SCTC: inference of developmental potential from single-cell transcriptional complexity.

Inferring the developmental potential of single cells from scRNA-Seq data and reconstructing the pseudo-temporal path of cell development are fundamental but challenging tasks in single-cell analysis. Although single-cell transcriptional diversity (SCTD) measured by the number of expressed genes per cell has been widely used as a hallmark of developmental potential, it may lead to incorrect estimation of differentiation states in some cases where gene expression does not decrease monotonously during the development process. In this study, we propose a novel metric called single-cell transcriptional complexity (SCTC), which draws on insights from the economic complexity theory and takes into account the sophisticated structure information of scRNA-Seq count matrix. We show that SCTC characterizes developmental potential more accurately than SCTD, especially in the early stages of development where cells typically have lower diversity but higher complexity than those in the later stages. Based on the SCTC, we provide an unsupervised method for accurate, robust, and transferable inference of single-cell pseudotime. Our findings suggest that the complexity emerging from the interplay between cells and genes determines the developmental potential, providing new insights into the understanding of biological development from the perspective of complexity theory.

Recognition of histone acetylation by the GAS41 YEATS domain promotes H2A.Z deposition in non-small cell lung cancer.

Histone acetylation is associated with active transcription in eukaryotic cells. It helps to open up the chromatin by neutralizing the positive charge of histone lysine residues and providing binding platforms for "reader" proteins. The bromodomain (BRD) has long been thought to be the sole protein module that recognizes acetylated histones. Recently, we identified the YEATS domain of AF9 (ALL1 fused gene from chromosome 9) as a novel acetyl-lysine-binding module and showed that the ENL (eleven-nineteen leukemia) YEATS domain is an essential acetyl-histone reader in acute myeloid leukemias. The human genome encodes four YEATS domain proteins, including GAS41, a component of chromatin remodelers responsible for H2A.Z deposition onto chromatin; however, the importance of the GAS41 YEATS domain in human cancer remains largely unknown. Here we report that GAS41 is frequently amplified in human non-small cell lung cancer (NSCLC) and is required for cancer cell proliferation, survival, and transformation. Biochemical and crystal structural studies demonstrate that GAS41 binds to histone H3 acetylated on H3K27 and H3K14, a specificity that is distinct from that of AF9 or ENL. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by high-throughput sequencing) analyses in lung cancer cells reveal that GAS41 colocalizes with H3K27ac and H3K14ac on the promoters of actively transcribed genes. Depletion of GAS41 or disruption of the interaction between its YEATS domain and acetylated histones impairs the association of histone variant H2A.Z with chromatin and consequently suppresses cancer cell growth and survival both in vitro and in vivo. Overall, our study identifies GAS41 as a histone acetylation reader that promotes histone H2A.Z deposition in NSCLC.

Immunosuppressive microvesicles-mimetic derived from tolerant dendritic cells to target T-lymphocytes for inflammation diseases therapy.

The utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis.

Clinical application of repetitive transcranial magnetic stimulation in improving functional impairments post-stroke: review of the current evidence and potential challenges.

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.

Effectiveness and feasibility of 5G-based remote interactive ultrasound training in critical care.

BACKGROUND: Ultrasound has widely used in various medical fields related to critical care. While online and offline ultrasound trainings are faced by certain challenges, remote ultrasound based on the 5G cloud platform has been gradually adopted in many clinics. However, no study has used the 5G remote ultrasound cloud platform operating system for standardized critical care ultrasound training. This study aimed to evaluate the feasibility and effectiveness of 5G-based remote interactive ultrasound training for standardized diagnosis and treatment in critical care settings. METHODS: A 5G-based remote interactive ultrasound training system was constructed, and the course was piloted among critical care physicians. From July 2022 to July 2023, 90 critical care physicians from multiple off-site locations were enrolled and randomly divided into experimental and control groups. The 45 physicians in the experimental group were trained using the 5G-based remote interactive ultrasound training system, while the other 45 in the control group were taught using theoretical online videos. The theoretical and practical ultrasonic capabilities of both groups were evaluated before and after the training sessions, and their levels of satisfaction with the training were assessed as well. RESULTS: The total assessment scores for all of the physicians were markedly higher following the training (80.7 ± 11.9) compared to before (42.1 ± 13.4) by a statistically significant margin (P < 0.001). Before participating in the training, the experimental group scored 42.2 ± 12.5 in the critical care ultrasound competency, and the control group scored 41.9 ± 14.3-indicating no significant differences in their assessment scores (P = 0.907). After participating in the training, the experimental group's assessment scores were 88.4 ± 6.7, which were significantly higher than those of the control group (72.9 ± 10.8; P < 0.001). The satisfaction score of the experimental group was 42.6 ± 2.3, which was also significantly higher than that of the control group (34.7 ± 3.1, P < 0.001). CONCLUSION: The 5G-based remote interactive ultrasound training system was well-received and effective for critical care. These findings warrant its further promotion and application.

Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

OBJECTIVES: To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV). DESIGN: A multicenter, single-blind, randomized, noninferiority trial. SETTING: Twenty-one centers across China from December 2020 to June 2021. PATIENTS: A total of 135 ICU patients 18 to 80 years old with endotracheal intubation and undergoing MV, who were expected to require sedation for 6-24 hours. INTERVENTIONS: One hundred thirty-five ICU patients were randomly allocated into ciprofol ( n = 90) and propofol ( n = 45) groups in a 2:1 ratio. Ciprofol or propofol were IV infused at loading doses of 0.1 mg/kg or 0.5 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Ciprofol or propofol were then immediately administered at an initial maintenance dose of 0.3 mg/kg/hr or 1.5 mg/kg/hr, to achieve the target sedation range of Richmond Agitation-Sedation Scale (+1 to -2). Besides, continuous IV remifentanil analgesia was administered (loading dose: 0.5-1 µg/kg, maintenance dose: 0.02-0.15 µg/kg/min). MEASUREMENTS AND MAIN RESULTS: Of the 135 patients enrolled, 129 completed the study. The primary endpoint-sedation success rates of ciprofol and propofol groups were 97.7% versus 97.8% in the full analysis set (FAS) and were both 100% in per-protocol set (PPS). The noninferiority margin was set as 8% and confirmed with a lower limit of two-sided 95% CI for the inter-group difference of -5.98% and -4.32% in the FAS and PPS groups. Patients who received ciprofol had a longer recovery time ( p = 0.003), but there were no differences in the remaining secondary endpoints (all p > 0.05). The occurrence rates of treatment-emergent adverse events (TEAEs) or drug-related TEAEs were not significantly different between the groups (all p > 0.05). CONCLUSIONS: Ciprofol was well tolerated, with a noninferior sedation profile to propofol in Chinese ICU patients undergoing MV for a period of 6-24 hours.

ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia.

Cancer cells are characterized by aberrant epigenetic landscapes and often exploit chromatin machinery to activate oncogenic gene expression programs. Recognition of modified histones by 'reader' proteins constitutes a key mechanism underlying these processes; therefore, targeting such pathways holds clinical promise, as exemplified by the development of bromodomain and extra-terminal (BET) inhibitors. We recently identified the YEATS domain as an acetyl-lysine-binding module, but its functional importance in human cancer remains unknown. Here we show that the YEATS domain-containing protein ENL, but not its paralogue AF9, is required for disease maintenance in acute myeloid leukaemia. CRISPR-Cas9-mediated depletion of ENL led to anti-leukaemic effects, including increased terminal myeloid differentiation and suppression of leukaemia growth in vitro and in vivo. Biochemical and crystal structural studies and chromatin-immunoprecipitation followed by sequencing analyses revealed that ENL binds to acetylated histone H3, and co-localizes with H3K27ac and H3K9ac on the promoters of actively transcribed genes that are essential for leukaemia. Disrupting the interaction between the YEATS domain and histone acetylation via structure-based mutagenesis reduced the recruitment of RNA polymerase II to ENL-target genes, leading to the suppression of oncogenic gene expression programs. Notably, disrupting the functionality of ENL further sensitized leukaemia cells to BET inhibitors. Together, our data identify ENL as a histone acetylation reader that regulates oncogenic transcriptional programs in acute myeloid leukaemia, and suggest that displacement of ENL from chromatin may be a promising epigenetic therapy, alone or in combination with BET inhibitors, for aggressive leukaemia.

[Research progress of Angelicae Sinensis Radix and predictive analysis on its quality markers].

Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.

Newly identified proviruses in Thermotogota suggest that viruses are the vehicles on the highways of interphylum gene sharing.

Phylogenomic analyses of bacteria from the phylum Thermotogota have shown extensive lateral gene transfer with distantly related organisms, particularly with Firmicutes. One likely mechanism of such DNA transfer is viruses. However, to date, only three temperate viruses have been characterized in this phylum, all infecting bacteria from the Marinitoga genus. Here we report 17 proviruses integrated into genomes of bacteria belonging to eight Thermotogota genera and induce viral particle production from one of the proviruses. All except an incomplete provirus from Mesotoga fall into two groups based on sequence similarity, gene synteny and taxonomic classification. Proviruses of Group 1 are found in the genera Geotoga, Kosmotoga, Marinitoga, Thermosipho and Mesoaciditoga and are similar to the previously characterized Marinitoga viruses, while proviruses from Group 2 are distantly related to the Group 1 proviruses, have different genome organization and are found in Petrotoga and Defluviitoga. Genes carried by both groups are closely related to Firmicutes and Firmicutes (pro)viruses in phylogenetic analyses. Moreover, one of the groups show evidence of recent gene exchange and may be capable of infecting cells from both phyla. We hypothesize that viruses are responsible for a large portion of the observed gene flow between Firmicutes and Thermotogota.

Prediction of mechanical ventilation greater than 24 hours in critically ill obstetric patients: ten years of data from a tertiary teaching hospital in mainland China.

BACKGROUND: Maternal admission to the intensive care unit (ICU) during pregnancy or in the postpartum period is a marker of severe acute maternal morbidity. Mechanical ventilation is an important and basic method of maintaining life support in the ICU, but prolonged mechanical ventilation (PMV) is associated with a prolonged length of hospital stay and other adverse outcomes. Therefore, we conducted this retrospective study to describe morbidity and further try to identify the risk factors for PMV in critically ill obstetric women. METHODS: The clinical data were obtained from a single-centre retrospective comparative study of 143 critically ill obstetric patients at a tertiary teaching hospital in mainland China between January 1, 2009, and December 31, 2019. PMV was defined as a mechanical ventilation length of more than 24 h. Clinical and obstetric parameters were collected to analyse the risk factors for PMV. Patients were separated into groups with and without PMV. Potential risk factors were identified by univariate testing. Multivariate logistic regression was used to evaluate independent predictors of PMV. RESULTS: Out of 29,236 hospital deliveries, 265 critically ill obstetric patients entered the ICU. One hundred forty-five (54.7%) of them were treated with mechanical ventilation. Two were excluded because of death within 24 h. Sixty-five critically ill obstetric patients (45.5%) underwent PMV. The independent risk factors for PMV included estimated blood loss (odds ratio (OR) =1.296, P=0.029), acute kidney injury (AKI) (OR=4.305, P=0.013), myocardial injury (OR=4.586, P=0.012), and PaO2/FiO2 (OR=0.989, P< 0.001). The area under the receiver operating characteristic (ROC) curve based on the predicted probability of the logistic regression was 0.934. CONCLUSIONS: Estimated blood loss, AKI, myocardial injury, and PaO2/FiO2 were independent risk factors for PMV in critically ill obstetric patients.

The related mechanism of complete Freund's adjuvant-induced chronic inflammation pain based on metabolomics analysis.

Chronic inflammation pain is a debilitating disease, and its mechanism still remains poorly understood. This study attempted to illuminate the metabolic mechanism of chronic inflammation pain induced by complete Freund's adjuvant (CFA) injection, especially at spinal level. The chronic inflammation pain model was established by CFA administration. Behavioral testing including mechanical allodynia and thermal hyperalgesia was performed. Meanwhile, a liquid chromatography-mass spectrometry-based metabolomics approach was applied to analyze potential metabolic biomarkers. The orthogonal partial least squares discrimination analysis mode was employed for determining metabolic changes, and a western blot was performed to detect the protein expression change. The results showed that 27 metabolites showed obviously abnormal expression and seven metabolic pathways were significantly enriched, comprising aminoacyl-tRNA biosynthesis, arginine and proline metabolism, histidine metabolism, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glutathione metabolism, and phenylalanine metabolism. Meanwhile, the results showed that the expression of arginase I and nitric oxide levels were elevated in the CFA group compared with the control group, while the argininosuccinate synthetase and argininosuccinatelyase proteins were not significantly different between the groups. These findings demonstrate that metabolic changes of the spinal cord may be implicated in neurotransmitter release and pain conductivity following CFA administration.

Thiomicrorhabdus indica sp. nov., an obligately chemolithoautotrophic, sulfur-oxidizing bacterium isolated from a deep-sea hydrothermal vent environment.

A new mesophilic bacterium, designated strain 13-15AT, was isolated from the deep-sea water from the Carlsberg Ridge, northwestern Indian Ocean. Cells were short rods and motile with a single polar flagellum. Growth was observed in the presence of 85-1700 mM NaCl (optimum 680 mM), at 10-45 °C (optimum, 28 °C) and pH 5.0-9.0 (optimum, pH 7.0). The isolate was an obligate chemolithoautotroph capable of growth using thiosulfate, sulfide, elemental sulfur or tetrathionate as the sole energy source, carbon dioxide as the sole carbon source, and molecular oxygen as the sole electron acceptor. Molecular hydrogen did not support growth. The major fatty acids were C16 : 1 (45.0 %), C18 : 1 (22.5 %) and C16 : 0 (20.1 %). The G+C content of the genomic DNA was 41.6 mol%. The results of phylogenetic analysis based on 16S rRNA gene sequences showed that the novel isolate belonged to the genus Thiomicrorhabdus and was most closely related to Thiomicrorhabdus hydrogeniphila MAS2T (94.8 % sequence similarity). On the basis of the taxonomic data obtained in this study, strain 13-15AT represents a novel species of the genus Thiomicrorhabdus, for which the name Thiomicrorhabdus indica sp. nov. is proposed, with the type strain 13-15AT (=MCCC 1A13986T=KCTC 15750T).

A Click Chemistry Approach Reveals the Chromatin-Dependent Histone H3K36 Deacylase Nature of SIRT7.

Using an engineered pyrrolysyl-tRNA synthetase mutant together with tRNACUAPyl, we have genetically encoded Nε-(7-azidoheptanoyl)-l-lysine (AzHeK) by amber codon in Escherichia coli for recombinant expression of a number of AzHeK-containing histone H3 proteins. We assembled in vitro acyl-nucleosomes from these recombinant acyl-H3 histones. All these acyl-nucleosomes contained an azide functionality that allowed quick click labeling with a strained alkyne dye for in-gel fluorescence analysis. Using these acyl-nucleosomes as substrates and click labeling as a detection method, we systematically investigated chromatin deacylation activities of SIRT7, a class III NAD+-dependent histone deacylase with roles in aging and cancer biology. Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37. We further demonstrated that this H3K36 deacylation activity is nucleosome dependent and can be significantly enhanced when appending the acyl-nucleosome substrate with a short double-stranded DNA that mimics the bridging DNA between nucleosomes in native chromatin. By overexpressing SIRT7 in human cells, we verified that SIRT7 natively removes acetylation from histone H3K36. Moreover, SIRT7-deficient cells exhibited H3K36 hyperacetylation in whole cell extracts, at rDNA sequences in nucleoli, and at select SIRT7 target loci, demonstrating the physiologic importance of SIRT7 in determining endogenous H3K36 acetylation levels. H3K36 acetylation has been detected at active gene promoters, but little is understood about its regulation and functions. Our findings establish H3K36 as a physiologic substrate of SIRT7 and implicate this modification in potential SIRT7 pathways in heterochromatin silencing and genomic stability.

DiseaseMeth version 2.0: a major expansion and update of the human disease methylation database.

The human disease methylation database (DiseaseMeth, http://bioinfo.hrbmu.edu.cn/diseasemeth/) is an interactive database that aims to present the most complete collection and annotation of aberrant DNA methylation in human diseases, especially various cancers. Recently, the high-throughput microarray and sequencing technologies have promoted the production of methylome data that contain comprehensive knowledge of human diseases. In this DiseaseMeth update, we have increased the number of samples from 3610 to 32 701, the number of diseases from 72 to 88 and the disease-gene associations from 216 201 to 679 602. DiseaseMeth version 2.0 provides an expanded comprehensive list of disease-gene associations based on manual curation from experimental studies and computational identification from high-throughput methylome data. Besides the data expansion, we also updated the search engine and visualization tools. In particular, we enhanced the differential analysis tools, which now enable online automated identification of DNA methylation abnormalities in human disease in a case-control or disease-disease manner. To facilitate further mining of the disease methylome, three new web tools were developed for cluster analysis, functional annotation and survival analysis. DiseaseMeth version 2.0 should be a useful resource platform for further understanding the molecular mechanisms of human diseases.

Towards a multi-bioassay-based index for toxicity assessment of fluvial waters.

Despite their proven reliability for revealing 'acceptable' degrees of toxicity in waste- and reclaimed waters, bioassays are rarely used to assess the toxicity of hazardous contaminants present in natural waters. In this study, we used organisms from different trophic levels to assess the toxicity of water samples collected from four different South Korean rivers. The main objective was to develop a multi-descriptor index of toxicity for undiluted river water. The responses of six test organisms (Aliivibrio fischeri, Pseudokirchneriella subcapitata, Heterocypris incongruens, Moina macrocopa, Danio rerio and Lemna minor) after laboratory exposure to water samples were considered for this index, as well as the frequency of teratologies in diatom assemblages. Each individual test was attributed a toxicity class and score (three levels; no toxicity = 0, low toxicity = 1, confirmed toxicity = 2) based on the organism's response after exposure and a total score was calculated. The proposed index also considers the number of test organisms that received the highest toxicity score (value = 2). An overall toxicity category was then attributed to the water sample based on those two metrics: A = no toxicity, B = slight toxicity, C = moderate toxicity; D = toxicity and E = high toxicity. The susceptibility of the test organisms varied greatly and the sensitivity of their response also differed among bioassays. The combined responses of organisms from different trophic levels and with different life strategies provided multi-level diagnostic information about the intensity and the nature of contamination.

Testing the toxicity of metals, phenol, effluents, and receiving waters by root elongation in Lactuca sativa L.

Phytotoxicity tests using higher plants are among the most simple, sensitive, and cost-effective of the methods available for ecotoxicity testing. In the present study, a hydroponic-based phytotoxicity test using seeds of Lactuca sativa was used to evaluate the water quality of receiving waters and effluents near two industrial sites (Soyo and Daejon) in Korea with respect to the toxicity of 10 metals (As, Cd, Cr, Cu, Fe, Pb, Mn, Hg, Ni, Zn) and phenol, and of the receiving waters and effluents themselves. First, the L. sativa hydroponic bioassay was used to determine whether the receiving water or effluents were toxic; then, the responsible toxicant was identified. The results obtained with the L. sativa bioassay ranked the EC50 toxicities of the investigated metal ions and phenol as: Cd > Ni > Cu > Zn > Hg > phenol > As > Mn > Cr > Pb > Fe. We found that Zn was the toxicant principally responsible for toxicity in Daejeon effluents. The Daejeon field effluent had a higher Zn concentration than permitted by the effluent discharge criteria of the Ministry of Environment of Korea. Our conclusion on the importance of Zn toxicity was supported by the results of the L. sativa hydroponic assay, which showed that the concentration of Zn required to inhibit root elongation in L. sativa by 50% (EC50) was higher in the Daejeon field effluent than that of pure Zn. More importantly, we proved that the L. sativa hydroponic test method can be applied not only as an alternative tool for determining whether a given waste is acceptable for discharge into public water bodies, but also as an alternative method for measuring the safety of aquatic environments using EC20 values, with respect to the water pollutants investigated (i.e., Cd, Cr, Cu, Pb, Mn, Hg, Ni, Zn, and phenol).

[Research progress on anti-inflammatory mechanism of natural sesquiterpenoids].

Sesquiterpenoid is a kind of compound widely distributed in nature, which has a wide range of biological activities, such as anti-inflammatory, anti-tumor and immunomodulatory activities. This paper would review the anti-inflammatory mechanism of sesquiterpenoid. The mechanism is mainly by inhibiting the activation of nuclear factor (NF-κB), mitogen-activated protein kinase (MAPKs) and signal transducers and activators of transcription (STAT) signaling pathways and down-regulating the inflammatory gene expression including tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), nitric oxide (NO), interleukin-1(IL-1), IL-6, IL-8 and other inflammatory factors. Thereby, the production and release of inflammatory cytokines are reduced to exert anti-inflammatory effect. This review is intended to provide reference for related research.

Deciphering the environmental chemical basis of muscle quality decline by interpretable machine learning models.

BACKGROUND: Sarcopenia is known as a decline in skeletal muscle quality and function that is associated with age. Sarcopenia is linked to diverse health problems, including endocrine-related diseases. Environmental chemicals (ECs), a broad class of chemicals released from industry, may influence muscle quality decline. OBJECTIVES: In this work, we aimed to simultaneously elucidate the associations between muscle quality decline and diverse EC exposures based on the data from the 2011-2012 and 2013-2014 survey cycles in the National Health and Nutrition Examination Survey (NHANES) project using machine learning models. METHODS: Six machine learning models were trained based on the EC and non-EC exposures from NHANES to distinguish low from normal muscle quality index status. Different machine learning metrics were evaluated for these models. The Shapley additive explanations (SHAP) approach was used to provide explainability for machine learning models. RESULTS: Random forest (RF) performed best on the independent testing data set. Based on the testing data set, ECs can independently predict the binary muscle quality status with good performance by RF (area under the receiver operating characteristic curve = 0.793; area under the precision-recall curve = 0.808). The SHAP ranked the importance of ECs for the RF model. As a result, several metals and chemicals in urine, including 3-phenoxybenzoic acid and cobalt, were more associated with the muscle quality decline. CONCLUSIONS: Altogether, our analyses suggest that ECs can independently predict muscle quality decline with a good performance by RF, and the SHAP-identified ECs can be closely related to muscle quality decline and sarcopenia. Our analyses may provide valuable insights into ECs that may be the important basis of sarcopenia and endocrine-related diseases in United States populations.

Effects of textured insoles on dynamic balance and ankle muscle activity in soccer players with and without chronic ankle instability.

BACKGROUND: Chronic ankle instability (CAI) poses challenges in sports. Textured insoles (TI) are a promising intervention for enhancing dynamic balance in CAI athletes. This study aimed to investigate the effects of TI on dynamic balance performance and ankle muscle activity in soccer players with and without CAI. METHODS: Thirty-eight soccer players (19 CAI, 19 non-CAI) participated. Participants performed a modified star excursion balance test (mSEBT) while wearing TI and standard insoles (SI). The %SEBT reach distance and electromyography (EMG) activity of tibialis anterior (TA), medial gastrocnemius (MG), and peroneus longus (PL) were measured during maximum reached in each direction of the mSEBT. RESULTS: No significant effects or interactions were found between ankle conditions (CAI vs. non-CAI) or insole types (TI vs. SI) on %SEBT reach. However, CAI players showed greater MG activity in posteromedial and posterolateral direction (P=0.04, P=0.01). CONCLUSIONS: Overall, the application of TI did not have immediate effects on dynamic balance performance or ankle muscle activity in either CAI or non-CAI soccer players. Nonetheless, CAI players seemed to employ a different ankle strategy involving the MG muscle, possibly to control stability during dynamic movement, particularly in the posteromedial and posterolateral directions.

Golden 2-like Transcription Factors Regulate Photosynthesis under UV-B Stress by Regulating the Calvin Cycle.

UV-B stress can affect plant growth at different levels, and although there is a multitude of evidence confirming the effects of UV-B radiation on plant photosynthesis, there are fewer studies using physiological assays in combination with multi-omics to investigate photosynthesis in alpine plants under stressful environments. Golden 2-like (G2-like/GLK) transcription factors (TFs) are highly conserved during evolution and may be associated with abiotic stress. In this paper, we used Handy-PEA and Imaging-PAM Maxi to detect chlorophyll fluorescence in leaves of Rhododendron chrysanthum Pall. (R. chrysanthum) after UV-B stress, and we also investigated the effect of abscisic acid (ABA) on photosynthesis in plants under stress environments. We used a combination of proteomics, widely targeted metabolomics, and transcriptomics to study the changes of photosynthesis-related substances after UV-B stress. The results showed that UV-B stress was able to impair the donor side of photosystem II (PSII), inhibit electron transfer and weaken photosynthesis, and abscisic acid was able to alleviate the damage caused by UV-B stress to the photosynthetic apparatus. Significant changes in G2-like transcription factors occurred in R. chrysanthum after UV-B stress, and differentially expressed genes localized in the Calvin cycle were strongly correlated with members of the G2-like TF family. Multi-omics assays and physiological measurements together revealed that G2-like TFs can influence photosynthesis in R. chrysanthum under UV-B stress by regulating the Calvin cycle. This paper provides insights into the study of photosynthesis in plants under stress, and is conducive to the adoption of measures to improve photosynthesis in plants under stress to increase yield.