Stabilizing hexagonally close-packed phase in single-component block copolymers through rational symmetry breaking.

Despite being predicted to be a thermodynamically equilibrium structure, the absence of direct experimental evidence of hexagonally close-packed spherical phase in single-component block copolymers raises uncomfortable concerns regarding the existing fundamental phase principles. This work presents a robust approach to regulate the phase behavior of linear block copolymers by deliberately breaking molecular symmetry, and the hexagonally close-packed lattice is captured in a rigorous single-component system. A collection of discrete A1BA2 triblock copolymers is designed and prepared through an iterative growth method. The precise chemical composition and uniform chain length eliminates inherent size distribution and other molecular defects. Simply by tuning the relative chain length of two end A blocks, a rich array of ordered nanostructures, including Frank-Kasper A15 and σ phases, are fabricated without changing the overall chemistry or composition. More interestingly, hexagonally close-packed spherical phase becomes thermodynamically stable and experimentally accessible attributed to the synergistic contribution of the two end blocks. The shorter A blocks are pulled out from the core domain into the matrix to release packing frustration, while the longer ones stabilize the ordered spherical phase against composition fluctuation that tends to disrupt the lattice. This study adds a missing puzzle piece to the block copolymer phase diagram and provides a robust approach for rational structural engineering.

Impact of health science popularization videos on user perceived value and continuous usage intention: based on the C-A-C and ECM model framework.

Objective: To enhance individuals' sustained intention to use health science popularization videos, this study investigated the path relationships and influencing mechanisms of health science popularization video factors on users' perceived value, expectancy confirmation, enjoyment, satisfaction, trust, and continuous usage intention based on the cognitive-affective-conative and expectation-confirmation model theoretical framework. Methods: This study adopted a cross-sectional design and collected data using self-administered questionnaires. The hypotheses were analyzed using the smart partial least squares (Smart-PLS) structural equation modeling method with a dataset containing 503 valid responses. Subsequently, comprehensive data analysis was conducted. Results: Blogger and video quality factors present in health science popularization videos substantially influenced users' perceived value (p < 0.001). Furthermore, users' expectancy confirmation exerted a positive influence on both users' perceived value (p < 0.001) and satisfaction (p < 0.01). Perceived value, in turn, positively impacted satisfaction (p < 0.001) and pleasure (p < 0.001). User satisfaction (p < 0.001) and pleasure (p < 0.001) directly enhanced trust, which, in turn, significantly and directly impacted continuous usage intention (p < 0.001). Discussion: This study offers both theoretical and practical insights into enhancing the quality of health science popularization videos. From a theoretical perspective, it expands upon the cognitive-affective-conative and expectation-confirmation model theoretical frameworks, enriches the theoretical model, and offers theoretical references for future research in this domain. From a practical perspective, enhancing the overall quality of health science popularization content significantly influences users' perceived value, emotional engagement, and continued usage intention to engage with the content.

Augmented Cornus officinalis Levels in Liuwei Dihuang Decoction Inhibits Nucleus Pulposus Cell Pyroptosis to Enhance Therapeutic Efficacy Against Intervertebral Disc Degeneration.

Background: Intervertebral disc (IVD) degeneration (IVDD) is highly prevalent among the elderly population and stands as a leading cause of low back pain. Our prior studies have highlighted the therapeutic potential of Liuwei Dihuang decoction (LWDHD) and its component Cornus officinalis (CO)-derived compounds in alleviating IVDD and osteoarthritis, suggesting beneficial effects of CO in treating degenerative osteoarthropathies. However, uncertainty remains regarding the optimal CO dosage within LWDHD and its potential mechanism for effectively treating IVDD. Objective: To ascertain the optimal dosage of CO within LWDHD for enhancing its therapeutic efficacy in treating IVDD, through a comparison of its effects across varied dosages using a mouse IVDD model. Methods: Eight-week-old male C57BL/6J mice were subjected to a lumbar spine instability surgery to induce an IVDD model and received a modified LWDHD formulation containing varied dosages of CO (original dose of CO, or 5- or 10-time dose of CO (referred to as 1 × CO, 5 × CO, and 10 × CO)) for 8 weeks. The therapeutic efficacy on IVDD was evaluated through changes in lumbar spine function, histopathological morphology, extracellular matrix metabolism, nucleus pulposus cell viability, sensory nerve ingrowth, and nucleus pulposus (NP) cell pyroptosis. Results: Augmenting CO levels in LWDHD led to a dose-dependent increase in the levels of CO-sourced active compounds in the plasma of mice. The modified LWDHD formulations, particularly the 5 × CO, exhibited a favorable pharmacological effect on lumbar function, structural integrity, ECM composition, NP cell viability, and sensory nerve ingrowth. Importantly, all 3 formulations notably mitigated NP cell pyroptosis by activating NRF2/KEAP1 pathway, with the 5 × CO formulation exhibiting superior efficacy. Additionally, a comprehensive score analysis indicated that 5 × CO formulation achieved the highest score. Conclusion: These data underscore that elevating the dosage of CO to a specific threshold can enhance the effectiveness of LWDHD in treating IVDD.

Synergistic interactions in core microbiome Rhizobiales accelerate 1,4-dioxane biodegradation.

Next-generation sequencing (NGS) has revolutionized taxa identification within contaminant-degrading communities. However, uncovering a core degrading microbiome in diverse polluted environments and understanding its associated microbial interactions remains challenging. In this study, we isolated two distinct microbial consortia, namely MA-S and Cl-G, from separate environmental samples using 1,4-dioxane as a target pollutant. Both consortia exhibited a persistent prevalence of the phylum Proteobacteria, especially within the order Rhizobiales. Extensive analysis confirmed that Rhizobiales as the dominant microbial population (> 90 %) across successive degradation cycles, constituting the core degrading microbiome. Co-occurrence network analysis highlighted synergistic interactions within Rhizobiales, especially within the Shinella and Xanthobacter genera, facilitating efficient 1,4-dioxane degradation. The enrichment of Rhizobiales correlated with an increased abundance of essential genes such as PobA, HpaB, ADH, and ALDH. Shinella yambaruensis emerged as a key degrader in both consortia, identified through whole-genome sequencing and RNA-seq analysis, revealing genes implicated in 1,4-dioxane degradation pathways, such as PobA and HpaB. Direct and indirect co-cultivation experiments confirmed synergistic interaction between Shinella sp. and Xanthobacter sp., enhancing the degradation of 1,4-dioxane within the core microbiome Rhizobiales. Our findings advocate for integrating the core microbiome concept into engineered consortia to optimize 1,4-dioxane bioremediation strategies.

Involvement of autophagy in mesaconitine-induced neurotoxicity in HT22 cells revealed through integrated transcriptomic, proteomic, and m6A epitranscriptomic profiling.

Background: Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb Aconitum carmichaelii, is commonly used to treat various diseases. Previous studies have indicated the potent toxicity of aconitum despite its pharmacological activities, with limited understanding of its effects on the nervous system and the underlying mechanisms. Methods: HT22 cells and zebrafish were used to investigate the neurotoxic effects of MA both in vitro and in vivo, employing multi-omics techniques to explore the potential mechanisms of toxicity. Results: Our results demonstrated that treatment with MA induces neurotoxicity in zebrafish and HT22 cells. Subsequent analysis revealed that MA induced oxidative stress, as well as structural and functional damage to mitochondria in HT22 cells, accompanied by an upregulation of mRNA and protein expression related to autophagic and lysosomal pathways. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed a correlation between the expression of autophagy-related genes and N6-methyladenosine (m6A) modification following MA treatment. In addition, we identified METTL14 as a potential regulator of m6A methylation in HT22 cells after exposure to MA. Conclusion: Our study has contributed to a thorough mechanistic elucidation of the neurotoxic effects caused by MA, and has provided valuable insights for optimizing the rational utilization of traditional Chinese medicine formulations containing aconitum in clinical practice.

Integrating Epigenetics, Proteomics, and Metabolomics to Reveal the Involvement of Wnt/ß-Catenin Signaling Pathway in Oridonin-Induced Reproductive Toxicity.

Oridonin is the primary active component in the traditional Chinese medicine Rabdosia rubescens, displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed in clinical therapy for acute and chronic pharyngitis, tonsillitis, as well as bronchitis. Nevertheless, the clinical application of oridonin is significantly restricted due to its reproductive toxicity, with the exact mechanism remaining unclear. The aim of this study was to investigate the mechanism of oridonin-induced damage to HTR-8/SVneo cells. Through the integration of epigenetics, proteomics, and metabolomics methodologies, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, ß-catenin, CLDN1, CCND1, and ZO-1 protein levels. This implied that the inhibition of the Wnt/ß-catenin signaling pathway and disruption of tight junction might be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8/SVneo cells.

MINK1 deficiency stimulates nucleus pulposus cell pyroptosis and exacerbates intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration, induced by aging and irregular mechanical strain, is highly prevalent in the elderly population, serving as a leading cause of chronic low back pain and disability. Evolving evidence has revealed the involvement of nucleus pulposus (NP) pyroptosis in the pathogenesis of IVD degeneration, while the precise regulatory mechanisms of NP pyroptosis remain obscure. Misshapen/Nck-interacting kinase (NIK)-related kinase 1 (MINK1), a serine-threonine protein kinase, has the potential to modulate the activation of NLRP3 inflammasome, indicating its pivotal role in governing pyroptosis. In this study, to assess the significance of MINK1 in NP pyroptosis and IVD degeneration, NP tissues from patients with varying degrees of IVD degeneration, and IVD tissues from both aging-induced and lumbar spine instability (LSI) surgery-induced IVD degeneration mouse models, with or without MINK1 ablation, were meticulously evaluated. Our findings indicated a notable decline in MINK1 expression in NP tissues of patients with IVD degeneration and both mouse models as degeneration progresses, accompanied by heightened matrix degradation and increased NP pyroptosis. Moreover, MINK1 ablation led to substantial activation of NP pyroptosis in both mouse models, and accelerating ECM degradation and intensifying the degeneration phenotype in mechanically stress-induced mice. Mechanistically, MINK1 deficiency triggered NF-κB signaling in NP tissues. Overall, our data illustrate an inverse correlation between MINK1 expression and severity of IVD degeneration, and the absence of MINK1 stimulates NP pyroptosis, exacerbating IVD degeneration by activating NF-κB signaling, highlighting a potential innovative therapeutic target in treating IVD degeneration.

Glutathione peroxidase 4 restrains temporomandibular joint osteoarthritis progression by inhibiting ferroptosis.

There are few effective therapeutic strategies for temporomandibular joint osteoarthritis (TMJOA) due to the unclear pathology and mechanisms. We aimed to confirm the roles of GPX4 and ferroptosis in TMJOA progression. ELISA assay was hired to evaluate concentrations of ferroptosis-related markers. The qRT-PCR assay was hired to assess gene mRNA level. Western blot assay and immunohistochemistry were hired to verify the protein level. CCK-8 assay was hired to detect cell viability. Human fibroblast-like synoviocytes (FLSs) were cultured to confirm the effects of GPX4 and indicated inhibitors, and further verified the effects of GPX4 and ferroptosis inhibitors in TMJOA model rats. Markers of ferroptosis including 8-hidroxy-2-deoxyguanosine (8-OHdG) and iron were notably increased in TMJOA tissues and primary OA-FLSs. However, the activity of the antioxidant system including the glutathione peroxidase activity, glutathione (GSH) contents, and glutathione/oxidized glutathione (GSH/GSSG) ratio was notably inhibited in TMJOA tissues, and the primary OA-FLSs. Furthermore, the glutathione peroxidase 4 (GPX4) expression was down-regulated in TMJOA tissues and primary OA-FLSs. Animal and cell experiments have shown that ferroptosis inhibitors notably inhibited ferroptosis and promoted HLS survival as well as up-regulated GPX4 expression. Also, GPX4 knockdown promoted ferroptosis and GPX4 overexpression inhibited ferroptosis. GPX4 also positively regulated cell survival which was the opposite with ferroptosis. In conclusion, GPX4 and ferroptosis regulated the progression of TMJOA. Targeting ferroptosis might be an effective therapeutic strategy for TMJOA patients in the clinic.

Nickel-Catalyzed Three-Component Unsymmetrical Bis-Allylation of Alkynes with Alkenes: A Density Functional Theory Study.

Density functional theory (DFT) characterizations were employed to resolve the structural and energetic aspects and product selectivities along the mechanistic reaction paths of the nickel-catalyzed three-component unsymmetrical bis-allylation of alkynes with alkenes. Our putative mechanism initiated with the in situ generation of the active catalytic species [Ni(0)L2] (L = NHC) from its precursors [Ni(COD)2, NHC·HCl] to activate the alkyne and alkene substrates to form the final skipped trienes. This proceeds via the following five sequential steps: oxidative addition (OA), ß-F elimination, ring-opening complexation, C-B cleavage and reductive elimination (RE). Both the OA and RE steps (with respective free energy barriers of 24.2 and 24.8 kcal·mol-1) contribute to the observed reaction rates, with the former being the selectivity-controlling step of the entire chemical transformation. Electrophilic/nucleophilic properties of selected substrates were accurately predicted through dual descriptors (based on Hirshfeld charges), with the chemo- and regio-selectivities being reasonably predicted and explained. Further distortion/interaction and interaction region indicator (IRI) analyses for key stationary points along reaction profiles indicate that the participation of the third component olefin (allylboronate) and tBuOK additive played a crucial role in facilitating the reaction and regenerating the active catalyst, ensuring smooth formation of the skipped triene product under a favorably low dosage of the Ni(COD)2 catalyst (5 mol%).

Multiple effects of dose-related GM-CSF on periodontal resorption in deep-frozen grafted teeth: A reverse study.

Autologous tooth grafting is a dental restorative modality based on periodontal ligament healing.Human periodontal ligament stem cells(PDLSCs) are involved in the formation and remodeling of periodontal tissue.Based on previous findings, the proliferation and differentiation of processing cryopreserved periodontal ligament stem cells (PDLSCs) exhibit similarities to those of fresh cells. However, there is evident absorption in the transplanted frozen tooth's roots and bones, with the underlying cause remaining unknown. Granulocyte macrophage colony-stimulating factor(GM-CSF) is named for its produce granulocyte and macrophage precursors from bone marrow precursors, and it also serves as one of the regulatory factors in inflammatory and osteoclast formation. This study aimed to investigate changes in GM-CSF expression in frozen PDLSCs (fhPDLSCs) and evaluate the impact of GM-CSF on PDLSCs with respect to cellular activity and osteogenic ability. The role of GM-CSF in periodontal absorption was further speculated by comparing with IL-1ß. The results revealed a significant increase in GM-CSF levels from fhPDLSCs compared to fresh cells, which exhibited an equivalent inflammatory stimulation effect as 1 ng/ml IL-1ß. Cell viability also increased with increasing concentrations of GM-CSF; however, the GM-CSF from fhPDLSCs was not sufficient to significantly trigger osteoclastic factors. Considering its interaction with IL-1ß and positive feedback mechanism, environments with high doses of GM-CSF derived from fhPDLSCs are more likely to activate osteoclastic responses.Therefore, for frozen tooth replantation, great attention should be paid to anti-inflammation and anti-infection.GM-CSF may serve as a potential therapeutic target for inhibiting periodontal resorption in delayed grafts.

Potential causal association between leisure sedentary behaviors and osteoporosis: A two-sample Mendelian randomization analysis.

Previous observational studies have observed a correlation between sedentary behavior and osteoporosis. However, conclusions from these studies have been contradictory. To explore the potential causal relationship between sedentary behavior and osteoporosis, we conducted a Mendelian randomization analysis. A two-sample Mendelian randomization was adopted to explore the causal relationship of leisure sedentary behavior with osteoporosis. We employed 5 methods to estimate the causal associations between leisure sedentary behavior and osteoporosis. Univariable Mendelian randomization results provided evidence for the causal relationship of the time spent on computer-use with the bone mineral density estimated by heel quantitative ultrasound (eBMD) (inverse variance weighted [IVW]: ß (95% confidence interval [CI]) - 0.150 (-0.270 to -0.031), P = .013; weighted median: ß (95%CI) - 0.195 (-0.336 to -0.055), P = .006). Similar associations were observed in the driving forearm bone mineral density (FABMD) (IVW: ß (95%CI) - 0.933 (-1.860 to -0.007), P = .048) and driving lumbar spine bone mineral density (IVW: ß (95%CI) - 0.649 (-1.175 to -0.124), P = .015). However, we did not find a significant causal relationship between the time spent on watching TV and bone mineral density. Research showed that there was a causal relationship between the time spent on computer use and driving time and eBMD, FABMD, and lumbar spine bone mineral density.

Reusable Architecture Growth for Continual Stereo Matching.

The remarkable performance of recent stereo depth estimation models benefits from the successful use of convolutional neural networks to regress dense disparity. Akin to most tasks, this needs gathering training data that covers a number of heterogeneous scenes at deployment time. However, training samples are typically acquired continuously in practical applications, making the capability to learn new scenes continually even more crucial. For this purpose, we propose to perform continual stereo matching where a model is tasked to 1) continually learn new scenes, 2) overcome forgetting previously learned scenes, and 3) continuously predict disparities at inference. We achieve this goal by introducing a Reusable Architecture Growth (RAG) framework. RAG leverages task-specific neural unit search and architecture growth to learn new scenes continually in both supervised and self-supervised manners. It can maintain high reusability during growth by reusing previous units while obtaining good performance. Additionally, we present a Scene Router module to adaptively select the scene-specific architecture path at inference. Comprehensive experiments on numerous datasets show that our framework performs impressively in various weather, road, and city circumstances and surpasses the state-of-the-art methods in more challenging cross-dataset settings. Further experiments also demonstrate the adaptability of our method to unseen scenes, which can facilitate end-to-end stereo architecture learning and practical deployment.

Fe-ZSM-5 zeolite catalyst for heterogeneous Fenton oxidation of 1,4-dioxane: effect of Si/Al ratios and contributions of reactive oxygen species.

Heterogeneous Fenton oxidation using traditional catalysts with H2O2 for the degradation of 1,4-dioxane (1,4-DX) still presents challenge. In this study, we explored the potential of Fe-ZSM-5 zeolites (Fe-zeolite) with three Si/Al ratios (25, 100, 300) as heterogeneous Fenton catalysts for the removal of 1,4-DX from aqueous solution. Fe2O3 or ZSM-5 alone provided ineffective in degrading 1,4-DX when combined with H2O2. However, the efficient removal of 1,4-DX using H2O2 was observed when Fe2O3 was loaded on ZSM-5. Notably, the Brønsted acid sites of Fe-zeolite played a crucial role during the degradation of 1,4-DX. Fe-zeolites, in combination with H2O2, effectively removed 1,4-DX via a combination of adsorption and oxidation. Initially, Fe-zeolites demonstrated excellent affinity for 1,4-DX, achieving adsorption equilibrium rapidly in about 10 min, followed by effective catalytic oxidative degradation. Among the Fe-ZSM-5 catalysts, Fe-ZSM-5 (25) exhibited the highest catalytic activity and degraded 1,4-DX the fastest. We identified hydroxyl radicals (·OH) and singlet oxygen (1O2) as the primary reactive oxygen species (ROS) responsible for 1,4-DX degradation, with superoxide anions (HO2·/O2·-) mainly converting into 1O2 and ·OH. The degradation primarily occurred at the Fe-zeolite interface, with the degradation rate constants proportional to the amount of Brønsted acid sites on the Fe-zeolite. Fe-zeolites were effective over a wide working pH range, with alkaline pH conditions favoring 1,4-DX degradation. Overall, our study provides valuable insights into the selection of suitable catalysts for effective removal of 1,4-DX using a heterogeneous Fenton technology.

Case report: remedial microdissection testicular sperm extraction after onco-microdissection testicular sperm extraction failure.

BACKGROUND: Testicular cancer (TC) mostly occurs in men aged 14 to 44. Studies have shown that TC seriously damages male fertility, and 6% to 24% of patients with TC were even found to suffer from azoospermia when they are diagnosed. At present, some studies have pointed out that onco-microdissection testicular sperm extraction (mTESE) can extract sperm from tumor testicles. However, there are almost no reports on remedial measures after onco-mTESE failure. Given the valuable opportunity for fertility preservation in patients with TC and azoospermia, it is necessary to provide effective remedial methods for patients with failed onco-mTESE. METHODS: Two young men, who were diagnosed with TC and also found to have azoospermia, tried onco-mTESE while undergoing radical orchiectomy for fertility preservation. However, sperm extraction failed in both patients. Subsequently, the isolated testicular tissue of the patient in case 1 suffered from TC again, and the patient in case 2 was scheduled to receive multiple cycles of gonadotoxic chemotherapy. Because both had a plan to have a birth in the future, we performed remedial mTESE. RESULTS: Sperm was successfully extracted from both patients. The patient recovered well, without complications. The patient couple in case 1 underwent 1 intracytoplasmic sperm injection (ICSI) cycle but did not achieve clinical pregnancy. CONCLUSIONS: There is still an opportunity to extract sperm successfully using onco-mTESE, despite the difficulty of fertility preservation in TC patients with azoospermia. If sperm extraction from the tumor testis fails, implementing remedial mTESE as early as possible would likely preserve the last chance of fertility for these patients.

Improved LEACH Protocol Based on Underwater Energy Propagation Model, Parallel Transmission, and Replication Computing for Underwater Acoustic Sensor Networks.

Underwater acoustic sensor networks (UASNs) are critical to a range of applications from oceanographic data collection to submarine surveillance. In these networks, efficient energy management is critical due to the limited power resources of underwater sensors. The LEACH protocol, a popular cluster-based protocol, has been widely used in UASNs to minimize energy consumption. Despite its widespread use, the conventional LEACH protocol faces challenges such as an unoptimized cluster number and low transmission efficiency, which hinder its performance. This paper proposes an improved LEACH protocol for cluster-based UASNs, where the cluster number is optimized with an underwater energy propagation model to reduce energy consumption, and a transmission scheduling algorithm is also employed to achieve conflict-free parallel data transmission. Replication computing is introduced to the LEACH protocol to reduce the signaling in the clustering and data transmission phases. The simulation results show that the proposed protocol outperforms several conventional methods in terms of normalized average residual energy, average number of surviving nodes, average round when the first death node occurs, and the number of packets received by the base station.

Active Disparity Sampling for Stereo Matching With Adjoint Network.

The sparse signals provided by external sources have been leveraged as guidance for improving dense disparity estimation. However, previous methods assume depth measurements to be randomly sampled, which restricts performance improvements due to under-sampling in challenging regions and over-sampling in well-estimated areas. In this work, we introduce an Active Disparity Sampling problem that selects suitable sampling patterns to enhance the utility of depth measurements given arbitrary sampling budgets. We achieve this goal by learning an Adjoint Network for a deep stereo model to measure its pixel-wise disparity quality. Specifically, we design a hard-soft prior supervision mechanism to provide hierarchical supervision for learning the quality map. A Bayesian optimized disparity sampling policy is further proposed to sample depth measurements with the guidance of the disparity quality. Extensive experiments on standard datasets with various stereo models demonstrate that our method is suited and effective in different stereo architectures and outperforms existing fixed and adaptive sampling methods under different sampling rates. Remarkably, the proposed method makes substantial improvements when generalized to heterogeneous unseen domains.

Recent Progress in Ferroptosis Induced Tumor Cell Death by Anti-tumor Metallic complexes.

Metal complexes represented by platinum complexes play a very important role in cancer treatment due to their diverse chemical structures and anti-tumor activities. Recently, ferroptosis has emerged as a newly occurring cell death form in the anti-tumor process. It has been reported that metal complexes could inhibit the proliferation and metastasis of tumors and combat chemotherapy resistance by targeting ferroptosis. In this review, we briefly describe ferroptosis as a fundamental process for tumor suppression and triggering anti-tumor immune responses. We summarize recent developments on metal complexes that induce ferroptosis. Finally, we outline the prospects for the application of metal complexes to the treatment of tumors based on ferroptosis and the associated problems that need to be solved, and discussed other potential research directions of metal complexes.

Reference values of gait parameters in healthy Chinese university students: A cross-sectional observational study.

BACKGROUND: Gait is influenced by race, age, and diseases type. Reference values for gait are closely related to numerous health outcomes. To gain a comprehensive understanding of gait patterns, particularly in relation to race-related pathologies and disorders, it is crucial to establish reference values for gait in daily life considering sex and age. Therefore, our objective was to present sex and age-based reference values for gait in daily life, providing a valuable foundation for further research and clinical applications. AIM: To establish reference values for lower extremity joint kinematics and kinetics during gait in asymptomatic adult women and men. METHODS: Spatiotemporal, kinematics and kinetics parameters were measured in 171 healthy adults (70 males and 101 females) using the computer-aided soft tissue foot model. Full curve statistical parametric mapping was performed using independent and paired-samples t-tests. RESULTS: Compared with females, males required more time (cycle time, double-limb support time, stance time, swing time, and stride time), and the differences were statistically significant. In addition, the step and stride lengths of males were longer. Compared to males, female cadence was faster, and statures-per-second and stride-per-minute were higher. There were no statistical differences in speed and stride width between the two groups. After adjusting for height, it was observed that women walked significantly faster than men, and they also had a higher cadence. However, in terms of step length, stride length, and stride width, both genders exhibited similarities. CONCLUSION: We established reference values for gait speed and spatiotemporal gait parameters in Chinese university students. This contributes to a valuable database for gait assessment and evaluation of preventive or rehabilitative programs.

Causal relationship between breakfast skipping and bone mineral density: a two-sample Mendelian randomized study.

Objective: To explore the causal association between breakfast skipping and bone mineral density (BMD) through two-sample Mendelian randomisation (MR) analysis. Methods: A two-sample MR approach was adopted to explore the causal relationship of breakfast skipping with BMDs (across three skeletal sites and five age groups). Publicly available genome-wide association study summary data were used for MR analysis. We used five methods to estimate the causal associations between breakfast skipping and BMDs: inverse-variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode. IVW was used for the main analysis and the remaining four methods were used as supplementary analyses. The heterogeneity of the MR results was determined using IVW and MR-Egger methods. The pleiotropy of the MR results was determined using MR-Egger intercept. Furthermore, a leave-one-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism. Results: With the IVW method, we did not find any causal relationship between breakfast skipping and forearm, femoral neck, and lumbar spine BMD. Subsequently, when we included BMD data stratified by five different age groups in the analysis, the results showed that there was no apparent causal effect between breakfast skipping and age-stratified BMD. This finding was supported by all four supplementary methods (P > 0.05 for all methods). No heterogeneity or horizontal pleiotropy was detected in any of the analyses (P > 0.05). The leave-one-out tests conducted in the analyses did not identify any single nucleotide polymorphism that could have influenced the MR results, indicating the reliability of our findings. Conclusion: No causal effect was found between breakfast skipping and BMD (across three skeletal sites and five age groups).

In vitro protective effect of recombinant prominin-1 combined with microRNA-29b on N-methyl-D-aspartate-induced excitotoxicity in retinal ganglion cells.

AIM: To determine the in vitro protective effect of recombinant prominin-1 (Prominin-1)+microRNA-29b (P1M29) on N-methyl-D-aspartate (NMDA)-induced excitotoxicity in retinal ganglion cells (RGCs). METHODS: RGC-5 cells were cultured, and NMDA-induced excitotoxicity at the range of 100-800 µmol/L was assessed using the MTT assay. NMDA (800 µmol/L) was selected as the appropriate concentration for preparing the cell model. To evaluate the protective effect of P1M29 on the cell model, Prominin-1 was added at the concentration of 1-6 ng/mL for 48h, and the cell survival was investigated with/without microRNA-29b. After obtaining the appropriate concentration and time of P1M29 at 48h, real-time polymerase chain reaction (PCR) was utilized to detect the relative mRNA expression of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-ß2. Western blot detection was applied to measure the phosphorylation levels of protein kinase B (AKT) and extracellular regulated protein kinases (ERK) in RGC-5 cells after treatment with Prominin-1. Apoptosis study of the cell model was conducted by flow cytometry for estimating the anti-apoptotic effect of P1M29. Immunofluorescence analysis was used to analyze the expression levels of VEGF and TGF-ß2. RESULTS: MTT cytotoxicity assays demonstrated that P1M29 group had significantly higher cell survival rate than Prominin-1 group (P<0.05). Real-time PCR data indicated that the expression levels of VEGF were significantly increased in both Prominin-1 and P1M29 groups compared NMDA and microRNA-29b group (P<0.05), while TGF-ß2 were significantly decreased in both microRNA-29b and P1M29 groups compared NMDA and Prominin-1 group (P<0.05). Western blot results showed that both Prominin-1 and P1M29 groups significantly increased the phosphorylation levels of AKT and ERK compared to NMDA and microRNA-29b groups (P<0.05). Flow cytometry analysis revealed that P1M29 could prevent RGC-5 cell apoptosis in the early stage of apoptosis, while immunofluorescence results showed that P1M29 group had higher expression of VEGF and lower expression of TGF-ß2 with a stronger green fluorescence than NMDA group. CONCLUSION: Prominin-1 combined with microRNA-29b can provide a suitable therapeutic option for ameliorating NMDA-induced excitotoxicity in RGC-5 cells.