Cadmium exposure disturbs myocardial lipid signature and induces inflammation in C57BL/6J mice.

Cadmium is a highly ubiquitous environmental pollutant that poses a serious threat to human health. In this study, we assessed the cardiotoxicity of Cd exposure and explored the possible mechanisms by which Cd exerts its toxic effects. The results demonstrated that exposure to Cd via drinking water containing CdCl2 10 mg/dL for eight consecutive weeks induced cardiac injury in C57BL/6J mice. The histopathological changes of myocardial hemolysis, widening of myocardial space, and fracture of myocardial fiber were observed. Meanwhile, elevated levels of cardiac enzyme markers and up-regulation of pro-apoptotic genes also indicated cardiac injury after Cd exposure. Non-targeted lipidomic analysis demonstrated that Cd exposure altered cardiac lipid metabolism, resulted in an increase in pro-inflammatory lipids, and changed lipid distribution abundance. In addition, Cd exposure affected the secretion of inflammatory cytokines by activating the NF-κB signaling pathway, leading to cardiac inflammation in mice. Taken together, results of our present study expand our understanding of Cd cardiotoxicity at the lipidomic level and provide new experimental evidence for uncovering the association of Cd exposure with cardiovascular diseases.

Chronic cadmium exposure induces Parkinson-like syndrome by eliciting sphingolipid disturbance and neuroinflammation in the midbrain of C57BL/6J mice.

Cadmium (Cd) is known as a widespread environmental neurotoxic pollutant. Cd exposure is recently recognized as an etiological factor of Parkinson's disease (PD) in humans. However, the mechanism underlying Cd neurotoxicity in relation to Parkinsonism pathogenesis is unclear. In our present study, C57BL/6 J mice were exposed to 100 mg/L CdCl2 in drinking water for 8 weeks. It was found Cd exposure caused motor deficits, decreased DA neurons and induced neuropathological changes in the midbrain. Non-targeted lipidomic analysis uncovered that Cd exposure altered lipid profile, increased the content of proinflammatory sphingolipid ceramides (Cer), sphingomyelin (SM) and ganglioside (GM3) in the midbrain. In consistency with increased proinflammatory lipids, the mRNA levels of genes encoding sphingolipids biosynthesis in the midbrain were dysregulated by Cd exposure. Neuroinflammation in the midbrain was evinced by the up-regulation of proinflammatory cytokines at mRNA and protein levels. Blood Cd contents and lipid metabolites in Parkinsonism patients by ICP-MS and LC-MS/MS analyses demonstrated that elevated blood Cd concentration and proinflammatory lipid metabolites were positively associated with the score of Unified Parkinson's Disease Rating Scale (UPDRS). 3 ceramide metabolites in the blood showed good specificity as the candidate biomarkers to predict and monitor Parkinsonism and Cd neurotoxicity (AUC>0.7, p < 0.01). In summary, our present study uncovered that perturbed sphingomyelin lipid metabolism is related to the Parkinsonism pathogenesis and Cd neurotoxicity, partially compensated for the deficiency in particular metabolic biomarkers for Parkinsonism in relation to Cd exposure, and emphasized the necessity of reducing Cd exposure at population level.

Functional Hearing Impairment, Psychological Resilience, and Social Well-Being Among Chinese Older Adults in Low-Income Households.

PURPOSE: Hearing loss (HL) is prevalent and relates to social health in old age. This study aims to examine the association between functional HL and social well-being (SWB) in older adults and to investigate whether psychological resilience mediates this association. METHOD: The analytical sample of 4,531 older adults aged ≥ 60 years was from the Sample Survey on Vulnerable Populations from Poor Families in Urban/Rural China (2018). SWB was measured by social networks and social engagement using the Lubben Social Network Scale and Index of Social Engagement Scale, respectively. Functional hearing impairment was defined by a dichotomized measure of self-perceived hearing difficulty. Psychological resilience was assessed by a 25-item Connor-Davidson Resilience Scale. Structural equation modeling was performed to determine associations of HL with SWB and the mediating roles of psychological resilience. RESULTS: Functional HL was associated with reduced SWB among older adults living in low-income households. Hearing-impaired individuals were more likely to be socially isolated and less socially engaged compared to those with normal hearing. The association persisted in gender subsamples and in non-low-income households but not in older adults aged ≥ 70 years. Psychological resilience partially mediated the association of hearing impairment with SWB, accounting for 50.9% of the variance in the change of SWB. CONCLUSIONS: Functional hearing impairment may be a modifiable risk factor for social restrictions and downstream older adults' health. Promotion of hearing health care and accessibility to coping resources including psychological support may improve social wellness among the older adults and benefit healthy aging. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22750736.

Cadmium exposure impairs skeletal muscle function by altering lipid signature and inducing inflammation in C57BL/6J mice.

Cadmium (Cd) is a well-known environmental pollutant with high toxicity. Despite a variety of studies have demonstrated that Cd exposure induces multiple organ damages in humans, there is still a lack of knowledge of Cd induced skeletal muscle impairment. Exercise is a non-invasive, effective intervention to improve human health and combat diseases. In this study, we aimed to evaluate the toxic effects of Cd exposure on skeletal muscle function and explore the possibility of exercise for attenuating skeletal muscle toxicity of chronic Cd exposure. C57BL/6J mice were exposed to Cd via drinking water containing CdCl2 10 mg/dL for 8 weeks while a moderate exercise was daily induced by a motorized treadmill to mice. It was found that Cd exposure significantly reduced the ratio of gastrocnemius and body weight, decreased mouse exercise capacity, weakened muscle strength, promoted lipid accumulation and up-regulated pro-apoptotic genes in the skeletal muscle. Non-targeted lipidomics analysis indicated that Cd exposure disturbed lipid metabolism, altered lipid signatures and elevated pro-inflammatory lipid species in the skeletal muscle. Moreover, Cd exposure evoked an intense inflammatory response in the skeletal muscle by up-regulating pro-inflammatory cytokine production such as Eotaxin (CCL11), TNF-α, IL-1ß, IL-6, RANTES (CCL5) and so on. Notably, treadmill exercise effectively protected against Cd induced skeletal muscle impairment indicated by the effects of inhibiting lipid metabolism disturbance, suppressing pro-inflammatory cytokine production and preserving skeletal muscle function. These results demonstrated that environment relevant Cd exposure impairs skeletal muscle function and exercise effectively antagonizes the Cd toxicity in the skeletal muscle and preserves skeletal muscle function. This study provided the novel evidence for unraveling Cd toxicity on the skeletal muscle function and highlighted the possibility of considering exercise as a countermeasure for Cd induced skeletal muscle impairment at population level.

An FPGA-Implemented Antinoise Fuzzy Recurrent Neural Network for Motion Planning of Redundant Robot Manipulators.

When a robot completes end-effector tasks, internal error noises always exist. To resist internal error noises of robots, a novel fuzzy recurrent neural network (FRNN) is proposed, designed, and implemented on field-programmable gated array (FPGA). The implementation is pipeline-based, which guarantees the order of overall operations. The data processing is based on across-clock domain, which is beneficial for computing units' acceleration. Compared with traditional gradient-based neural networks (NNs) and zeroing neural networks (ZNNs), the proposed FRNN has faster convergence rate and higher correctness. Practical experiments on a 3 degree-of-freedom (DOs) planar robot manipulator show that the proposed fuzzy RNN coprocessor needs 496 lookup table random access memories (LUTRAMs), 205.5 block random access memories (BRAMs), 41 384 lookup tables (LUTs), and 16 743 flip-flops (FFs) of the Xilinx XCZU9EG chip.

Distribution of the compression and expansion of morbidity in 194 countries and territories, 1990-2016: The role of income inequality.

Studies on detailed types of health changes and the associations between the types and income inequality are inadequate. This study analyses the global distribution of the compression and expansion of morbidity in 194 countries and territories between 1990 and 2016, and investigates the role of income inequality in the distribution. This study shows that all seven types of health changes coexist, despite being distributed unevenly. The relative expansion of morbidity with increased or constant life expectancy (Type 6, 54.48%) is the most popular type, followed by the relative compression of morbidity with increased or constant life expectancy (Type 3, 30.71%). Income distribution within a society matters for health changes. Societies with greater income inequality tend to have Type 6, a worse scenario of health changes. Measures to reduce income inequality or mitigate its adverse effects will contribute to the relative compression of morbidity with increased or constant life expectancy.

Study on the Evolution and Optimization of the Spatial Structure of the Oasis in the Arid Area: A Case Study of the Aksu River Basin in China.

To achieve high-quality sustainable development in arid areas based on the concept of ecological civilization, it is necessary to deeply study the territorial spatial structure characteristics. Taking the Aksu River Basin, an important ecological security barrier in northwest China, as an example, this paper follows the research idea of "feature analysis-suitability evaluation-conflict identification analysis-optimization" and constructs a comprehensive model based on the AHP-entropy weight comprehensive evaluation method, ArcGIS spatial identification analysis, variance coefficient-TOPSIS method, and NRCA. A comprehensive model based on the AHP-entropy power integrated evaluation method, ArcGIS spatial identification analysis, variance coefficient-TOPSIS method, and NRCA was constructed to guide the optimization of the territorial spatial layout by exploring the characteristics of territorial spatial pattern, the suitability of territorial spatial development, the identification of territorial spatial conflicts, and the efficiency and functional advantage of territorial spatial utilization in the study area. The results show that: (1) The spatial type of territorial space in the Aksu River Basin from 2000 to 2020 is dominated by ecological space, agricultural space, and urban space, and the three spatial boundaries are irregularly interlaced. (2) The spatial utilization conflict pattern of the Aksu River Basin has formed, and the general conflict area is overgrowing. (3) The overall efficiency of territorial utilization in the Aksu River Basin is low, with significant differences among county administrative units. (4) After optimization, the three types of space in the watershed are adjusted and refined into six functional areas: basic farmland protection area, rural development area, ecological protection red line area, ecological control area, urban development area, and industrial supporting construction area.

Paraquat exposure induces Parkinsonism by altering lipid profile and evoking neuroinflammation in the midbrain.

Paraquat (PQ) is the most widely used herbicide in the world and a well-known potent neurotoxin for humans. PQ exposure has been linked to increase the risk of Parkinson's disease (PD). However, the mechanism underlying its neurotoxic effects in PD pathogenesis is unclear. In our present study, C57BL/6J mice treated with PQ manifested severe motor deficits indicated by the significant reductions in suspension score, latency to fall from rotarod, and grip strength at 8 weeks after PQ exposure. Pathological hallmarks of Parkinsonism in the midbrain such as dopaminergic neuron loss, increased α-synuclein protein, and dysregulated PD-related genes were observed. Non-targeted lipidome analysis demonstrated that PQ exposure alters lipid profile and abundance, increases pro-inflammatory lipids.27 significantly altered subclasses of lipids belonged to 6 different lipid categories. Glycerophospholipids, sphingolipids, and glycerides were the most abundant lipids. Abundance of pro-inflammatory lipids such as Cer, LPC, LPS, and LPI was significantly increased in the midbrain. mRNA expressions of genes regulating ceramide biosynthesis in the midbrain were markedly up-regulated. Moreover, PQ exposure increased serum pro-inflammatory cytokines and provoked neuroinflammation in the midbrain. Pro-inflammatory lipids and cytokines in the midbrain were positively correlated with motor deficits. PQ poisoning in humans significantly also elevated serum pro-inflammatory cytokines and induced an intense systemic inflammation. In summary, we presented initial investigations of PQ induced molecular events related to the PD pathogenesis, capturing aspects of disturbed lipid metabolism, neuroinflammation, impairment of dopaminergic neurons in the midbrain, and an intense systemic inflammation. These neurotoxic effects of PQ exposure may mechanistically contribute to the pathogenesis of PQ induced Parkinsonism. Results of this study also strongly support the hypothesis that ever-increasing prevalence of Parkinson's disease is etiologically linked to the health risk of exposure to neurotoxic environmental pollutants.

Study on the Measurement and Influencing Factors of Care Service Demand of Disabled Elderly in Urban and Rural China.

Caregiving services are currently the weakest part of China's social security system for the elderly. It is well needed to investigate the fac-tors affecting the unmet care needs of the elderly with disabilities. Based on the Behavioral Model of Health Services Use (BMHSU), this paper explores the needs and influencing factors of care services for the disabled elderly in urban and rural areas using data from the 2018 Project of Social Policy Support System for Disadvantaged Families in China. The demand for care services of the disabled elderly in central and western areas is significantly higher than that in eastern, along with that in rural areas significantly higher than that in urban areas. The demands for care services of the disabled elderly in urban and rural areas are significantly affected by tendency factors, resource factors, and need factors. Urban and rural attributes, worried pension and LCI are the common influencing factors for the care service demand of the disabled elderly from economically disadvantaged families and ordinary families. The demands for care services of the disabled elderly were associated with tendencies, resources, and needs, increased chronic disease prevention and mental health services benefit caregivers.

Cadmium induces ferroptosis mediated inflammation by activating Gpx4/Ager/p65 axis in pancreatic ß-cells.

Cadmium (Cd) is a widely distributed endocrine disruptor and has been reported to be closely correlated to the pathogenesis of diabetes. Since pancreatic ß-cells loss and dysfunction are central to pathogenesis of diabetes, studying Cd toxicity on pancreatic ß-cells and its molecular mechanism is an important scientific issue. However, less attention has been payed to study how Cd induces pancreatic ß-cells death and dysfunction in recent years. Thus, our study aims to explore the toxic mechanism of Cd treatment on pancreatic ß-cells using both cellular and animal models. Firstly, it was confirmed that Cd induced decreased cell viability and insulin secretion in a dose-and time-dependent manner in MIN6 cells. To explore the underlying mechanism, transcriptomic analysis was employed to screen the differentially expressed genes and disturbed metabolic pathways. Go and KEGG analysis showed that Cd exposure triggered ferroptosis process in MIN6 cells. We further validated that Cd led to GSH depletion, Gpx4 reduction, lipid peroxidation, mitochondrial membrane potential loss and ultrastructural damage at mitochondrial level. Since immune system process was also perturbed based on GO analysis, we found that Cd activated Ager/Pkc/p65 inflammatory process. Moreover, ferroptosis inhibitor Fer-1 could effectively antagonized the activation of Ager-mediated immune process. It was also revealed that Cd induced iron accumulation as well as decreased Gpx4 expression in mice islets. We also uncovered that Cd led to systemic and pancreatic inflammation as early as third week after Cd exposure. Our study emphasizes the importance of ferroptotic cell death on Cd-induced systemic chronic inflammation. A novel target is provided to prevent Cd-induced pancreatic ß-cells dysfunction and improve the chronic inflammatory state for prediabetes prevention.

A Highly Sensitive and Flexible Strain Sensor Based on Dopamine-Modified Electrospun Styrene-Ethylene-Butylene-Styrene Block Copolymer Yarns and Multi Walled Carbon Nanotubes.

As wearable electronic devices have become commonplace in daily life, great advances in wearable strain sensors occurred in various fields including healthcare, robotics, virtual reality and other sectors. In this work, a highly stretchable and sensitive strain sensor based on electrospun styrene-ethylene-butene-styrene copolymer (SEBS) yarn modified by dopamine (DA) and coated with multi-walled carbon nanotubes (MWCNTs) was reported. Due to the process of twisting, a strain senor stretched to a strain of 1095.8% while exhibiting a tensile strength was 20.03 MPa. The strain sensor obtained a gauge factor (GF of 1.13 × 105) at a maximum strain of 215%. Concurrently, it also possessed good stability, repeatability and durability under different strain ranges, stretching speeds and 15,000 stretching-releasing cycles. Additionally, the strain sensor exhibited robust washing fastness under an ultrasonic time of 120 min at 240 W and 50 Hz. Furthermore, it had a superior sensing performance in monitoring joint motions of the human body. The high sensitivity and motion sensing performance presented here demonstrate that PDA@SEBS/MWNCTs yarn has great potential to be used as components of wearable devices.

Cadmium perturbed metabolomic signature in pancreatic beta cells correlates with disturbed metabolite profile in human urine.

Cd exposure has been demonstrated to induce a variety of metabolic disorders accompanied with imbalance of glucose and lipid homeostasis. The metabolic toxicity of Cd exposure at metabolome-wide level remains elusive. In our study, we demonstrated that Cd exposure via drinking water increased blood glucose levels, decreased serum insulin levels, led to glucose intolerance and suppressed insulin expression in the pancreas of C57/6J mice. Cd exposure significantly inhibited cell viability and suppressed insulin secretion in MIN6 cells in vitro. Since pancreatic ß-cells are the only source of insulin production in the body and play a pivotal role in modulating glucose and lipid metabolisms, we further delineated the metabolomic signatures of Cd exposure in insulin-secreting MIN6 cells by using non-target metabolomics. PCA and OPLS-DA analysis clearly suggested that Cd exposure led to a marked metabolic alteration in MIN6 cells. 76 perturbed metabolites were identified after Cd exposure. Classification of metabolites suggested that Cd perturbed metabolites belong to nucleosides, nucleotides and analogues, organic acids and derivatives, and lipids and lipid-like molecules. 28 perturbed metabolites existed in mitochondrion, suggesting mitochondrion as the major target organelle in metabolic toxicity of Cd exposure. KEGG pathway analysis revealed that 20 metabolic pathways were disturbed by Cd exposure. Mitochondrial TCA cycle and glycerophospholipid metabolism were remarkably disturbed. The mRNA expressions of genes in mitochondrial TCA cycle and fatty acid oxidation in pancreas and MIN6 cells were significantly dysregulated by Cd exposure. Disturbances in mitochondrial TCA cycle and glycerophospholipid metabolism result in producing perturbed metabolites in pancreatic ß-cells. Moreover, 14 perturbed metabolites identified in MIN6 cells co-existed in the urine of Cd exposed workers. 11 biomarkers of diabetes mellitus were also found to be significantly altered in the urine of Cd exposed workers. In conclusion, findings of this study greatly extend our understanding of metabolic toxicity of Cd exposure in pancreatic ß-cells at metabolome-wide level and offer some new clues for linking Cd exposure to development of diabetes mellitus. Results of this study also support the notion that Cd induced metabolic toxicity could be monitored by examining perturbed urinary metabolites in humans and highlight the significance of reducing Cd exposure via drinking water at population level.

Cadmium exposure suppresses insulin secretion through mtROS-mediated mitochondrial dysfunction and inflammatory response in pancreatic beta cells.

BACKGROUND: Cadmium (Cd) exposure is a worldwide environmental threat to the public health and participates in the pathogenesis of multiple diseases. Epidemiologic research have established a direct relation between Cd exposure and diabetes development in humans. Although pancreatic ß-cell dysfunction has been considered as the major culprit in the pathogenesis of diabetes, there is a paucity of studies to elucidate the molecular mechanism of Cd toxicity on ß-cells. METHODS: To unveil the toxic effect and its underlying mechanism of Cd exposure on ß-cells, we used an in vitro MIN6 cell model of environment-relevant Cd exposure to elucidate the crucial role of mtROS-mediated mitochondrial dysfunction and inflammatory response in suppression of pancreatic ß-cell insulin secretion. RESULTS: We uncovered that Cd treatment suppresses cell viability and induces insulin secretion dysfunction in a dose-dependent manner. Moreover, Cd exposure elicits the inflammatory response, as indicated by increased IL-1ß, IL-6 and TNF-α expressions. Significant elevations of intracellular ROS and mitochondrial ROS levels were detected as early as 3 h after Cd treatment. In mitochondrial function analysis, we demonstrated that Cd treatment induced mitochondrial dysfunction and disorder of mitochondrial fission indicated by the significant decline in ATP production, the marked depolarization of mitochondrial membrane potential, the decrease in mtDNA copy numbers, the suppressions of mitochondrial transcription factor A (Tfam) and mitochondrial fission-related gene Drp1 expressions. Pretreatment with TEMPO, a specific mitochondrial ROS (mtROS) scavenger, efficiently antagonizes Cd cytotoxicity, which is indicated by attenuating Cd-induced mitochondrial dysfunction, suppressing IL-1ß, IL-6 and TNF-α expressions, ameliorating insulin production dysfunction and preserving cell viability in MIN6 cells. CONCLUSION: Our study demonstrates that Cd exposure induces an inflammatory response through mtROS-mediated mitochondrial dysfunction. Antagonism of mtROS production might be an effective strategy to prevent pancreatic toxicity from environment-relevant Cd exposure.

Household indebtedness and depressive symptoms among older adults in China: The moderating role of social network and anticipated support.

BACKGROUND: Examine the association of household financial indebtedness with depressive symptoms in old age, and investigate whether social network and support anticipation moderate the association. METHODS: Data were obtained from Sample Survey on Vulnerable Populations from Poor Families in Urban/Rural China (2018), with a sample of 5 934 older adults included. Center for Epidemiologic Studies Depression Scales was applied to measure depressive symptoms. Household indebtedness was measured in several ways, including whether the household was indebted, the amount of debts, and types of debts. We used the 6-item Lubben Social Network Scale to measure individual's social network. Socio-demographic, socioeconomic status and physical health variables were included as covariates. RESULTS: Household indebtedness, in form of being indebted and increased amount of debts, was associated with greater depressive symptoms in the Chinese elderly. The association of indebtedness and depressive symptoms may be driven by consumption and emergency debts. The moderating roles of social network and anticipation of support in the association of household indebtedness and depressive symptoms were found. Among those with household debts, older adults with larger size of social network and/or higher anticipation of being supported in the future reported with less symptoms of depressed. LIMITATIONS: Due to a lack of information on the duration and debtor of household debt, we were not able to present a precise estimate for the exact impact of household indebtedness on mental health of elderly. CONCLUSION: Familial financial strain was associated with aging mental well-being, increased social networks and social protections benefit aging health.

Recognition of soybean pods and yield prediction based on improved deep learning model.

As a leaf homologous organ, soybean pods are an essential factor in determining yield and quality of the grain. In this study, a recognition method of soybean pods and estimation of pods weight per plant were proposed based on improved YOLOv5 model. First, the YOLOv5 model was improved by using the coordinate attention (CA) module and the regression loss function of boundary box to detect and accurately count the pod targets on the living plants. Then, the prediction model was established to reliably estimate the yield of the whole soybean plant based on back propagation (BP) neural network with the topological structure of 5-120-1. Finally, compared with the traditional YOLOv5 model, the calculation and parameters of the proposed model were reduced by 17% and 7.6%, respectively. The results showed that the average precision (AP) value of the improved YOLOv5 model reached 91.7% with detection rate of 24.39 frames per millisecond. The mean square error (MSE) of the estimation for single pod weight was 0.00865, and the average coefficients of determination R2 between predicted and actual weight of a single pod was 0.945. The mean relative error (MRE) of the total weight estimation for all potted soybean plant was 0.122. The proposed method can provide technical support for not only the research and development of the pod's real-time detection system, but also the intelligent breeding and yield estimation.