Reversible acetylation of HDAC8 regulates cell cycle.

HDAC8, a member of class I HDACs, plays a pivotal role in cell cycle regulation by deacetylating the cohesin subunit SMC3. While cyclins and CDKs are well-established cell cycle regulators, our knowledge of other regulators remains limited. Here we reveal the acetylation of K202 in HDAC8 as a key cell cycle regulator responsive to stress. K202 acetylation in HDAC8, primarily catalyzed by Tip60, restricts HDAC8 activity, leading to increased SMC3 acetylation and cell cycle arrest. Furthermore, cells expressing the mutant form of HDAC8 mimicking K202 acetylation display significant alterations in gene expression, potentially linked to changes in 3D genome structure, including enhanced chromatid loop interactions. K202 acetylation impairs cell cycle progression by disrupting the expression of cell cycle-related genes and sister chromatid cohesion, resulting in G2/M phase arrest. These findings indicate the reversible acetylation of HDAC8 as a cell cycle regulator, expanding our understanding of stress-responsive cell cycle dynamics.

SnapHiC-D: a computational pipeline to identify differential chromatin contacts from single-cell Hi-C data.

Single-cell high-throughput chromatin conformation capture technologies (scHi-C) has been used to map chromatin spatial organization in complex tissues. However, computational tools to detect differential chromatin contacts (DCCs) from scHi-C datasets in development and through disease pathogenesis are still lacking. Here, we present SnapHiC-D, a computational pipeline to identify DCCs between two scHi-C datasets. Compared to methods designed for bulk Hi-C data, SnapHiC-D detects DCCs with high sensitivity and accuracy. We used SnapHiC-D to identify cell-type-specific chromatin contacts at 10 Kb resolution in mouse hippocampal and human prefrontal cortical tissues, demonstrating that DCCs detected in the hippocampal and cortical cell types are generally associated with cell-type-specific gene expression patterns and epigenomic features. SnapHiC-D is freely available at https://github.com/HuMingLab/SnapHiC-D.

An intellectual disability-related MED23 mutation dysregulates gene expression by altering chromatin conformation and enhancer activities.

Transcriptional Mediator controls diverse gene programs for various developmental and pathological processes. The human Mediator MED23/R617Q mutation was reported in a familial intellectual disability (ID) disorder, although the underlying mechanisms remain poorly understood. Constructed by gene editing, the Med23/R617Q knock-in mutant mice exhibited embryonic lethality due to the largely reduced Med23/R617Q protein level, but the R617Q mutation in HEK293T cells didn't change its expression and incorporation into Mediator Complex. RNA-seq revealed that MED23/R617Q mutation disturbed gene expression, related to neural development, learning and memory. Specifically, R617Q mutation reduced the MED23-dependent activities of ELK1 and E1A, but in contrast, upregulated the MAPK/ELK1-driven early immediate genes (IEGs) JUN and FOS. ChIP-seq and Hi-C revealed that the MED23 R617Q mutation reprogramed a subset of enhancers and local chromatin interactions, which correlated well with the corresponding gene expression. Importantly, the enhancers and chromatin interactions surrounding IEGs were unchanged by the R617Q mutation, but DACH1, an upstream repressor of IEGs, showed reduced enhancer-promoter interactions and decreased expression in mutant cells, thus relieving its inhibition to the intellectual-related IEGs. Overall, unraveling the MED23-DACH1-IEG axis provides a mechanistic explanation for the effects of the MED23/R617Q mutation on gene dysregulation and inherited ID.

Blood molecular markers associated with COVID-19 immunopathology and multi-organ damage.

COVID-19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19-infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19-infected patients experiencing milder disease symptoms showed robust T-cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19.

SnapHiC: a computational pipeline to identify chromatin loops from single-cell Hi-C data.

Single-cell Hi-C (scHi-C) analysis has been increasingly used to map chromatin architecture in diverse tissue contexts, but computational tools to define chromatin loops at high resolution from scHi-C data are still lacking. Here, we describe Single-Nucleus Analysis Pipeline for Hi-C (SnapHiC), a method that can identify chromatin loops at high resolution and accuracy from scHi-C data. Using scHi-C data from 742 mouse embryonic stem cells, we benchmark SnapHiC against a number of computational tools developed for mapping chromatin loops and interactions from bulk Hi-C. We further demonstrate its use by analyzing single-nucleus methyl-3C-seq data from 2,869 human prefrontal cortical cells, which uncovers cell type-specific chromatin loops and predicts putative target genes for noncoding sequence variants associated with neuropsychiatric disorders. Our results indicate that SnapHiC could facilitate the analysis of cell type-specific chromatin architecture and gene regulatory programs in complex tissues.

Targeting tumour surface collage with hydrogel probe: a new strategy to enhance intraoperative imaging sensitivity and stability of bladder cancer.

PURPOSE: The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity. METHODS: The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues. RESULTS: The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%. CONCLUSION: CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC.

Fibrous Conductive Metallogels with Hybrid Electron/Ion Networks for Boosted Extreme Sensitivity and High Linearity Strain Sensor.

Fibrous strain sensing materials with both high sensitivity and high linearity are of significant importance for wearable sensors, yet they still face great challenges. Herein, a photo-spun reaction encapsulation strategy is proposed for the continuous fabrication of fibrous strain sensor materials (AMGF) with a core-sheath structure. Metallogels (MOGs) formed by bacterial cellulose (BC) nanofibers and Ag nanoparticles (AgNPs), and thermoplastic elastomers (TPE) are employed as the core and sheath, respectively. The in situ ultraviolet light reduction of Ag+ ensured AgNPs to maintain the interconnections between the BC nanofibers and form electron conductive networks (0.31 S m-1 ). Under applied strain, the BC nanofibers experience separation, bringing AMGF a high sensitivity (gauge factor 4.36). The concentration of free ions in the MOGs uniformly varies with applied deformation, endowing AMGF with high linearity and a goodness-of-fit of 0.98. The sheath TPE provided AMGF sensor with stable working life (>10 000 s). Furthermore, the AMGF sensors are demonstrated to monitor complex deformations of the dummy joints in real-time as a wearable sensor. Therefore, the fibrous hybrid conductive network fibers fabricated via the photo-spun reaction encapsulation strategy provide a new route for addressing the challenge of achieving both high sensitivity and high linearity.

Serum secretoneurin as a promising biomarker for predicting poor prognosis in intracerebral hemorrhage: A prospective cohort study.

OBJECTIVE: Secretoneurin may play a brain-protective role. We aim to discover the relationship between serum secretoneurin levels and severity plus neurological outcome after intracerebral hemorrhage (ICH). METHODS: In this prospective cohort study, serum secretoneurin levels were measured in 110 ICH patients and 110 healthy controls. Glasgow Coma Scale (GCS) and hematoma volume were used to assess stroke severity. Poor prognosis was defined as Glasgow Outcome Scale (GOS) scores of 1-3 at 90 days after ICH. A multivariate logistic regression model was constructed to determine independent correlation of serum secretoneurin levels with severity and poor prognosis. Under receiver operating characteristic (ROC) curve, prognostic ability of serum secretoneurin levels was assessed. Restricted cubic spline (RCS) model and subgroups analysis were used for discovering association of serum secretoneurin levels with risk of poor prognosis. Calibration curve and decision curve were evaluated to confirm performance of nomogram. RESULTS: Serum secretoneurin levels of patients were significantly higher than those of healthy controls. Serum secretoneurin levels of patients were independently correlated with GCS scores and hematoma volume. There were 42 patients with poor prognosis at 90 days following ICH. Serum secretoneurin levels were significantly higher in patients with poor outcome than in those with good outcome. Under the ROC curve, serum secretoneurin levels significantly differentiated poor outcome. Serum secretoneurin levels ≥ 22.8 ng/mL distinguished patients at risk of poor prognosis at 90 days with a sensitivity of 66.2% and a specificity of 81.0%. Besides, serum secretoneurin levels independently predicted a 90-day poor prognosis. Subgroup analysis showed that serum secretoneurin levels had non-significant interactions with other variables. The nomogram, including independent prognostic predictors, showed reliable prognosis capability using calibration curve and decision curve. Area under the curve of the predictive model was significantly higher than those of GCS scores and hematoma volume. CONCLUSION: Serum secretoneurin levels are strongly related to ICH severity and poor prognosis at 90 days after ICH. Thus, serum secretoneurin may be a promising prognostic biomarker in ICH.

A two-center prospective cohort study of serum RIP-3 as a potential biomarker in relation to severity and prognosis after severe traumatic brain injury.

Receptor-interacting protein kinase-3 (RIP-3) is a key component for inducing necroptosis following acute brain injury. Purpose of this study is to unveil whether serum RIP-3 levels are related to severity and clinical outcomes after human severe traumatic brain injury (sTBI). In this two-center prospective cohort study, serum RIP-3 levels were detected in 127 healthy controls coupled with 127 sTBI patients. The prognostic indicators encompassed posttraumatic 180-day mortality, overall survival and poor prognosis (defined as extended Glasgow outcome scale scores of 1-4). The prognosis associations were verified via multivariate analysis. There was a significant incremental serum RIP-3 levels in patients with sTBI, relative to the controls. RIP-3 levels of patients were independently correlated with Rotterdam Computed Tomography (CT) scores and Glasgow coma scale (GCS) scores, as well as were independently predictive of mortality, overall survival and poor prognosis. Mortality and poor prognosis were effectively predicted by serum RIP-3 levels under the receiver operating characteristic curve. Linear relationships between RIP-3 levels and their risks were verified. Mortality and poor prognosis models of serum RIP-3 levels combined with GCS and Rotterdam CT scores displayed efficient predictive abilities. The two models were graphically represented, which were of clinical stability and value by employing the calibration and decision curves. Increased serum RIP-3 levels after sTBI are closely linked to heightened trauma severity and poor prognosis, signifying that serum RIP-3 may be an encouraging biomarker for evaluating severity and predicting clinical outcome of sTBI.

Temporal change of serum xanthine oxidase levels and its relation to clinical outcome of severe traumatic brain injury: a prospective cohort study.

Xanthine oxidase (XO) may be involved in the induction of oxidative stress and inflammation. We measured serum XO levels at multiple days to determine whether it is associated with the severity and prognosis of severe traumatic brain injury (sTBI). In this prospective cohort study, we quantified serum XO levels in 112 sTBI patients and 112 controls. Serum XO levels of patients were measured at admission and at days 1, 3, 5, 7, and 10 after sTBI. Extended Glasgow outcome scale scores of 1-4 at post-trauma 180 days were defined as a poor prognosis. Multivariate analysis was employed to determine the relationship between poor prognosis and serum XO levels at multiple days. Serum XO levels were significantly increased at admission among patients, afterwards elevated gradually, peaked at day 3, and then diminished gradually until day 10, and were substantially higher during 10 days in patients than in controls. Serum XO levels at 6 different days were all correlated with admission Rotterdam computed tomography (CT) scores and Glasgow coma scale (GCS) scores. Serum XO levels at 6 different days were all substantially higher in patients with poor prognosis than in those with good prognosis. Serum XO levels at days 7 and 10, but not at days 1, 3, and 5, had significantly lower area under receiver operating characteristic (AUC) than those at admission. Serum XO levels at admission and at days 1 and 3, but not at day 5, were independently associated with 180-day poor prognosis. Prognostic prediction model containing GCS scores, Rotterdam CT scores, and serum XO levels at admission (or at days 1 and 3) showed substantially higher AUC than GCS scores and Rotterdam CT scores alone. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. Elevated serum XO levels during early period of sTBI are more closely associated with trauma severity and clinical adverse outcomes, assuming that serum XO may serve as a potential prognostic biomarker in sTBI.

Differential photoregulation of the nuclear and cytoplasmic CRY1 in Arabidopsis.

Arabidopsis cryptochrome 1 (CRY1) is a blue light receptor distributed in the nucleus and cytoplasm. The nuclear CRY1, but not cytoplasmic CRY1, mediates blue light inhibition of hypocotyl elongation. However, the photobiochemical mechanisms distinguishing the CRY1 protein in the two subcellular compartments remains unclear. Here we show that the nuclear CRY1, but not the cytoplasmic CRY1, is regulated by phosphorylation, polyubiquitination and 26S proteasome-dependent proteolysis in response to blue light. The blue light-dependent CRY1 degradation is observed only under high fluences of blue light. The nuclear specificity and high fluence dependency of CRY1 explain why this photochemical regulatory mechanism of CRY1 was not observed previously and it further supports the hypothesis that CRY1 is a high light receptor regulating photomorphogenesis. We further show that the nuclear CRY1, but not cytoplasmic CRY1, undergoes blue light-dependent phosphorylation by photoregulatory protein kinase 1 (PPK1) followed by polyubiquitination by the E3 ubiquitin ligase Cul4COP1/SPAs , resulting in the blue light-dependent proteolysis. Both phosphorylation and ubiquitination of nuclear CRY1 are inhibited by blue-light inhibitor of cryptochromes 1 (BIC1), demonstrating the involvement of photo-oligomerization of the nuclear CRY1. These finding reveals a photochemical mechanism that differentially regulates the physiological activity of the CRY1 photoreceptor in distinct subcellular compartments.

A clinical study of a CD44v6-targeted fluorescent agent for the detection of non-muscle invasive bladder cancer.

BACKGROUND: Bladder cancer is the fifth most common malignancy in humans. Cystoscopy under white light imaging is the gold standard for bladder cancer diagnosis, but some tumors are difficult to visualize and can be overlooked, resulting in high recurrence rates. We previously developed a phage display-derived peptide-based near-infrared imaging probe, PLSWT7-DMI, which binds specifically to bladder cancer cells and is nontoxic to animals. Here, we report a clinical research of this probe for near-infrared fluorescence endoscopic detection of bladder cancer. RESULTS: The purity, efficacy, safety, and nontoxicity of PLSWT7-DMI were confirmed prior to its clinical application. Twenty-two patients diagnosed with suspected non-muscle invasive bladder cancer were enrolled in the present study. Following intravesical administration of the probe, the entire mucosa was imaged under white and near-infrared imaging using an in-house developed endoscope that could switch between these two modes. The illuminated lesions under near-infrared light were biopsied and sent for histopathological examination. We observed a 5.1-fold increase in the fluorescence intensity in the tumor samples compared to normal tissue, and the probe demonstrated a sensitivity and specificity of 91.2% and 90%, respectively. Common diagnostic challenges, such as small satellite tumors, carcinoma in situ, and benign suspicious mucosa, were visualized and could be distinguished from cancer. Furthermore, no adverse effects were observed in humans. These first-in-human results indicate that PLSWT7-DMI-based near-infrared fluorescence endoscopy is a safe and effective approach for the improved detection of bladder cancer, and may enable thorough resection to prevent recurrence.

Nanomaterials: small particles show huge possibilities for cancer immunotherapy.

With the economy's globalization and the population's aging, cancer has become the leading cause of death in most countries. While imposing a considerable burden on society, the high morbidity and mortality rates have continuously prompted researchers to develop new oncology treatment options. Anti-tumor regimens have evolved from early single surgical treatment to combined (or not) chemoradiotherapy and then to the current stage of tumor immunotherapy. Tumor immunotherapy has undoubtedly pulled some patients back from the death. However, this strategy of activating or boosting the body's immune system hardly benefits most patients. It is limited by low bioavailability, low response rate and severe side effects. Thankfully, the rapid development of nanotechnology has broken through the bottleneck problem of anti-tumor immunotherapy. Multifunctional nanomaterials can not only kill tumors by combining anti-tumor drugs but also can be designed to enhance the body's immunity and thus achieve a multi-treatment effect. It is worth noting that the variety of nanomaterials, their modifiability, and the diversity of combinations allow them to shine in antitumor immunotherapy. In this paper, several nanobiotics commonly used in tumor immunotherapy at this stage are discussed, and they activate or enhance the body's immunity with their unique advantages. In conclusion, we reviewed recent advances in tumor immunotherapy based on nanomaterials, such as biological cell membrane modification, self-assembly, mesoporous, metal and hydrogels, to explore new directions and strategies for tumor immunotherapy.

Stereotactic body radiation therapy for non-small cell lung cancer using the non-coplanar radiation of Cyberknife and Varian linac.

PURPOSE: This study aims to evaluate the planned dose of stereotactic body radiation therapy (SBRT) for treating early peripheral non-small cell lung cancer (NSCLC) using the non-coplanar radiation from Cyberknife and Varian linac. Moreover, this study investigates whether Cyberknife and Varian linac are qualified for non-coplanar radiation SBRT for treating early peripheral NSCLC, and which one is better for protecting organs at risk (OARs). METHODS: Retrospective analysis was performed based on the Cyberknife radiation treatment plans (RTPs) and Varian Eclipse RTPs of 10 patients diagnosed with early peripheral NSCLC. The dose distributions in the target and OARs were compared between the RTPs of Cyberknife and Varian Eclipse using Mim medical imaging software. RESULTS: For PTV, no significant difference in D98 and D95 between the Cyberknife and Eclipse was observed (t = -0.35, -1.67, P > 0.05). The homogeneity indexes (HIs) of Cyberknife plans are higher (t = 71.86, P < 0.05) than those of Eclipse plans. The V10, V15, V20, V25, V30 and Dmean of the lung with NSCLC and the V20 of the whole lung for Cyberknife were less than those for Eclipse (t = -4.73, -5.62, -7.75, -6.38, -6.89, -3.14, -7.09, respectively, P < 0.05). Cyberknife plans have smaller spinal cord Dmax, trachea Dmax, heart Dmax, chest wall Dmax (t = -2.49, -2.57, -3.71, -3.56, respectively, P < 0.05) and esophagus Dmax (t = -1.95, P > 0.05) than Varian Eclipse plans. CONCLUSION: To fulfill SBRT by non-coplanar radiation, Cyberknife is recommended for the institutions equipped with Cyberknife, while Varian linac can be applied for the institutions that have not adopted Cyberknife in clinical radiotherapy yet.

New model for explaining the over-response phenomenon in percentage of depth dose curve measured using inorganic scintillating materials for optical fiber radiation sensors.

Inorganic scintillating material used in optical fibre sensors (OFS) when used as dosimeters for measuring percentage depth dose (PDD) characteristics have exhibited significant differences when compared to those measured using an ionization chamber (IC), which is the clinical gold standard for quality assurance (QA) assessments. The percentage difference between the two measurements is as high as 16.5% for a 10 × 10 cm2 field at 10 cm depth below the surface. Two reasons have been suggested for this: the presence of an energy effect and Cerenkov radiation. These two factors are analysed in detail and evaluated quantitatively. It is established that the influence of the energy effect is only a maximum of 2.5% difference for a beam size 10 × 10 cm2 compared with the measured ionization chamber values. And the influence of the Cerenkov radiation is less than 0.14% in an inorganic scintillating material in the case of OFS when using Gd2O2S:Tb as the luminescent material. Therefore, there must be other mechanisms leading to over-response. The luminescence mechanism of inorganic scintillating material is theoretically analysed and a new model is proposed and validated that helps explain the over-response phenomenon.

Complete nucleotide sequence of jasmine virus H, a new member of the family Tombusviridae.

Jasmine virus H (JaVH) is a novel virus associated with symptoms of yellow mosaic on jasmine. The JaVH genome is 3,867 nt in length with five open reading frames (ORFs) encoding a 27-kDa protein (ORF 1), an 87-kDa replicase protein (ORF 2), two centrally located movement proteins (ORF 3 and 4), and a 37-kDa capsid protein (ORF 5). Based on genomic and phylogenetic analysis, JaVH is predicted to be a member of the genus Pelarspovirus in the family Tombusviridae.

A novel nomogram for predicting the risk of persistent hyperparathyroidism after kidney transplantation.

PURPOSE: Persistent hyperparathyroidism (PTHPT) in kidney transplant recipients is associated with bone loss, graft dysfunction and cardiovascular mortality. There is no clear consensus on the management of PTHPT. Accurate risk prediction of the disease is needed to support individualized treatment decisions. We aim to develop a useful predictive model to provide early intervention for hyperparathyroidism in these patients. METHODS: We retrospectively analyzed 263 kidney transplantations in the urology department of China-Japan Friendship Hospital from January 2018 to December 2022. The overall cohort was randomly assigned 70% of the patients to the training cohort and 30% to the validation cohort. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for PTHPT and to construct the predictive model. This model was assessed regarding discrimination, consistency, and clinical benefit. RESULTS: The occurrence of PTHPT was 25.9% (68 out of 263 patients) in this study. Dialysis duration, postoperative 3-month intact parathyroid hormone (iPTH), 3-month corrected calcium (cCa), and 3-month phosphorus (P) are independent risk factors for the development of PTHPT. The nomogram showed good discrimination with the area under the curve (AUC) value of 0.926 in the training cohort and 0.903 in the validation cohort. The calibration curve and decision curve also showed that the model was well-evaluated. CONCLUSION: We developed a validated nomogram model to predict PTHPT after kidney transplantation. This can help the clinic prevent and control PTHPT early and improve patients' prognosis.

Correction: Facile preparation of a Ni-imidazole compound with high activity for ethylene dimerization.

Correction for 'Facile preparation of a Ni-imidazole compound with high activity for ethylene dimerization' by Zhaohui Liu et al., Chem. Commun., 2024, 60, 188-191, https://doi.org/10.1039/D3CC04794F.

Characterizing upper limb motor dysfunction with temporal and spatial distribution of muscle synergy extracted from high-density surface electromyography.

OBJECTIVE: To promote the development of objective and comprehensive motion function assessment for patients, based on high-density surface electromyography (HD-sEMG), this study investigates the temporal and spatial variations of neuromuscular activities related to upper limb motor dysfunction. APPROACH: Patients with unilateral upper limb motor dysfunction and healthy controls were enrolled in the study. HD-sEMG was collected from both arms while they were performing eight hand and wrist movements. Muscle synergies were extracted from the HD-sEMG. Symmetry of bilateral upper limb synergies and synergy differences between motions were proposed as spatial indicators to measure alterations in synergy spatial distribution. Additionally, as a temporal characteristic, the correlation of bilateral upper limb activation coefficient was proposed to describe the coordination control of the central nervous system (CNS). All temporal and spatial indicators were compared between patients and healthy subjects. MAIN RESULTS: The patients showed a significant decrease (p<0.05) in the symmetry of bilateral upper limb synergy spatial distribution and correlation of bilateral upper limb activation coefficient. Patients with motor dysfunction also showed an increase in synergy similarity between motions, indicating altered spatial distribution of muscle synergies. SIGNIFICANCE: These findings provide valuable insights into specific patterns associated with motor dysfunction, informing motor function assessment, and guiding targeted interventions and rehabilitation strategies for neurologically disordered patients.

Swine farming shifted the gut antibiotic resistome of local people.

Antibiotic resistance genes (ARGs) are prevalent in the livestock environment, but little is known about impacts of animal farming on the gut antibiotic resistome of local people. Here we conducted metagenomic sequencing to investigate gut microbiome and resistome of residents in a swine farming village as well as environmental relevance by comparing with a nearby non-farming village. Results showed a shift of gut microbiome towards unhealthy status in the residents of swine farming village, with an increased abundance and diversity in pathogens and ARGs. The resistome composition in human guts was more similar with that in swine feces and air than that in soil and water. Mobile gene elements were closely associated with the prevalence of gut resistome. Some plasmid-borne ARGs were colocalized in similar genetic contexts in gut and environmental samples. Metagenomic binning obtained 47 ARGs-carrying families in human guts, and therein Enterobacteriaceae posed the highest threats in antibiotic resistance and virulence. Several ARGs-carrying families were shared by gut and environmental samples (mainly in swine feces and air), and the ARGs were evolutionarily conservative within genera. The findings highlight that swine farming can shape gut resistome of local people with close linkage to farm environmental exposures.