Search

Abstract Nowadays, what captures consumers' primary attention is how to purchase electric vehicles with long range and desirable price. Lightweight construction stands as one of the most effective approaches for prolonging range and lowering costs. As a consequence, it is particularly imperative to undertake lightweight design optimization for the battery bracket of new energy vehicles by applying 3D printing technology. To actualize this goal, Rhino software was initially employed for 3D modeling to design the battery bracket system for a pure electric vehicle in China. Subsequently, topology optimization design of the battery bracket was carried out by adopting Altair Inspire software. Last but not least, manufacturing and assembly inspection were completed using a 3D printer. The results show that the maximum displacement of the battery lower tray bracket after topology optimization is 3.20 mm, which is slightly higher than before, but still relatively small. The maximum Mises equivalent stress rose to 240.7 MPa post-optimization, but brought about a uniform stress distribution at the bottom of the bracket. In comparison, the minimum factor of safety met design requirements at 1. The mass was lessened to 0.348 kg, representing a 49.2% decrease in comparison with pre-optimization levels. The 3D-printed bracket was fabricated by employing a 3D printer, thereby achieving the aforementioned mass abatement. The battery pack parts exhibited a bright surface with low roughness and no discernible warping or deformation defects. As revealed by the assembly results, the components of the battery pack bracket are tightly coordinated with each other, with no evident assembly conflicts, revealing that the dimensional accuracy and fit of the completed parts meet production requirements. These findings lay solid groundwork for the mass production of high-performance battery pack brackets.

AimsTo evaluate the effectiveness of a multicomponent exercise intervention and to clarify the underlying mechanisms of the program in community-dwelling older adults with cognitive frailty. Additionally, the perception of participants in the program will be explored.DesignA mixed-methods design, including a randomized controlled trial and an exploratory qualitative study, was used.MethodsEach group consists of 41 participants. The experimental group will undergo a 12-week multicomponent exercise intervention, including warm-up, exergaming aerobic exercise, elastic-band resistance exercise, and cool-down. This intervention was developed based on the Health Belief Model (HBM) and Self-Efficacy Model (SEM). The control group will not receive any intervention. Physical frailty and cognitive function will be considered as primary outcomes. Data will be collected both at baseline and at the end of the intervention period. Fisher’s exact test, analysis of covariance, and generalized linear models will be conducted to compare mean changes between the two groups. Additionally, the mediation models will be used to examine whether any intervention effects are mediated through exercise self-efficacy.DiscussionThe findings of this study are anticipated to provide valuable insights for healthcare providers, enabling them to learn about effective strategies to enhance exercise adherence and promote improved functionality, independence, and quality of life for older adults with cognitive frailty.Clinical trial registration: [https://clinicaltrials.gov/], identifier [ChiCTR2200058850].

BackgroundPeripheral neuropathy (PN) is prevalent in people with human immunodeficiency virus (PHIV) with no Food and Drug Administration-approved treatment. Therapeutic Chinese massage (TCM) is a promising noninvasive and non-harmful intervention for HIV-related PN. However, relevant research is lacking. The purpose of this study is to evaluate the feasibility of TCM for HIV-related PN.MethodWe conducted a pilot, single-centered, two-arm, double-blinded, randomized controlled trial. Twenty eligible PHIV were recruited primarily from the AIDS Foundation Houston, Inc. in Texas and were randomly assigned into two groups. Ten participants in the intervention group received three weekly 25-min TCM sessions by a certified TCM therapist. The remaining ten control group participants received the same therapist’s three weekly 25-min placebo massage sessions on their lower extremities. The outcome was the feasibility of this study as measured by recruitment and completion rates, participant safety, and treatment adherence and compliance, as well as the effect size of the intervention.ResultsThe study population comprised 20 PHIV (mean age 55.23). This study showed high feasibility as measured by a high rate of recruitment, a 100% rate of completion, and zero serious adverse events. As we inquired 21 respondents for eligibility for the study, all except one had HIV-related PN. All respondents were willing to participate in the study and adhered to the group assignment after they enrolled in the study. The participants’ baseline pain was at a medium to a high level (6.30 [2.15] out of 10).ConclusionChinese massage is a feasible intervention in PHIV. Future relevant randomized controlled trials are expected.Clinical trial registrationhttps://clinicaltrials.gov/, NCT05379140.

ObjectivesPrevious research has suggested connections between specific inflammatory cytokines and nasal conditions, including Allergic Rhinitis (AR), Chronic Rhinosinusitis (CRS), and Nasal Polyps (NP). However, a lack of robust research establishing the causal underpinnings of them. This Mendelian Randomization (MR) study aims to evaluate the causal relationships between 41 inflammatory cytokines and the incidence of AR, CRS and NP.MethodsThis study employed a two-sample MR design, harnessing genetic variations derived from publicly accessible genome-wide association studies (GWAS) datasets. AR data was sourced from a GWAS with 25,486 cases and 87,097 controls (identifier: ukb-b-7178). CRS data originated from a GWAS encompassing 1,179 cases and 360,015 controls (identifier: ukb-d-J32). NP data was extracted from a GWAS involving 1,637 cases and 335,562 controls (identifier: ukb-a-541). The data for 41 inflammatory cytokines were obtained from an independent GWAS encompassing 8,293 participants. Inverse variance weighted (IVW), MR Egger regression and Weighted median were used to evaluate the causalities of exposures and outcomes. A range of sensitivity analyses were implemented to assess the robustness of the results.ResultsThe results revealed significant associations between elevated circulating levels of MIP-1α (odds ratio, OR: 1.01798, 95% confidence interval, CI: 1.00217–1.03404, p = 0.02570) and TNF-α (OR: 1.01478, 95% CI: 1.00225–1.02746, p = 0.02067) with an augmented risk of AR in the IVW approach. Heightened levels of circulating IL-2 exhibited a positive correlation with an increased susceptibility to NP in the IVW approach (OR: 1.00129, 95% CI: 1.00017–1.00242, p = 0.02434), whereas elevated levels of circulating PDGF-BB demonstrated a decreased risk of NP (OR: 0.99920, 95% CI: 0.99841–0.99999, p = 0.047610). The MR analysis between levels of 41 inflammatory cytokines and the incidence of CRS yielded no positive outcomes.ConclusionThis investigation proposes a potential causal association between elevated levels of MIP-1α and TNF-α with an elevated risk of AR, as well as an increased risk of NP linked to elevated IL-2 levels. Furthermore, there appears to be a potential association between increased levels of circulating PDGF-BB and a reduced risk of NP.

BackgroundThe evidence from observational studies on the association between the use of aspirin and the risk of hayfever or allergic rhinitis is conflicting, with a dearth of high-quality randomized controlled trials.ObjectiveThis study aims to investigate the causal relationship between aspirin use and the risk of hayfever or allergic rhinitis.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. We utilized publicly available summary statistics datasets from genome-wide association studies (GWAS) meta-analyses on aspirin use in individuals of European descent (n = 337,159) as the exposure variable, and a GWAS on doctor-diagnosed hayfever or allergic rhinitis in individuals from the UK Biobank (n = 83,529) as the outcome variable.ResultsWe identified 7 single nucleotide polymorphisms (SNPs) at genome-wide significance from the GWASs associated with aspirin use as instrumental variables (P

Abstract M1 macrophages secrete a large number of proinflammatory factors and promote the expansion of atherosclerotic plaques and processes. Salvianolic acid B (Sal B) exerts anti-inflammatory, antitumor and other effects, but no study has addressed whether Sal B can regulate the polarization of macrophages to exert these anti-atherosclerotic effects. Therefore, we investigated the inhibition of Sal B in M1 macrophage polarization and the underlying mechanism. The effects of different treatments on cell viability, gene expression and secretion of related proteins, phenotypic markers and cytokines were detected by MTT and western blot assays, RT‒qPCR and ELISAs. Cell viability was not significantly changed when the concentration of Sal B was less than 200 μM, and Lipopolysaccharide (LPS) (100 ng/mL) + interferon-γ (IFN-γ) (2.5 ng/mL) successfully induced M1 polarization. RT‒qPCR and ELISAs indicated that Sal B can downregulate M1 marker (Inducible Nitric Oxide Synthase (iNOS), Tumor Necrosis Factor-α (TNF-α), and Interleukin-6 (IL-6)) and upregulate M2 marker (Arginase-1 (Arg-1) and Interleukin-10 (IL-10)) expression. Western blotting was performed to measure the expression of Nuclear Factor-κB (NF-κB), p-Akt, p-mTOR, LC3-II, Beclin-1, and p62, and the results suggested that Sal B inhibits the M1 polarization of RAW264.7 macrophages by promoting autophagy via the NF-κB signalling pathway. The study indicated that Sal B inhibits M1 macrophage polarization by inhibiting NF-κB signalling pathway activation and downregulating Akt/mTOR activation to promote autophagy.

This study aims to examine the feasibility of DNA methylation age as a biomarker for symptoms and resilience in cancer survivors with multiple chronic conditions (MCCs). We included ten participants from our parent study, an ongoing randomized control trial study. Participants’ symptoms and resilience were assessed, and peripheral blood was collected. DNA methylation age calculation was performed using DNAge® analysis. Data were analyzed using Spearman’s correlation analysis and the Mann–Whitney U test. Participants in the intervention group tended to have a decrease in DNA methylation age and age acceleration after completing an exercise program (mean difference = −0.83 ± 1.26). The change in DNA methylation age was significantly correlated with the change in resilience score (r = −0.897, p = 0.015). The preliminary results suggest that DNA methylation age can be a potential biomarker for improving resilience in cancer survivors with multiple chronic conditions. This finding is limited by the small sample size, and a larger study is needed.

Against the update of load design standards and requirement of long-term service, many latticed towers using steel angles subjected to gradual performance degradation must be retrofitted for bearing further social functions, e.g., electric power transmission and fifth-generation mobile communication. Therefore, this paper proposed a non-destructive reinforcement method for steel angles by avoiding unnecessary new construction or complex reinforcement procedure. The non-destructive reinforcement of a steel angle is composed of a steel angle, reinforcement plate, and fixture. Standardized fixtures are used to connect the reinforcement plate and steel angle to achieve steel angle reinforcement. In retrofitting tests, built-up steel angle members were loaded under axial compression, in which the failure mode and reinforcement effect of key parameters (e.g., clamp type, slenderness ratio, and clamp distance) were analyzed and compared, where a significant reinforcement effect was obtained with the capacity increment within 39~174%; the clamp types and clamp distance had a slight effect on bearing capacity; and the proposed reinforcement method was more effective for slender members. Based on the mechanical mechanism analysis and failure mode, the accuracy of the design method for calculating the bearing capacity of those built-up steel angle members was suggested and verified, in which a simplified mechanical model for the flexural-buckling mode was developed. The design method based on AISC360-16 agreed well with the test result and could be effectively used for calculating the flexural–torsional bearing capacity of those built-up steel angles. This study can provide a valuable reference for the design and application of non-destructive reinforcement of angle steel towers.

Background: Prehypertension is common in China, but its causes and associated factors have not been well studied. This study aimed to examine the age and gender-specific associations between CVD risk factor clustering and prehypertension among adults in China. Methods: This cross-sectional study used data from participants (n = 8735) aged over 45 in the China Health and Retirement Longitudinal Study (CHARLS) Baseline conducted from 2011–2012. The participants’ data were collected using standard questionnaires, anthropometric, and biochemical tests. Logistic regression analyses were used to examine the associations between cardiovascular risk factors, their clustering and prehypertension. Results: Overall, 21.1%, 39.5%, 27.6% and 11.8% participants had 0, 1, 2, ≥ 3 CVD risk factors in prehypertension group, respectively. Diabetes and overweight/obesity were significantly associated with prehypertension (OR, 1.24; 95% confidence interval [CI], 1.06–1.44; OR, 1.55; 95% CI, 1.38–1.75) in the overall population, and diabetes was associated with prehypertension only in men (OR, 1.26; 95% CI, 1.00–1.58) and older adults (OR, 1.32; 95% CI, 1.03–1.69). Moreover, participants with 1, 2 and ≥3 risk factors had increased odds of having prehypertension (OR, 1.29; 95% CI, 1.12–1.49; OR, 1.59; 95% CI, 1.31–1.78; OR, 2.05; 95% CI, 1.66–2.53, respectively) and existed dose-response relationship, regardless of age and gender. Conclusions: This study indicated that CVD risk factor clustering was significantly associated with prehypertension and hypertension. These results provide valuable information for health professionals to better understand the impact of CVD risk factor clustering on prehypertension and hypertension.

The TIPE2 (tumor necrosis factor-alpha-induced protein 8-like 2) protein is a major regulator of cancer and inflammatory diseases. The availability of its sequence and structure, as well as the critical amino acids involved in its ligand binding, provides insights into its function and helps greatly identify novel drug candidates against TIPE2 protein. With the current advances in deep learning and molecular dynamics simulation-based drug screening, large-scale exploration of inhibitory candidates for TIPE2 becomes possible. In this work, we apply deep learning-based methods to perform a preliminary screening against TIPE2 over several commercially available compound datasets. Then, we carried a fine screening by molecular dynamics simulations, followed by metadynamics simulations. Finally, four compounds were selected for experimental validation from 64 candidates obtained from the screening. With surprising accuracy, three compounds out of four can bind to TIPE2. Among them, UM-164 exhibited the strongest binding affinity of 4.97 µM and was able to interfere with the binding of TIPE2 and PIP2 according to competitive bio-layer interferometry (BLI), which indicates that UM-164 is a potential inhibitor against TIPE2 function. The work demonstrates the feasibility of incorporating deep learning and MD simulation in virtual drug screening and provides high potential inhibitors against TIPE2 for drug development.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus poses serious threats to the global public health and leads to worldwide crisis. No effective drug or vaccine is readily available. The viral RNA-dependent RNA polymerase (RdRp) is a promising therapeutic target. A hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected market available drug candidates, Pralatrexate and Azithromycin were confirmed to effectively inhibit SARS-CoV-2 replication in vitro with EC50 values of 0.008μM and 9.453 μM, respectively. For the first time, our study discovered that Pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than Remdesivir within the same experimental conditions. The paper demonstrates the feasibility of fast and accurate anti-viral drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.

Objectives: To describe perceptions and beliefs about daytime sleepiness and napping along with subjective and objective daytime sleep characteristics in nursing-home eligible community dwelling older adults. Methods: A mixed methods study; we conducted semi-structured interviews and measured sleep variables via Actigraphy, sleep diary, and Epworth Sleepiness Scale (ESS). Napping was defined as >10 minutes; anything less was considered dozing. Results: Final sample ( n = 40) was primarily female (85%), Black (100%), with a mean age of 72 ± 9.5 years. Few (25%) reported daytime sleepiness (ESS >10). However, average duration of napping per day was 33.1 ± 11.5 minutes with a nap frequency of 2.5 ± 1.5 naps. Conclusion: Our sample napped frequently throughout the day, yet the majority reported no daytime sleepiness. These older adults did not always recognize napping or how much they napped.

In order to research the competitive binding with CaM between metal ions and Ca2+, electrochemical impedance spectroscopy (EIS) of ion (such as Ca2+,Cd2+,Al3+,Fe3+) -loaded CaM self-assembled membrane on Au electrode in 0.15 mol/L NaCl solution containing 2 mmol/L 3-/4- at pH 6.5 is investigated. The results indicate that the ion-binding property of CaM can be detected by the change of the electrochemical reaction resistance. Ca2+,Cd2+ and Al3+ can combine with CaM,and Fe3+ can’t combine with CaM. The binding ability of Ca2+ to CaM is stronger than that of Al3+. Ca2+ binding site of CaM is different from that of Al3+ and same as that of Cd2+. Electrochemical impedance spectroscopy provides a new method for the research of metal ions and CaM competition binding.

Worldwide, there is a dramatic shortage of nurses. An increase in the migration of nurses from their home countries to recipient countries is having a global effect on the healthcare system. This global phenomenon stems from historical, economical, social, and political factors. Migration has a significant impact on both the individual and national level. This article summarizes the factors that contribute to nurse migration form the perspective of the source and recipient countries. Additionally, the impacts and issues surrounding nurse migration were also analyzed.

Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.

This randomized controlled pilot trial tested the preliminary effect of a 24-week mHealth-facilitated, personalized intervention on physical activity (PA) and sleep in 21 community-dwelling older adults. The intervention included a personalized exercise prescription, training, goal setting, and financial incentives. mHealth strategies, including self-monitoring, motivational messages, activity reminders, and phone coaching, were used to facilitate PA participation. PA and sleep were measured using actigraphy and questionnaires at baseline and 8-, 16-, and 24-week visits. Participants in the intervention group had lower objective PA levels at 24 weeks than at 8 and 16 weeks, although levels of PA remained higher than at baseline. Compared with the control group, the intervention increased PA at 8, 16, and 24 weeks; improved subjective sleep quality at 16 and 24 weeks; and increased actigraphy-measured sleep duration and sleep efficiency at 24 weeks. mHealth PA interventions may benefit PA and sleep in older adults. Strategies for maintaining long-term PA behavioral changes are needed. [ABSTRACT FROM AUTHOR]

Abstract The anterior cruciate ligament is anchored to the femur and tibia via specialized interfaces known as entheses. These play a critical role in ligament homeostasis and joint stability by transferring forces, varying in magnitude and direction between structurally and functionally dissimilar tissues. However, the precise structural and mechanical characteristics underlying the femoral and tibial entheses and their intricate interplay remain elusive. In this study, two thin-graduated mineralization regions in the femoral enthesis (~21 μm) and tibial enthesis (~14 μm) are identified, both exhibiting distinct biomolecular compositions and mineral assembly patterns. Notably, the femoral enthesis interface exhibits progressively maturing hydroxyapatites, whereas the mineral at the tibial enthesis interface region transitions from amorphous calcium phosphate to hydroxyapatites with increasing crystallinity. Proteomics results reveal that Matrix Gla protein uniquely enriched at the tibial enthesis interface, may stabilize amorphous calcium phosphate, while C-type lectin domain containing 11 A, enriched at the femoral enthesis interface, could facilitate the interface mineralization. Moreover, the finite element analysis indicates that the femoral enthesis model exhibited higher resistance to shearing, whereas the tibial enthesis model contributes to tensile resistance, suggesting that the discrepancy in biomolecular expression and the corresponding mineral assembly heterogeneities collectively contribute to the superior mechanical properties of both the femoral enthesis and tibial enthesis models. These findings provide novel perspectives on the structure-function relationships of anterior cruciate ligament entheses, paving the way for improved management of anterior cruciate ligament injury and regeneration.