched energy levels between Ce t1u/t2u-O and CoOh t2g-O π type bond in the calculated crystal orbital Hamilton population and partial density of states profiles, stimulates a π-donation between O 2p and π-symmetric Ce 4fyz 2 orbital, consequently facilitating the electrons hopping from t2g to eg orbital of CoOh. This work offers an in-depth insight into understanding the 4f and 3d orbital coupling for spin state optimization in composite oxides.

Sparse Wasserstein stationary subspace analysis for fault detection and diagnosis of nonstationary industrial processes.

Fault detection and diagnosis of nonstationary processes are crucial for ensuring the safety of industrial production systems. However, the nonstationarity of process data poses multifaceted challenges to them. First, conventional stationary fault detection methods encounter difficulties in discerning evolving trends within nonstationary data. Secondly, the majority of current nonstationary fault detection methods directly extract features from all variables, rendering them susceptible to redundant interference. Moreover, nonstationary trends possess the capacity to conceal and modify the correlations among variables. Coupled with the smearing effect of faults, it is challenging to achieve accurate fault diagnosis. To address these challenges, this paper proposes sparse Wasserstein stationary subspace analysis (SWSSA). Specifically, a ℓ2,p-norm constraint is introduced to endow the stationary subspace model with excellent sparse representation capability. Furthermore, recognizing that fault variables within the sparse stationary subspace influence only a limited subset of stationary sources, this paper proposes a novel contribution analysis method based on local dynamic preserving projection (LDPP), termed LDPPBC, which can effectively mitigate the smearing effect on nonstationary fault diagnosis. LDPPBC establishes a LDPP matrix by extracting the latent positional information of fault variables within the stationary subspace. This allows LDPPBC to selectively analyze the contributions of variables within the latent fault subspace to achieve precise fault diagnosis while avoiding the interference of variable contributions from the fault-free subspace. Finally, the superiority of the proposed method is thoroughly validated through a numerical simulation, a continuous stirred tank reactor, and a real industrial roaster.

Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases.

Fundus neovascularization diseases are a series of blinding eye diseases that seriously impair vision worldwide. Currently, the means of treating these diseases in clinical practice are continuously evolving and have rapidly revolutionized treatment opinions. However, key issues such as inadequate treatment effectiveness, high rates of recurrence, and poor patient compliance still need to be urgently addressed. Multifunctional nanomedicine can specifically respond to both endogenous and exogenous microenvironments, effectively deliver drugs to specific targets and participate in activities such as biological imaging and the detection of small molecules. Nano-in-micro (NIM) delivery systems such as metal, metal oxide and up-conversion nanoparticles (NPs), quantum dots, and carbon materials, have shown certain advantages in overcoming the presence of physiological barriers within the eyeball and are widely used in the treatment of ophthalmic diseases. Few studies, however, have evaluated the efficacy of NIM delivery systems in treating fundus neovascular diseases (FNDs). The present study describes the main clinical treatment strategies and the adverse events associated with the treatment of FNDs with NIM delivery systems and summarizes the anatomical obstacles that must be overcome. In this review, we wish to highlight the principle of intraocular microenvironment normalization, aiming to provide a more rational approach for designing new NIM delivery systems to treat specific FNDs.

Machine Learning-Based Integrated Multiomics Characterization of Colorectal Cancer Reveals Distinctive Metabolic Signatures.

The metabolic signature identification of colorectal cancer is critical for its early diagnosis and therapeutic approaches that will significantly block cancer progression and improve patient survival. Here, we combined an untargeted metabolic analysis strategy based on internal extractive electrospray ionization mass spectrometry and the machine learning approach to analyze metabolites in 173 pairs of cancer samples and matched normal tissue samples to build robust metabolic signature models for diagnostic purposes. Screening and independent validation of metabolic signatures from colorectal cancers via machine learning methods (Logistic Regression_L1 for feature selection and eXtreme Gradient Boosting for classification) was performed to generate a panel of seven signatures with good diagnostic performance (the accuracy of 87.74%, sensitivity of 85.82%, and specificity of 89.66%). Moreover, seven signatures were evaluated according to their ability to distinguish between cancer and normal tissues, with the metabolic molecule PC (30:0) showing good diagnostic performance. In addition, genes associated with PC (30:0) were identified by multiomics analysis (combining metabolic data with transcriptomic data analysis) and our results showed that PC (30:0) could promote the proliferation of colorectal cancer cell SW480, revealing the correlation between genetic changes and metabolic dysregulation in cancer. Overall, our results reveal potential determinants affecting metabolite dysregulation, paving the way for a mechanistic understanding of altered tissue metabolites in colorectal cancer and design interventions for manipulating the levels of circulating metabolites.

Electron Accumulation Induced by Electron Injection-Incomplete Discharge on NiFe LDH for Enhanced Oxygen Evolution Reaction.

Optimizing the local electronic structure of electrocatalysts can effectively lower the energy barrier of electrochemical reactions, thus enhancing the electrocatalytic activity. However, the intrinsic contribution of the electronic effect is still experimentally unclear. In this work, the electron injection-incomplete discharge approach to achieve the electron accumulation (EA) degree on the nickel-iron layered double hydroxide (NiFe LDH) is proposed, to reveal the intrinsic contribution of EA toward oxygen evolution reaction (OER). Such NiFe LDH with EA effect results in only 262 mV overpotential to reach 50 mA cm-2, which is 51 mV-lower compared with pristine NiFe LDH (313 mV), and reduced Tafel slope of 54.8 mV dec-1 than NiFe LDH (107.5 mV dec-1). Spectroscopy characterizations combined with theoretical calculations confirm that the EA near concomitant Vo can induce a narrower energy gap and lower thermodynamic barrier to enhance OER performance. This study clarifies the mechanism of the EA effect on OER activity, providing a direct electronic structure modulation guideline for effective electrocatalyst design.

MSRB2 Ameliorates H2O2-induced Chondrocyte Oxidative Stress and Suppresses Apoptosis in Osteoarthritis.

BACKGROUND: Chondrocyte oxidative stress and apoptosis are critical factors contributing to the pathogenesis of osteoarthritis (OA). Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial protein that protects cells from oxidative stress and is involved in apoptosis. This study aimed to investigated the expression of MSRB2 in articular cartilage tissues and elucidated its effect on H2O2-stimulated chondrocytes. METHODS: Human chondrocytes were cultured in Dulbecco's modified Eagle's medium (DMEM)/F12. MSRB2 overexpression in chondrocytes was achieved by transfecting with an MSRB2 overexpression plasmid. Western blot, quantitative RT-PCR, Immunofluorescence staining, and TUNEL assay were employed in this study. RESULTS: MSRB2 expression was found to be reduced in OA patients. Furthermore, overexpression of MSRB2 in H2O2-induced chondrocytes mitigated apoptosis and enhanced cell viability. Elevated MSRB2 expression diminished chondrocyte ROS contents, decreased cytochrome C (Cyc) in the cytoplasm, and regulated mitochondrial membrane potential to maintain mitochondrial homeostasis. Interestingly, knockdown of charged multivesicular body protein 5 (CHMP5) led to a decreased inMSRB2 expression in chondrocytes. Additionally, protein levels of CHMP5 and MSRB2 were reduced in H2O2-stimulated chondrocytes, and silencing CHMP5 reduced MSRB2 expression. Knockdown of CHMP5 increased cleaved caspase-3 expression in H2O2-induced chondrocytes and elevated TUNEL-positive chondrocytes. CONCLUSION: MSRB2 decreased in OA, and overexpression of MSRB2 alleviated oxidative stress and apoptosis of chondrocyte.

Strengthening the Synergy between Oxygen Vacancies in Electrocatalysts for Efficient Glycerol Electrooxidation.

Defect-engineered bimetallic oxides exhibit high potential for the electrolysis of small organic molecules. However, the ambiguity in the relationship between the defect density and electrocatalytic performance makes it challenging to control the final products of multi-step multi-electron reactions in such electrocatalytic systems. In this study, controllable kinetics reduction is used to maximize the oxygen vacancy density of a Cu─Co oxide nanosheet (CuCo2O4 NS), which is used to catalyze the glycerol electrooxidation reaction (GOR). The CuCo2O4-x NS with the highest oxygen-vacancy density (CuCo2O4-x-2) oxidizes C3 molecules to C1 molecules with selectivity of almost 100% and a Faradaic efficiency of ≈99%, showing the best oxidation performance among all the modified catalysts. Systems with multiple oxygen vacancies in close proximity to each other synergistically facilitate the cleavage of C─C bonds. Density functional theory calculations confirm the ability of closely spaced oxygen vacancies to facilitate charge transfer between the catalyst and several key glycolic-acid (GCA) intermediates of the GOR process, thereby facilitating the decomposition of C2 intermediates to C1 molecules. This study reveals qualitatively in tuning the density of oxygen vacancies for altering the reaction pathway of GOR by the synergistic effects of spatial proximity of high-density oxygen vacancies.

CHMP5 attenuates osteoarthritis via inhibiting chondrocyte apoptosis and extracellular matrix degradation: involvement of NF-κB pathway.

BACKGROUND: Osteoarthritis (OA), the most common joint disease, is linked with chondrocyte apoptosis and extracellular matrix (ECM) degradation. Charged multivesicular body protein 5 (CHMP5), a member of the multivesicular body, has been reported to serve as an anti-apoptotic protein to participate in leukemia development. However, the effects of CHMP5 on apoptosis and ECM degradation in OA remain unclear. METHODS: In this study, quantitative proteomics was performed to analyze differential proteins between normal and OA patient articular cartilages. The OA mouse model was constructed by the destabilization of the medial meniscus (DMM). In vitro, interleukin-1 beta (IL-1ß) was used to induce OA in human chondrocytes. CHMP5 overexpression and silencing vectors were created using an adenovirus system. The effects of CHMP5 on IL-1ß-induced chondrocyte apoptosis were investigated by CCK-8, flow cytometry, and western blot. The effects on ECM degradation were examined by western blot and immunofluorescence. The potential mechanism was explored by western blot and Co-IP assays. RESULTS: Downregulated CHMP5 was identified by proteomics in OA patient cartilages, which was verified in human and mouse articular cartilages. CHMP5 overexpression repressed cell apoptosis and ECM degradation in OA chondrocytes. However, silencing CHMP5 exacerbated OA chondrocyte apoptosis and ECM degradation. Furthermore, we found that the protective effect of CHMP5 against OA was involved in nuclear factor kappa B (NF-κB) signaling pathway. CONCLUSIONS: This study demonstrated that CHMP5 repressed IL-1ß-induced chondrocyte apoptosis and ECM degradation and blocked NF-κB activation. It was shown that CHMP5 might be a novel potential therapeutic target for OA in the future.

A spatiotemporal atlas of mouse liver homeostasis and regeneration.

The mechanism by which mammalian liver cell responses are coordinated during tissue homeostasis and perturbation is poorly understood, representing a major obstacle in our understanding of many diseases. This knowledge gap is caused by the difficulty involved with studying multiple cell types in different states and locations, particularly when these are transient. We have combined Stereo-seq (spatiotemporal enhanced resolution omics-sequencing) with single-cell transcriptomic profiling of 473,290 cells to generate a high-definition spatiotemporal atlas of mouse liver homeostasis and regeneration at the whole-lobe scale. Our integrative study dissects in detail the molecular gradients controlling liver cell function, systematically defining how gene networks are dynamically modulated through intercellular communication to promote regeneration. Among other important regulators, we identified the transcriptional cofactor TBL1XR1 as a rheostat linking inflammation to Wnt/ß-catenin signaling for facilitating hepatocyte proliferation. Our data and analytical pipelines lay the foundation for future high-definition tissue-scale atlases of organ physiology and malfunction.