The impact of widowhood on the quality of life of older adults: the mediating role of intergenerational support from children.

BACKGROUND: China's transition into an aging society is accelerated by the simultaneous decline in fertility rates and the prolonged life expectancy of older adults. The impact of widowhood, a significant stressor in old age, has emerged as a crucial factor affecting the quality of life among the elderly. METHODS: This study is based on data from the 2018 China Health and Aging Tracking Survey. Multiple linear regression models were employed to investigate the influence of widowhood on the quality of life of older adults in China. Additionally, Bootstrap mediation effects were utilized to assess the mediating role of intergenerational support, considering both financial and emotional support from children. RESULTS: The findings indicate a substantial reduction in the quality of life index among older adults following widowhood. Moreover, the impact is more pronounced among older men compared to older women. Rural older adults experience a significant decline in quality of life post-widowhood, while the effect on urban counterparts is not statistically significant. CONCLUSIONS: Intergenerational financial support was identified as a partial mediator between widowhood and the quality of life among older adults. This underscores the importance of familial financial assistance in mitigating the adverse effects of widowhood on the well-being of the elderly. These results offer valuable insights into the nuanced impact of widowhood on the quality of life among older adults in China, emphasizing the need for targeted interventions, especially in rural areas. CLINICAL TRIAL: Not applicable.

Prognostic Model and Immune Response of Clear Cell Renal Cell Carcinoma Based on Co-Expression Genes Signature.

BACKGROUND: The identification of reliable prognostic markers is crucial for optimizing patient management and improving clinical outcomes in clear cell renal cell carcinoma (ccRCC). METHODS: We used the GSE89563 dataset from the GEO database and the Kidney Clear Cell Carcinoma (KIRC) dataset from the TCGA database to develop a prognostic model based on weighted gene co-expression network analysis (WGCNA) and non-negative matrix factorization (NMF) to predict disease progression and prognosis in ccRCC. RESULT: We utilized WGCNA to identify risk genes and applied NMF to stratify high-risk populations in ccRCC. We characterized the immune gene features of these high-risk groups and ultimately developed a risk prediction model for ccRCC patients using a Lasso regression approach. The risk score was calculated as follows: Risk score = SUM (-0.136394797 ANK3 + 0.004238138 BIVM_ERCC5 - 0.046248451 C4orf19 - 0.036013206 F2RL3 - 0.125531316 GNG7 - 0.012698109 METTL7A + 0.078462369 MSTO1 - 0.050450656 PINK1 - 0.059446590 SLC16A12 - 0.039883686 SLC2A9 + 0.083310722 TLCD1 - 0.059801739 WDR72 + 0.071430088 ZNF117). CONCLUSION: We develop a prognostic model for clear cell renal cell carcinoma and analyzed immune response in subgroups and confirmed protein-level expression concordance.

Deterministic switching of perpendicular magnetization by out-of-plane anti-damping magnon torques.

Spin-wave excitations of magnetic moments (or magnons) can transport spin angular momentum in insulating magnetic materials. This property distinguishes magnonic devices from traditional electronics, where power consumption results from electrons' movement. Recently, magnon torques have been used to switch perpendicular magnetization in the presence of an external magnetic field. Here we present a material system composed of WTe2/antiferromagnetic insulator NiO/ferromagnet CoFeB heterostructures that allows magnetic field-free switching of the perpendicular magnetization. The magnon currents, with a spin polarization canting of -8.5° relative to the sample plane, traverse the 25-nm-thick polycrystalline NiO layer while preserving their original polarization direction, subsequently exerting an out-of-plane anti-damping magnon torque on the ferromagnetic layer. Using this mechanism, we achieve a 190-fold reduction in power consumption in PtTe2/WTe2/NiO/CoFeB heterostructures compared to Bi2Te3/NiO/CoFeB control samples, which only exhibit in-plane magnon torques. Our field-free demonstration contributes to the realization of all-electric, low-power, perpendicular magnetization switching devices.

Robust BEV 3D Object Detection for Vehicles with Tire Blow-Out.

The bird's-eye view (BEV) method, which is a vision-centric representation-based perception task, is essential and promising for future Autonomous Vehicle perception. It has advantages of fusion-friendly, intuitive, end-to-end optimization and is cheaper than LiDAR. The performance of existing BEV methods, however, would be deteriorated under the situation of a tire blow-out. This is because they quite rely on accurate camera calibration which may be disabled by noisy camera parameters during blow-out. Therefore, it is extremely unsafe to use existing BEV methods in the tire blow-out situation. In this paper, we propose a geometry-guided auto-resizable kernel transformer (GARKT) method, which is designed especially for vehicles with tire blow-out. Specifically, we establish a camera deviation model for vehicles with tire blow-out. Then we use the geometric priors to attain the prior position in perspective view with auto-resizable kernels. The resizable perception areas are encoded and flattened to generate BEV representation. GARKT predicts the nuScenes detection score (NDS) with a value of 0.439 on a newly created blow-out dataset based on nuScenes. NDS can still obtain 0.431 when the tire is completely flat, which is much more robust compared to other transformer-based BEV methods. Moreover, the GARKT method has almost real-time computing speed, with about 20.5 fps on one GPU.

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.1.351 variant inactivated vaccine candidate (B.1.351V) generated strong binding and neutralizing antibody responses in BALB/c mice against the B.1.351 virus and other SARS-CoV-2 variants after two doses within 28 days. Immunized K18-hACE2 mice also exhibited elevated levels of live virus-neutralizing antibodies against various SARS-CoV-2 viruses. Following infection with these viruses, K18-hACE2 mice displayed a stable body weight, a high survival rate, minimal virus copies in lung tissue, and no lung damage compared to the control group. These findings indicate that B.1.351V offered protection against infection with multiple SARS-CoV-2 variants in mice, providing insights for the development of a vaccine targeting SARS-CoV-2 VOCs for human use.

Metabolomic and lipidomic profiling of the spinal cord in type 2 diabetes mellitus rats with painful neuropathy.

In this paper we investigated lipid and metabolite changes in diabetic neuropathy, using untargeted lipidomics and metabolomics analyses of the spinal cords from streptozotocin-treated diabetic rats.170 metabolites and 45 lipids were dysregulated in the painful diabetic neuropathy (PDN) phase. Pathway enrichment analysis revealed perturbations in starch and sucrose, tryptophan, pyrimidine, cysteine and methionine, thiamine, tyrosine, and nucleotides. The disturbance of tyrosine, tryptophan, methionine, triacylglycerol, and phosphatidylethanolamine metabolism indicated that pathological mechanisms in the PDN involved energy metabolism, oxidative stress, and neural reparative regeneration. These revelations offered potential biomarkers for PDN and enriched the comprehension of the complex molecular mechanisms characterizing PDN, establishing a solid foundation for subsequent inquiries into neural convalescence and recovery after PDN.

Resilient Output Control of Multiagent Systems With DoS Attacks and Actuator Faults: Fully Distributed Event-Triggered Approach.

This article investigates the fully distributed resilient practical leader-follower bipartite output consensus (LFBOC) problem for heterogeneous linear multiagent systems (MASs) with denial-of-service (DoS) attacks and actuator faults. To estimate the leader matrix and state in the presence of DoS attacks, two novel adaptive event-triggered observers are proposed based on newly developed lemmas, and then the adaptive event-triggered fault-tolerant controller without chattering behavior is developed to solve the LFBOC problem. Different from most existing resilient practical LFBOC working with DoS attacks and actuator faults, our method does not rely on any global information, event-triggered communication between neighbors and discrete update controllers are implemented simultaneously. Finally, an example is presented to well illustrate the effectiveness of developed method.

Field-Free Manipulation of Two-Dimensional Ferromagnet CrTe2 by Spin-Orbit Torques.

Electrical manipulation of magnetic states in two-dimensional ferromagnetic systems is crucial in information storage and low-dimensional spintronics. Spin-orbit torque presents a rapid and energy-efficient method for electrical control of the magnetization. In this letter, we demonstrate a wafer-scale spin-orbit torque switching of two-dimensional ferromagnetic states. Using molecular beam epitaxy, we fabricate two-dimensional heterostructures composed of low crystal-symmetry WTe2 and ferromagnet CrTe2 with perpendicular anisotropy. By utilizing out-of-plane spins generated from WTe2, we achieve field-free switching of the CrTe2 perpendicular magnetization. The threshold switching current density in CrTe2/WTe2 is 1.2 × 106 A/cm2, 20 times smaller than that of the CrTe2/Pt control sample even with an external magnetic field. In addition, the switching behavior can be modulated by external magnetic fields and crystal symmetry. Our findings demonstrate a controllable and all-electric manipulation of perpendicular magnetization in a two-dimensional ferromagnet, representing a significant advancement toward the practical implementation of low-dimensional spintronic devices.

Physiologically Based Pharmacokinetic Modeling and Clinical Extrapolation for Topical Application of Pilocarpine on Eyelids: A Comprehensive Study.

Exploiting a convenient and highly bioavailable ocular drug delivery approach is currently one of the hotspots in the pharmaceutical industry. Eyelid topical application is seen to be a valuable strategy in the treatment of chronic ocular diseases. To further elucidate the feasibility of eyelid topical administration as an alternative route for ocular drug delivery, pharmacokinetic and pharmacodynamic studies of pilocarpine were conducted in rabbits. Besides, a novel physiologically based pharmacokinetic (PBPK) model describing eyelid transdermal absorption and ocular disposition was developed in rabbits. The PBPK model of rabbits was extrapolated to human by integrating the drug-specific permeability parameters and human physiological parameters to predict ocular pharmacokinetic in human. After eyelid topical application of pilocarpine, the concentration of pilocarpine in iris peaked at 2 h with the value of 18,724 ng/g and the concentration in aqueous humor peaked at 1 h with the value of 1,363 ng/mL. Significant miotic effect were observed from 0.5 h to 4.5 h after eyelid topical application of pilocarpine in rabbits, while that were observed from 0.5 h to 3.5 h after eyedrop instillation. The proposed eyelid PBPK model was capable of reasonably predicting ocular exposure of pilocarpine after application on the eyelid skin and based on the PBPK model, the human ocular concentration was predicted to be 10-fold lower than that in rabbits. And it was suggested that drugs applied on the eyelid skin could transfer into the eyeball through corneal pathway and scleral pathway. This work could provide pharmacokinetic and pharmacodynamic data for the development of eyelid drug delivery, as well as the reference for clinical applications.

In-situ direct seawater electrolysis using floating platform in ocean with uncontrollable wave motion.

Direct hydrogen production from inexhaustible seawater using abundant offshore wind power offers a promising pathway for achieving a sustainable energy industry and fuel economy. Various direct seawater electrolysis methods have been demonstrated to be effective at the laboratory scale. However, larger-scale in situ demonstrations that are completely free of corrosion and side reactions in fluctuating oceans are lacking. Here, fluctuating conditions of the ocean were considered for the first time, and seawater electrolysis in wave motion environment was achieved. We present the successful scaling of a floating seawater electrolysis system that employed wind power in Xinghua Bay and the integration of a 1.2 Nm3 h-1-scale pilot system. Stable electrolysis operation was achieved for over 240 h with an electrolytic energy consumption of 5 kWh Nm-3 H2 and a high purity (>99.9%) of hydrogen under fluctuating ocean conditions (0~0.9 m wave height, 0~15 m s-1 wind speed), which is comparable to that during onshore water electrolysis. The concentration of impurity ions in the electrolyte was low and stable over a long period of time under complex and changing scenarios. We identified the technological challenges and performances of the key system components and examined the future outlook for this emerging technology.

Above-room-temperature chiral skyrmion lattice and Dzyaloshinskii-Moriya interaction in a van der Waals ferromagnet Fe3-xGaTe2.

Skyrmions in existing 2D van der Waals (vdW) materials have primarily been limited to cryogenic temperatures, and the underlying physical mechanism of the Dzyaloshinskii-Moriya interaction (DMI), a crucial ingredient for stabilizing chiral skyrmions, remains inadequately explored. Here, we report the observation of Néel-type skyrmions in a vdW ferromagnet Fe3-xGaTe2 above room temperature. Contrary to previous assumptions of centrosymmetry in Fe3-xGaTe2, the atomic-resolution scanning transmission electron microscopy reveals that the off-centered FeΙΙ atoms break the spatial inversion symmetry, rendering it a polar metal. First-principles calculations further elucidate that the DMI primarily stems from the Te sublayers through the Fert-Lévy mechanism. Remarkably, the chiral skyrmion lattice in Fe3-xGaTe2 can persist up to 330 K at zero magnetic field, demonstrating superior thermal stability compared to other known skyrmion vdW magnets. This work provides valuable insights into skyrmionics and presents promising prospects for 2D material-based skyrmion devices operating beyond room temperature.

Too Good to be Nice: The interplay between the Cause marketing and information acquisition.

Cause marketing (CM) has become an important tool for firms to fulfill their social responsibility strategies. However, in reality, although some consumers have responded positively to the firm's CM strategies, others have doubts due to their lack of trust in the effectiveness of the firm or business. Therefore, in this paper, we consider a case that the supplier is a dual-purpose corporation that engage in a CM campaign and the consumer social preference is uncertainty and is unknown initially but can be resolved by the retailer's acquisition behaviour. By examining the two information acquisition strategies: committed acquisition and contingent acquisition. We find that, under either strategy, the retailer would like to acquire information only when the cost of information acquisition is small. Moreover, compared to contingent acquisition, the retailer is more willing to prefer committed acquisition. Additionally, we show that the supplier always prefers the committed acquisition strategy. However, the retailer's preference toward these two information acquisition strategies is related to the acquire cost. Specifically, when acquisition cost is small or large, the retailer is indifferent between these two strategies, when acquisition cost is in an intermediate range, the retailer will shift her strategy from the contingent strategy to the committed strategy. We also use numerical studies to illustrate main results. These findings provide theoretical support and management insights for managers to integrate CM into business transactions.

Synthesis of ß,ß-Dithioketones by Merging C-C and C-S Bond Cleavage in [1 + 1 + 1 + 1 + 1 + 1] Annulation.

An unconventional [1 + 1 + 1 + 1 + 1 + 1] annulation process was developed for the construction of ß,ß-dithioketones by merging C-C and C-S bond cleavage. In this reaction, rongalite concurrently served as triple C1 units, dual sulfur(II) synthons, and a reductant for the first time. Mechanism investigation indicated that the reaction involved the self-mediated valence state change of rongalite. By performing this step-economical method, the challenging construction of C5-substituted 1,3-dithiane can be achieved under mild and simple conditions.

Spin-orbit torque manipulation of sub-terahertz magnons in antiferromagnetic α-Fe2O3.

The ability to electrically manipulate antiferromagnetic magnons, essential for extending the operating speed of spintronic devices into the terahertz regime, remains a major challenge. This is because antiferromagnetic magnetism is challenging to perturb using traditional methods such as magnetic fields. Recent developments in spin-orbit torques have opened a possibility of accessing antiferromagnetic magnetic order parameters and controlling terahertz magnons, which has not been experimentally realised yet. Here, we demonstrate the electrical manipulation of sub-terahertz magnons in the α-Fe2O3/Pt antiferromagnetic heterostructure. By applying the spin-orbit torques in the heterostructure, we can modify the magnon dispersion and decrease the magnon frequency in α-Fe2O3, as detected by time-resolved magneto-optical techniques. We have found that optimal tuning occurs when the Néel vector is perpendicular to the injected spin polarisation. Our results represent a significant step towards the development of electrically tunable terahertz spintronic devices.

Quantitation of Enterovirus A71 Empty and Full Particles by Sedimentation Velocity Analytical Ultracentrifugation.

The enterovirus A71 (EV71) inactivated vaccine is an effective intervention to control the spread of the virus and prevent EV71-associated hand, foot, and mouth disease (HFMD). It is widely administered to infants and children in China. The empty particles (EPs) and full particles (FPs) generated during production have different antigenic and immunogenic properties. However, the antigen detection methods currently used were established without considering the differences in antigenicity between EPs and FPs. There is also a lack of other effective analytical methods for detecting the different particle forms, which hinders the consistency between batches of products. In this study, we analyzed the application of sedimentation velocity analytical ultracentrifugation (SV-AUC) in characterizing the EPs and FPs of EV71. Our results showed that the proportions of the two forms could be quantified simultaneously by SV-AUC. We also determined the repeatability and accuracy of this method and found that both parameters were satisfactory. We assessed SV-AUC for bulk vaccine quality control, and our findings indicated that SV-AUC can be used effectively to analyze the percentage of EPs and FPs and monitor the consistency of the process to ensure the quality of the vaccine.

SIRT3 alleviates painful diabetic neuropathy by mediating the FoxO3a-PINK1-Parkin signaling pathway to activate mitophagy.

INTRODUCTION: Painful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development of PDN, but its pathogenesis and mechanism have not been fully investigated. METHODS: In this study, we used high-fat diet/low-dose streptozotocin-induced rats as a model of type 2 diabetes mellitus. Behavioral testing, whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons, and complex sensory nerve conduction velocity studies were used to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, and transmission electron microscopy were used to evaluate the function and morphology of mitochondria in DRG. Real-time PCR, western blot, and immunofluorescence were performed to investigate the mechanism. RESULTS: We found that damaged mitochondria were accumulated and mitophagy was inhibited in PDN rats. The expression of sirtuin 3 (SIRT3), which is an NAD+-dependent deacetylase in mitochondria, was inhibited. Overexpression of SIRT3 in DRG neurons by intrathecally administered LV-SIRT3 lentivirus ameliorated neurological and mitochondrial dysfunctions. This was evidenced by the reversal of allodynia and nociceptor hyperexcitability, as well as the restoration of MMP and ATP levels. Overexpression of SIRT3 restored the inhibited mitophagy by activating the FoxO3a-PINK1-Parkin signaling pathway. The effects of SIRT3 overexpression, including the reversal of allodynia and nociceptor hyperexcitability, the improvement of impaired mitochondria and mitophagy, and the restoration of PINK1 and Parkin expression, were counteracted when FoxO3a siRNA was intrathecally injected. CONCLUSION: These results showed that SIRT3 overexpression ameliorates PDN via activation of FoxO3a-PINK1-Parkin-mediated mitophagy, suggesting that SIRT3 may become an encouraging therapeutic strategy for PDN.

Modeling the complexity of drug-drug interactions: A physiologically-based pharmacokinetic study of Lenvatinib with Schisantherin A/Schisandrin A.

BACKGROUND: Lenvatinib's efficacy as a frontline targeted therapy for radioactive iodine-refractory thyroid carcinoma and advanced hepatocellular carcinoma owes to its inhibition of multiple tyrosine kinases. However, as a CYP3A4 substrate, lenvatinib bears susceptibility to pharmacokinetic modulation by co-administered agents. Schisantherin A (STA) and schisandrin A (SIA) - bioactive lignans abundant in the traditional Chinese medicinal Wuzhi Capsule - act as CYP3A4 inhibitors, engendering the potential for drug-drug interactions (DDIs) with lenvatinib. METHODS: To explore potential DDIs between lenvatinib and STA/SIA, we developed a physiologically-based pharmacokinetic (PBPK) model for lenvatinib and used it to construct a DDI model for lenvatinib and STA/SIA. The model was validated with clinical trial data and used to predict changes in lenvatinib exposure with combined treatment. RESULTS: Following single-dose administration, the predicted area under the plasma concentration-time curve (AUC) and maximum plasma concentrations (Cmax) of lenvatinib increased 1.00- to 1.03-fold and 1.00- to 1.01-fold, respectively, in the presence of STA/SIA. Simulations of multiple-dose regimens revealed slightly greater interactions, with lenvatinib AUC0-t and Cmax increasing up to 1.09-fold and 1.02-fold, respectively. CONCLUSION: Our study developed the first PBPK and DDI models for lenvatinib as a victim drug. STA and SIA slightly increased lenvatinib exposure in simulations, providing clinically valuable information on the safety of concurrent use. Given the minimal pharmacokinetic changes, STA/SIA are unlikely to interact with lenvatinib through pharmacokinetic alterations synergistically but rather may enhance efficacy through inherent anti-cancer efficacy of STA/ SIA.

The European livestock resistome.

Metagenomic sequencing has proven to be a powerful tool in the monitoring of antimicrobial resistance (AMR). Here, we provide a comparative analysis of the resistome from pigs, poultry, veal calves, turkey, and rainbow trout, for a total of 538 herds across nine European countries. We calculated the effects of per-farm management practices and antimicrobial usage (AMU) on the resistome in pigs, broilers, and veal calves. We also provide an in-depth study of the associations between bacterial diversity, resistome diversity, and AMR abundances as well as co-occurrence analysis of bacterial taxa and antimicrobial resistance genes (ARGs) and the universality of the latter. The resistomes of veal calves and pigs clustered together, as did those of avian origin, while the rainbow trout resistome was different. Moreover, we identified clear core resistomes for each specific food-producing animal species. We identified positive associations between bacterial alpha diversity and both resistome alpha diversity and abundance. Network analyses revealed very few taxa-ARG associations in pigs but a large number for the avian species. Using updated reference databases and optimized bioinformatics, previously reported significant associations between AMU, biosecurity, and AMR in pig and poultry farms were validated. AMU is an important driver for AMR; however, our integrated analyses suggest that factors contributing to increased bacterial diversity might also be associated with higher AMR load. We also found that dispersal limitations of ARGs are shaping livestock resistomes, and future efforts to fight AMR should continue to emphasize biosecurity measures.IMPORTANCEUnderstanding the occurrence, diversity, and drivers for antimicrobial resistance (AMR) is important to focus future control efforts. So far, almost all attempts to limit AMR in livestock have addressed antimicrobial consumption. We here performed an integrated analysis of the resistomes of five important farmed animal populations across Europe finding that the resistome and AMR levels are also shaped by factors related to bacterial diversity, as well as dispersal limitations. Thus, future studies and interventions aimed at reducing AMR should not only address antimicrobial usage but also consider other epidemiological and ecological factors.

A wheel-shaped Zr-substituted phosphotungstate [{Zr(C2O4)2}3 (PO4)(P6W39O150)]39- with tunable proton conduction properties.

A wheel-shaped Zr-substituted phosphotungstate, [N(CH3)4]2K16Na10.5H10.5[{Zr(C2O4)2}3(PO4)(P6W39O150)]·45H2O (1), was synthesised from a hexavacant Dawson-type precursor [H2P2W12O48]12-via a conventional solution method. Compound 1 features a wheel-shaped polyanion comprising an annular [P6W39O150]36- cluster supported by a turbine-shaped [{Zr(C2O4)2}3(PO4)]3- fragment, with three oxalate groups covalently anchored to W atoms. Compound 1 was systematically characterized by IR, UV, PXRD, TGA and 31P NMR spectra. The 31P NMR spectra over time were monitored to verify the stability of 1 in aqueous solution. This compound possesses remarkable proton conductive behavior with a high conductivity of 1.18 × 10-2 S cm-1 at 368 K.

Research on the mechanism of government-industry-university-research collaboration for cultivating innovative talent based on game theory.

The assessment of colleges' effectiveness heavily relies on the employment status of graduates. Government-industry-university-research (GIUR) collaboration in cultivation talent is the key to improving the employment rate of college graduates. Based on the theoretical framework of the triple helix, this study develops a tripartite evolutionary game model that encompasses government, enterprises, and university research institutions. The research findings indicate (1) the evolutionary convergence of strategies among the subjects of the three-party game. (2) The attainment of a stable ideal evolution state for (1,1,1) is possible when the requisite conditions are met. This suggests that the cultivation of aligned talent in GIUR collaborations should coordinate the interests of various stakeholders. (3) Drawing inspiration from parameter-sensitive simulation, the problem of mismatch between talent cultivation and social demand can be effectively addressed through measures such as reducing the cost of cooperation, balancing the distribution of benefits, and implementing appropriate reward and punishment mechanisms. In response to these implications, we put forward some management insights and suggestions.