miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

A feature enhanced EEG compression model using asymmetric encoding-decoding network.

Objective.Recently, the demand for wearable devices using electroencephalography (EEG) has increased rapidly in many fields. Due to its volume and computation constraints, wearable devices usually compress and transmit EEG to external devices for analysis. However, current EEG compression algorithms are not tailor-made for wearable devices with limited computing and storage. Firstly, the huge amount of parameters makes it difficult to apply in wearable devices; secondly, it is tricky to learn EEG signals' distribution law due to the low signal-to-noise ratio, which leads to excessive reconstruction error and suboptimal compression performance.Approach.Here, a feature enhanced asymmetric encoding-decoding network is proposed. EEG is encoded with a lightweight model, and subsequently decoded with a multi-level feature fusion network by extracting the encoded features deeply and reconstructing the signal through a two-branch structure.Main results.On public EEG datasets, motor imagery and event-related potentials, experimental results show that the proposed method has achieved the state of the art compression performance. In addition, the neural representation analysis and the classification performance of the reconstructed EEG signals also show that our method tends to retain more task-related information as the compression ratio increases and retains reliable discriminative information after EEG compression.Significance.This paper tailors an asymmetric EEG compression method for wearable devices that achieves state-of-the-art compression performance in a lightweight manner, paving the way for the application of EEG-based wearable devices.

Empowering Caregivers of Children with Bronchiolitis Obliterans: The Effectiveness of an Internet-based Follow-up Platform.

OBJECTIVE: Limited evidence on home care and need for long-term individualized follow-up highlight the importance of developing an Internet-based follow-up platform to support caregivers of children with Bronchiolitis obliterans (BO). This Study aims to explore and test the potential benefits of this platform by comparing family management,medication compliance and clinical systems. STUDY DESIGN AND METHODS: A two-arm, single-blind randomized controlled trial was conducted on 168 children with BO and their families from January 2022 to October 2022. Families were randomly divided into Internet-based follow-up group and conventional follow-up group with a ratio of 1:1. Scores of family management measures (FaMM), 8-item of Morisky Medication Adherence (8-MMAS) and BO clinical symptoms of both groups were collected at three points of time: the day of discharge(T1), 3 months after discharge (T2), and 6 months after discharge (T3). The changes of each group due to intervention were compared by repeated-measures ANOVA. RESULTS: 90 families completed the trial, including 48 in the Internet-based follow-up group and 42 in the conventional follow-up group. The results showed a significant difference in the group-by-time interaction on the scores of Child's Daily Life, Condition Management Ability and Parental Mutuality (p<0.05). No group-by-time effect was found on the scores of View of Condition Impact and Family Life Difficulty. Scores of BO clinical symptoms and MMAS-8 showed intragroup, intergroup, and group-by-time effects. CONCLUSIONS: the Internet-based follow-up platform can empower caregivers in enhancing effective family management, improving medication compliance in children with BO, and relieving patients' clinical symptoms. TRIAL REGISTRATION: Chinese Clinical Trials Registry of ChiCTR2200065121 (04/28/2022).

Engineering miniature CRISPR-Cas Un1Cas12f1 for efficient base editing.

Adeno-associated virus (AAV) is a relatively safe and efficient vector for gene therapy. However, due to its 4.7-kb limit of cargo, SpCas9-mediated base editors cannot be packaged into a single AAV vector, which hinders their clinical application. The development of efficient miniature base editors becomes an urgent need. Un1Cas12f1 is a class II V-F-type CRISPR-Cas protein with only 529 amino acids. Although Un1Cas12f1 has been engineered to be a base editor in mammalian cells, the base-editing efficiency is less than 10%, which limits its therapeutic applications. Here, we developed hypercompact and high-efficiency base editors by engineering Un1Cas12f1, fusing non-specific DNA binding protein Sso7d, and truncating single guide RNA (sgRNA), termed STUminiBEs. We demonstrated robust A-to-G conversion (54% on average) by STUminiABEs or C-to-T conversion (45% on average) by STUminiCBEs. We packaged STUminiCBEs into AAVs and successfully introduced a premature stop codon on the PCSK9 gene in mammalian cells. In sum, STUminiBEs are efficient miniature base editors and could readily be packaged into AAVs for biological research or biomedical applications.

Organophotoelectrocatalytic C(sp2)-H alkylation of heteroarenes with unactivated C(sp3)-H compounds.

An organophotoelectrocatalytic method for the C(sp2)-H alkylation of heteroarenes with unactivated C(sp3)-H compounds through dehydrogenation cross-coupling has been developed. The C(sp2)-H alkylation combines organic catalysis, photochemistry and electrochemistry, avoiding the need for external metal-reagents, HAT-reagents, and oxidants. This protocol exhibits good substrate tolerance and functional group compatibility, providing a straightforward and powerful pathway to access a variety of alkylated heteroarenes under green conditions.

HydrogelFinder: A Foundation Model for Efficient Self-Assembling Peptide Discovery Guided by Non-Peptidal Small Molecules.

Self-assembling peptides have numerous applications in medicine, food chemistry, and nanotechnology. However, their discovery has traditionally been serendipitous rather than driven by rational design. Here, HydrogelFinder, a foundation model is developed for the rational design of self-assembling peptides from scratch. This model explores the self-assembly properties by molecular structure, leveraging 1,377 self-assembling non-peptidal small molecules to navigate chemical space and improve structural diversity. Utilizing HydrogelFinder, 111 peptide candidates are generated and synthesized 17 peptides, subsequently experimentally validating the self-assembly and biophysical characteristics of nine peptides ranging from 1-10 amino acids-all achieved within a 19-day workflow. Notably, the two de novo-designed self-assembling peptides demonstrated low cytotoxicity and biocompatibility, as confirmed by live/dead assays. This work highlights the capacity of HydrogelFinder to diversify the design of self-assembling peptides through non-peptidal small molecules, offering a powerful toolkit and paradigm for future peptide discovery endeavors.

The roles of adenosine signaling in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiple etiological factors. Immune disorder contributes to SLE development and is an important clinical manifestation of SLE patients. Immune dysfunction is characterized by abnormal of B cells, T cells, monocyte-macrophages and dendritic cells (DCs), in both quantity and quality. Adenosine is a critical factor for human immune homeostasis, which acts as an immunosuppressive signal and can prevent the hyperactivity of human immune system. Adenosine levels are significant decreased in serum from SLE patients. Adenosine level is regulated by the CD39, CD73 and adenosine deaminase (ADA). CD39/CD73/ADA catalyzed the cascade enzymatic reaction, which contained the adenosine generation and degradation. Adenosine affects the function of various immune cells via bind to the adenosine receptors, which are expressed on the cell surface. This review aims to export the changes of immune cells and adenosine signal pathway in SLE, as well as the effect of adenosine signal pathway in SLE development.

How is work-family conflict linked to nurse-assessed patient safety among intensive care unit nurses? A serial multiple mediation analysis.

AIM: The aim of this study was to test whether rumination and negative affectivity mediate the relationship between work-family conflict and nurse-assessed patient safety among intensive care unit nurses. BACKGROUND: Most intensive care unit nurses experience work-family conflicts that jeopardise patient safety. Although prior studies have explored the effect of work-family conflict on patient safety, few have investigated whether work-family conflict is associated with patient safety through rumination and negative affectivity among intensive care unit nurses. DESIGN: Cross-sectional study. METHODS: This study included 209 intensive care unit nurses from five general hospitals. The Work-Family Conflict Scale, the Ruminative Response Scale, the Positive and Negative Affect Schedule-Negative Affectivity, and three items indicating nurses' perception of overall patient safety were used to gather data. Associations between work-family conflict, rumination, negative affectivity, and nurse-assessed patient safety were assessed using correlation and serial multiple mediation analysis. RESULTS: Work-family conflict, rumination, negative affectivity, and nurse-assessed patient safety were significantly correlated (p < 0.01). Work-family conflict can have not only a direct negative impact on the nurse-assessed patient safety (effect = -0.0234; standard error [SE] = 0.0116; 95% confidence interval [CI]: lower limit [LL] = -0.0464, upper limit [UL] = -0.0005) but also an indirect impact on nurse-assessed patient safety through three paths: the independent mediating role of rumination (effect = -0.0118; SE = 0.0063; 95% CI: LL = -0.0251, UL = -0.0006), the independent mediating role of negative affectivity (effect = -0.0055; SE = 0.0039; 95% CI: LL = -0.0153, UL = -0.0001), and the chain-mediating role of rumination and negative affectivity (effect = -0.0078; SE = 0.0031; 95% CI: LL = -0.0152, UL = -0.0027). CONCLUSION: Our findings indicated that work-family conflict could influence nurse-assessed patient safety through increasing rumination and negative affectivity among intensive care unit nurses. Based on the results, interventions aimed at decreasing work-family conflict would be beneficial for intensive care unit nurses' emotional stability and patient safety.

Progress on Copper-Based Anode Materials for Sodium-Ion Batteries.

Fossil fuels have clearly failed to meet people's growing energy needs due to their limited reserves, potential pollution of the environment, and high costs. The development of cleaner, renewable energy sources as well as secondary batteries for energy storage is imminent, in a modern society where energy demand is soaring. Sodium-ion batteries (SIBs) have become the focus of large-scale energy storage systems as a promising alternative to lithium-ion batteries. The development of SIBs relies on the construction of high performance electrode materials. The design of low cost and high performance anode materials is a key link in this regard. Copper-based anodes are characterised by high theoretical capacity, abundant reserves, low cost and environmental friendliness. A variety of copper-based anode materials, which include cobalt oxides, sulfides, selenides and phosphides, have been synthesised and evaluated in the scientific literature for sodium storage. In detail, the preparation methods, response mechanisms, strengths and weaknesses, the relationship between morphology structure and electrochemical performance are discussed, as well as highlighting strategies to improve the  electrochemical performance of copper-based anode materials. Finally, we offer our perspective on the challenges and potential for the development of copper-based anodes as a means of developing practical and high performing SIBs.

Promotive effect of skin precursor-derived Schwann cells on brachial plexus neurotomy and motor neuron damage repair through milieu-regulating secretome.

Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP-SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.

Automated individual cortical parcellation via consensus graph representation learning.

Cortical parcellation plays a pivotal role in elucidating the brain organization. Despite the growing efforts to develop parcellation algorithms using functional magnetic resonance imaging, achieving a balance between intra-individual specificity and inter-individual consistency proves challenging, making the generation of high-quality, subject-consistent cortical parcellations particularly elusive. To solve this problem, our paper proposes a fully automated individual cortical parcellation method based on consensus graph representation learning. The method integrates spectral embedding with low-rank tensor learning into a unified optimization model, which uses group-common connectivity patterns captured by low-rank tensor learning to optimize subjects' functional networks. This not only ensures consistency in brain representations across different subjects but also enhances the quality of each subject's representation matrix by eliminating spurious connections. More importantly, it achieves an adaptive balance between intra-individual specificity and inter-individual consistency during this process. Experiments conducted on a test-retest dataset from the Human Connectome Project (HCP) demonstrate that our method outperforms existing methods in terms of reproducibility, functional homogeneity, and alignment with task activation. Extensive network-based comparisons on the HCP S900 dataset reveal that the functional network derived from our cortical parcellation method exhibits greater capabilities in gender identification and behavior prediction than other approaches.

Traditional Chinese medicine improved diabetic kidney disease through targeting gut microbiota.

CONTEXT: Diabetic kidney disease (DKD) affects nearly 40% of diabetic patients, often leading to end-stage renal disease that requires renal replacement therapies, such as dialysis and transplantation. The gut microbiota, an integral aspect of human evolution, plays a crucial role in this condition. Traditional Chinese medicine (TCM) has shown promising outcomes in ameliorating DKD by addressing the gut microbiota. OBJECTIVE: This review elucidates the modifications in gut microbiota observed in DKD and explores the impact of TCM interventions on correcting microbial dysregulation. METHODS: We searched relevant articles from databases including Web of Science, PubMed, ScienceDirect, Wiley, and Springer Nature. The following keywords were used: diabetic kidney disease, diabetic nephropathy, gut microbiota, natural product, TCM, Chinese herbal medicine, and Chinese medicinal herbs. Rigorous criteria were applied to identify high-quality studies on TCM interventions against DKD. RESULTS: Dysregulation of the gut microbiota, including Lactobacillus, Streptococcus, and Clostridium, has been observed in individuals with DKD. Key indicators of microbial dysregulation include increased uremic solutes and decreased short-chain fatty acids. Various TCM therapies, such as formulas, tablets, granules, capsules, and decoctions, exhibit unique advantages in regulating the disordered microbiota to treat DKD. CONCLUSION: This review highlights the importance of targeting the gut-kidney axis to regulate microbial disorders, their metabolites, and associated signaling pathways in DKD. The Qing-Re-Xiao-Zheng formula, the Shenyan Kangfu tablet, the Huangkui capsule, and the Bekhogainsam decoction are potential candidates to address the gut-kidney axis. TCM interventions offer a significant therapeutic approach by targeting microbial dysregulation in patients with DKD.

[Pollution Characteristics and Source Analysis of Soil Heavy Metal in Coal Mine Area near the Yellow River in Shandong].

To explore the pollution characteristics and source of soil heavy metal in a coal mine area near the Yellow River in Shandong, the geo-accumulation index method and improved Nemerow pollution index method were used to evaluate the pollution characteristics of soil heavy metal. The absolute principal component-multiple linear regression model (APCS-MLR) was used to quantitatively analyze the source of soil heavy metal, and the spatial distribution of Hg and Cd were analyzed using the Kriging spatial difference method in ArcGIS. The result accuracy of the APCS-MLR model was further verified. The results showed that:The measured contents of soil heavy metal Cu, Zn, Pb, Cr, Cd, Ni, As, and Hg all exceeded the normal site, among which, Hg and Cd exceeded the background values of soil elements in Shandong. The coefficient of variation (CV) of Hg was higher than 0.500, indicating significant spatial heterogeneity. Moreover, the correlation between Hg and other heavy metals was generally low, and the possibility of the same pollution source was small. The results of the geo-accumulation index and improved Nemerow pollution index showed that the overall soil heavy metal pollution was at a moderate level, among which the Hg pollution level was the highest, and its maximum value was at a slanted-heavy pollution level; Cu, Cd, and As in soil caused local pollution, which were at a slanted-light pollution level. Soil heavy metal pollution was closely related to mining activities, rehabilitation, and engineering construction in the coal mine area. The two major pollution sources of soil heavy metal in the research area were the compound source of the parent material and industrial and mining transportation sources (known source 1) and the compound source of atmospheric sedimentation and coal production (known source 2), the contribution rates of which were 76.705% and 16.171%, respectively. The results of the APCS-MLR model were shown to be reliable by analyzing the content distribution of Hg and Cd using the Kriging space difference mode. This research can provide scientific basis for the precise control and improvement of soil heavy metal pollution, ensuring the safety of food and agricultural products and improving the quality of the ecological environment in the coal mine area in the Shandong section of the Yellow River Basin.

Phytochemical analysis and anticancer effect of Camellia oleifera bud ethanol extract in non-small cell lung cancer A549 cells.

Camellia oleifera is a medicine food homology plant widely cultivated in the Yangtze River Basin and southern China due to its camellia oil. Camellia oleifera bud and fruit exist simultaneously, and its bud is largely discarded as waste. However, C. oleifera bud has been used in traditional Chinese medicine to treat a variety of ailments. Thus, the purpose of this study was to identify the chemical components of C. oleifera bud ethanol extract (EE) and first evaluate its anticancer effects in non-small cell lung cancer A549 cells. Based on UHPLC-Q-Orbitrap-MS analysis, seventy components were identified. For anticancer activity, C. oleifera bud EE had remarkable cytotoxic effect on non-small cell lung cancer A549 (IC50: 57.53 ± 1.54 µg/mL) and NCI-H1299 (IC50: 131.67 ± 4.32 µg/mL) cells, while showed lower cytotoxicity on non-cancerous MRC-5 (IC50 > 320 µg/mL) and L929 (IC50: 179.84 ± 1.08 µg/mL) cells. It dramatically inhibited the proliferation of A549 cells by inducing cell cycle arrest at the G1 phase. Additionally, it induced apoptosis in A549 cells through a mitochondria-mediated pathway, which decreased mitochondrial membrane potential, upregulated Bax, activated caspase 9 and caspase 3, and resulted in PARP cleavage. Wound healing and transwell invasion assays demonstrated that C. oleifera bud EE inhibited the migration and invasion of A549 cells in a dose-dependent manner. The above findings indicated that C. oleifera bud EE revealed notable anticancer effects by inhibiting proliferation, inducing apoptosis, and suppressing migration and invasion of A549 cells. Hence, C. oleifera bud ethanol extract could serve as a new source of natural anticancer drugs.

Washed microbiota transplantation for Crohn's disease: A metagenomic, metatranscriptomic, and metabolomic-based study.

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported. AIM: To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT. METHODS: We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure. RESULTS: Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT. CONCLUSION: WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

Identification of Escherichia coli multidrug resistance transporters involved in anthocyanin biosynthesis.

The anthocyanin compound cyanidin 3-O-glucoside (C3G) is a natural pigment widely used in food and nutraceutical industries. Its microbial synthesis by E. coli is a promising alternative to the traditional extraction methods. However, part of the synthesized C3G accumulates in the cytoplasm, thus potentially causing growth inhibition and product degradation. Therefore, it is necessary to enhance C3G secretion via exploration of native transporters facilitating C3G export. In this study, we report the screening and verification of native multidrug resistance transporters from 40 candidates in E. coli that can improve the extracellular C3G production when using catechin as the substrate. Overexpression of single transporter genes including fsr, yebQ, ynfM, mdlAB, and emrKY were found to increase C3G production by 0.5- to 4.8-fold. Genetic studies indicated that mdlAB and emrKY are vital transporters in the secretion of C3G. Our study reveals a set of new multidrug resistance transporters for the improvement of microbial biosynthesis of C3G and other anthocyanins.

Exploring the Structural Plasticity Mechanism of Corticospinal Tract during Stroke Rehabilitation Based Automated Fiber Quantification Tractography.

BACKGROUND: Corticospinal tract (CST) is the principal motor pathway; we aim to explore the structural plasticity mechanism in CST during stroke rehabilitation. METHODS: A total of 25 patients underwent diffusion tensor imaging before rehabilitation (T1), 1-month post-rehabilitation (T2), 2 months post-rehabilitation (T3), and 1-year post-discharge (T4). The CST was segmented, and fractional anisotropy (FA), axial diffusion (AD), mean diffusivity (MD), and radial diffusivity (RD) were determined using automated fiber quantification tractography. Baseline level of laterality index (LI) and motor function for correlation analysis. RESULTS: The FA values of all segments in the ipsilesional CST (IL-CST) were lower compared with normal CST. Repeated measures analysis of variance showed time-related effects on FA, AD, and MD of the IL-CST, and there were similar dynamic trends in these 3 parameters. At T1, FA, AD, and MD values of the mid-upper segments of IL-CST (around the core lesions) were the lowest; at T2 and T3, values for the mid-lower segments were lower than those at T1, while the values for the mid-upper segments gradually increased; at T4, the values for almost entire IL-CST were higher than before. The highest LI was observed at T2, with a predominance in contralesional CST. The LIs for the FA and AD at T1 were positively correlated with the change rate of motor function. CONCLUSIONS: IL-CST showed aggravation followed by improvement from around the lesion to the distal end. Balance of interhemispheric CST may be closely related to motor function, and LIs for FA and AD may have predictive value for mild-to-moderate stroke rehabilitation. Clinical Trial Registration. URL: http://www.chictr.org.cn; Unique Identifier: ChiCTR1800019474.

The role of the cytochrome P450 superfamily in the skin.

In mammals, the skin acts as a barrier to prevent harmful environmental stimuli from entering the circulation. CYP450s are involved in drug biotransformation, exogenous and endogenous substrate metabolism, and maintaining the normal physiological function of the skin, as well as facilitating homeostasis of the internal environment. The expression pattern of CYP450s in the skin is tissue-specific and thus differs from the liver and other organs. The development of skin topical medications, and knowledge of the toxicity and side effects of these medications require a detailed understanding of the expression and function of skin-specific CYP450s. Thus, we summarized the expression of CYP450s in the skin, their function in endogenous metabolic physiology, aberrant CYP450 expression in skin diseases and the influence of environmental variables and medications. This information will serve as a crucial foundation for future studies on the skin, as well as for the design and development of new drugs for skin diseases including topical medications.

Prevalence and Clustering of Cardiovascular Disease Risk Factors among Adults Along the Lancang-Mekong River: A Cross-Sectional Study from Low- and Middle-Income Countries.

Background: Progress in cardiovascular health is increasingly concentrated in high-income countries, while the burden of cardiovascular disease (CVD) is high in low- and middle-income countries, a clear health inequity that must be urgently addressed. Objective: This study aims to evaluate the prevalence and clustering of CVD risk factors in the three Lancang-Mekong regions. Methods: We conducted a population-based cross-sectional survey from January 2021 to March 2023 in China, Laos, and Cambodia. We compared the prevalence and clustering of CVD risk factors-including hypertension, dyslipidemia, diabetes mellitus, overweight/obesity, current smoking status, current drinking status, inadequate vegetable and fruit intake, and insufficient physical activity-across the three regions, further stratifying the data by gender and age. Multivariate logistic regression models were performed to explore factors influencing the aggregation of CVD risk factors (≥2, ≥3, ≥4). Results: A total of 11,005 adults were included in the study. Hypertension emerged as the primary metabolic risk factor in Laos (36.8%) and Cambodia (23.5%), whereas overweight/obesity was the primary risk factor in China (37.6%). In terms of behavioral risk factors, participants in all three regions showed insufficient vegetable and fruit intake. The prevalence of individuals without CVD risk factors was 10% in China, 1.9% in Laos, and 5.2% in Cambodia. Meanwhile, the prevalence of two or more risk factors was 64.6% in China, 79.2% in Laos, and 76.0% in Cambodia. Multivariate logistic regression models revealed that the propensity for CVD risk factors clustering was higher in men and increased with age in all three countries. Conclusions: CVD risk factors and multiple clustering are pressing health threats among adults in low- and middle-income areas along the Lancang-Mekong River Basin. This study highlights the urgent need for proactive tailored strategies to control CVD risk factors.

Anti-aging effect of glycerophosphocholine in Steinernema kraussei 0657L.

Glycerophosphocholine (GPC) is a water-soluble small molecule found naturally in humans and foods such as milk and soybeans. It can activate the IIS pathway by regulating the expression of daf-2, ins-18 and daf-16 genes, sek-1 and skn-1 genes of MAPK pathway, sod-3, ctl-1, gst-4 and other antioxidant genes. GPC can relieve symptoms related to aging in organisms. The aim of this study was to probe the effects of GPC on the longevity and stress resistance of the entomopathogenic nematode (EPN) Steinernema kraussei 0657L strain. The results showed that the lifespan of S. kraussei 0657L was significantly prolonged by 50 mM GPC treatment, which was 54.55% longer than that of the control (0 mM GPC). GPC significantly inhibited reactive oxygen species (ROS) and lipofuscin accumulation, but the body size and fecundity of S. kraussei 0657L had little changed. At the same time, the longevity of S. kraussei 0657L exposed to heat shock and UV-B radiation was significantly prolonged than that with no external stress. GPC supplementation increased the activity of antioxidant enzymes and corresponding gene expression. Under treatment with 50 mM GPC, the activities of superoxide dismutase and catalase were increased by 1.90- and 4.13-fold, respectively, the expression of the sod-3 and ctl-1 genes was increased by 3.60- and 0.60-fold, respectively, and harmful reactive oxygen species were removed. In addition, the expression levels of the ins-18, skn-1, sek-1 and gst-4 genes related to the insulin/IGF-1 signaling pathway were upregulated 1.04-, 1.84-, 2.21- and 1.24-fold, respectively. These results indicate that GPC is mainly involved in the lifespan regulation of S. kraussei 0657L and plays an important role in resistance to external stress by activating the insulin/IGF-1 signaling pathway and downstream PI3K/MAPK kinase, creating a new idea for improving the commercial efficacy of S. kraussei. It also laid a theoretical foundation for its further efficient development and utilization in the field of biological control.