Quantitative prediction of water quality in Dongjiang Lake watershed based on LUCC.

Land Use/ Cover Change (LUCC) plays a crucial role in influencing hydrological processes, nutrient cycling, and sediment transport in watersheds, ultimately impacting water quality on both spatial and temporal scales. Accurately predicting changes in watershed water quality is beneficial for the sustainable management of water resources. Current models often lack the ability to effectively predict water quality changes in a dynamic spatio-temporal context, particularly in complex watershed environments. The overall purpose of the study is to establish a comprehensive and dynamic modeling framework that links LUCC with water quality, allowing for accurate predictions of future water quality under varying land use scenarios. The model, which uses water quality as the dependent variable and LUCC as the independent variable, was developed to quantitatively predict changes in watershed water quality. To achieve this, annual multi-period remote sensing images from Landsat-5, Landsat-8 or Sentinel-2 satellites spanning from 1992 to 2022 were analyzed. Random Forest (achieving a Kappa coefficient of 0.9468) were employed to classify land use within the watershed. Based on classification results, a Cellular Automata-Markov chain model (CA-Markov) was constructed to simulate and predict the spatio-temporal patterns of land use, incorporating driving factors such as proximity to water systems, roads, elevation, and slope. Validation of the model using LUCC data from 2020 yielded a high prediction accuracy with a Kappa coefficient of 0.9505. The CA-Markov model was further utilized to project LUCC under three different scenarios-natural development, ecological protection, and arable land protection-between 2023 and 2033. Based on these projections, the coupled water quality and LUCC model was employed to predict water quality changes in the watershed over the same period. Key findings indicate that water quality is likely to improve under ecological protection scenario, while deterioration is expected under natural development scenario and cropland protection scenario due to urban expansion, agricultural practices, and water diversion for irrigation. This study provides a robust framework for watershed management, offering scientific guidance for source management and water purification efforts, thereby contributing significantly to the sustainable development of water resources.

The impact of toe spring and foot strike angle on forefoot running biomechanics: a finite element analysis.

The surge in popularity of running has led to a multitude of designs in running shoe technology, notably, there is an increasing trend in toe spring elevation. However, the impact of this design on foot structures during running remains an essential exploration. To investigate the effects of toe spring on the foot during forefoot running, we employed finite element simulation to create two sole models with different toe spring heights (6.5 cm and 8 cm) and ground contact angles (5°, 10°, and 15°). We established and validated two foot-shoe coupling models and compared stress variations in metatarsal bones and the big toe under identical loading and environmental conditions. Higher toe spring resulted in lower peak stress and reduced stress concentration in metatarsal bones. The fourth and fifth metatarsals exhibited increasing stress trends with ground contact angle, with the fifth metatarsal experiencing the most significant stress concentration. In the case of low toe spring, stress on the fifth metatarsal increased from 15.917 MPa (5°) to 27.791 MPa (15°), indicating a rise of 11.874 MPa. Conversely, the first metatarsal showed lower stress, indicating relative safety but reduced functional significance. Moreover, higher toe spring running shoes exerted less pressure on the big toe, with an increasing trend in stress on the big toe with an increase in ground contact angle. Shoes with a higher toe spring design result in reduced pressure on the big toe. Therefore, it is advisable to avoid landing angles greater than 15° to prevent stress fractures resulting from repetitive loading.

Triclosan exposure causes abnormal bile acid metabolism through IL-1ß-NF-κB-Fxr signaling pathway.

Triclosan (TCS) is an eminent antibacterial agent. However, extensive usage causes potential health risks like hepatotoxicity, intestinal damage, kidney injury, etc. Existing studies suggested that TCS would disrupt bile acid (BA) enterohepatic circulation, but its toxic mechanism remains unclear. Hence, the current study established an 8-week TCS exposure model to explore its potential toxic mechanism. The results discovered 8 weeks consecutive administration of TCS induced distinct programmed cell death, inflammatory cell activation and recruitment, and excessive BA accumulation in liver. Furthermore, the expression of BA synthesis and transport associated genes were significantly dysregulated upon TCS treatment. Additional mechanism exploration revealed that Fxr inhibition induced by TCS would be the leading cause for unusual BA biosynthesis and transport. Subsequent Fxr up-stream investigation uncovered TCS exposure caused pyroptosis and its associated IL-1ß would be the reason for Fxr reduction mediated by NF-κB. NF-κB blocking by dimethylaminoparthenolide ameliorated TCS induced BA disorder which confirmed the contribution of NF-κB in Fxr repression. To sum up, our findings conclud TCS-caused BA disorder is attributed to Fxr inhibition, which is regulated by the IL-1ß-NF-κB signaling pathway. Hence, we suggest Fxr would be a potential target for abnormal BA stimulated by TCS and its analogs.

Equol exerts anti-tumor effects on choriocarcinoma cells by promoting TRIM21-mediated ubiquitination of ANXA2.

Choriocarcinoma is a malignant cancer that belongs to gestational trophoblastic neoplasia (GTN). Herein, serum metabolomic analysis was performed on 29 GTN patients and 30 healthy individuals to characterize the metabolic variations during GTN progression. Ultimately 24 differential metabolites (DMs) were identified, of which, Equol was down-regulated in GTN patients, whose VIP score is the 3rd highest among the 24 DMs. As an intestinal metabolite of daidzein, the anticancer potential of Equol has been demonstrated in multiple cancers, but not choriocarcinoma. Hence, human choriocarcinoma cell lines JEG-3 and Bewo were used and JEG-3-derived subcutaneous xenograft models were developed to assess the effect of Equol on choriocarcinoma. The results suggested that Equol treatment effectively suppressed choriocarcinoma cell proliferation, induced cell apoptosis, and reduced tumorigenesis. Label-free quantitative proteomics showed that 136 proteins were significantly affected by Equol and 20 proteins were enriched in Gene Ontology terms linked to protein degradation. Tripartite motif containing 21 (TRIM21), a E3 ubiquitin ligase, was up-regulated by Equol. Equol-induced effects on choriocarcinoma cells could be reversed by TRIM21 inhibition. Annexin A2 (ANXA2) interacted with TRIM21 and its ubiquitination was modulated by TRIM21. We found that TRIM21 was responsible for proteasome-mediated degradation of ANXA2 induced by Equol, and the inhibitory effects of Equol on the malignant behaviors of choriocarcinoma cells were realized by TRIM21-mediated down-regulation of ANXA2. Moreover, ß-catenin activation was inhibited by Equol, which also depended on TRIM21-mediated down-regulation of ANXA2. Taken together, Equol may be a novel candidate for the treatment for choriocarcinoma.

All-aqueous synthesis of alginate complexed with fibrillated protein microcapsules for membrane-bounded culture of tumor spheroids.

Water-in-water (W/W) emulsions provide bio-compatible all-aqueous compartments for artificial patterning and assembly of living cells. Successful entrapment of cells within a W/W emulsion via the formation of semipermeable capsules is a prerequisite for regulating on the size, shape, and architecture of cell aggregates. However, the high permeability and instability of the W/W interface, restricting the assembly of stable capsules, pose a fundamental challenge for cell entrapment. The current study addresses this problem by synthesizing multi-armed protein fibrils and controlling their assembly at the W/W interface. The multi-armed protein fibrils, also known as 'fibril clusters', were prepared by cross-linking lysozyme fibrils with multi-arm polyethylene glycol (PEG) via click chemistry. Compared to linear-structured fibrils, fibril clusters are strongly adsorbed at the W/W interface, forming an interconnected meshwork that better stabilizes the W/W emulsion. Moreover, when fibril clusters are complexed with alginate, the hybrid microcapsules demonstrate excellent mechanical robustness, semi-permeability, cytocompatibility and biodegradability. These advantages enable the encapsulation, entrapment and long-term culture of tumor spheroids, with great promise for applications for anti-cancer drug screening, tumor disease modeling, and tissue repair engineering.

The association between dietary zinc intake and osteopenia, osteoporosis in patients with rheumatoid arthritis.

BACKGROUND: Diet has been shown to be associated with rheumatoid arthritis (RA), of which osteoporosis is the most common and important complication, and zinc has been shown to inhibit the inflammatory response, but studies on the relationship between dietary zinc and osteoporosis in patients with RA are limited and inconclusive. In this study, we aimed to explore the relationship between dietary zinc intake and osteoporosis or osteopenia in patients with RA. METHODS: Data on RA patients were derived from the National Health and Nutrition Examination Survey (NHANES) 2007 to 2010, 2013 to 2014, and 2017 to 2020. Weighted univariate and multivariate logistic regression models were performed to explore the association between dietary zinc intake and osteoporosis or osteopenia in RA patients. The relationship was further investigated in different age, body mass index (BMI), nonsteroidal use, dyslipidemia, diabetes, and hypertension population. All results were presented as odds ratios (ORs) and confidence intervals (CIs). RESULTS: In total, 905 RA patients aged ≥ 40 years were included. After adjusting all covariates, higher dietary zinc intake was associated with lower odds of osteopenia or osteoporosis (OR = 0.39, 95%CI: 0.18-0.86) in RA patients. The relationship between dietary zinc intake ≥ 19.52 mg and lower odds of osteopenia or osteoporosis were also found in those aged ≥ 60 years (OR = 0.38, 95%CI: 0.16-0.91), BMI normal or underweight (OR = 0.16, 95%CI: 0.03-0.84), nonsteroidal use (OR = 0.14, 95%CI: 0.02-0.82), dyslipidemia (OR = 0.40, 95%CI: 0.17-0.92), diabetes (OR = 0.37, 95%CI: 0.14-0.95), and hypertension (OR = 0.37, 95%CI: 0.16-0.86). CONCLUSION: Higher dietary zinc intake was associated with reduced incidence of osteopenia or osteoporosis in patients with RA. Further longitudinal and randomized trials are necessary to validate our findings and explore the underling mechanisms. Adequate dietary zinc intake may beneficial to the bone health in RA patients.

Dominant role of soil iron and organic matters in arsenic transfer from soil to plant in a mine area in Hunan Province, Central China.

The transfer of arsenic (As) from soil to plant could be significantly influenced by soil parameters through regulating soil As bioavailability. To distinguish the bioavailable As provided by soil and the As uptaken by plants, herein two different soil bioavailable were defined, namely potential soil bioavailable As (evaluated through the bioavailable fraction of As) and actual soil bioavailable As (assessed through plant bioaccumulation factor, BF, and BFavailable). To identify the dominant soil parameters for the two soil bioavailable As forms, soil and plant samples were collected from a former As mine site. The results showed that the potential bioavailable As only accounted for 1.77 to 11.43% in the sampled soils, while the BF and BFavailable in the sampled vegetables ranged from 0.00 to 1.01 and 0.01 to 17.87, respectively. Despite a similar proportion of As in the residual fraction, soil with higher pH and organic matter (OM) content and lower iron (Fe) content showed a higher potential soil bioavailable As. Correlation analysis indicated a relationship between the soil pH and potential soil bioavailable As (r = 0.543, p < 0.01) and between the soil Fe and actual soil bioavailable As (r = - 0.644, p < 0.05, r = - 0.594, p < 0.05). Stepwise multiple linear regression (SMLR) analysis was employed to identify the dominant soil parameters and showed that soil pH and phosphorus (P) content could be used to predict the potential soil bioavailable As (R2 = 0.69, p < 0.001). On the other hand, soil Fe and OM could be used to predict the actual soil bioavailable As (R2 = 0.18-0.86, p < 0.001-0.015, in different vegetables). These results suggest that different soil parameters affect potential and actual soil bioavailable As. Hence, soil Fe and OM are the most important parameters controlling As transfer from soil to plant in the investigated area.

A retrospective analysis of spinal teratomas and spinal lipomas: overlaps and differences in presentation, surgical treatments, and outcomes.

BACKGROUND: Spinal teratomas and lipomas, both adult and pediatric cases, are rare diseases with many similarities, but have yet to be systematically compared. PURPOSE: To systematically compare spinal teratomas and lipomas to optimize management. STUDY DESIGN: Retrospective PATIENT SAMPLE: Symptomatic spinal teratoma and lipoma patients surgically treated at our center. OUTCOME MEASURES: Anatomical distribution, clinical manifestations, resection status, and outcomes. METHODS: Spinal teratoma and lipoma patients with complete data treated during 2008-2023 in our center were enrolled. Electrophysiological monitoring was routinely performed after 2012. Patient characteristics, anatomical distribution, clinical manifestations, surgical resection, and outcomes were analyzed. RESULTS: We enrolled 86 teratoma patients (71 adults) and 51 lipoma patients (39 adults). Most tumors were lumbosacral lesions; cervical/thoracic involvement was more common with lipomas. Pain, the most frequent manifestation, was more common in teratomas. Gross total resection (GTR) was achieved in 51.1% and 49% of teratomas and lipomas, respectively. Electrophysiological monitoring increased the GTR rate from 38.8% to 48.6%. Age independently predicted (OR: 1.040, 95% CI: 1.008-1.078) GTR/near-total resection (NTR). Symptom relief occurred in 81.4% teratoma patients and 64.7% lipoma patients. Recurrence/symptomatic progression occurred in 19 teratomas and 7 lipomas after a median of 95 and 115 months, respectively. Adult lipoma patients without spinal dysraphism had lower recurrence rates. GTR (HR: 0.172, 95% CI: 0.02557-0.7028) and lesion length (HR: 1.351, 95% CI: 1.138-1.607) independently predicted recurrence/progression. CONCLUSIONS: GTR should be pursued for adult/pediatric spinal teratomas and pediatric spinal lipomas. For adult spinal lipoma patients without dysraphism, conservative surgery could be considered.

Almost Sure Stability and Stabilization of Composite Switched Systems With Persistent Dwell Time Constraint.

This article is devoted to the exponential almost sure (EAS) stability and stabilization of continuous-time composite switched systems (CSSs) by employing a novel dual-switching mechanism, which incorporates both persistent dwell time (PDT) switching and a set of Markov processes. The interrelation between the parameters under the PDT constraint is established by ensuring that switching frequency remains within the maximum permissible range, which serves as a pivotal consideration in the stability analysis of CSSs subject to above-mentioned dual-switching mechanism. Furthermore, the sufficient conditions for achieving EAS-stability and stabilization of CSSs are established with the designed switching strategy. Our results, in contrast to previous works that are special cases of our study, are more general and less conservative. Three examples are presented to validate the developed theoretical results.

Effect of onion skin powder on color, lipid, and protein oxidative stability of premade beef patty during cold storage.

The impact of premade beef patty (BBP) with red onion skin powder (OSP) at 0, 1, 2, and 3% levels on color, lipid, and protein oxidative stability, and infection degree of microorganisms during cold storage was investigated. The objective was to determine the effect of color by L*, a*, b*, and the content of MetMb. The inhibitory effect of OSP on the oxidation of lipid and protein was studied based on TBARS and the carbonyl content of protein in samples at different storage times. TVB-N content was used to characterize the degree of infection of microorganisms and their effect on meat quality. The results showed that the addition of OSP reduced the pH, L *, a*, and b * values of BBP, and improved the hardness, springiness, gumminess, and cohesiveness of BBP, but had no significant effect on the chewiness of BBP (p > 0.05). After 12 days of storage, the carbonyl group and TBARS content in the BBP supplemented with 3%OSP was significantly lower than that in the control group (p < 0.05). Furthermore, the addition of OSP significantly inhibited the TVB-N increase during beef patty storage. These results indicated that OSP has a good research prospect as a natural antioxidant or preservative.

Advances and clinical challenges of mesenchymal stem cell therapy.

In recent years, cell therapy has provided desirable properties for promising new drugs. Mesenchymal stem cells are promising candidates for developing genetic engineering and drug delivery strategies due to their inherent properties, including immune regulation, homing ability and tumor tropism. The therapeutic potential of mesenchymal stem cells is being investigated for cancer therapy, inflammatory and fibrotic diseases, among others. Mesenchymal stem cells are attractive cellular carriers for synthetic nanoparticles for drug delivery due to their inherent homing ability. In this review, we comprehensively discuss the various genetic and non-genetic strategies of mesenchymal stem cells and their derivatives in drug delivery, tumor therapy, immune regulation, tissue regeneration and other fields. In addition, we discuss the current limitations of stem cell therapy and the challenges in clinical translation, aiming to identify important development areas and potential future directions.

The efficacy and tendency of the gender digital divide and Smart Aging Policy in China.

China is one of the most rapidly aging countries in the world, challenging the sustainable aging. The booming of digital technology is a double-edged sword. According to the Smart Aging Policies (SAPs), digital technology is supposed to be an effective way to address the challenges of the elder care system. However, the digital divide is causing additional problems. In this study, researchers aim to investigate whether the digital divide among older people could lead to gender-based discrepancies in elder care utilization, using data from the "China Elder Care Satisfaction Survey (CECSS)." Through logit regression analysis, in this study, researchers assessed the relationship between gender and digital elder care utilization, indicating the presence of a gender digital divide among older people. Our findings have important implications for facilitating minority groups to benefit more from SAPs and for advancing research on the gender digital divide among elders to promote sustainable aging.

Association between heavy metals exposure and persistent infections: the mediating role of immune function.

Introduction: Persistent infections caused by certain viruses and parasites have been associated with multiple diseases and substantial mortality. Heavy metals are ubiquitous environmental pollutants with immunosuppressive properties. This study aimed to determine whether heavy metals exposure suppress the immune system, thereby increasing the susceptibility to persistent infections. Methods: Using data from NHANES 1999-2016, we explored the associations between heavy metals exposure and persistent infections: Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Hepatitis C Virus (HCV), Herpes Simplex Virus Type-1 (HSV-1), Toxoplasma gondii (T. gondii), and Toxocara canis and Toxocara cati (Toxocara spp.) by performing logistic regression, weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models. Mediation analysis was used to determine the mediating role of host immune function in these associations. Results: Logistic regression analysis revealed positive associations between multiple heavy metals and the increased risk of persistent infections. In WQS models, the heavy metals mixture was associated with increased risks of several persistent infections: CMV (OR: 1.58; 95% CI: 1.17, 2.14), HCV (OR: 2.94; 95% CI: 1.68, 5.16), HSV-1 (OR: 1.25; 95% CI: 1.11, 1.42), T. gondii (OR: 1.97; 95% CI: 1.41, 2.76), and Toxocara spp. (OR: 1.76; 95% CI: 1.16, 2.66). BKMR models further confirmed the combined effects of heavy metals mixture and also identified the individual effect of arsenic, cadmium, and lead. On mediation analysis, the systemic immune inflammation index, which reflects the host's immune status, mediated 12.14% of the association of mixed heavy metals exposure with HSV-1 infection. Discussion: The findings of this study revealed that heavy metals exposure may increase susceptibility to persistent infections, with the host's immune status potentially mediating this relationship. Reducing exposure to heavy metals may have preventive implications for persistent infections, and further prospective studies are needed to confirm these findings.

High-performance Mg-Zn alloy achieved by the ultrafine grain and nanoparticle design.

Improving the comprehensive performance of low alloyed Mg is a significant challenge for biomedical applications. This paper developed a high-performance Mg-Zn alloy with uniform ultrafine grains and nano-precipitates through a straightforward, high-temperature reciprocating equal channel angle extrusion (ECAP) process and researched the microstructure, mechanical property, degradation behaviour, and biocompatibility of the developed alloy. Results showed that the lean Mg-2Zn alloy successfully refined grain to about 1 µm and produced plenty of nano-particles with uniform distribution, providing high comprehensive mechanical properties (YS: 235 MPa, UTS: 267 MPa, EL: 15.6 %). Additionally, Zn-riched nano-particles in the matrix could decrease the Zn aggregation at the corrosion layer-matrix interface and form a dense oxide film, achieving a low degradation rate (0.13 mm/year in vivo). Finally, this work realizes the low alloy content, low cost, and good properties of one biodegradable Mg alloy, which will benefit the promotion of future clinical applications.

The value of multiparametric MRI-based habitat imaging for differentiating uterine sarcomas from atypical leiomyomas: a multicentre study.

PURPOSE: To explore the feasibility of multiparametric MRI-based habitat imaging for distinguishing uterine sarcoma (US) from atypical leiomyoma (ALM). METHODS: This retrospective study included the clinical and preoperative MRI data of 69 patients with US and 225 patients with ALM from three hospitals. At both the individual and cohort levels, the K-means and Gaussian mixture model (GMM) algorithms were utilized to perform habitat imaging on MR images, respectively. Specifically, T2-weighted images (T2WI) and contrast-enhanced T1-weighted images (CE-T1WI) were clustered to generate structural habitats, while apparent diffusion coefficient (ADC) maps and CE-T1WI were clustered to create functional habitats. Parameters of each habitat subregion were extracted to construct distinct habitat models. The integrated models were constructed by combining habitat and clinical independent predictors. Model performance was assessed using the area under the curve (AUC). RESULTS: Abnormal vaginal bleeding, lactate dehydrogenase (LDH), and white blood cell (WBC) counts can serve as clinical independent predictors of US. The GMM-based functional habitat model at the cohort level had the highest mean AUC (0.766) in both the training and validation cohorts, followed by the GMM-based structural habitat model at the cohort level (AUC = 0.760). Within the integrated models, the K-means functional habitat model based on the cohort level achieved the highest mean AUC (0.905) in both the training and validation cohorts. CONCLUSION: Habitat imaging based on multiparametric MRI has the potential to distinguish US from ALM. The combination of clinical independent predictors with the habitat models can effectively improve the performance.

Repurposing Anidulafungin for Alzheimer's Disease via Fragment-Based Drug Discovery.

The misfolding and aggregation of beta-amyloid (Aß) peptides have been implicated as key pathogenic events in the early stages of Alzheimer's disease (AD). Inhibiting Aß aggregation represents a potential disease-modifying therapeutic approach to AD treatment. Previous studies have identified various molecules that inhibit Aß aggregation, some of which share common chemical substructures (fragments) that may be key to their inhibitory activity. Employing fragment-based drug discovery (FBDD) methods may facilitate the identification of these fragments, which can subsequently be used to screen new inhibitors and provide leads for further drug development. In this study, we used an in silico FBDD approach to identify 17 fragment clusters that are significantly enriched among Aß aggregation inhibitors. These fragments were then used to screen anti-infective agents, a promising drug class for repurposing against amyloid aggregation. This screening process identified 16 anti-infective drugs, 5 of which were chosen for further investigation. Among the 5 candidates, anidulafungin, an antifungal compound, showed high efficacy in inhibiting Aß aggregation in vitro. Kinetic analysis revealed that anidulafungin selectively blocks the primary nucleation step of Aß aggregation, substantially delaying Aß fibril formation. Cell viability assays demonstrated that anidulafungin can reduce the toxicity of oligomeric Aß on BV2 microglia cells. Molecular docking simulations predicted that anidulafungin interacted with various Aß species, including monomers, oligomers, and fibrils, potentially explaining its activity against Aß aggregation and toxicity. This study suggests that anidulafungin is a potential drug to be repurposed for AD, and FBDD is a promising approach for discovering drugs to combat Aß aggregation.

Association of Life's Essential 8 cardiovascular health with breast cancer incidence and mortality according to genetic susceptibility of breast cancer: a prospective cohort study.

BACKGROUND: Accumulating evidence suggests that cardiovascular diseases and breast cancer share a number of common risk factors, however, evidence on the association between cardiovascular health (CVH) and breast cancer is limited. The present study aimed to assess the association of CVH, defined by Life's Essential 8 (LE8) and genetic risk with breast cancer incidence and mortality among premenopausal and postmenopausal women. METHODS: We used data from the UK Biobank and conducted the multivariate Cox proportional-hazards models to examine associations of LE8 score and genetic risk with breast cancer incidence and mortality. Date on LE8 score was collected between 2006 and 2010 and composed of eight components, including behavioral metrics (diet, tobacco or nicotine exposure, physical activity, and sleep health), and biological metrics (body mass index, blood lipids, blood glucose, and blood pressure). The polygenic risk score (PRS) was calculated as the sum of effect sizes of individual genetic variants multiplied by the allele dosage. RESULTS: A total of 150,566 premenopausal and postmenopausal women were included. Compared to postmenopausal women with low LE8 score, those with high LE8 score were associated with 22% lower risk of breast cancer incidence (HR: 0.78, 95% CI: 0.70-0.87) and 43% lower risk of breast cancer mortality (HR: 0.57, 95% CI: 0.36-0.90). By contrast, we did not observe the significant association among premenopausal women. Further analyses stratified by PRS categories showed that high LE8 score was associated with 28% and 71% decreased risk of breast cancer incidence (HR: 0.72, 95% CI: 0.60-0.87) and mortality (HR: 0.29, 95% CI: 0.10-0.83) compared to low LE8 score among high genetic risk groups, but no significant associations were found among low genetic risk groups. Furthermore, compared with postmenopausal women with high LE8 score and low genetic risk, those with low LE8 score and high genetic risk were associated with increased risk of breast cancer incidence (HR: 6.26, 95% CI: 4.43-8.84). CONCLUSIONS: The present study suggests that better CVH is a protective factor for both breast cancer incidence and mortality among postmenopausal women. Moreover, the risk of developing breast cancer caused by high genetic susceptibility could be largely offset by better CVH.

Co-CoSe heterogeneous fibers with strong interfacial built-in electric field as bifunctional electrocatalyst for high-performance Zn-air battery.

The explorations of efficient electrocatalysts to accelerate oxygen reactions in a wide temperature range is a crucial issue to the development of zinc-air batteries (ZAB) for all-climate applications. Herein, the Co-CoSe heterogeneous furry fibers (Co-CoSe@NHF) are developed as a bifunctional oxygen electrocatalyst for ZAB towards wide-temperature range applications. The Co-CoSe heterostructure with large work function difference (ΔWF) endows interfacial electron redistribution, which builds strong interfacial built-in electric field (BIEF) and improves the oxygen reactions. Meanwhile, the Co-CoSe heterostructure is encapsulated by in-situ grown carbon nanotubes, and forms the hollow fiber (NHF) with furry surface and beads-on-string configuration. The highly porous and conductive NHF configuration facilitates the fast kinetics and favors to accommodates volume change during cycling. As a result, the Co-CoSe@NHF achieves the superior bifunctional properties and good reliability for oxygen reactions. Integrated with the Co-CoSe@NHF fiber, the ZAB cell delivers the superior power density (301 mW cm-2) and long-term cycling stability over 280 h at 25 °C, and maintains the power densities of 126 mW cm-2 even the temperature decreases to -25 °C. Moreover, the solid-state ZAB exhibits significant flexibility and superior properties in a wide temperature range. Therefore, this work not only proposes a new strategy to design the high-performance bifunctional electrocatalysts, but also propels the development of flexible power sources for all-climate applications.

Genetic profiles of multiple system atrophy revealed by exome sequencing, long-read sequencing and spinocerebellar ataxia repeat expansion analysis.

BACKGROUND AND PURPOSE: Multiple system atrophy (MSA) is a progressive, adult-onset neurodegenerative disorder clinically characterized by combinations of autonomic failure, parkinsonism, cerebellar ataxia and pyramidal signs. Although a few genetic factors have been reported to contribute to the disease, its mutational profiles have not been systemically studied. METHODS: To address the genetic profiles of clinically diagnosed MSA patients, exome sequencing and triplet repeat detection was conducted in 205 MSA patients, including one familial case. The pathogenicity of variants was determined according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. RESULTS: In the familial patient, a novel heterozygous COQ2 pathogenic variant (p.Ala351Thr) was identified in the MSA pedigree. In the sporadic patients, 29 pathogenic variants were revealed in 21 genes, and the PARK7 p.Ala104Thr variant was significantly associated with MSA (p = 0.0018). Moreover, burden tests demonstrated that the pathogenic variants were enriched in cerebellar ataxia-related genes in patients. Furthermore, repeat expansion analyses revealed that two patients carried the pathogenic CAG repeat expansion in the CACNA1A gene (SCA6), one patient carried the (ACAGG)exp/(ACAGG)exp expansion in RFC1 and one carried the GAA-pure expansion in FGF14 gene. CONCLUSION: In conclusion, a novel COQ2 pathogenic variant was identified in a familial MSA patient, and repeat expansions in CACNA1A, RFC1 and FGF14 gene were detected in four sporadic patients. Moreover, a PARK7 variant and the burden of pathogenic variants in cerebellar ataxia-related genes were associated with MSA.