Advances in Hydrogel-Based Drug Delivery Systems.

Hydrogels, with their distinctive three-dimensional networks of hydrophilic polymers, drive innovations across various biomedical applications. The ability of hydrogels to absorb and retain significant volumes of water, coupled with their structural integrity and responsiveness to environmental stimuli, renders them ideal for drug delivery, tissue engineering, and wound healing. This review delves into the classification of hydrogels based on cross-linking methods, providing insights into their synthesis, properties, and applications. We further discuss the recent advancements in hydrogel-based drug delivery systems, including oral, injectable, topical, and ocular approaches, highlighting their significance in enhancing therapeutic outcomes. Additionally, we address the challenges faced in the clinical translation of hydrogels and propose future directions for leveraging their potential in personalized medicine and regenerative healthcare solutions.

Celecoxib attenuates hindlimb unloading-induced muscle atrophy via suppressing inflammation, oxidative stress and ER stress by inhibiting STAT3.

Improving inflammation may serve as useful therapeutic interventions for the hindlimb unloading-induced disuse muscle atrophy. Celecoxib is a selective non-steroidal anti-inflammatory drug. We aimed to determine the role and mechanism of celecoxib in hindlimb unloading-induced disuse muscle atrophy. Celecoxib significantly attenuated the decrease in soleus muscle mass, hindlimb muscle function and the shift from slow- to fast-twitch muscle fibers caused by hindlimb unloading in rats. Importantly, celecoxib inhibited the increased expression of inflammatory factors, macrophage infiltration in damaged soleus muscle. Mechanistically, Celecoxib could significantly reduce oxidative stress and endoplasmic reticulum stress in soleus muscle of unloaded rats. Furthermore, celecoxib inhibited muscle proteolysis by reducing the levels of MAFbx, MuRF1, and autophagy related proteins maybe by inhibiting the activation of pro-inflammatory STAT3 pathway in vivo and in vitro. This study is the first to demonstrate that celecoxib can attenuate disuse muscle atrophy caused by hindlimb unloading via suppressing inflammation, oxidative stress and endoplasmic reticulum stress probably, improving target muscle function and reversing the shift of muscle fiber types by inhibiting STAT3 pathways-mediated inflammatory cascade. This study not only enriches the potential molecular regulatory mechanisms, but also provides new potential therapeutic targets for disuse muscle atrophy.

MiR-136-5p in cancer: Roles, mechanisms, and chemotherapy resistance.

MicroRNAs (miRNAs) have emerged as important regulators of gene expression, and the deregulation of their activity has been linked to the onset and progression of a variety of human malignancies. Among these miRNAs, miR-136-5p has attracted significant attention due to its diverse roles in cancer biology. Mostly, miR-136-5p is downregulated in malignancies. It could inhibit viability, proliferation, migration, invasion and promote apoptosis of tumor cells. This review article provides a comprehensive overview of the current understanding of miR-136-5p in different sorts of human cancers: genital tumors, head and neck tumors, tumors from the digestive and urinary systems, skin cancers, neurologic tumors, pulmonary neoplasms and other cancers by discussing its molecular mechanisms, functional roles, and impact in chemotherapies. In conclusion, miR-136-5p could be a promising new biomarker and potential clinical therapeutic target.

MuSCs and IPCs: roles in skeletal muscle homeostasis, aging and injury.

Skeletal muscle is a highly specialized tissue composed of myofibres that performs crucial functions in movement and metabolism. In response to external stimuli and injuries, a range of stem/progenitor cells, with muscle stem cells or satellite cells (MuSCs) being the predominant cell type, are rapidly activated to repair and regenerate skeletal muscle within weeks. Under normal conditions, MuSCs remain in a quiescent state, but become proliferative and differentiate into new myofibres in response to injury. In addition to MuSCs, some interstitial progenitor cells (IPCs) such as fibro-adipogenic progenitors (FAPs), pericytes, interstitial stem cells expressing PW1 and negative for Pax7 (PICs), muscle side population cells (SPCs), CD133-positive cells and Twist2-positive cells have been identified as playing direct or indirect roles in regenerating muscle tissue. Here, we highlight the heterogeneity, molecular markers, and functional properties of these interstitial progenitor cells, and explore the role of muscle stem/progenitor cells in skeletal muscle homeostasis, aging, and muscle-related diseases. This review provides critical insights for future stem cell therapies aimed at treating muscle-related diseases.

The association between physical activity and sleep in adult ADHD patients with stimulant medication use.

Background: Adults with attention-deficit/hyperactivity disorder (ADHD) may experience sleep problems doubly suffering from the disease and side effects of stimulant medications. Physical activity (PA) is known to produce numerous beneficial effects in adults. However, it was not well-characterized whether PA would still be effective in this situation. The main objective of the current study was to examine the relationship between PA and sleep among adult ADHD patients who were using stimulant medications and quantify the form of this association. Methods: Adult ADHD participants with stimulant medications use condition from the National Health and Nutrition Examination Survey (NHANES) database between January 1, 2013, and March 2020 (prepandemic) were included in the cross-sectional analysis. Weighted logistic regression was performed to assess the relationship between PA level and sleep. A restricted cubic spline model was used to relax the linear relationship assumptions and investigate the associations between the risk of trouble sleeping and time spent engaging in moderate-to-vigorous PA per week. Results: A total of 162 eligible adult ADHD participants who reported using stimulant medicines were included. Participants who adhered to the general recommendation of guidelines in the US of 150 min per week of moderate-to-vigorous PA had a significant lower risk of complaining of trouble sleeping (OR: 0.26, 95% CI: 0.10-0.67, p = 0.006), and this association was seen in men (OR: 0.23, 95% CI: 0.09-0.56, p = 0.002), but was not seen in women (OR: 0.71, 95% CI: 0.27-1.88, p = 0.500). Restricted cubic spline analysis showed that the incidence of trouble sleeping gradually decreased after at least 105 min of moderate-intensity PA per week in participants (OR: 1.02, 95% CI: 0.92-1.14). A significant difference appeared after 341 min (OR: 0.87, 95% CI: 0.76-0.99), and the curve leveled after 1,250 min (OR: 0.60, 95% CI: 0.46-0.79). Conclusion: Our findings observed associations between PA and sleep condition in the adult ADHD patients with stimulant medication use population. Moderate-to-vigorous PA may be beneficial to sleep in adults with ADHD who were using stimulants and thus should be recommended as part of a healthy lifestyle. Gender difference should be considered as an important factor for further studies to examine these associations and explore potential mechanisms.

Transcriptome sequencing promotes insights on the molecular mechanism of SKP-SC-EVs mitigating denervation-induced muscle atrophy.

BACKGROUND: Complex pathophysiological changes accompany denervation-induced skeletal muscle atrophy, but no effective treatment strategies exist. Our previous study indicated that extracellular vesicles derived from skin-derived precursors-derived Schwann cells (SKP-SC-EVs) can effectively mitigate denervation-induced muscle atrophy. However, the specific molecular mechanism remains unclear. METHODS AND RESULTS: In this study, we used bioinformatics methods to scrutinize the impact of SKP-SC-EVs on gene expression in denervation-induced skeletal muscle atrophy. We found that SKP-SC-EVs altered the expression of 358 genes in denervated skeletal muscles. The differentially expressed genes were predominantly participated in biological processes, including cell cycle, inflammation, immunity, and adhesion, and signaling pathways, such as FoxO and PI3K.Using the Molecular Complex Detection (MCODE) plugin, we identified the two clusters with the highest score: cluster 1 comprised 37 genes, and Cluster 2 consisted of 24 genes. Then, fifty hub genes were identified using CytoHubba. The intersection of Hub genes and genes obtained by MCODE showed that all 23 genes related to the cell cycle in Cluster 1 were hub genes, and 5 genes in Cluster 2 were hub genes and associated with inflammation. CONCLUSIONS: Overall, the differentially expressed genes in denervated skeletal muscle following SKP-SC-EVs treatment are primarily linked to the cell cycle and inflammation. Consequently, promoting proliferation and inhibiting inflammation may be the critical process in which SKP-SC-EVs delay denervation-induced muscle atrophy. Our findings contribute to a better understanding of the molecular mechanism of SKP-SC-EVs delaying denervation-induced muscle atrophy, offering a promising new avenue for muscle atrophy treatment.

Single-Cell RNA Sequencing Analysis of Microglia Dissected the Energy Metabolism and Revealed Potential Biomarkers in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease, accompanied by the gradual loss of motor neuron, even life-threatening. However, the pathogenesis, early diagnosis, and effective strategies of ALS are not yet completely understood. In this study, the function of differentially expressed genes (DEGs) in non-neuronal cells of the primary motor cortex of ALS patients (DATA1), the brainstem of SOD1 mutant ALS mice (DATA2), and the whole blood tissue of ALS patients (DATA3) were explored. The results showed that the functions of DEGs in non-neuronal cells were mainly related to energy metabolism (such as oxidative phosphorylation) and protein synthesis. In non-neuronal cells, six upregulated DEGs (HSPA8, SOD1, CALM1, CALM2, NEFL, COX6C) and three downregulated DEGs (SNRNP70, HSPA1A, HSPA1B) might be key factors in regulating ALS. Microglia played a key role in the development of ALS. The expression of SOD1 and TUBA4A in microglia in DATA1 was significantly increased. The integration analysis of DEGs in DATA1 and DATA2 showed that SOD1 and CALM1 might be potential biomarkers. The integration analysis of DEGs in DATA1 and DATA3 showed that CALM2 and HSPA1A might be potential biomarkers. Cell interaction showed that the interaction between microglia and other cells was reduced in high oxidative phosphorylation states, which might be a risk factor in ALS. Our research provided evidence for the pathogenesis, early diagnosis, and potential targeted therapy for ALS.

Altered m6A RNA methylation governs denervation-induced muscle atrophy by regulating ubiquitin proteasome pathway.

BACKGROUND: Denervation-induced muscle atrophy is complex disease involving multiple biological processes with unknown mechanisms. N6-methyladenosine (m6A) participates in skeletal muscle physiology by regulating multiple levels of RNA metabolism, but its impact on denervation-induced muscle atrophy is still unclear. Here, we aimed to explore the changes, functions, and molecular mechanisms of m6A RNA methylation during denervation-induced muscle atrophy. METHODS: During denervation-induced muscle atrophy, the m6A immunoprecipitation sequencing (MeRIP-seq) as well as enzyme-linked immunosorbent assay analysis were used to detect the changes of m6A modified RNAs and the involved biological processes. 3-deazidenosine (Daa) and R-2-hydroxyglutarate (R-2HG) were used to verify the roles of m6A RNA methylation. Through bioinformatics analysis combined with experimental verification, the regulatory roles and mechanisms of m6A RNA methylation had been explored. RESULTS: There were many m6A modified RNAs with differences during denervation-induced muscle atrophy, and overall, they were mainly downregulated. After 72 h of denervation, the biological processes involved in the altered mRNA with m6A modification were mainly related to zinc ion binding, ubiquitin protein ligase activity, ATP binding and sequence-specific DNA binding and transcription coactivator activity. Daa reduced overall m6A levels in healthy skeletal muscles, which reduced skeletal muscle mass. On the contrary, the increase in m6A levels mediated by R-2HG alleviated denervation induced muscle atrophy. The m6A RNA methylation regulated skeletal muscle mass through ubiquitin-proteasome pathway. CONCLUSION: This study indicated that decrease in m6A RNA methylation was a new symptom of denervation-induced muscle atrophy, and confirmed that targeting m6A alleviated denervation-induced muscle atrophy.

Myasthenia gravis: Molecular mechanisms and promising therapeutic strategies.

Myasthenia gravis (MG) is a type of autoimmune disease caused by the blockage of neuromuscular junction transmission owing to the attack of autoantibodies on transmission-related proteins. Related antibodies, such as anti-AChR, anti-MuSK and anti-LRP4 antibodies, can be detected in most patients with MG. Although traditional therapies can control most symptoms, several challenges remain to be addressed, necessitating the development of more effective and safe treatment strategies for MG. With the in-depth exploration on the mechanism and immune targets of MG, effective therapies, especially therapies using biologicals, have been reported recently. Given the important roles of immune cells, cytokines and intercellular interactions in the pathological process of MG, B-cell targeted therapy, T-cell targeted therapy, proteasome inhibitors targeting plasma cell, complement inhibitors, FcRn inhibitors have been developed for the treatment of MG. Although these novel therapies exert good therapeutic effects, they may weaken the immunity and increase the risk of infection in MG patients. This review elaborates on the pathogenesis of MG and discusses the advantages and disadvantages of the strategies of traditional treatment and biologicals. In addition, this review emphasises that combined therapy may have better therapeutic effects and reducing the risk of side effects of treatments, which has great prospects for the treatment of MG. With the deepening of research on immunotherapy targets in MG, novel opportunities and challenges in the treatment of MG will be introduced.

Analysis of severe ozone-related human health and weather influence over China in 2019 based on a high-resolution dataset.

Ozone pollution in 2019 in China is particularly severe posing a tremendous threat to the health of Chinese inhabitants. In this study, we constructed a more reliable and accurate 1-km gridded dataset for 2019 with as many sites as possible using the inverse distance weight interpolation method to analyze spatiotemporal ozone pollution characteristics and health burden attributed to ozone exposure from the perspective of different diseases and weather influence. The accuracy of this new dataset is higher than other public datasets, with the coefficient of determination of 0.84 and root-mean-square error of 8.77 ppb through the validation of 300 external sites which were never used for establishing retrieval methods by the datasets mentioned-above. The averaged MDA8 (the daily maximum 8 h average) ozone concentrations over China was 43.5 ppb, and during April-July, 83.9% of total grids occurred peak-month ozone concentrations. Overall, the highest averaged exceedance days (60 days) and population-weighted ozone concentrations (55.0 ppb) both concentrated in central-eastern China including 9 provinces (only 11.4% of the national territory); meanwhile, all-cause premature deaths attributable to ozone exposure reached up to 142,000 (54.9% of national total deaths) with higher deaths for cardiovascular and respiratory, and the provincial per capita premature mortality was 0.27~0.44‰. The six most polluted weather types in the central-eastern China are in order as follows: westerly (SW and W), cyclonic, northerly, and southerly (NW, N, and S) types, which accounts for approximately 73.2% of health burden attributed to daily ozone exposure and poses the greatest public health risk with mean daily premature deaths ranging from 466 to 610. Our findings could provide an effective support for regional ozone pollution control and public health management in China.

Maximizing ozone control by spatial sensitivity-oriented mitigation strategy in the Pearl River Delta Region, China.

The Pearl River Delta (PRD) has long been plagued by severe O3 pollution, particularly during the autumn. A regional O3 pollution episode influenced by the Western Pacific Subtropical High in September 2021 was characterized by near-surface O3 escalation due to strong photochemical reactions within the planetary boundary layer. This event was targeted to develop effective control strategies through investigation of precursor control type and scope based on the high-order decoupled direct method (HDDM) and integrated source apportionment method (ISAM) of CMAQ. Generally, the majority of areas (67.0 %) were under NOx-limited regime, which should strengthen afternoon NOx control inferred by positive convex O3 responses. However, high emission and heavily polluted areas located in central PRD were under VOC-limited regime (11.6 %) or mixed regime (15.0 %). The remaining areas (6.4 %) were under NOx-titration or insensitive conditions. Regarding source apportionment, Guangdong province contributed 32.3 %-58.4 % to MDA8 O3 of PRD, especially higher proportion (>50 %) to central areas. Overall, local-focused NOx/VOC emission reductions had limited effects on O3 mitigation for receptor cities compared to regional-cooperative regulation. When region-wide VOC emission reduction was implemented, MDA8 O3 in VOC-limited grids exhibited the largest declines (2.3 %-4.1 %, 3.9- 7.0 µg·m-3). However, unified NOx control contributed to increasing MDA8 O3 in VOC-limited grids (most stations located for air quality evaluation) whereas decreased MDA8 O3 by 2.1 %- 5.7 %, 3.0- 8.2 µg·m-3 in large-scale NOx-limited grids. The sensitivity-oriented regional control avoided O3 rebound and achieved the greatest decline of 3.4 %- 5.0 %, 5.7- 8.4 µg·m-3 in VOC-limited grids; additionally, time-refined dynamic aggressive NOx control decreased peak O3 by an extra 1.2- 6 µg·m-3, both of which facilitate the regulation for the forecasting O3 episodes. These findings suggest that in heavily polluted environments, the enhancement of O3 regulation benefits requires meticulous, coordinated, and dynamic NOx and VOC controls spanning the entire region based on high-resolution analysis of heterogeneous O3-NOx-VOC sensitivity. Furthermore, emission reduction gains should be more reasonably reflected through increasing in-situ observations covering multi-sensitivity regions.

Contrasting effects of clean air actions on surface ozone concentrations in different regions over Beijing from May to September 2013-2020.

Due to the nonlinear impacts of meteorology and precursors, the response of ozone (O3) trends to emission changes is very complex over different regions in megacity Beijing. Based on long-term in-situ observations at 35 air quality sites (four categories, i.e., urban, traffic, northern suburban and southern suburban sites) and satellite data, spatiotemporal variability of O3, gaseous precursors, and O3-VOCs-NOx sensitivity were explored through multiple metrics during the warm season from 2013 to 2020. Additionally, the contribution of meteorology and emissions to O3 was separated by a machine-learning-based de-weathered method. The annual averaged MDA8 O3 and O3 increased by 3.7 and 2.9 µg/m3/yr, respectively, with the highest at traffic sites and the lowest in northern suburb, and the rate of Ox (O3 + NO2) was 0.2 µg/m3/yr with the highest in southern suburb, although NO2 declined strongly and HCHO decreased slightly. However, the increment of O3 and Ox in the daytime exhibited decreasing trends to some extent. Additionally, NOx abatements weakened O3 loss through less NO titration, which drove narrowing differences in urban-suburban O3 and Ox. Due to larger decrease of NO2 in urban region and HCHO in northern suburb, the extent of VOCs-limited regime fluctuated over Beijing and northern suburb gradually shifted to transition or NOx-limited regime. Compared with the directly observed trends, the increasing rate of de-weathered O3 was lower, which was attributed to favorable meteorological conditions for O3 generation after 2017, especially in June (the most polluted month); whereas the de-weathered Ox declined except in southern suburb. Overall, clean air actions were effective in reducing the atmospheric oxidation capacity in urban and northern suburban regions, weakening local photochemical production over Beijing and suppressing O3 deterioration in northern suburb. Strengthening VOCs control and keeping NOx abatement, especially in June, will be vital to reverse O3 increase trend in Beijing.

Mitochondrial dysfunction: roles in skeletal muscle atrophy.

Mitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, and damage to mitochondria can lead to a series of pathophysiological changes. Mitochondrial dysfunction can lead to skeletal muscle atrophy, and its molecular mechanism leading to skeletal muscle atrophy is complex. Understanding the pathogenesis of mitochondrial dysfunction is useful for the prevention and treatment of skeletal muscle atrophy, and finding drugs and methods to target and modulate mitochondrial function are urgent tasks in the prevention and treatment of skeletal muscle atrophy. In this review, we first discussed the roles of normal mitochondria in skeletal muscle. Importantly, we described the effect of mitochondrial dysfunction on skeletal muscle atrophy and the molecular mechanisms involved. Furthermore, the regulatory roles of different signaling pathways (AMPK-SIRT1-PGC-1α, IGF-1-PI3K-Akt-mTOR, FoxOs, JAK-STAT3, TGF-ß-Smad2/3 and NF-κB pathways, etc.) and the roles of mitochondrial factors were investigated in mitochondrial dysfunction. Next, we analyzed the manifestations of mitochondrial dysfunction in muscle atrophy caused by different diseases. Finally, we summarized the preventive and therapeutic effects of targeted regulation of mitochondrial function on skeletal muscle atrophy, including drug therapy, exercise and diet, gene therapy, stem cell therapy and physical therapy. This review is of great significance for the holistic understanding of the important role of mitochondria in skeletal muscle, which is helpful for researchers to further understanding the molecular regulatory mechanism of skeletal muscle atrophy, and has an important inspiring role for the development of therapeutic strategies for muscle atrophy targeting mitochondria in the future.

Comprehensive Genomic Analysis Reveals Extensive Diversity of Type I and Type IV Secretion Systems in Klebsiella pneumoniae.

The diversity and distribution of secretion systems in Klebsiella pneumoniae are unclear. In this study, the six common secretion systems (T1SS-T6SS) were comprehensively investigated in the genomes of 952 K. pneumoniae strains. T1SS, T2SS, type T subtype of T4SS, T5SS, and subtype T6SSi of T6SS were found. The findings indicated fewer types of secretion systems in K. pneumoniae than reported in Enterobacteriaceae, such as Escherichia coli. One conserved T2SS, one conserved T5SS, and two conserved T6SS were detected in more than 90% of the strains. In contrast, the strains displayed extensive diversity of T1SS and T4SS. Notably, T1SS and T4SS were enriched in the hypervirulent and classical multidrug resistance pathotypes of K. pneumoniae, respectively. The results expand the epidemiological knowledge of the virulence and transmissibility of pathogenic K. pneumoniae and contribute to identify the potential strains for safe applications.

A genome-scale metabolic model of the effect of dissolved oxygen on 1,3-propanediol fermentation by Klebsiella pneumoniae.

Although 1,3-propanediol (1,3-PD) is usually considered an anaerobic fermentation product from glycerol by Klebsiella pneumoniae, microaerobic conditions proved to be more conducive to 1,3-PD production. In this study, a genome-scale metabolic model (GSMM) specific to K. pneumoniae KG2, a high 1.3-PD producer, was constructed. The iZY1242 model contains 2090 reactions, 1242 genes and 1433 metabolites. The model was not only able to accurately characterise cell growth, but also accurately simulate the fed-batch 1,3-PD fermentation process. Flux balance analyses by iZY1242 was performed to dissect the mechanism of stimulated 1,3-PD production under microaerobic conditions, and the maximum yield of 1,3-PD on glycerol was 0.83 mol/mol under optimal microaerobic conditions. Combined with experimental data, the iZY1242 model is a useful tool for establishing the best conditions for microaeration fermentation to produce 1,3-PD from glycerol in K. pneumoniae.

Identification and validation of MSMB as a critical gene for prostate cancer development in obese people.

Prostate cancer (PCA) is one of the most common types of cancer and can seriously endanger the health of older men. Obesity is prevalent all around the world and triggered by lots of factors such as diet, environment and fat metabolism disorder can cause many neoplasms, including PCA. Evidence suggests that genetic changes increase the risk of PCA and obesity. However, the specific obesity-related genes leading to PCA are unknown. Obesity-related genes associated with PCA were identified and analyzed though three public electronic databases: Gene Expression Omnibus, The Cancer Genome Atlas, and Chinese Prostate Cancer Genome and Epigenome Atlas. The effect of obesity-related genes in PCA were analyzed using clinical data from different databases, while associations with immune cells were determined by TIMER web tool. The expression and function of obesity-related genes were verified using clinical samples from obese patients with PCA and PCA cells. We found that four genes, MSMB, BMP5, THBS4, and POPDC3, may lead to PCA occurrence in patients with obesity. In Gene Expression Omnibus database, MSMB and BMP5 were downregulated, while THBS4 and POPDC3 were upregulated. This trend was mainly preserved in the other electronic databases. We also discovered MSMB and THBS4 can affect PCA progression, and all these genes were risk factors for castration-resistant prostate cancer. Moreover, MSMB can impact disease-free survival status of patients with PCA. These obesity-related genes were also correlated with immune cells and immune cell infiltration in PCA. We further uncovered that MSMB was downregulated in clinical PCA and castration-resistant prostate cancer samples from patients with obesity and MSMB decreased PCA cells proliferation. These results indicate that MSMB is essential for PCA development in people with obesity and can be a biomarker for predicting PCA occurrence and progression in obese people.

Duchenne muscular dystrophy: pathogenesis and promising therapies.

Duchenne muscular dystrophy (DMD) is a severe, progressive, muscle-wasting disease, characterized by progressive deterioration of skeletal muscle that causes rapid loss of mobility. The failure in respiratory and cardiac muscles is the underlying cause of premature death in most patients with DMD. Mutations in the gene encoding dystrophin result in dystrophin deficiency, which is the underlying pathogenesis of DMD. Dystrophin-deficient myocytes are dysfunctional and vulnerable to injury, triggering a series of subsequent pathological changes. In this review, we detail the molecular mechanism of DMD, dystrophin deficiency-induced muscle cell damage (oxidative stress injury, dysregulated calcium homeostasis, and sarcolemma instability) and other cell damage and dysfunction (neuromuscular junction impairment and abnormal differentiation of muscle satellite). We also describe aberrant function of other cells and impaired muscle regeneration due to deterioration of the muscle microenvironment, and dystrophin deficiency-induced multiple organ dysfunction, while summarizing the recent advances in the treatment of DMD.

Research advances in endometriosis-related signaling pathways: A review.

Endometriosis (EM) is characterized by the existence of endometrial mucosa outside the uterine cavity, which causesinfertility, persistent aches, and a decline in women's quality of life. Both hormone therapies and nonhormone therapies, such as NSAIDs, are ineffective, generic categories of EM drugs. Endometriosis is a benign gynecological condition, yet it shares a number of features with cancer cells, including immune evasion, survival, adhesion, invasion, and angiogenesis. Several endometriosis-related signaling pathways are comprehensively reviewed in this article, including E2, NF-κB, MAPK, ERK, PI3K/Akt/mTOR, YAP, Wnt/ß-catenin, Rho/ROCK, TGF-ß, VEGF, NO, iron, cytokines and chemokines. To find and develop novel medications for the treatment of EM, it is essential to implicitly determine the molecular pathways that are disordered during EM development. Additionally, research on the shared pathways between EM and tumors can provide hypotheses or suggestions for endometriosis therapeutic targets.

Comparative effectiveness of various physical exercise interventions on executive functions and related symptoms in children and adolescents with attention deficit hyperactivity disorder: A systematic review and network meta-analysis.

Background: Physical exercise has been recommended as an important nonpharmacological therapeutic strategy for managing attention deficit hyperactivity disorder (ADHD). We conducted a network meta-analysis (NMA) to assess the comparative impact of different physical exercise modalities on enhancing executive functions (EFs) and alleviating symptoms in children and adolescents with ADHD. Methods: We searched Web of Science, PubMed, Embase, Cochrane Central Register of Controlled Trials, SPORTDiscus, PsycINFO, CNKI, and clinical trials databases from inception to October 20, 2022. Randomized controlled trials (RCTs) and quasi-experimental studies investigating physical exercise for ADHD-related symptoms of hyperactivity/impulsivity and inattention, and executive functions were included. The frequentist random-effect NMA method was applied to pool the results. Results: A total of 59 studies (including 39 RCTs, 5 quasi-RCTs, and 15 self-controlled trials) published between 1983 and 2022 were incorporated into the systematic review, of which 44 studies with 1757 participants were eligible for meta-analysis. All types of physical exercise were effective in improving EFs (SMD = 1.15, 95% CI: 0.83 to 1.46), and open-skill activities which require participants to react in a dynamically changing and externally paced environment induced the most incredible benefits for executive functions (SUCRA = 98.0%, SMD = 1.96, and 95% CI: 1.15 to 2.77). Subgroup analyses for EFs revealed varied findings that open-skill activities were the most promising physical exercise type for improving inhibitory control (SUCRA = 99.1%, SMD = 1.94, and 95% CI: 1.24 to 2.64), and closed-skill activities dominated by aerobic exercises had a slightly higher probability of being the most promising physical exercise intervention for working memory (SUCRA = 75.9%, SMD = 1.21, and 95% CI: -0.22 to 2.65), and multicomponent physical exercise tended to be the most effective in cognitive flexibility (SUCRA = 70.3%, SMD = 1.44, and 95% CI: -0.19 to 3.07). Regarding ADHD-related symptoms, closed-skill activities dominated by aerobic exercises might be more advantageous for hyperactivity/impulsivity (SUCRA = 72.5%, SMD = -1.60, and 95% CI: -3.02 to -0.19) and inattention (SUCRA = 96.3%, SMD = -1.51, and 95% CI: -2.33 to -0.69) improvement. Conclusion: Physical exercise can significantly help to alleviate the symptoms of ADHD and improve executive functions in children and adolescents with ADHD. Most of all, to promote adherence to treatment, they should be encouraged to perform the physical exercises that they enjoy most.

Deep Reinforcement Learning-Based Intelligent Security Forwarding Strategy for VANET.

The vehicular ad hoc network (VANET) constitutes a key technology for realizing intelligent transportation services. However, VANET is characterized by diverse message types, complex security attributes of communication nodes, and rapid network topology changes. In this case, how to ensure safe, efficient, convenient, and comfortable message services for users has become a challenge that should not be ignored. To improve the flexibility of routing matching multiple message types in VANET, this paper proposes a secure intelligent message forwarding strategy based on deep reinforcement learning (DRL). The key supporting elements of the model in the strategy are reasonably designed in combination with the scenario, and sufficient training of the model is carried out by deep Q networks (DQN). In the strategy, the state space is composed of the distance between candidate and destination nodes, the security attribute of candidate nodes and the type of message to be sent. The node can adaptively select the routing scheme according to the complex state space. Simulation and analysis show that the proposed strategy has the advantages of fast convergence, well generalization ability, high transmission security, and low network delay. The strategy has flexible and rich service patterns and provides flexible security for VANET message services.