A deep-learning-based threshold-free method for automated analysis of rodent behavior in the forced swim test and tail suspension test.

BACKGROUND: The forced swim test (FST) and tail suspension test (TST) are widely used to assess depressive-like behaviors in animals. Immobility time is used as an important parameter in both FST and TST. Traditional methods for analyzing FST and TST rely on manually setting the threshold for immobility, which is time-consuming and subjective. NEW METHOD: We proposed a threshold-free method for automated analysis of mice in these tests using a Dual-Stream Activity Analysis Network (DSAAN). Specifically, this network extracted spatial information of mice using a limited number of video frames and combined it with temporal information extracted from differential feature maps to determine the mouse's state. To do so, we developed the Mouse FSTST dataset, which consisted of annotated video recordings of FST and TST. RESULTS: By using DSAAN methods, we identify immobility states at accuracies of 92.51 % and 88.70 % for the TST and FST, respectively. The predicted immobility time from DSAAN is nicely correlated with a manual score, which indicates the reliability of the proposed method. Importantly, the DSAAN achieved over 80 % accuracy for both FST and TST by utilizing only 94 annotated images, suggesting that even a very limited training dataset can yield good performance in our model. COMPARISON WITH EXISTING METHOD(S): Compared with DBscorer and EthoVision XT, our method exhibits the highest Pearson correlation coefficient with manual annotation results on the Mouse FSTST dataset. CONCLUSIONS: We established a powerful tool for analyzing depressive-like behavior independent of threshold, which is capable of freeing users from time-consuming manual analysis.

Life's essential 8, genetic susceptibility, and risk of inflammatory bowel diseases: a population-based cohort study.

BACKGROUND: Evidence has shown that the individual metrics in Life's Essential 8 (LE8), an updated cardiovascular health (CVH) concept proposed by the American Heart Association, play a role in the development of inflammatory bowel disease (IBD). However, epidemiological evidence on the overall LE8 on IBD risk remains limited. We aimed to assess the longitudinal associations of LE8-defined CVH and the risks of IBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD). We also tested whether genetic susceptibility could modify these associations. METHODS: A total of 260,836 participants from the UK Biobank were included. LE8 scores were determined by 8 metrics (physical activity, diet, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and blood lipids), and were divided into three levels: low CVH (0-49), moderate CVH (50-79), and high CVH (80-100). Cox proportional hazards models were used to calculate the hazard ratios (HRs) and confidence intervals (CIs) of the risk of IBD in relation to CVH status. RESULTS: Over a median follow-up 12.3 years, we documented 1,500 IBD cases (including 1,070 UC and 502 CD). Compared to participants with low CVH, the HRs (95% CIs) of those with high CVH for IBD, UC, and CD were 0.67 (0.52, 0.83), 0.70 (0.52, 0.93), and 0.55 (0.38, 0.80), respectively. These associations were not modified by genetic susceptibility (all P for interactions > 0.05). The lowest HR (UC: 0.30, 95% CI: 0.20-0.45; CD: 0.33, 95% CI: 0.20-0.57) was observed in participants with both high CVH and low genetic risk. CONCLUSIONS: Better CVH, defined by LE8, was associated with significantly lower risks of IBD, UC, and CD, irrespective of genetic predisposition. Our results underscore the importance of adherence to LE8 guidelines for maintaining CVH as a potential strategy in the prevention of IBD.

Physical frailty, genetic predisposition, and the risks of severe non-alcoholic fatty liver disease and cirrhosis: a cohort study.

BACKGROUND: Frailty, defined as a phenotype of decreased physiological reserves and diminished ability to respond to stressors, has been linked to the development of chronic diseases. Epidemiological evidence connecting frailty to non-alcoholic fatty liver disease (NAFLD) and cirrhosis risks remain sparse. We aimed to assess the longitudinal associations of frailty with the risks of severe NAFLD and cirrhosis in middle-aged to older adults and further explore the modification role of genetic risk on these associations. METHODS: This study included a total of 398 386 participants from the UK Biobank. Incident cases of severe NAFLD and cirrhosis were ascertained through linked hospital records and death registries. Frailty status was assessed by a modified version of the frailty phenotype, encompassing five key components: weight loss, tiredness, physical activity, gait speed, and grip strength. Participants were classified as pre-frailty if they met one or two of these criteria, and as frailty if they met three or more. Genetic predisposition to NAFLD and cirrhosis was estimated by genetic risk score (GRS) and further categorized into high, intermediate, and low genetic risk levels according to tertiles of GRSs. Cox proportional hazards regression model was employed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for their associations. RESULTS: The mean (standard deviation) age of the study population was 56.6 (8.03) years. 214 408 (53.8%) of the participants was female; 14 924 (3.75%) of participants met the criteria for frailty, 170 498 (42.8%) for pre-frailty, and 212 964 (53.5%) for non-frailty. Over a median follow-up of 12.0 years, we documented 4439 incident severe NAFLD and 3323 incident cirrhosis cases, respectively. Compared with non-frailty, both pre-frailty (HR: 1.50; 95% CI: 1.40-1.60) and frailty (HR: 1.98; 95% CI: 1.77-2.21) were associated with increased risk of NAFLD. Similar associations were observed for cirrhosis, the corresponding HRs (95% CIs) for non-frailty, pre-frailty, and frailty were 1.00 (reference), 1.29 (1.20, 1.38), and 1.90 (1.66, 2.18). Such associations were consistent across all genetic risk levels, with no observed interactions between frailty and GRSs (all P for interactions ≥0.10). Compared with participants with frailty and a low level of genetic risk, the greatest risk increasement in developing severe NAFLD (HR: 3.36; 95% CI: 2.83-3.99) and cirrhosis (HR: 2.81; 95% CI: 2.29-3.44) was both observed in those with frailty and a high level of genetic risk. CONCLUSIONS: Our findings indicate that frailty is a significant predictor of severe NAFLD and cirrhosis, irrespective of genetic predisposition.

In Situ Polymerization Bi-Functional Gel Polymer Electrolyte for High Performance Quasi-Solid-State Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are expected to be the next-generation energy storage system due to the ultrahigh theoretical energy density and low cost. However, the notorious shuttle effect of higher-order polysulfides and the uncontrollable lithium dendrite growth are the two biggest challenges for commercially viable Li-S batteries. Herein, these two main challenges are solved by in situ polymerization of bi-functional gel polymer electrolyte (GPE). The initiator (SiCl4) not only drives the polymerization of 1,3-dioxolane (DOL) but also induces the construction of a hybrid solid electrolyte interphase (SEI) with inorganic-rich compositions on the Li anode. In addition, diatomaceous earth (DE) is added and anchored in the GPE to obtain PDOL-SiCl4-DE electrolyte through in situ polymerization. Combined with density functional theory (DFT) calculations, the hybrid SEI provides abundant adsorption sites for the deposition of Li+, inhibiting the growth of lithium dendrites. Meanwhile, the shuttle effect is greatly alleviated due to the strong adsorption capacity of DE toward lithium polysulfides. Therefore, the Li/Li symmetric cell and Li-S full cell assembled with PDOL-SiCl4-DE exhibit excellent cycling stability. This study offers a valuable reference for the development of high performance and safe Li-S batteries.

Pulmonary function, genetic predisposition, and the risk of cirrhosis: A prospective cohort study.

OBJECTIVE: Pulmonary function is associated with the development of chronic liver disease. However, evidence of the association between pulmonary function and cirrhosis risk is still lacking. This study aimed to investigate the longitudinal associations of pulmonary function with the development of cirrhosis, and to explore whether genetic predisposition to cirrhosis could modify these associations. METHODS: Of 294,835 participants free of cirrhosis and had undergone spirometry at baseline from the UK Biobank were included. Cirrhosis diagnoses were ascertained through linked hospital records and death registries. Cox proportional hazard models were employed to investigate the longitudinal associations between pulmonary function, genetic predisposition, and cirrhosis risk. RESULTS: During a median follow-up of 12.0 years, 2598 incident cirrhosis cases were documented. Compared to individuals with normal spirometry findings, those with preserved ratio impaired spirometry (PRISm) findings (hazard ratio [HR] and 95% confidence interval [CI]: 1.32 [1.18, 1.48]) and airflow obstruction (HR [95%CI]: 1.19 [1.07, 1.31]) had a higher risk of developing cirrhosis after adjustments. These associations were consistent across all categories of genetic predisposition, with no observed modifying effect of genetic predisposition. In joint exposure analyses, the highest risk was observed in individuals with both a high genetic predisposition for cirrhosis and PRISm findings (HR [95% CI]: 1.74 [1.45, 2.08]). CONCLUSIONS: Our findings indicate that worse pulmonary function is a significant risk factor of cirrhosis, irrespective of genetic predisposition. Early identification and appropriate intervention for pulmonary function may lead to more effective healthcare resource utilization and reduce the burden associated with cirrhosis.

A dynamic online nomogram for predicting renal outcomes of idiopathic membranous nephropathy.

BACKGROUND: Because spontaneous remission is common in IMN, and there are adverse effects of immunosuppressive therapy, it is important to assess the risk of progressive loss of renal function before deciding whether and when to initiate immunosuppressive therapy. Therefore, this study aimed to establish a risk prediction model to predict patient prognosis and treatment response to help clinicians evaluate patient prognosis and decide on the best treatment regimen. METHODS: From September 2019 to December 2020, a total of 232 newly diagnosed IMN patients from three hospitals in Liaoning Province were enrolled. Logistic regression analysis selected the risk factors affecting the prognosis, and a dynamic online nomogram prognostic model was constructed based on extreme gradient boost, random forest, logistic regression machine learning algorithms. Receiver operating characteristic and calibration curves and decision curve analysis were utilized to assess the performance and clinical utility of the developed model. RESULTS: A total of 130 patients were in the training cohort and 102 patients in the validation cohort. Logistic regression analysis identified four risk factors: course ≥ 6 months, UTP, D-dimer and sPLA2R-Ab. The random forest algorithm showed the best performance with the highest AUROC (0.869). The nomogram had excellent discrimination ability, calibration ability and clinical practicability in both the training cohort and the validation cohort. CONCLUSIONS: The dynamic online nomogram model can effectively assess the prognosis and treatment response of IMN patients. This will help clinicians assess the patient's prognosis more accurately, communicate with the patient in advance, and jointly select the most appropriate treatment plan.

Life's Essential 8, genetic susceptibility, and the risk of psoriatic disease: a prospective cohort study.

BACKGROUND: Psoriatic disease (PsD) is closely associated with cardiovascular diseases. The Life's Essential 8 (LE8) score is a new metric for assessing cardiovascular health (CVH), where a higher score indicates better CVH. However, the longitudinal association between LE8 score and the risk of PsD remains uncertain. The main aim of the present study was to explore the association between LE8 scores and the risk of PsD. OBJECTIVE: To investigate the associations between LE8 score, genetic susceptibility, and the risk of PsD within a cohort design. METHODS: This cohort study included 261,642 participants from the UK Biobank without PsD at baseline. LE8 comprises eight indicators: diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. Cox proportional hazard models were employed to examine the association between the participants' LE8 scores, PsD genetic risk, and the risk of PsD. Hazard ratios (HRs) and 95% confidential intervals (CIs) were calculated. RESULTS: During an average follow-up of 12.32 years, 1,501 participants developed PsD. Compared to participants with low LE8 scores, the HRs (95% CIs) of developing PsD for those with moderate and high LE8 scores were 0.51 (0.43, 0.59) and 0.34 (0.27, 0.42) after adjustments, respectively. Dose-response analysis revealed a linear negative association between continuous LE8 score and the risk of developing PsD (P < 0.001), with no evidence of non-linear association detected. The genetic susceptibility to PsD did not modify this association (P for interaction = 0.63). Subgroup analyses revealed that women demonstrated a more pronounced beneficial association between LE8 scores and PsD risk (P for interaction = 0.02). CONCLUSIONS: Our study suggests that a higher LE8 score, regardless of genetic risk, was associated with a lower risk of PsD, particularly among women. Consequently, maintaining a high CVH status is recommended to prevent PsD and assess associated risks.

Plasma Coupled Electrolyte Additive Strategy for Construction of High-Performance Solid Electrolyte Interphase on Li Metal Anodes.

High-performance lithium metal anodes are crucial for the development of advanced Li metal batteries. Herein, this work reports a novel plasma coupled electrolyte additive strategy to prepare high-quality composite solid electrolyte interphase (SEI) on Li metal to achieve enhanced performance and stability. With the guidance of calculations, this work selects diethyl dibromomalonate (DB) as an additive to optimize the solvation structure of electrolytes to modify the SEI. Meanwhile, this work groundbreakingly develops DB plasma technology coupled with DB electrolyte additive to construct a combinatorial SEI: inner plasma-induced SEI layer composed of LiBr and Li2CO3 plus additive-reduced SEI containing LiBr/Li2CO3/organic lithium compounds as an outer compatible layer. The optimized hybrid SEI has strong affinity toward Li+ and good mechanical properties, thereby inducing horizontal dispersion and uniform deposition of Li+ and keep structure stable. Accordingly, the symmetrical cells exhibit enhanced cycling stability for 1200 h at an overpotential of 23.8 mV with average coulombic efficiency (99.51%). Additionally, the full cells with LiNi0.8Co0.1Mn0.1O2 cathode deliver a capacity retention of 81.7% after 300 cycles at 0.5 C, and the pouch cell achieves a volumetric specific energy of ≈664 Wh L‒1. This work provides new enlightenment on plasma technology for fabrication of advanced metal anodes for energy storage.

Enhancing Layer-Engineered Interlayer Exciton Emission and Valley Polarization in van der Waals Heterostructures via Strain.

Layer-engineered interlayer excitons from heterostructures of transition-metal dichalcogenides (TMDCs) exhibit a rich variety of emissive states and intriguing valley spin-selection rules, the effective modulation of which is crucial for excitonic physics and related device applications. Strain or high pressure provides the possibility to tune the energy of the interlayer excitons; however, the reported emission intensity is substantially quenched, which greatly limits their practical application in optoelectronic devices. Here, via applying uniaxial strain based on polyvinyl alcohol (PVA) encapsulation technique, we report enhanced layer-engineered interlayer exciton emission intensity with largely modulated emission energy in WSe2/WS2 heterobilayer and heterotrilayer. Both momentum-direct and momentum-indirect interlayer excitons were observed, and their emission energies show an opposite shift tendency upon applied strain, which agrees with our DFT calculations. We further demonstrate that intralayer and interlayer exciton states with low phonon interactions can be modulated through the mechanical strain applied to the PVA substrate at low temperatures. Due to strain-induced breaking of the 3-fold rotational symmetry, we observe the enhanced valley polarization of interlayer excitons. Our study contributes to the understanding and modulation of the optical properties of interlayer excitons, which could be exploited for optoelectronic device applications.

A Plastic-Crystal Electrolyte Layer Promotes Interfacial Stability of Ni-Rich Oxide Cathode in Li6PS5Cl-Based All-Solid-State Rechargeable Li Batteries.

Unfavorable parasitic reactions between the Ni-rich layered oxide cathode and the sulfide solid electrolyte have plagued the realization of all-solid-state rechargeable Li batteries. The accumulation of inactive by-products (P2Sx, S, POxn-and SOxn-) at the cathode-sulfide interface impedes fast Li-ion transfer, which accounts for sluggish reaction kinetics and significant loss of cathode capacity. Herein, we proposed an easily scalable approach to stabilize the cathode electrochemistry via coating the cathode particles by a uniform, Li+-conductive plastic-crystal electrolyte nanolayer on their surface. The electrolyte, which simply consists of succinonitrile and Li bis(trifluoromethanesulphonyl)imide, serves as an interfacial buffer to effectively suppress the adverse phase transition in highly delithiated cathode materials, and the loss of lattice oxygen and generation of inactive oxygenated by-products at the cathode-sulfide interface. Consequently, an all-solid-state rechargeable Li battery with the modified cathode delivers high specific capacities of 168 mAh g-1 at 0.1 C and a high capacity retention >80% after 100 cycles. Our work sheds new light on rational design of electrode-electrolyte interface for the next-generation high-energy batteries.

KLF7 promotes neuroblastoma differentiation through the GTPase signaling pathway by upregulating neuroblast differentiation-associated protein AHNAKs and glycerophosphodiesterase GDPD5.

The arrest of neural crest-derived sympathoadrenal neuroblast differentiation contributes to neuroblastoma formation, and overriding this blocked differentiation is a clear strategy for treating high-risk neuroblastoma. A better understanding of neuroblast or neuroblastoma differentiation is essential for developing new therapeutic approaches. It has been proposed that Krueppel-like factor 7 (KLF7) is a neuroblastoma super-enhancer-associated transcription factor gene. Moreover, KLF7 was found to be intensely active in postmitotic neuroblasts of the developing nervous system during embryogenesis. However, the role of KLF7 in the differentiation of neuroblast or neuroblastoma is unknown. Here, we find a strong association between high KLF7 expression and favorable clinical outcomes in neuroblastoma. KLF7 induces differentiation of neuroblastoma cells independently of the retinoic acid (RA) pathway and acts cooperatively with RA to induce neuroblastoma differentiation. KLF7 alters the GTPase activity and multiple differentiation-related genes by binding directly to the promoters of neuroblast differentiation-associated protein (AHNAK and AHNAK2) and glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5) and regulating their expression. Furthermore, we also observe that silencing KLF7 in neuroblastoma cells promotes the adrenergic-to-mesenchymal transition accompanied by changes in enhancer-mediated gene expression. Our results reveal that KLF7 is an inducer of neuroblast or neuroblastoma differentiation with prognostic significance and potential therapeutic value.

Assessment of post-trauma microstructural alterations in the rabbit knee cartilage and subchondral bone.

Early diagnosis of post-traumatic osteoarthritis (PTOA) is critical for designing better treatments before the degradation becomes irreversible. We utilized multimodal high-resolution imaging to investigate early-stage deterioration in articular cartilage and the subchondral bone plate from a sub-critical impact to the knee joint, which initiates PTOA. The knee joints of 12 adult rabbits were mechanically impacted once on the femoral articular surface to initiate deterioration. At 2- and 14-week post-impact surgery, cartilage-bone blocks were harvested from the impact region in the animals (N = 6 each). These blocks were assessed for deterioration using polarized light microscopy (PLM), microcomputed tomography (µCT), and biochemical analysis. Statistically significant changes were noted in the impact tissues across the calcified zone (CZ) at 14 weeks post-impact: the optical retardation values in the CZ of impact cartilage had a drop of 29.0% at 14 weeks, while the calcium concentration in the CZ of impact cartilage also had a significant drop at 14 weeks. A significant reduction of 6.3% in bone mineral density (BMD) was noted in the subchondral bone plate of the impact samples at 14 weeks. At 2 weeks post-impact, only minor, non-significant changes were measured. Furthermore, the impact knees after 14 weeks had greater structural changes compared with the 2-week impact knees, indicating progressive degradation over time. The findings of this study facilitated a connection between mineralization alterations and the early deterioration of knee cartilage after a mechanical injury. In a broader context, these findings can be beneficial in improving clinical strategies to manage joint injuries.

Associations between frailty, genetic predisposition, and chronic kidney disease risk in middle-aged and older adults: A prospective cohort study.

OBJECTIVES: Cross-sectional evidence has shown that frailty is highly prevalent in patients with chronic kidney disease (CKD). However, there is limited evidence of the longitudinal associations between frailty, genetic predisposition to CKD, and the risk of CKD in the general population. Therefore, this study aimed to examine such associations among participants in the UK Biobank. STUDY DESIGN: This is a prospective cohort study included 370,965 middle-aged and older adults from the UK Biobank. Physical frailty was assessed using a modified version of the Fried phenotype classification. A weighted genetic risk score was built using 263 variants associated with estimated glomerular filtration rate. MAIN OUTCOME MEASURES: Incident CKD was identified from hospital inpatient records. RESULTS: Over a median follow-up of 12.3 years, we documented a total of 11,121 incident CKD cases. Time-dependent Cox proportional hazards regression models indicated that individuals with frailty (hazard ratio [HR]: 1.94, 95 % confidence interval [CI]: 1.81-2.08) and pre-frailty (HR: 1.27, 95 % CI: 1.22-1.33) had an increased risk of developing CKD, compared with non-frail individuals. No significant interaction between frailty and genetic risk score was observed (P for interaction = 0.41). The highest risk was observed among the individuals with high genetic risk and frailty (HR: 2.31, 95 % CI: 2.00-2.68). CONCLUSION: Our results demonstrated that frailty and pre-frailty were associated with increased risk of incident CKD in middle-age and older adults, regardless of genetic risk of CKD. Our study underscores the importance of frailty screening and intervention as a potential strategy to prevent CKD. Future clinical trials are needed to validate our findings.

Study of the collagen tissue nanostructure by analyzing the echo decay obtained using the MRI technique.

The multicomponent relaxation observed in nuclear magnetic resonance experiments in biological tissues makes it difficult to establish a correlation between specific relaxation times and tissue structural parameters. The analysis of a nanostructure (the characteristic size of 10-1000 nm) is usually based on formulas for relaxation times which depend on structural parameters at the atomic or molecular levels in the size range of 0.1-5 nm. We have recently developed an analysis method in which relaxation times' anisotropy in a sample is explicitly related to its structure of nanocavities containing a liquid or gas. However, the method is based on the analysis of experimental data on the anisotropy of relaxation times obtained by using the standard NMR technique and rotating the sample relative to a magnetic field and requires a series of experiments. In the present study, to address this challenge, we develop a new method of analysis of a multi-exponential magnetic resonance signal that does not require determining relaxation times and eliminates the sample rotation and the necessity of a series of experiments. Using the magnetic resonance imaging (MRI) technique, the total signal from the whole sample was obtained as a sum of the signals (echo decays) from all voxels. In contrast to previous research, the volumes of nanocavities and their angular distribution can be obtained by analyzing a single total signal for the entire cartilage. In addition, within the framework of this approach, it is possible to identify the reason for the multicomponent nature of relaxation. The proposed method for analyzing a single multi-exponential signal (transverse relaxation) was implemented on cartilage. Using the signal, three anatomical zones of cartilage were studied, revealing significant structural differences between them. The proposed method not only avoids the need for sample rotation but also enables repeated application of layer-by-layer magnetic resonance imaging with micron resolution. The study results allow us to suggest that water molecules contributing to the echo decay are more likely located in nanocavities formed by the fibrillar structure rather than inside the fibrils.

Inflammation-based lung adenocarcinoma molecular subtype identification and construction of an inflammation-related signature with bulk and single-cell RNA-seq data.

The role of inflammation is increasingly understood to have a central influence on therapeutic outcomes and prognosis in lung adenocarcinoma (LUAD). However, the detailed molecular divisions involved in inflammatory responses are yet to be fully elucidated. Our study identified two main inflammation-oriented LUAD grades: the inflammation-low (INF-low) and the inflammation-high (INF-high) subtypes. Both presented with unique clinicopathological features, implications for prognosis, and distinctive tumor microenvironment profiles. Broadly, the INF-low grade, marked by its dominant immunosuppressive tumor microenvironment, was accompanied by less favorable prognostic outcomes and a heightened prevalence of oncogenic mutations. In contrast, the INF-high grade exhibited more optimistic clinical trajectories, underscored by its immune-active environment. In addition, our efforts led to the conceptualization and empirical validation of an inflammation-centric predictive model with considerable predictive potency. Our study paves the way for a refined inflammation-centric LUAD classification and fosters a deeper understanding of tumor microenvironment intricacies.

Intensity-Specific Physical Activity Measured by Accelerometer, Genetic Susceptibility, and the Risk of Kidney Stone Disease: Results From the UK Biobank.

RATIONALE & OBJECTIVE: Kidney stone disease (KSD), a significant health care problem within both developed and developing countries, has been associated with genetic risk factors. An association between physical activity and KSD risk also has been hypothesized, but studies have yielded inconsistent findings. This study investigated the association between the intensity of physical activity and the incidence of KSD accounting for genetic risk. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 80,473 participants from the UK Biobank Study. EXPOSURE: Physical activity levels, including total physical activity (TPA), moderate-to-vigorous intensity physical activity (MVPA), and light-intensity physical activity (LPA), were measured using accelerometers and quantified using a machine learning model. A polygenic risk score (PRS) for KSD was also constructed. OUTCOME: Individuals with KSD were identified using the International Classification of Diseases, Tenth Revision (ICD-10), and procedure codes for KSD surgery. ANALYTICAL APPROACH: A Fine and Gray survival model was used to estimate the associations of incident KSD with TPA, MVPA, LPA, and PRS (as categorical variables). Restricted cubic splines were used to examine potential nonlinear associations within the fully adjusted models. RESULTS: During an average follow-up of 6.19 years, 421 participants developed KSD. Participants in the highest quartiles of TPA, MVPA, and LPA had lower adjusted rates of KSD compared with those in the lowest quartiles: HR, 0.50 (95% CI, 0.44-0.56), 0.57 (95% CI, 0.51-0.64), and 0.66 (95% CI, 0.59-0.74), respectively. TPA, MVPA, and LPA were associated with a lower risk of KSD in participants with low and high genetic predisposition for KSD. LIMITATIONS: Selection bias as participants who provided accelerometry data may have been more adherent to health care. CONCLUSIONS: Physical activity was negatively associated with the risk of KSD, regardless of the genetic risk. Future large studies are warranted to confirm and explain the mechanisms underlying these associations. PLAIN-LANGUAGE SUMMARY: The association between the intensity of physical activity (PA) and the incidence of kidney stone disease (KSD) after accounting for genetic risk is unclear. We conducted a comprehensive prospective cohort study utilizing participants from the UK Biobank to assess the intensity of PA using accelerometers. Our study findings indicated that greater total PA, moderate-to-vigorous-intensity PA, and light-intensity PA were each associated with a lower risk of KSD irrespective of an individual's genetic risk. Our study informs the understanding of risk factors for KSD.

BECN1 regulates FADD/RIPK1/Caspase-8 complex formation via RIPK1 ubiquitination by downregulating OTUD1 in MI/R induced myocyte apoptosis.

BACKGROUND: Cardiomyocyte apoptosis plays a vital role in myocardial ischemia-reperfusion (MI/R) injury; however, the role of beclin1 (BECN1) remains unclear. This study aimed at revealing the function of BECN1 during cardiomyocyte apoptosis after MI/R injury. METHODS: In vivo, TTC and Evan's blue double staining was applied to verify the gross morphological alteration in both wild type (WT) mice and BECN1 transgene mice (BECN1-TG), and TUNEL staining and western blot were adopted to evaluate the cardiomyocyte apoptosis. In vitro, a hypoxia/reoxygenation (H/R) model was established in H9c2 cells to simulate MI/R injury. Proteomics analysis was preformed to verify if apoptosis occurs in the H/R cellular model. And apoptosis factors, RIPK1, Caspase-1, Caspase-3, and cleaved Caspase-3, were investigated using western bolting. In addition, the mRNA level were verified using RT-PCR. To further investigate the protein interactions small interfering RNA and lentiviral transfection were used. To continue investigate the protein interactions, immunofluorescence and coimmunoprecipitation were applied. RESULTS: Morphologically, BECN1 significantly attenuated the apoptosis from TTC-Evan's staining, TUNEL, and cardiac tissue western blot. After H/R, a RIPK1-induced complex (complex II) containing RIPK1, Caspase-8, and FADD was formed. Thereafter, cleaved Caspase-3 was activated, and myocyte apoptosis occurred. However, BECN1 decreased the expression of RIPK1, Caspase-8, and FADD. Nevertheless, BECN1 overexpression increased RIPK1 ubiquitination before apoptosis by inhibiting OTUD1. CONCLUSIONS: BECN1 regulates FADD/RIPK1/Caspase-8 complex formation via RIPK1 ubiquitination by downregulating OTUD1 in C-Caspase-3-induced myocyte apoptosis after MI/R injury. Therefore, BECN1 can function as a cardioprotective candidate.

Intensity-specific physical activity measured by accelerometer and the risk of mortality among individuals with cardiometabolic diseases: A prospective study from the UK Biobank.

BACKGROUND: While the health benefits of physical activity for general population are well-recognized, the prospective associations of physical activity volume and intensity with mortality among cardiometabolic disease individuals remain unclear. OBJECTIVE: The objective of this study was to investigate the associations of accelerometer-measured intensity-specific physical activity with mortality risk among population with cardiometabolic disease. DESIGN: Prospective cohort study. SETTING: Participants were recruited from the United Kingdom (UK) across 22 assessment centers from 2006 to 2010. PARTICIPANTS: A total of 9524 participants from the UK Biobank (median: 67.00 years, interquartile range: 61.00-70.00 years) were included in final study. METHODS: Accelerometer-measured total volume, moderate-to-vigorous and light intensity physical activity collecting from 2013 to 2015 were quantified using a machine learning model. Multivariable restricted cubic splines and Cox proportional hazard models with hazard ratios (HRs) and 95 % confidence intervals (CIs) were employed to examine the associations of interests. RESULTS: During the follow-up period (median: 6.87 years; interquartile range: 6.32-7.39 years), there were 659 (6.92 %) death events with 218 (2.29 %) cardiovascular disease-related deaths and 441 (4.63 %) non-cardiovascular disease-related deaths separately. In the fully adjusted models, compared with participants in the lowest quartiles of total volume, moderate-to-vigorous and light physical activities, the adjusted HRs (95 % CIs) of all-cause mortality for those in the highest quartiles were 0.40 (0.31, 0.52), 0.48 (0.37, 0.61), and 0.56 (0.44, 0.71) while those for cardiovascular diseases-related mortality were 0.35 (0.22, 0.55), 0.52 (0.35, 0.78) and 0.59 (0.39, 0.88), and for non-cardiovascular diseases-related mortality, they were 0.42 (0.30, 0.59), 0.40 (0.29, 0.54) and 0.54 (0.40, 0.73), separately. The optimal moderate-to-vigorous-intensity physical activity level for cardiovascular diseases-related mortality reduction was found to be in the third quartile (17.75-35.33 min/day). Furthermore, the observed inverse associations were mainly non-linear. CONCLUSIONS: Promoting physical activity, regardless of intensity, is essential for individuals with cardiometabolic disease to reduce mortality risk. For both all-cause and cardiovascular disease-related and non-cardiovascular disease-related mortality, the observed decrease in risk seems to level off at a moderate level. The current findings deriving from precise device-based physical activity data provide inference for secondary prevention of cardiometabolic disease.

The influence of electrode types to the visually induced gamma oscillations in mouse primary visual cortex.

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.

Ultrafast-Loaded Nickel Sulfide on Vertical Graphene Enabled by Joule Heating for Enhanced Lithium Metal Batteries.

The design and fabrication of a lithiophilic skeleton are highly important for constructing advanced Li metal anodes. In this work, a new lithiophilic skeleton is reported by planting metal sulfides (e.g., Ni3S2) on vertical graphene (VG) via a facile ultrafast Joule heating (UJH) method, which facilitates the homogeneous distribution of lithiophilic sites on carbon cloth (CC) supported VG substrate with firm bonding. Ni3S2 nanoparticles are homogeneously anchored on the optimized skeleton as CC/VG@Ni3S2, which ensures high conductivity and uniform deposition of Li metal with non-dendrites. By means of systematic electrochemical characterizations, the symmetric cells coupled with CC/VG@Ni3S2 deliver a steady long-term cycle within 14 mV overpotential for 1800 h (900 cycles) at 1 mA cm-2 and 1 mAh cm-2. Meanwhile, the designed CC/VG@Ni3S2-Li||LFP full cell shows notable electrochemical performance with a capacity retention of 92.44% at 0.5 C after 500 cycles and exceptional rate performance. This novel synthesis strategy for metal sulfides on hierarchical carbon-based materials sheds new light on the development of high-performance lithium metal batteries (LMBs).