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Summary: Atrial fibrillation (AF) is the most common arrhythmia in the world. Human genetics can provide strong AF therapeutic candidates, but the identification of the causal genes and their functions remains challenging. Here, we applied an AF fine-mapping strategy that leverages results from a previously published cross-ancestry genome-wide association study (GWAS), expression quantitative trait loci (eQTLs) from left atrial appendages (LAAs) obtained from two cohorts with distinct ancestry, and a paired RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) LAA single-nucleus assay (sn-multiome). At nine AF loci, our co-localization and fine-mapping analyses implicated 14 genes. Data integration identified several candidate causal AF variants, including rs7612445 at GNB4 and rs242557 at MAPT. Finally, we showed that the repression of the strongest AF-associated eQTL gene, LINC01629, in human embryonic stem cell-derived cardiomyocytes using CRISPR inhibition results in the dysregulation of pathways linked to genes involved in the development of atrial tissue and the cardiac conduction system.

Abstract Objective To investigate the differences in the niacin skin flushing response of adolescent depressed patients and healthy adolescents and its diagnostic value in adolescent depression. Methods Thirty-eight cases of acute episodes of depression in unmedicated adolescents and 47 age- and sex-matched healthy controls were included as study subjects, and sociodemographic and clinical data were collected, all of which were stimulated with six concentration gradients (up to 60 mmol/L, followed by sequential 3-fold gradient dilution to a minimum of 0.25 mmol/L) of niacin solution on the forearm skin, and the skin flushing area was applied as an assessment index. Results The total area of redness of the skin in response to niacin was significantly lower in the adolescent depression group than in the healthy adolescent group (Z=-3.36, p = 0.001) and was able to distinguish the adolescent depression group from the healthy adolescent group (area under curve = 0.713, sensitivity 51.1%, specificity 83.2%). Conclusions Niacin sensitivity is reduced in adolescent depressed patients, and the niacin skin flush response has potential clinical value as a diagnostic biomarker for adolescent depression.

Abstract Background Research on the impact of COVID-19-induced home isolation on the physical fitness of college students is limited. This study aims to compare and analyze the physical fitness test scores of college students in two groups: those who experienced home isolation and those who did not, over three consecutive years after enrolment, to investigate the effects of home isolation on the physical fitness development of Chinese college students. Methods This comparative study included two longitudinal surveys conducted among medical college students. The participants were divided into an experimental group and a control group. The physical fitness indicators measured included body mass index (BMI), vital capacity (VC), 50-metre run, sit-and-reach, standing long jump, 1000/800-metre runs (males/females), pull-ups (males) and sit-ups (females). Repeated measures analysis of variance (ANOVA) was employed, and the Greenhouse-Geisser correction was applied when Mauchly’s assumption of sphericity was violated. Pairwise comparisons were conducted using the Bonferroni method. Results A total of 6580 students participated in the study, with 3360 students (1490 males, 1870 females) enrolled in 2019 as the experimental group and 3220 students (1326 males, 1894 females) enrolled in 2017 as the control group. All participants completed the physical fitness tests for three consecutive years. The results showed that the experimental group exhibited decreased performance in the 1000-metre and 800-metre runs, and improved performance in the sit-and-reach test. After the end of home isolation, there was an improvement in the performance of the 1000-metre run and 800-metre run, while no significant differences were observed in the trends of the other tested indicators. Conclusion The findings of this study indicate that the home isolation environment during COVID-19 had a significant impact on the physical fitness of college students, specifically in terms of endurance and flexibility qualities, as well as male BMI. To better prepare for future public health emergencies and mitigate the effects of isolation, teaching students endurance exercises that can be performed at home should be prioritized. Furthermore, physical education programs should be improved to enhance student flexibility.

Abstract Background Dilated cardiomyopathy (DCM) is a severe, non-ischemic heart disease which ultimately results in heart failure (HF). Decades of research on DCM have revealed diverse aetiologies. Among them, familial DCM is the major form of DCM, with pathogenic variants in LMNA being the second most common form of autosomal dominant DCM. LMNA DCM is a multifactorial and complex disease with no specific treatment thus far. Many studies have demonstrated that perturbing candidates related to various dysregulated pathways ameliorate LMNA DCM. However, it is unknown whether these candidates could serve as potential therapeutic targets especially in long term efficacy. Methods We evaluated 14 potential candidates including Lmna gene products (Lamin A and Lamin C), key signaling pathways (Tgfβ/Smad, mTor and Fgf/Mapk), calcium handling, proliferation regulators and modifiers of LINC complex function in a cardiac specific Lmna DCM model. Positive candidates for improved cardiac function were further assessed by survival analysis. Suppressive roles and mechanisms of these candidates in ameliorating Lmna DCM were dissected by comparing marker gene expression, Tgfβ signaling pathway activation, fibrosis, inflammation, proliferation and DNA damage. Furthermore, transcriptome profiling compared the differences between Lamin A and Lamin C treatment. Results Cardiac function was restored by several positive candidates (Smad3, Yy1, Bmp7, Ctgf, aYAP1, Sun1, Lamin A, and Lamin C), which significantly correlated with suppression of HF/fibrosis marker expression and cardiac fibrosis in Lmna DCM. Lamin C or Sun1 shRNA administration achieved consistent, prolonged survival which highly correlated with reduced heart inflammation and DNA damage. Importantly, Lamin A treatment improved but could not reproduce long term survival, and Lamin A administration to healthy hearts itself induced DCM. Mechanistically, we identified this lapse as caused by a dose-dependent toxicity of Lamin A, which was independent from its maturation. Conclusions In vivo candidate evaluation revealed that supplementation of Lamin C or knockdown of Sun1 significantly suppressed Lmna DCM and achieve prolonged survival. Conversely, Lamin A supplementation did not rescue long term survival and may impart detrimental cardiotoxicity risk. This study highlights a potential of advancing Lamin C and Sun1 as therapeutic targets for the treatment of LMNA DCM. Graphical Abstract

Selection of the target site is an inherent question for any project aiming for directed transgene integration. Genomic safe harbour (GSH) loci have been proposed as safe sites in the human genome for transgene integration. Although several sites have been characterised for transgene integration in the literature, most of these do not meet criteria set out for a GSH and the limited set that do have not been characterised extensively. Here, we conducted a computational analysis using publicly available data to identify 25 unique putative GSH loci that reside in active chromosomal compartments. We validated stable transgene expression and minimal disruption of the native transcriptome in three GSH sites in vitro using human embryonic stem cells (hESCs) and their differentiated progeny. Furthermore, for easy targeted transgene expression, we have engineered constitutive landing pad expression constructs into the three validated GSH in hESCs.

Various applications of oil palm empty fruit bunches (OPEFB) would be hindered by the presence of residual oil. This study aimed to remove and recover the residual oil from OPEFB using an integrated system, high pressure water spray system (HPWSS). The performance of the HPWSS was evaluated at different temperatures and water pressures, and the residual oil collected was recovered through water shaking method and tested for biodiesel application. A maximum of 84.9% of residual oil was removed by HPWSS at 60 °C and 8960 kPa and the highest residual oil recovery of 58.8% was observed at 95 °C, using power shaking 5 and 90% of dilution. The following ranges of deterioration of bleachability index (DOBI), free fatty acid (FFA), and peroxide value (PV) for the residual oil were 1.21 to 2.67, 7.11 to 10.4%, and 4.85 to 7.56, respectively. Biodiesel with different blends of recovered residual oil (5%, 10%, and 15%) showed lower values (9.87, 9.57, and 9.56 Nm) of brake torque as compared with diesel (10.89 Nm). Overall, this study showed the potential of HPWSS to obtain an acceptable quality of residual oil from OPEFB to be used in any value-added product generation.

Abstract Traditional offline cable diagnosis methods need power outages during detection, affecting power supply reliability. Here, a hierarchical diagnosis method of cable aged segment based on transfer function is proposed. Firstly, the calculation model of cable transfer function with the aged segment is established; on this basis, the correlation between transfer function and cable aging is analysed. Then, a structure with combined sparse autoencoder and convolutional neural network is trained to estimate the aging location, and a hierarchical diagnosis model of distribution cable based on transfer function is proposed. The sensitivity and accuracy of aged segment detection are improved after hierarchical diagnosis. Finally, the simulation results show that the method proposed in this paper can effectively realize the online identification and location of the cable aged segment. The proposed method makes use of the advantage that the cable transfer function can be obtained online. Compared with the existing methods, this method does not need power outages in the diagnosis process, and the aged segment can be located without a lot of additional equipment.

Due to the high specific stiffness, high specific strength, good fatigue resistance and high structural reliability, the integrally stiffened shells are widely applied in the sealed cabins. In order to enhance the detection distance of the deep space and improve the payload detection capability, it is of great significance to carry out lightweight design for the integrally stiffened shells. However, it is challenging to perform optimization for the structures due to the strict loading conditions, complicated structures and short development cycles. In this work, a novel layout design framework for the integrally stiffened shells under complex loading conditions is proposed. The topology optimization method is employed to obtain an innovative layout design of the integrally stiffened shells firstly, and then the mesh-mapping technique is utilized to assist the reconstruction and modeling process of the optimization result. Compared with the traditional design of orthogonal stiffeners, the weight of the optimized configuration of the integrally stiffened shell reduces by 17.1%, demonstrating excellent lightweight design effects. Moreover, a sealed cabin is constructed based on the optimization and numerical analysis result by taking the manufacturing requirement into consideration. With the purpose of assessing the bearing ability of the welded seam and evaluating the airtight performance of the sealed cabin, experimental validations of the hydrostatic test and airtight test are carried out, and the experimental results validate the applicability and effectiveness of the proposed framework.

Abstract Rho GTPases and Hippo kinases are key regulators of cardiomyoblast differentiation. However, how these signaling axes are coordinated spatiotemporally remains unclear. Here, the central and multifaceted roles of the BCH domain containing protein, BNIP‐2, in orchestrating the expression of two key cardiac genes (cardiac troponin T [cTnT] and cardiac myosin light chain [Myl2]) in H9c2 and human embryonic stem cell‐derived cardiomyocytes are delineated. This study shows that BNIP‐2 mRNA and protein expression increase with the onset of cTnT and Myl2 and promote the alignment of H9c2 cardiomyocytes. Mechanistically, BNIP‐2 is required for the inactivation of YAP through YAP phosphorylation and its cytosolic retention. Turbo‐ID proximity labeling corroborated by super‐resolution analyses and biochemical pulldown data reveals a scaffolding role of BNIP‐2 for LATS1 to phosphorylate and inactivate YAP in a process that requires BNIP‐2 activation of cellular contractility. The findings identify BNIP‐2 as a pivotal signaling scaffold that spatiotemporally integrates RhoA/Myosin II and LATS1/YAP mechanotransduction signaling to drive cardiomyoblast differentiation, by switching the genetic programming from YAP‐dependent growth to YAP‐silenced differentiation. These findings offer insights into the importance of scaffolding proteins in bridging the gap between mechanical and biochemical signals in cell growth and differentiation and the prospects in translational applications.

Purpose: Carotid artery web (CaW) is a rare focal fibromuscular dysplasia that can lead to embolic strokes with large vessel occlusion. This condition can be effectively treated with endovascular thrombectomy (EVT). Our study aims to assess the prevalence of CaW among patients with acute ischemic stroke (AIS) who underwent EVT and to compare the clinical characteristics of CaW with other carotid artery pathologies. Methods: We enrolled consecutive patients with AIS who underwent EVT at a single medical center and two regional teaching hospitals in Taiwan from September 2014 to December 2021. We compared CaW with carotid dissection (CaD) and carotid large artery atherosclerosis (CaLAA) in terms of patient demographics and thrombus histological findings. Results: Of the 576 AIS patients who underwent EVT, four (mean age: 50 years) were diagnosed with CaW, resulting in a prevalence of 0.69%. Among these four patients, three experienced successful reperfusion after EVT and achieved functional independence (defined as a modified Rankin Scale score ≤2) three months post-stroke. Importantly, none of the CaW patients suffered a recurrent stroke within one year. Patients with CaW were younger than those with CaD or CaLAA, and exhibited fewer vascular risk factors. Additionally, CaW was associated with distal occlusion sites. The thrombus composition in CaW patients was similar to that in CaD patients. Conclusion: In conclusion, CaW is a rare finding among Asian patients with carotid artery disease who undergo for AIS. It is more prevalent in younger patients with a limited number of vascular risk factors.

Wushu course is a basic content in physical education teaching in colleges and universities. The teaching content of Wushu course is mainly routine teaching. Because Wushu routine is composed of many individual movements, the direction, route, rhythm and body posture are complicated and different from the students’ daily activities and other sports teaching materials, many students feel that Wushu is “difficult to learn” and “forget quickly “. In order to overcome the phenomena of “difficult to teach “,” difficult to learn” and “forget quickly “, we must deeply study the teaching methods in order to improve the teaching effect of martial arts. Demonstration teaching method is the main teaching method used in Wushu teaching, and it is also one of the effective ways to improve the teaching effect of Wushu. As multimedia teaching is more and more used in teaching, demonstration teaching method also has more new teaching methods. [1] This paper analyzes the effect of martial arts teachers in the teaching process through the experimental study of three classes in the martial arts curriculum of physical education major in Dehong Teachers College. In order to study the teaching effect of different intuitive teaching methods in martial arts class.

The paper analyzed static strain measurement principle and dynamic acceleration measurement principle of steel structure of rapid quantitative loading station, and introduced arrangement of measuring points, choosing of measuring time and working conditions taking conventional loading station as an example. It achieved evaluation and analysis of running status of the loading station with different loads by field static and dynamic measurement. The test results show that lateral displacement of steel structure of the tested loading station is less than the lateral displacement of open-air trestle column allowed in steel structure design standard, and the maximum stress of the main column is less than the allowable value, so that the steel structure of the loading station is safe and reliable.

Soil alkalization is a major challenge for global crop production. This study reveals a novel defense mechanism in rice seedlings against alkaline stress, involving methyl jasmonate (MeJA) and auxin pathways. Under alkaline stress (15 mM Na2CO3), rice seedlings exhibited elevated levels of endogenous MeJA and upregulation of JA-responsive genes. Pre-treatment with MeJA (50 µM) significantly improved seedling survival, growth, and mitigated root damage under alkaline stress. This treatment also upregulated genes associated with cell death suppression (OsBI1) and stress tolerance (OsJRL, OsNAC). Notably, MeJA pre-treatment increased auxin (indole-3-acetic acid, IAA) levels in roots, and upregulated genes involved in IAA synthesis (OASA1, OASA2) and auxin signaling (Aux/IAA, ARFs). Blocking auxin transport with N-1-naphthylphthalamic acid intensified root damage under alkaline stress and diminished the protective effect of MeJA. These results highlight the crucial role of MeJA-induced activation of auxin pathway in enhancing rice tolerance to alkaline stress, and provide valuable insights for developing strategies to improve crop resilience in alkaline soils.