Crystal structure of Trichinella spiralis calreticulin and the structural basis of its complement evasion mechanism involving C1q.

Helminths produce calreticulin (CRT) to immunomodulate the host immune system as a survival strategy. However, the structure of helminth-derived CRT and the structural basis of the immune evasion process remains unclarified. Previous study found that the tissue-dwelling helminth Trichinella spiralis produces calreticulin (TsCRT), which binds C1q to inhibit activation of the complement classical pathway. Here, we used x-ray crystallography to resolve the structure of truncated TsCRT (TsCRTΔ), the first structure of helminth-derived CRT. TsCRTΔ was observed to share the same binding region on C1q with IgG based on the structure and molecular docking, which explains the inhibitory effect of TsCRT on C1q-IgG-initiated classical complement activation. Based on the key residues in TsCRTΔ involved in the binding activity to C1q, a 24 amino acid peptide called PTsCRT was constructed that displayed strong C1q-binding activity and inhibited C1q-IgG-initiated classical complement activation. This study is the first to elucidate the structural basis of the role of TsCRT in immune evasion, providing an approach to develop helminth-derived bifunctional peptides as vaccine target to prevent parasite infections or as a therapeutic agent to treat complement-related autoimmune diseases.

A New Lunar Lineament Extraction Method Based on Improved UNet++ and YOLOv5.

Lineament is a unique geological structure. The study of Lunar lineament structure has great significance on understanding its history and evolution of Lunar surface. However, the existing geographic feature extraction methods are not suitable for the extraction of Lunar lineament structure. In this paper, a new lineament extraction method is proposed based on improved-UNet++ and YOLOv5. Firstly, new lineament dataset is created containing lineaments structure based on CCD data from LROC. At same time the residual blocks are replaced with the VGG blocks in the down sample part of the UNet++ with adding the attention block between each layer. Secondly, the improved-UNet++ and YOLO networks are trained to execute the object detection and semantic segmentation of lineament structure respectively. Finally, a polygon-match strategy is proposed to combine the results of object detection and semantic segmentation. The experiment result indicate that this new method has relatively better and more stable performance compared with current mainstream networks and the original UNet++ network in the instance segmentation of lineament structure. Additionally, the polygon-match strategy is able to perform preciser edge detail in the instance segmentation of lineament structure result.

Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1.

Ubiquitination, catalyzed usually by a three-enzyme cascade (E1, E2, E3), regulates various eukaryotic cellular processes. E3 ligases are the most critical components of this catalytic cascade, determining both substrate specificity and polyubiquitination linkage specificity. Here, we reveal the mechanism of a naturally occurring E3-independent ubiquitination reaction of a unique human E2 enzyme UBE2E1 by solving the structure of UBE2E1 in complex with substrate SETDB1-derived peptide. Guided by this peptide sequence-dependent ubiquitination mechanism, we developed an E3-free enzymatic strategy SUE1 (sequence-dependent ubiquitination using UBE2E1) to efficiently generate ubiquitinated proteins with customized ubiquitinated sites, ubiquitin chain linkages and lengths. Notably, this strategy can also be used to generate site-specific branched ubiquitin chains or even NEDD8-modified proteins. Our work not only deepens the understanding of how an E3-free substrate ubiquitination reaction occurs in human cells, but also provides a practical approach for obtaining ubiquitinated proteins to dissect the biochemical functions of ubiquitination.

Finite element analysis of a customized coronoid prosthesis for traumatic coronoid deficiency.

BACKGROUND: Traumatic coronoid deficiency with persistent elbow instability is a challenging condition. Autologous bone graft reconstruction is often associated with a range of additional clinical problems and the outcome is often unpredictable. The purpose of this study was to design a prosthetic device that can reconstruct coronoid deficiency of any height and to evaluate its mechanical properties using finite element analysis. MATERIALS AND METHODS: A customized coronoid prosthesis was designed based on image registration, automatic measurement, and computer-aided design. After pilot study and sample size calculation, image data collected from 6 patients who underwent bilateral complete upper extremity CT scans were reconstructed. The test was divided into 3 groups: coronoid intact, prosthesis and autograft. Regan-Morrey type II and autologous olecranon osteotomy models were established. The prosthesis and autogenous olecranon were assembled to the coronoid base. Stress was applied axially along the proximal humeral diaphysis and implant micromotion and contact mechanics of the humeroulnar joint were measured at 30°, 45°, 60° and 90° of joint flexion respectively. RESULTS: At all flexion angles, the maximum stress on the coronoid articular surface was significantly reduced in the prosthesis and autograft groups, with the reduction being more significant in the latter (P < .001). With increasing flexion, the maximum stress at the coronoid articular surface increased significantly after autograft reconstruction (7.2 to 68 MPa, P < .001), whereas the humeroulnar joint obtained a similar contact mechanics pattern to that of the control group after prosthetic reconstruction. As the flexion angle increased, the relative micromotion of both the prosthesis and autograft increased significantly (0.5-1.6 vs. 0.2-1.2, Pmeasure time < 0.001, Pgroups < 0.001). Contact pressure and center-of-force paths of the humeroulnar joint experience abrupt stress changes at approximately 60° of flexion. CONCLUSION: The contact stress pattern in the humeroulnar joint is similar in prosthesis and intact coronoid groups. Autograft reconstruction increases contact stresses at the articular surface and alters the joint center-of-force path. The "stress surge phenomenon" in the humeroulnar joint surface before and after 60° of flexion may be one of the mechanisms of traumatic elbow degeneration.

Clinical and pathologic features of Sturge-Weber syndrome in patients with refractory epilepsy.

OBJECTIVES: We aimed to investigate the clinicopathologic features of and genetic changes in Sturge-Weber syndrome (SWS) in patients with refractory epilepsy. METHODS: Clinical data were retrospectively analyzed. H&E and immunohistochemistry were performed to assess pathologic changes. Targeted amplicon sequencing was applied to investigate the somatic GNAQ (c.548G>A) mutation. The potential predictors of seizure outcomes were estimated by univariate and multivariate statistical analyses. RESULTS: Forty-eight patients with SWS and refractory epilepsy were enrolled. According to the imaging data and pathologic examination, ipsilateral hippocampal sclerosis (HS), calcification of leptomeningeal arteries, and focal cortical dysplasia were found in 14 (29.2%), 31 (64.6%), and 37 (77.1%) patients, respectively. A high frequency of GNAQ alteration was detected in both cerebral cortex (57.7%) and ipsilateral hippocampus (50.0%) from patients with SWS. During follow-up, 43 of 48 patients (85.4%) had achieved seizure control (Engel class I). Statistically, HS signs on imaging were found to be independent predictors of unfavorable seizure outcomes (P = .015). CONCLUSIONS: Calcification of leptomeningeal arteries, focal cortical dysplasia, and GNAQ alteration are common features in SWS pathology. Patients with refractory epilepsy caused by SWS can achieve satisfactory seizure control after surgery, but seizure control was compromised in patients with comorbid HS.

Dual-Specificity Inhibitor Targets Enzymes of the Trehalose Biosynthesis Pathway.

To reduce the risk of resistance development, a novel fungicide with dual specificity is demanded. Trehalose is absent in animals, and its synthases, trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP), are safe fungicide targets. Here, we report the discovery of a dual-specificity inhibitor of MoTps1 (Magnaporthe oryzae Tps1, TPS) and MoTps2 (M. oryzae Tps2, TPP). The inhibitor, named A1-4, was obtained from a virtual screening and subsequent surface plasmon resonance screening. In in vitro assays, A1-4 interacts with MoTps1 and MoTps2-TPP (MoTps2 TPP domain) and inhibits their enzyme activities. In biological activity assays, A1-4 not only inhibits the virulence of M. oryzae on host but also causes aggregation of conidia cytosol, which is a characteristic phenotype of MoTps2. Furthermore, hydrogen/deuterium exchange mass spectrometry assays support the notion that A1-4 binds to the substrate pockets of TPS and TPP. Collectively, A1-4 is a promising hit compound for the development of safe fungicide with dual-target specificity.

ASC/Caspase-1-activated endothelial cells pyroptosis is involved in vascular injury induced by arsenic combined with high-fat diet.

Environmental arsenic (As) or high-fat diet (HFD) exposure alone are risk factors for the development of cardiovascular disease (CVDs). However, the effects and mechanisms of co-exposure to As and HFD on the cardiovascular system remain unclear. The current study aimed to investigate the combined effects of As and HFD on vascular injury and shed some light on the underlying mechanisms. The results showed that co-exposure to As and HFD resulted in a significant increase in serum lipid levels and significant lipid accumulation in the aorta of rats compared with exposure to As or HFD alone. Meanwhile, the combined exposure altered blood pressure and disrupted the morphological structure of the abdominal aorta in rats. Furthermore, As combined with HFD exposure upregulated the expression of vascular endothelial cells pyroptosis-related proteins (ASC, Pro-caspase-1, Caspase-1, IL-18, IL-1ß), as well as the expression of vascular endothelial adhesion factors (VCAM-1 and ICAM-1). More importantly, we found that with increasing exposure time, vascular injury-related indicators were significantly higher in the combined exposure group compared with exposure to As or HFD alone, and the vascular injury was more severe in female rats compared with male rats. Taken together, these results suggested that the combination of As and HFD induced vascular endothelial cells pyroptosis through activation of the ASC/Caspase-1 pathway. Therefore, vascular endothelial cells pyroptosis may be a potential molecular mechanism for vascular injury induced by As combined with HFD exposure.

Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling.

Toll-like receptors (TLRs) are a class of proteins that play critical roles in recognizing pathogens and initiating innate immune responses. TASL, a recently identified innate immune adaptor protein for endolysosomal TLR7/8/9 signaling, is recruited by the lysosomal proton-coupled amino-acid transporter SLC15A4, and then activates IRF5, which in turn triggers the transcription of type I interferons and cytokines. Here, we report three cryo-electron microscopy (cryo-EM) structures of human SLC15A4 in the apo monomeric and dimeric state and as a TASL-bound complex. The apo forms are in an outward-facing conformation, with the dimeric form showing an extensive interface involving four cholesterol molecules. The structure of the TASL-bound complex reveals an unprecedented interaction mode with solute carriers. During the recruitment of TASL, SLC15A4 undergoes a conformational change from an outward-facing, lysosomal lumen-exposed state to an inward-facing state to form a binding pocket, allowing the N-terminal helix of TASL to be inserted into. Our findings provide insights into the molecular basis of regulatory switch involving a human solute carrier and offers an important framework for structure-guided drug discovery targeting SLC15A4-TASL-related human autoimmune diseases.

A New Lunar Dome Detection Method Based on Improved YOLOv7.

Volcanism is an important geological evolutionary process on the Moon. The study of lunar volcanic features is of great significance and value to understanding the geological evolution of the Moon better. Lunar domes are one of the essential volcanic features of the Moon. However, the existing lunar dome detection methods are still traditional manual or semiautomatic identification approaches that require extensive prior knowledge and have a complex identification process. Therefore, this paper proposes an automatic detection method based on improved YOLOv7 for lunar dome detection. First, a new lunar dome dataset was created by digital elevation model (DEM) data, and the effective squeeze and excitation (ESE) attention mechanism module was added to the backbone and neck sections to reduce information loss in the feature map and enhance network expressiveness. Then, a new SPPCSPC-RFE module was proposed by adding the receptive field enhancement (RFE) module into the neck section, which can adapt to dome feature maps of different shapes and sizes. Finally, the bounding box regression loss function complete IOU (CIOU) was replaced by wise IOU (WIOU). The WIOU loss function improved the model's performance for the dome detection effect. Furthermore, this study combined several data enhancement strategies to improve the robustness of the network. To evaluate the performance of the proposed model, we conducted several experiments using the dome dataset developed in this study. The experimental results indicate that the improved method outperforms related methods with a mean average precision (mAP@0.5) value of 88.7%, precision (P) value of 85.6%, and recall (R) value of 86.4%. This study provides an effective solution for lunar dome detection.

MWG-UNet: Hybrid Deep Learning Framework for Lung Fields and Heart Segmentation in Chest X-ray Images.

Deep learning technology has achieved breakthrough research results in the fields of medical computer vision and image processing. Generative adversarial networks (GANs) have demonstrated a capacity for image generation and expression ability. This paper proposes a new method called MWG-UNet (multiple tasking Wasserstein generative adversarial network U-shape network) as a lung field and heart segmentation model, which takes advantages of the attention mechanism to enhance the segmentation accuracy of the generator so as to improve the performance. In particular, the Dice similarity, precision, and F1 score of the proposed method outperform other models, reaching 95.28%, 96.41%, and 95.90%, respectively, and the specificity surpasses the sub-optimal models by 0.28%, 0.90%, 0.24%, and 0.90%. However, the value of the IoU is inferior to the optimal model by 0.69%. The results show the proposed method has considerable ability in lung field segmentation. Our multi-organ segmentation results for the heart achieve Dice similarity and IoU values of 71.16% and 74.56%. The segmentation results on lung fields achieve Dice similarity and IoU values of 85.18% and 81.36%.

Phylotranscriptomics unveil a Paleoproterozoic-Mesoproterozoic origin and deep relationships of the Viridiplantae.

The Viridiplantae comprise two main clades, the Chlorophyta (including a diverse array of marine and freshwater green algae) and the Streptophyta (consisting of the freshwater charophytes and the land plants). Lineages sister to core Chlorophyta, informally refer to as prasinophytes, form a grade of mainly planktonic green algae. Recently, one of these lineages, Prasinodermophyta, which is previously grouped with prasinophytes, has been identified as the sister lineage to both Chlorophyta and Streptophyta. Resolving the deep relationships among green plants is crucial for understanding the historical impact of green algal diversity on marine ecology and geochemistry, but has been proven difficult given the ancient timing of the diversification events. Through extensive taxon and gene sampling, we conduct large-scale phylogenomic analyses to resolve deep relationships and reveal the Prasinodermophyta as the lineage sister to Chlorophyta, raising questions about the necessity of classifying the Prasinodermophyta as a distinct phylum. We unveil that incomplete lineage sorting is the main cause of discordance regarding the placement of Prasinodermophyta. Molecular dating analyses suggest that crown-group green plants and crown-group Prasinodermophyta date back to the Paleoproterozoic-Mesoproterozoic. Our study establishes a plausible link between oxygen levels in the Paleoproterozoic-Mesoproterozoic and the origin of Viridiplantae.

Factors related to dietary quality among older stroke high-risk population in Tianjin community, China: a multicenter study.

BACKGROUND: Stroke is a common and frequently-occurring disease in older people. It has the characteristics of high morbidity, high mortality, high recurrence rate and high disability rate. Most stroke risk studies are based on pathophysiology, however psychosocial factors such as diet quality are often understudied. The aim of this study was to assess stroke risk in urban community residents in Tianjin and investigate the factors that affect the dietary quality of older stroke high-risk populations. METHODS: Using a cross-sectional, multicenter study, recruit people aged 60 to 80 in Tianjin. Dietary intake data were obtained through a validated food frequency questionnaire, which were used to calculate Alternate Healthy Eating Index-2010 (AHEI-2010) and to analyze its association with sociodemographic characteristics, stroke risk factors and health marker variables. RESULTS: A total of 1068 participants from 4 community health service centers in Tianjin were recruited, including 300 low-risk individuals and 768 high-risk individuals. Compared with the low-risk group (62.75 ± 3.59), the AHEI-2010 mean score of the high-risk group (56.83 ± 6.54) was significantly lower. The top three most common risk factors among participants were dyslipidemia (80.3%), hypertension (60.6%), and physical inactivity (58.2%). Multiple logistic regression showed that diet quality was independently and significantly associated with stroke risk (OR = 0.765; 95%CI: 0.690-0.848, p < 0.001). CONCLUSION: The diet quality of high-risk stroke population in Tianjin is far from ideal. At the same time, public health knowledge needs to be disseminated and educated, especially among those at high risk of cerebrovascular disease, with a focus on improving psychosocial factors such as diet quality.

Decomposition and decoupling analysis of multi-sector CO2 emissions based on LMDI and Tapio models: Case study of Henan Province, China.

The peak carbon dioxide emissions at the provincial level is the foundation for achieving the national target of carbon emission peak, thus it is important to analyze the characteristics of provincial CO2 emissions. However, there is a lack of comprehensive analysis and research on quantifying the contributions of the driving factors to decoupling at the provincial level. Therefore, taking Henan Province as the research object, this study establishes the decoupling effort model by combining the traditional LMDI model and Tapio model based on compiling the CO2 emission inventories from 2006 to 2019. The results showed that total CO2 emissions increased from 2006 to 2011, and decreased after 2011 in Henan Province. Raw coal was the primary fuel source of Henan's CO2 emissions, and the sector of "power and heat production" was the major industrial source, accounting for above 45% of the total emissions. Economic output and energy intensity were the major factors promoting and restraining the increase in Henan's CO2 emissions, respectively. In terms of the decoupling state, Henan achieved the transformation from weak decoupling to strong decoupling from 2006 to 2019. Industry presented a strong decoupling condition, while weak decoupling was detected in the agriculture sector during the study period. The changing trend of energy intensity decoupling effort was consistent with that of total decoupling effort, indicating that energy intensity is a crucial factor in achieving decoupling. This study is helpful to grasp the CO2 emission characteristics of Henan Province and provide the theoretical basis for formulating emission mitigation measures of peak carbon dioxide emissions in Henan and other provinces.

Mitigation of maternal fecal microbiota transplantation on neurobehavioral deficits of offspring rats prenatally exposed to arsenic: Role of microbiota-gut-brain axis.

It is established that gut microbiota dysbiosis is implicated in arsenic (As)-induced neurotoxic process, however, the underlying mode of action remains largely unclear. Here, through remodeling gut microbiota on As-intoxicated pregnancy rats using fecal microbiota transplantation (FMT) from Control rats, neuronal loss and neurobehavioral deficits in offspring prenatally exposed to As were significantly alleviated after maternal FMT treatment. In prenatal As-challenged offspring after maternal FMT treatment, remarkably, suppressed expression of inflammatory cytokines in tissues (colon, serum, and striatum) were observed along with reversed mRNA and protein expression of tight junction related molecules in intestinal barrier and blood-brain barrier (BBB); Further, expression of serum lipopolysaccharide (LPS), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and nuclear transcription factor-κB (NF-κB) in colonic and striatal tissues were repressed with activation of astrocytes and microglia inhibited. In particular, tightly correlated and enriched microbiomes were identified such as higher-expressed g_Prevotella, g_UCG_005, and lower-expressed p_Desulfobacterota, g_Eubacterium_xylanophilum_group. Collectively, our results first demonstrated that reconstruction of normal gut microbiota by maternal FMT treatment alleviated prenatal As-induced overall inflammatory state and impairments of intestinal barrier and BBB integrity by impeding LPS-mediated TLR4/Myd88/NF-κB signaling pathway through microbiota-gut-brain axis, which provides a novel therapeutic avenue for developmental arsenic neurotoxicity.

Urinary microbiota and metabolic signatures associated with inorganic arsenic-induced early bladder lesions.

Inorganic arsenic (iAs) contamination in drinking water is a global public health problem, and exposure to iAs is a known risk factor for bladder cancer. Perturbation of urinary microbiome and metabolome induced by iAs exposure may have a more direct effect on the development of bladder cancer. The aim of this study was to determine the impact of iAs exposure on urinary microbiome and metabolome, and to identify microbiota and metabolic signatures that are associated with iAs-induced bladder lesions. We evaluated and quantified the pathological changes of bladder, and performed 16S rDNA sequencing and mass spectrometry-based metabolomics profiling on urine samples from rats exposed to low (30 mg/L NaAsO2) or high (100 mg/L NaAsO2) iAs from early life (in utero and childhood) to puberty. Our results showed that iAs induced pathological bladder lesions, and more severe effects were noticed in the high-iAs group and male rats. Furthermore, six and seven featured urinary bacteria genera were identified in female and male offspring rats, respectively. Several characteristic urinary metabolites, including Menadione, Pilocarpine, N-Acetylornithine, Prostaglandin B1, Deoxyinosine, Biopterin, and 1-Methyluric acid, were identified significantly higher in the high-iAs groups. In addition, the correlation analysis demonstrated that the differential bacteria genera were highly correlated with the featured urinary metabolites. Collectively, these results suggest that exposure to iAs in early life not only causes bladder lesions, but also perturbs urinary microbiome composition and associated metabolic profiles, which shows a strong correlation. Those differential urinary genera and metabolites may contribute to bladder lesions, suggesting a potential for development of urinary biomarkers for iAs-induced bladder cancer.

Co-exposure to arsenic and fluoride to explore the interactive effect on oxidative stress and autophagy in myocardial tissue and cell.

Co-contamination of arsenic and fluoride is widely distributed in groundwater. However, little is known about the interactively influence of arsenic and fluoride, especially the combined mechanism in cardiotoxicity. Cellular and animal models exposure to arsenic and fluoride were established to assess the oxidative stress and autophagy mechanism of cardiotoxic damage using the factorial design, a widely used statistical method for assessing two factor interventions. In vivo, combined exposure to high arsenic (50 mg/L) and high fluoride (100 mg/L) induced myocardial injury. The damage is accompanied by accumulation of myocardial enzyme, mitochondrial disorder, and excessive oxidative stress. Further experiment identified that arsenic and fluoride induced the accumulation of autophagosome and increased expression level of autophagy related genes during the cardiotoxicity process. These findings were further demonstrated through the in vitro model of arsenic and fluoride-treated the H9c2 cells. Additionally, combined of arsenic-fluoride exposure possesses the interactively influence on oxidative stress and autophagy, contributing to the myocardial cell toxicity. In conclusion, our data suggest that oxidative stress and autophagy are involved in the process of cardiotoxic injury, and that these indicators showed interaction effect in response to the combined exposure of arsenic and fluoride.

An integrated framework for industrial symbiosis performance evaluation in an energy-intensive industrial park in China.

Industrial symbiosis (IS) is an important tool to achieve green development for industrial parks. It is necessary to evaluate the IS performance for monitoring and managing the development of IS system. This study proposed an integrated framework to assess the IS performance based on the energy-intensive industrial park. Firstly, we established a Conceptual model of symbiotic coupling of three industries (iron and steel, thermal power, and cement). Then, the conceptual model was applied to extend the existing IS system in the energy-intensive industrial park. Finally, the IS performance of the extended IS system was evaluated. We verified this framework in Red flag cannel park (RFCP). The IS performance assessment in RFCP found that the existing IS activities produced significant multiple benefits and environmental impact reduction. For example, the existing IS activities produced 970.20 kt of low-carbon benefits, which accounted for 19% of the CO2 emissions in RFCP. However, after extending the existing symbiotic system combined with the conceptual model proposed in this study, we found that there still was a large amount of symbiotic potential (the reuse of waste heat, BF slag, gypsum) waiting to be developed in RFCP. In addition, we also found that the resilience of existing IS network in RFCP was weak and need to be further perfected. In general, in the further development and perfection of IS system in RFCP, the manager should not only focus on the development of IS activities among energy-intensive enterprises but also strive to foster more influential enterprises to enhance the anti-risk ability of IS network. The result indicates the integrated framework can provide support for the development and perfection of IS system in energy-intensive industrial parks.

Identifying Serum Metabolites and Gut Bacterial Species Associated with Nephrotoxicity Caused by Arsenic and Fluoride Exposure.

Co-contamination of arsenic (As) and fluoride (F) is widely distributed in groundwater, which are known risk factors for the nephrotoxicity. Emerging evidence has linked environmentally associated nephrotoxicity with the disturbance of gut microbiota and blood metabolites. In this study, we generated gut microbiota and blood metabolomic profile and identified multiple serum metabolites and gut bacteria species, which were associated with kidney injury on rat model exposed to As and F alone or combined. Combined As and F exposure significantly increased creatinine level. Abnormal autophagosomes and lysosome were observed, and the autophagic genes were enhanced in kidney tissue after single and combined As and F exposure. The metabolome data showed that single and combined As and F exposure remarkably altered the serum metabolites associated with the proximal tubule reabsorption function pathway, with glutamine and alpha-ketoglutarate level decreased in all exposed group. Furthermore, phosphatidylethanolamine (PE), the key contributor of autophagosomes, was decreased significantly in As and F + As exposed groups during the screen of autophagy-animal pathway. Multiple altered gut bacterial microbiota at phylum and species levels post As and F exposure were associated with targeted kidney injury, including p_Bacteroidetes, s_Chromohalobacter_unclassified, s_Halomonas_unclassified, s_Ignatzschineria_unclassified, s_Bacillus_subtilis, and s_Brevundimonas_sp._NA6. Meanwhile, our analysis indicated that As and F co-exposure possessed an interactive influence on gut microbiota. In conclusion, single or combined As and F exposure leads to the disruption of serum metabolic and gut microbiota profiles. Multiple metabolites and bacterial species are identified and associated with nephrotoxicity, which have potential to be developed as biomarkers of As and/or F-induced kidney damage.

Cognitive Dysfunction and Its Risk Factors in Patients Undergoing Maintenance Hemodialysis.

Objective: Cognitive impairment (CI) in Maintenance hemodialysis (MHD) is attracting increasing attention. This study aims to clarify the prevalence and risk factors for cognitive dysfunction in patients on MHD who have no history of stroke. Methods: A total of 99 patients with no history of stroke undergoing MHD were enrolled. Global cognitive function was evaluated using the Montreal Cognitive Assessment scale. Attention and executive functions were evaluated by the Digital Span (DS) test and the Color Trail Test (CTT). The Hamilton Depression and Anxiety scales were used to assess depression and anxiety status. The effects of patient background factors, laboratory indicators, anxiety, and depression on cognitive dysfunction were examined by regression analysis. Results: There were 69.70% of the patients had general CI, 65.65% had depression, and 57.57% had anxiety. The forward and backward DS in the cognitively impaired (CI) group were shorter than in the normal cognitive function (NCF) group (P<0.05). Times required for CTT-I, CTT-II, and CTT II - CTT I were longer in the CI group than in the NCF group (P<0.05). Hemoglobin levels were lower, and parathyroid hormone (PTH) and uric acid levels were higher in the CI group than in the NCF group (P<0.05). Hemoglobin levels were negatively correlated with CI in these patients (odds ratio [OR] 0.634, P<0.05) and PTH, and uric acid levels were positively correlated with CI (OR 1.028, P<0.05; and OR 1.011, P<0.05). The proportions of patients with diabetes and depression were higher in the CI group (P<0.05). Conclusion: There was a high prevalence of CI with significant impairment of attention and executive ability in MHD patients who had no stroke history. Hemoglobin may protect cognitive function, while diabetes, PTH, and uric acid levels may be risk factors. Depressive and anxiety states may aggravate CI in MHD patients.

Gait Disorders and Magnetic Resonance Imaging Characteristics in Older Adults with Cerebral Small Vessel Disease.

BACKGROUND: This study aims to explore the features of gait disorders with cerebral small vessel disease (CSVD), and results from magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) were analyzed. METHODS: The 139 patients with CSVD were divided into two groups by the Tinetti scale scores: the gait disorder (GD) group with a score <24 (63 patients) and the normal gait (GN) group with a score ≥24 (76 patients). A series of scales and 3.0T MRI with DTI were used to analyze the correlation between the abnormal gaits and imaging findings. RESULTS: The differences in the Barthel Index, Unified Parkinson's Disease Rating Scale part III, and Montreal Cognitive Assessment (MoCA) scores between the two groups were significant (p < 0.05), and there were significant correlations between MoCA and total gait scores (r = 0.201, p = 0.002). The GD group had a more degraded gait score, widened gait base, and degraded gait length than the GN group (p < 0.05). There were significant differences between the two groups (p < 0.05) in white matter (WM) hyperintensities (WMH) of the Fazekas scale grade 2-3 and lacunes. The GD group had a greater total MRI burden than the GN group (p < 0.05). In DTI parameters, the GD group had lower fractional anisotropy (FA) and higher mean diffusion (MD) values in WM tracts in many areas around the ventricles (family-wise error corrected, p < 0.05). Significant correlations were observed between FA and the total gait score (r = 0.467, p < 0.01), and also between MD and total gait score (r  = -0.422, p < 0.01). CONCLUSIONS: Patients with CSVD with gait disorders had more WMH of Fazekas scale grade 2-3, lacunes, and total MRI burden than the GN patients, and those with gait disorders may suffer from demyelination of nerve fibers and damage to the fibers' microstructures.