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IntroductionIn vitro fertilization (IVF) is a technology that assists couples experiencing infertility to conceive children. However, unsuccessful attempts can lead to significant physical and financial strain. Some individuals opt for electro-acupuncture (EA) during IVF, even though there is limited evidence regarding the efficacy of this practice. Thus, this pilot study aims to explore the effectiveness and safety of EA during IVF on pregnancy outcomes.Methods and analysisThis clinical trial is a parallel, randomized, sham-controlled study. It aims to include a total of 118 infertile women who intend to undergo IVF. The participants will be randomly divided into three groups in a 1:1:1 ratio: the EA + IVF group, the placebo electro-acupuncture (pEA) +IVF group, and the IVF control group. All of the patients will be required to use ovarian stimulation drugs, while those in the EA + IVF and pEA + IVF groups will receive acupuncture treatment at three sessions per week (every other day) until trigger day with a minimum five session. The primary outcome of this trial will focus on the clinical pregnancy rate (CPR). CPR is defined as the rate of achieving clinical pregnancy from the first fresh/frozen embryo transfer cycle with an ultrasound-confirmed gestational sac in the uterine cavity. The secondary outcomes will assess embryology data, biochemical pregnancy rate, early miscarriage rate, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Fertile Quality of Life (FertiQoL), patient retention rate, treatment adherence, and safety outcomes.Ethics and disseminationEthics approval was obtained from the Ethics Committee of Sichuan Jinxin Xi’nan Women and Children Hospital (number 2021–007). The results will be disseminated through peer-reviewed publications. The participants gave informed consent to participate in the study before taking part in it.Clinical trial registrationhttps://www.chictr.org.cn, identifier ChiCTR2300074455.

In the study of cavitation in room-temperature fluids, the heat transfer between gas and liquid in bubble oscillation is usually assumed to be an adiabatic process for simplification. However, this heat transfer and thermodynamic mechanism is not yet understood in cryogenic fluids, especially under small amplitude oscillation conditions excited by ultrasonic field. This article studies bubble thermodynamic model under an external ultrasonic field based on the heat transfer equation for cryogenic fluids. The temperature changes inside bubbles are calculated, and the heat transfer mechanism is briefly analyzed. The results indicate that the heat transfer mechanism of bubbles depends on the relationship between ultrasonic frequency and bubble resonance frequency. By analyzing two special cases of dual-bubble and high-pressure environment, it is believed that heat transfer can be approximated as an adiabatic process under high-pressure conditions with ultrasonic frequency far from the resonance frequency. This conclusion can provide a theoretical basis for subsequent accurate calculation of heat-transfer polytropic coefficient, or void faction measurement in cryogenic two-phase flow.

ObjectiveTo study the effect of family type on depression symptoms among high school students in Jiangsu province and to provide evidence for mental health interventions among students. MethodsA self-administered anonymous electronic questionnaire survey was conducted from September to November 2020 among 22 076 high school students recruited from 13 prefectures in Jiangsu province using stratified multistage cluster random sampling. The Center for Epidemiologic Studies Depression Scale (CES-D) and the Internet Addiction Test (IAT) were used to assess students' mental health status and internet addiction. The propensity score matching method was used to balance potential confounders of depression symptoms between two groups of students from normal (nuclear/extended) and abnormal (single-parent/reconstituted/grandparent-grandchild) families, and a total of 4 027 pairs (8 054) of students were matched with balanced confounders. A univariate logistic regression analysis model was used to examine the association between family type and depression symptoms among students. ResultsAmong all students, 26.1% were found to have symptoms of depression. The detection rate of depression symptoms among the 1 : 1 propensity score matched students was 27.3% for 4 027 individuals from normal families, with subgroup detection rates of 27.4%/27.1% for urban/suburban students and 29.7%/25.6% for boarding/day students, whereas the detection rate was 32.6% for 4 027 individuals from abnormal families, with subgroup rates of 32.9%/32.2% for urban/suburban students and 33.8%/31.9% for boarding/day students. The results of univariate logistic analysis of the data after propensity score matching indicated that students from abnormal families had an increased risk of depression symptoms compared with those from normal families (odds ratio [OR] = 1.29, 95% confidence interval [CI]: 1.17 – 1. 42); further subgroup analysis showed that the increased risk of depression symptoms was significant among students from abnormal families living in both urban (OR = 1.30, 95%CI: 1.15 – 1.48) and suburban (OR = 1.28, 95%CI: 1.10 – 1.48) areas, and among boarding students (OR = 1.20, 95%CI: 1.04 – 1.40) and day students (OR = 1.36, 95%CI: 1.20 – 1.54), respectively. ConclusionFamily type has a significant effect on the occurrence of depression symptoms among high school students in Jiangsu province. More attention should be paid to high school students living in abnormal family situations.

There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia (CNS-ALL). Integrin α6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression. The targeted peptide D(RWYD) (abbreviated RD), with nanomolar affinity to integrin α6 was identified by peptide scanning techniques such as alanine scanning, truncation, and D-substitution. Herein, we developed a therapeutic nanoparticle based on the integrin α6-targeted peptide for treating CNS-ALL. The self-assembled proapoptotic nanopeptide D(RWYD)-D(KLAKLAK)2-GD(FFY) (abbreviated RD-KLA-Gffy) contains the integrin α6-targeted peptide RD, the well-known proapoptotic peptide D(KLAKLAK)2 (abbreviated KLA), and the self-assembling tetrapeptide GD(FFY) (abbreviated Gffy). The functional mechanism of RD-KLA-Gffy is clarified using different experiments. Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis, thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity. Moreover, the combined use of RD-KLA-Gffy and methotrexate (MTX) shows a potent antitumor effect in treating CNS-ALL, indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX, which shows promise for application in CNS-ALL therapy.

Abstract Introduction The Guangdong-Hong Kong-Macao Greater-Bay-Area of South China has an 86 million population and faces a significant challenge of Alzheimer’s disease (AD). However, the characteristics and prevalence of AD in this area are still unclear due to the rarely available community-based neuroimaging AD cohort. Methods Following the standard protocols of the Alzheimer’s Disease Neuroimaging Initiative, the Greater-Bay-Area Healthy Aging Brain Study (GHABS) was initiated in 2021. GHABS participants completed clinical assessments, plasma biomarkers, genotyping, magnetic resonance imaging (MRI), β-amyloid (Aβ) positron emission tomography (PET) imaging, and tau PET imaging. The GHABS cohort focuses on pathophysiology characterization and early AD detection in the Guangdong-Hong Kong-Macao Greater Bay Area. In this study, we analyzed plasma Aβ42/Aβ40 (A), p-Tau181 (T), neurofilament light, and GFAP by Simoa in 470 Chinese older adults, and 301, 195, and 70 had MRI, Aβ PET, and tau PET, respectively. Plasma biomarkers, Aβ PET, tau PET, hippocampal volume, and temporal-metaROI cortical thickness were compared between normal control (NC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia groups, controlling for age, sex, and APOE-ε4. The prevalence of plasma A/T profiles and Aβ PET positivity were also determined in different diagnostic groups. Results The aims, study design, data collection, and potential applications of GHABS are summarized. SCD individuals had significantly higher plasma p-Tau181 and plasma GFAP than the NC individuals. MCI and dementia patients showed more abnormal changes in all the plasma and neuroimaging biomarkers than NC and SCD individuals. The frequencies of plasma A+/T+ (NC; 5.9%, SCD: 8.2%, MCI: 25.3%, dementia: 64.9%) and Aβ PET positivity (NC: 25.6%, SCD: 22.5%, MCI: 47.7%, dementia: 89.3%) were reported. Discussion The GHABS cohort may provide helpful guidance toward designing standard AD community cohorts in South China. This study, for the first time, reported the pathophysiology characterization of plasma biomarkers, Aβ PET, tau PET, hippocampal atrophy, and AD-signature cortical thinning, as well as the prevalence of Aβ PET positivity in the Guangdong-Hong Kong-Macao Greater Bay Area of China. These findings provide novel insights into understanding the characteristics of abnormal AD pathological changes in South China’s older population.

Abstract Introduction Few studies focused on the Pre-Exposure Prophylaxis (PrEP) -related aspects, and the applicability of prior evidence to young men who have sex with men (YMSM) students was unknown. This study aimed to assess the awareness, willingness, uptake, and adherence (AWUA) to PrEP among YMSM students in China and to explore the associated factors with these stages. Methods A cross-sectional survey with a sizable sample of 1151 was conducted among YMSM students aged 16 and above, who self-identified as men who have sex with men(MSM) and resided in mainland China between October 20 and December 20, 2021. The chi-square test and Fisher’s exact test were used for univariate analysis, followed by multivariable logistic regression analysis of influencing factors at all levels. Results According to the cascade analysis approach, 88.71% of the participants were aware of PrEP, among which 66.7% expressed willingness to use it. Among those who were willing to use PrEP, only 13.80% took it, and of those who took it, 44.68% adhered to it. The students taking PrEP were those with higher education (OR = 4.239, 95% CI: 1.334–13.467), residence in pilot cities (OR = 2.791, 95% CI: 1.498–5.198), residence in high-risk areas (OR = 5.082, 95% CI: 2.224–11.612), engagement in multi-person sexual behavior (OR = 2.186, 95% CI: 1.236–3.867), and substance use (OR = 1.908, 95% CI: 1.167–3.118). Furtherly, students with higher adherence to PrEP were likely to have receptive sexual behaviors (OR = 8.702, 95% CI: 2.070-36.592), absence of substance use (OR = 4.468, 95% CI: 1.371–14.561), and uptake of PrEP through daily oral route. (OR = 7.065, 95% CI: 1.699–29.371). Conclusion YMSM students exhibit distinct patterns of “high awareness, low willingness, low uptake, and low adherence” to PrEP. Strategies for reduction in the acquisition of HIV prioritizing the current features of utilizing PrEP were urgently warranted.

Abstract The rapid emergence and spread of colistin-resistant gram-negative bacteria has raised worldwide public health concerns, and phosphoethanolamine (PEtn) transferase modification-mediated colistin resistance has been widely documented in multiple gram-negative bacterial species. However, whether such a mechanism exists in the zoonotic pathogen Pasteurella multocida is still unknown. Recently, a novel PEtn transferase, PetL, was identified in P. multocida, but whether it is associated with colistin resistance remains to be elucidated. In this study, we found that PetL in P. multocida (PetLPM) exhibited structural characteristics similar to those of the mobile-colistin-resistant (MCR) protein and the PEtn transferase characterized in Neisseria meningitidis. The transformation of petL PM into E. coli or K. pneumoniae changed the phenotype of several tested strains from colistin sensitive to colistin resistant. Deletion of this gene decreased the colistin minimum inhibitory concentration (MIC) of P. multocida by 64-fold. Our extensive analysis by MALDI-TOF–MS demonstrated that PetLPM participated in the modification of bacterial lipopolysaccharide (LPS)-lipid A. Deletion of petL PM led to an increase in membrane charge but a decrease in cell-surface hydrophobicity and cell permeability in P. multocida. The present study is the first to report the presence of PEtn transferase-mediated colistin resistance in the zoonotic pathogen P. multocida.

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH; however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

[Introduction] Under the background of "carbon peak and neutrality" target and "ocean power" strategy, the integration of ocean renewable energy represented by offshore wind power and ocean resources represented by marine ranch is the new direction, new situation and new opportunity for the future development and utilization of ocean resources. The article reviews and analyzes the integrated development mode and key technical problems of offshore wind power and marine pasture, in order to provide technical references to the relevant research and engineering projects in China. [Method] Taking the integration of China's marine resources development needs as the guide, the global development trend of offshore wind power and marine ranch integration was analyzed, and the current situation and shortcomings of China's wind-fishery integration development were clarified. On this basis, the integration mode, equipment design, engineering cases and key technical problems of the integration development of offshore wind power and ocean ranch were analyzed in detail. Finally, a future outlook on the integration development of offshore wind power and ocean ranch in China was discussed. [Result] Through the analysis of the integrated development mode and key technical problems of the integration of offshore wind power and marine ranch development, the bottlenecks and technical challenges are clarified, and the key breakthrough directions are pointed out, providing scientific guidance and reference basis for the comprehensive development and utilization of offshore resources in China. [Conclusion] The article illustrates the necessity and feasibility of integrating the development of offshore wind power and marine ranch, and proposes a feasible way to integrate offshore wind power and marine ranch in China.

Abstract The Silent Information Regulator 2 (SIR2) protein is widely implicated in antiviral response by depleting the cellular metabolite NAD+. The defense-associated sirtuin 2 (DSR2) effector, a SIR2 domain-containing protein, protects bacteria from phage infection by depleting NAD+, while an anti-DSR2 protein (DSR anti-defense 1, DSAD1) is employed by some phages to evade this host defense. The NADase activity of DSR2 is unleashed by recognizing the phage tail tube protein (TTP). However, the activation and inhibition mechanisms of DSR2 are unclear. Here, we determine the cryo-EM structures of DSR2 in multiple states. DSR2 is arranged as a dimer of dimers, which is facilitated by the tetramerization of SIR2 domains. Moreover, the DSR2 assembly is essential for activating the NADase function. The activator TTP binding would trigger the opening of the catalytic pocket and the decoupling of the N-terminal SIR2 domain from the C-terminal domain (CTD) of DSR2. Importantly, we further show that the activation mechanism is conserved among other SIR2-dependent anti-phage systems. Interestingly, the inhibitor DSAD1 mimics TTP to trap DSR2, thus occupying the TTP-binding pocket and inhibiting the NADase function. Together, our results provide molecular insights into the regulatory mechanism of SIR2-dependent NAD+ depletion in antiviral immunity.

Abstract Tomosyns are widely thought to attenuate membrane fusion by competing with synaptobrevin-2/VAMP2 for SNARE-complex assembly. Here, we present evidence against this scenario. In a novel mouse model, tomosyn-1/2 deficiency lowered the fusion barrier and enhanced the probability that synaptic vesicles fuse, resulting in stronger synapses with faster depression and slower recovery. While wild-type tomosyn-1m rescued these phenotypes, substitution of its SNARE motif with that of synaptobrevin-2/VAMP2 did not. Single-molecule force measurements indeed revealed that tomosyn’s SNARE motif cannot substitute synaptobrevin-2/VAMP2 to form template complexes with Munc18-1 and syntaxin-1, an essential intermediate for SNARE assembly. Instead, tomosyns extensively bind synaptobrevin-2/VAMP2-containing template complexes and prevent SNAP-25 association. Structure-function analyses indicate that the C-terminal polybasic region contributes to tomosyn’s inhibitory function. These results reveal that tomosyns regulate synaptic transmission by cooperating with synaptobrevin-2/VAMP2 to prevent SNAP-25 binding during SNARE assembly, thereby limiting initial synaptic strength and equalizing it during repetitive stimulation.

Abstract Introduction The term “health poverty trap” describes a vicious cycle in which developing countries or regions become trapped in low levels of health and poverty during the process of modernization. Although significant progress has been made in alleviating poverty in China, there is still a need to further enhance the living conditions of its impoverished population. Methods This research utilizes the data of the three national representative panel surveys from 2014 to 2020. The primary objective is to gain a better understanding of the intricate relationship between health and poverty. To examine the self-reinforcing effects of the cumulative cycle between health and poverty, we employ unconditional quantile regression analysis. Result The low-income group exhibits lower overall health status compared to the average level. Economic constraints partially hinder the ability of low-income individuals to access healthcare resources, thereby reinforcing the cyclical relationship between health and poverty. Additionally, the unique psychological and behavioral preferences of individuals in health poverty act as indirect factors that further strengthen this cycle. Health poverty individuals can generate endogenous force to escape the “health poverty trap” by enhancing their confidence levels and digital literacy. Conclusions The research examines the coexistence of health gradients and economic inequality among Chinese residents. Additionally, the study explores the endogenous force mechanism of escaping the health poverty trap from psychological and behavioral perspectives. This research also offers insights into optimizing government poverty alleviation programs to effectively address this issue.

Abstract Objective Renal function can modify the outcomes of large vessel occlusion (LVO) stroke across stroke etiologies in disparate degrees. The presence of renal function deficit can also impair the pharmacokinetics of tirofiban. Hence, this study aimed to investigate the roles of renal function in determining efficacy and safety of intravenous tirofiban before endovascular treatment (EVT) for acute ischemic stroke patients with large vessel occlusion (LVO). Methods This study was a post hoc exploratory analysis of the RESCUE‐BT trial. The primary outcome was the proportion of patients achieving functional independence (modified Rankin scale 0–2) at 90 days, and the primary safety outcome was the rate of symptomatic intracranial hemorrhage (sICH). Results Among 908 individuals with available serum creatinine, decreased estimated glomerular filtration rate (eGFR) status was noted more commonly in patients with cardioembolic stroke (CE), while large artery atherosclerosis (LAA) was predominant in patients with normal renal function. In LAA with normal renal function, tirofiban was associated with higher rates of functional independence at 90 days (41.67% vs 59.80%, p = 0.003). However, for LVO patients with renal dysfunction, tirofiban did not improve functional outcomes for any of the etiologies (LAA, p = 0.876; CE, p = 0.662; others, p = 0.894) and significantly increased the risk of sICH among non‐LAA patients (p = 0.020). Mediation analysis showed tirofiban reduced thrombectomy passes (12.27%) and drug/placebo to recanalization time (14.25%) mediated its effects on functional independence. Conclusion This present study demonstrated the importance of evaluating renal function before administering intravenous tirofiban among patients with LVO who are planned to undergo EVT.

Abstract This paper thoroughly explores the role of object detection in smart cities, specifically focusing on advancements in deep learning-based methods. Deep learning models gain popularity for their autonomous feature learning, surpassing traditional approaches. Despite progress, challenges remain, such as achieving high accuracy in urban scenes and meeting real-time requirements. The study aims to contribute by analyzing state-of-the-art deep learning algorithms, identifying accurate models for smart cities, and evaluating real-time performance using the Average Precision at Medium Intersection over Union (IoU) metric. The reported results showcase various algorithms’ performance, with Dynamic Head (DyHead) emerging as the top scorer, excelling in accurately localizing and classifying objects. Its high precision and recall at medium IoU thresholds signify robustness. The paper suggests considering the mean Average Precision (mAP) metric for a comprehensive evaluation across IoU thresholds, if available. Despite this, DyHead stands out as the superior algorithm, particularly at medium IoU thresholds, making it suitable for precise object detection in smart city applications. The performance analysis using Average Precision at Medium IoU is reinforced by the Average Precision at Low IoU (APL), consistently depicting DyHead’s superiority. These findings provide valuable insights for researchers and practitioners, guiding them toward employing DyHead for tasks prioritizing accurate object localization and classification in smart cities. Overall, the paper navigates through the complexities of object detection in urban environments, presenting DyHead as a leading solution with robust performance metrics.

Abstract Background Episodic memory loss is a prominent clinical manifestation of Alzheimer’s disease (AD), which is closely related to tau pathology and hippocampal impairment. Due to the heterogeneity of brain neurons, the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain unclear. Therefore, further investigation is necessary. Methods We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis, social behavioural tests, hippocampal electrophysiology, immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and iGABASnFR. Additionally, we utilized optogenetics and administered ursolic acid (UA) via oral gavage to examine the effects of these agents on social memory in mice. Results The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1 (vCA1) under both physiological conditions and AD-like tau pathology. As tau progressively accumulated, vCA1, especially its excitatory and parvalbumin (PV) neurons, were fully filled with mislocated and phosphorylated tau (p-Tau). This finding was not observed for dorsal hippocampal CA1 (dCA1). The overexpression of human tau (hTau) in excitatory and PV neurons mimicked AD-like tau accumulation, significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1. Photoactivating excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social memory. Notably, 1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB (TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social memory. Conclusion This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation. Notably, our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.

Objective: Some patients exhibit septic symptoms following laparoscopic surgery, leading to a poor prognosis. Effective clinical subphenotyping is critical for guiding tailored therapeutic strategies in these cases. By identifying predisposing factors for postoperative sepsis, clinicians can implement targeted interventions, potentially improving outcomes. This study outlines a workflow for the subphenotype methodology in the context of laparoscopic surgery, along with its practical application. Methods: This study utilized data routinely available in clinical case systems, enhancing the applicability of our findings. The data included vital signs, such as respiratory rate, and laboratory measures, such as blood sodium levels. The process of categorizing clinical routine data involved technical complexities. A correlation heatmap was used to visually depict the relationships between variables. Ordering points were used to identify the clustering structure and combined with Consensus K clustering methods to determine the optimal categorization. Results: Our study highlighted the intricacies of identifying clinical subphenotypes following laparoscopic surgery, and could thus serve as a valuable resource for clinicians and researchers seeking to explore disease heterogeneity in clinical settings. By simplifying complex methodologies, we aimed to bridge the gap between technical expertise and clinical application, fostering an environment where professional medical knowledge is effectively utilized in subphenotyping research. Conclusion: This tutorial could primarily serve as a guide for beginners. A variety of clustering approaches were explored, and each step in the process contributed to a comprehensive understanding of clinical subphenotypes.

Abstract Cardio-metabolic traits have been reported to be associated with the development of sepsis. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability, or are confounded by environmental factors. We performed three analyses to explore the relationships between cardio-metabolic traits and sepsis. Mendelian randomization (MR) study to evaluate the causal effects of multiple cardio-metabolic traits on sepsis. Global genetic correlation analysis to explore the correlations between cardio-metabolic traits and sepsis. Local genetic correlation (GC) analysis to explore shared genetic heritability between cardio-metabolic traits and sepsis. Some loci were further examined for related genes responsible for the causal relationships. Genetic associations were obtained from the UK Biobank data or published large-scale genome-wide association studies with sample sizes between 200,000 to 750,000. In MR, we found causality between BMI and sepsis (OR: 1.53 [1.4–1.67]; p

Alpha-L-arabinofuranosidase (α-L-AFase) belongs to glycosyl hydrolases. Its main function is to hydrolyze the arabinose substituents in arabinoxylan and promote the hydrolysis of hemicellulose with other hydrolases synergistically, so as to improve the biotransformation rate of hemicellulose. In this article, the recent research advances on the enzymatic characteristic and its improvement, structure, catalytic mechanism and synergistic catalytic effect of α-L-AFase from microorganisms are reviewed. It is found that the physicochemical properties, molecular structures and catalytic mechanisms of α-L-AFases from different microbial sources are diverse, and the method of recombinant expression could effectively improve the enzymatic activity and stability of α-L-AFase. This synergistic catalysis of α-L-AFase with other hemicelluloses hydrolases can significantly improve the substrate conversion efficiency. α-L-AFase has been widely used in many fields such as improving the texture of fermented dough, juice clarification, optimizing the brewing technique, preparation of high digestion feed, and preparing the functional health products. This review provides some references for the subsequent fundamental research, development and utilization of α-L-AFase in the future.

Constitutive activation of GNAQ/11 is the initiative oncogenic event in uveal melanoma (UM). Direct targeting GNAQ/11 has yet to be proven feasible as they are vital for a plethora of cellular functions. In search of genetic vulnerability for UM, we found that inhibition of euchromatic histone lysine methyltransferase 2 (EHMT2) expression or activity significantly reduced the proliferation and migration capacity of cancer cells. Notably, elevated expression of EHMT2 had been validated in UM samples. Furthermore, Kaplan–Meier survival analysis indicated high EHMT2 protein level was related to poor recurrence-free survival and a more advanced T stage. Chromatin immunoprecipitation sequencing analysis and the following mechanistic investigation showed that ARHGAP29 was a downstream target of EHMT2. Its transcription was suppressed by EHMT2 in a methyltransferase-dependent pattern in GNAQ/11-mutant UM cells, leading to elevated RhoA activity. Rescuing constitutively active RhoA in UM cells lacking EHMT2 restored oncogenic phenotypes. Simultaneously blocking EHMT2 and GNAQ/11 signaling in vitro and in vivo showed a synergistic effect on UM growth, suggesting the driver role of these two key molecules. In summary, our study shows evidence for an epigenetic program of EHMT2 regulation that influences UM progression and indicates inhibiting EHMT2 and MEK/ERK simultaneously as a therapeutic strategy in GNAQ/11-mutant UM.

Context: Data on racial disparities among patients with metastatic castration-resistant prostate cancer (mCRPC) are limited and there is no uniform conclusion on differences by race in this setting. Objective: To provide the latest evidence on racial disparities in survival outcomes between Black and White patients receiving systemic therapies for mCRPC. Evidence acquisition: Our study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We systematically searched the PubMed, Web of Science, and Cochrane Library databases up to September 2023 to identify potentially relevant studies. Overall survival (OS) and progression-free survival (PFS) were the outcomes of interest. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were evaluated. Evidence synthesis: Nine studies involving 9462 patients with mCRPC (2058 Black and 7404 White men) met the eligibility criteria and were included. Pooled estimates demonstrated significantly better OS for Black than for White men (HR 0.75, 95% CI 0.70–0.80; p

In view of the electromagnetic interference existing in the well, it can greatly interfere with the voltage signal of the operational amplifier terminal collected by the dynamometer, and then affect the accuracy of the pressure value measured by the sensor. The design uses the domestic HC32L176 micro controller unit as the main control chip. Develop a dynamometer which uses the chip. Collect the voltage signal through the oscilloscope. Select the appropriate wavelet basis function, the number of decomposition layers, threshold rule and threshold function to decomposesignals containing noise. Filter out the high-frequency components of different layers,and then reconstruct the signal to obtain the denoising signal . Through Matlab simulation and practical test, the results show that the wavelet transform can achieve a good denoising of the collected voltage signal, and improve the reliability and stability of the bolt and cable dynamometer.

Abstract Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder with long preclinical and prodromal phases in older people. Molecular imaging is a promising approach for noninvasive in vivo identification and tracking pathophysiological changes. In particular, nuclear neuroimaging in AD has extended beyond traditional evaluation of brain perfusion and glucose metabolism, and has achieved substantial progress over the past 2 decades. To gain a comprehensive understanding of nuclear neuroimaging with different targets in the brain, this review provides an overview of the literature on the current status and recent progress of the development of radioligands for definitive and differential diagnosis of AD.

This paper was concerned with the following Kirchhoff type equation involving the fractional Laplace operator $ (-\Delta)^{s} $ $ \begin{cases} \left(1+\alpha\int_{\mathbb{R}^{3}}|(-\Delta)^{\frac{s}{2}}u|^{2}dx\right)(-\Delta)^{s} u+\mu K(x)u = g(x)|u|^{p-2}u, &{\rm in}\ \mathbb{R}^{3}, \\ u\in H^{s}(\mathbb{R}^{3}), \ \end{cases} $ where $ \alpha, \ \mu > 0 $, $ s\in [\frac{3}{4}, 1) $, $ 2 < p < 4 $. By filtration of the Nehari manifold and variational techniques, we obtained the existence of one and two positive solutions under some conditions imposed on $ K $ and $ g $.

Abstract Background and objectives The psychological problems of hemodialysis (HD) patients are prominent, and benefit finding (BF) have been proven beneficial to physical and mental health, fewer researchers explored BF in HD patients. The aim of this study was to investigate the current status of BF in patients with chronic kidney disease and to analyze the factors influencing it in order to provide a reference for subsequent interventions. Methods A cross-sectional study was done on 246 HD patients by convenience sampling in the hemodialysis center of a 3 A hospital in Shanghai from March to September 2019. The measures include General Information Questionnaire, Benefit Finding Scale, Perceived Social Support Scale, General Self-efficacy Scale, and Simplified Coping Style scale. Results The median (interquartile range, IQR) score of BF was 66 (IQR = 19) and it was lower compared with other chronic diseases. Significant differences in BF scores were found between different age groups, HD duration categories, and understanding degrees of HD. Taking BF as the dependent variable, the results of multiple linear regression analysis showed that age, duration of HD, family support, other support, positive coping, and self-efficacy entered the regression equation to explain 43.8% of the total variation. Social support played an indirect effect in the relationship between positive coping and BF, accounting for 54.1% of the total effect. Conclusion The BF of HD patients is worrisome and affected by many factors. Medical staff could pay attention to the positive psychology of HD patients, and construct individualized interventions according to the influencing factors to improve their BF level and achieve physical and mental health.

Abstract Endometrial cancer (EC) is a common gynecological tumor in females with an increasing incidence over the past few decades. Alcohol consumption has been linked to the occurrence of various cancers; However, epidemiological studies have shown inconsistent associations between alcohol consumption and EC risk. In order to avoid the influence of potential confounding factors and reverse causality in traditional epidemiological studies, we used a method based on genetic principles-Mendelian randomization (MR) analysis to test whether there is a causal relationship between alcohol consumption and EC. MR analysis was conducted using publicly available summary-level data from genome-wide association studies (GWAS). Fifty-seven single nucleotide polymorphisms (SNPs) were extracted as instrumental variables for alcohol exposure from the GWAS and Sequencing Consortium of Alcohol and Nicotine GWAS summary data involving 941,287 participants of European ancestry. SNPs for EC were obtained from the Endometrial Cancer Association Consortium, the Endometrial Cancer Epidemiology Consortium, and the UK Biobank, involving 121,885 European participants. The inverse variance weighted (IVW) method was used as the primary method to estimate the causal effect, and the MR-Egger regression and weighted median method were used as supplementary methods. Sensitivity analyses were conducted using the Mendelian Randomization Pleiotropy RESidual Sum and Outlier global test, MR-Egger intercept test, and leave-one-out analysis to evaluate the impact of pleiotropy on causal estimates. An increase of 1 standard deviation of genetically predicted log-transformed alcoholic drinks per day was associated with a 43% reduction in EC risk [odds ratio (OR) = 0.57, 95% confidence interval (CI) 0.41–0.79, P

Abstract Background Sofosbuvir/Velpatasvir (Epclusa, ECS) is the first pan-genotype direct-acting antiviral agent (DAA) for hepatitis C virus (HCV) infection, and Danoprevir (DNV) is the first DAA developed by a Chinese local enterprise, which is suitable for combined use with other drugs to treat genotype 1b chronic hepatitis C. However, previous reports have never compared the real-world data of ECS and DNV. Patients and methods 178 chronic hepatitis C patients were retrospectively recruited, and 94cases were accepted with Sofosbuvir/Velpatasvir ± Ribavirin (ECS group), and others (n = 84 treated with DNV combination therapy (DNV group). The HCV genotype, virological response, adverse effects and some laboratory biochemical indexes were contrasted between above two groups in the real world study. Results DNV group had significantly lower level of alpha-fetoprotein (AFP), lower rates of decompensated cirrhosis ( P

Abstract Objectives To develop and compare noninvasive models for differentiating between combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and HCC based on serum tumor markers, contrast-enhanced ultrasound (CEUS), and computed tomography (CECT). Methods From January 2010 to December 2021, patients with pathologically confirmed cHCC-CCA or HCC who underwent both preoperative CEUS and CECT were retrospectively enrolled. Propensity scores were calculated to match cHCC-CCA and HCC patients with a near-neighbor ratio of 1:2. Two predicted models, a CEUS-predominant (CEUS features plus tumor markers) and a CECT-predominant model (CECT features plus tumor markers), were constructed using logistic regression analyses. Model performance was evaluated by the area under the curve (AUC), sensitivity, specificity, and accuracy. Results A total of 135 patients (mean age, 51.3 years ± 10.9; 122 men) with 135 tumors (45 cHCC-CCA and 90 HCC) were included. By logistic regression analysis, unclear boundary in the intratumoral nonenhanced area, partial washout on CEUS, CA 19-9 > 100 U/mL, lack of cirrhosis, incomplete tumor capsule, and nonrim arterial phase hyperenhancement (APHE) volume 100 U/mL shows excellent sensitivity. Critical relevance statement Combining lack of cirrhosis, incomplete tumor capsule, and nonrim arterial phase hyperenhancement (APHE) volume 100 U/mL shows excellent sensitivity in differentiating cHCC-CCA from HCC. Key points 1. Accurate differentiation between cHCC-CCA and HCC is essential for treatment decisions. 2. The CECT-predominant model provides higher accuracy than the CEUS-predominant model for CHCC-CCA. 3. Combining CECT features and CA 19-9 levels shows a sensitivity of 93.3% in diagnosing cHCC-CCA. Graphical Abstract

Abstract Objective To develop and validate a deep learning model based on multi-lesion and time series CT images in predicting overall survival (OS) in patients with stage IV gastric cancer (GC) receiving anti-HER2 targeted therapy. Methods A total of 207 patients were enrolled in this multicenter study, with 137 patients for retrospective training and internal validation, 33 patients for prospective validation, and 37 patients for external validation. All patients received anti-HER2 targeted therapy and underwent pre- and post-treatment CT scans (baseline and at least one follow-up). The proposed deep learning model evaluated the multiple lesions in time series CT images to predict risk probabilities. We further evaluated and validated the risk score of the nomogram combining a two-follow-up lesion-based deep learning model (LDLM-2F), tumor markers, and clinical information for predicting the benefits from treatment (Nomo-LDLM-2F). Results In the internal validation and prospective cohorts, the one-year AUCs for Nomo-LDLM-2F using the time series medical images and tumor markers were 0.894 (0.728–1.000) and 0.809 (0.561–1.000), respectively. In the external validation cohort, the one-year AUC of Nomo-LDLM-2F without tumor markers was 0.771 (0.510–1.000). Patients with a low Nomo-LDLM-2F score derived survival benefits from anti-HER2 targeted therapy significantly compared to those with a high Nomo-LDLM-2F score (all p

Abstract Background Prognosis prediction for pancreatic cancer has always been difficult in clinical practice because of its high heterogeneity and mortality. The aim of the study was to assess the value of prognostic immune-inflammatory-nutritional (PIIN) score on overall survival (OS) in postoperative patients with pancreatic cancer and to develop a nomogram incorporating PIIN score. Methods This study retrospectively analyzed the clinic pathological data of 155 patients with pancreatic cancer who underwent radical surgery. PIIN score was calculated by measuring the fibrinogen (FIB), neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII), albumin-bilirubin (ALBI) score, and prognostic nutritional index (PNI). Patients were divided into two groups by PIIN score levels over a threshold of 37.2. Univariate and multivariate analysis were performed using the Cox regression analysis model. The time-dependent receiver operating characteristic (ROC) curve was plotted to compare the prognostic values of the scoring systems. Finally, a nomogram based on PIIN score was constructed and validated. Results Multivariate regression analysis showed that PIIN score (hazard ratio (HR) = 2.171, 95% confidence interval (CI) = 1.207–3.906, P = 0.010), lymphovascular invasion (HR = 1.663, 95% CI = 1.081–2.557, P = 0.021), poor tumor grade (HR = 2.577, 95% CI = 1.668–3.982, P

Abstract Background R140Q mutation in isocitrate dehydrogenase 2 (IDH2) promotes leukemogenesis. Targeting IDH2/R140Q yields encouraging therapeutic effects in the clinical setting. However, therapeutic resistance occurs in 12% of IDH2/R140Q inhibitor treated patients. The IDH2/R140Q mutant converted TF-1 cells to proliferate in a cytokine-independent manner. This study investigated the signaling pathways involved in TF-1(R140Q) cell proliferation conversion as alternative therapeutic strategies to improve outcomes in patients with acute myeloid leukemia (AML) harboring IDH2/R140Q. Methods The effects of IDH2/R140Q mutation on TF-1 cell survival induced by GM-CSF withdrawal were evaluated using flow cytometry assay. The expression levels of apoptosis-related proteins, total or phosphorylated STAT3/5, ERK, and AKT in wild-type TF-1(WT) or TF-1(R140Q) cells under different conditions were evaluated using western blot analysis. Cell viability was tested using MTT assay. The mRNA expression levels of GM-CSF, IL-3, IL-6, G-CSF, leukemia inhibitory factor (LIF), oncostatin M (OSM), and IL-11 in TF-1(WT) and TF-1(R140Q) cells were quantified via RT-PCR. The secretion levels of GM-CSF, OSM, and LIF were determined using ELISA. Results Our results showed that STAT3 and STAT5 exhibited aberrant constitutive phosphorylation in TF-1(R140Q) cells compared with TF-1(WT) cells. Inhibition of STAT3/5 phosphorylation suppressed the cytokine-independent proliferation of TF-1(R140Q) cells. Moreover, the autocrine GM-CSF, LIF and OSM levels increased, which is consistent with constitutive STAT5/3 activation in TF-1(R140Q) cells, as compared with TF-1(WT) cells. Conclusions The autocrine cytokines, including GM-CSF, LIF, and OSM, contribute to constitutive STAT3/5 activation in TF-1(R140Q) cells, thereby modulating IDH2/R140Q-mediated malignant proliferation in TF-1 cells. Targeting STAT3/5 phosphorylation may be a novel strategy for the treatment of AML in patients harboring the IDH2/R140Q mutation. Video Abstract

Abstract Background Eye examinations and eyeglasses acquisition are typically integrated into a cohesive procedure in China. We conducted a randomized controlled trial using incognito standardized patient (SP) approach to evaluate the impact of separating eyeglasses sales on the accuracy of final prescription. Methods 52 SPs were trained to provide standardized responses during eye examinations, and undergoing refraction by a senior ophthalmologist at a national-level clinical center. SPs subsequently received eye examinations at 226 private optical shops and public hospitals in Shaanxi, northwestern China. The visits were randomly assigned to either control group, where SPs would typically purchase eyeglasses after refraction, or treatment group, where SPs made an advance declaration not to purchase eyeglasses prior to refraction. The dioptric difference between the final prescriptions provided by local refractionists and expert in the better-seeing eye was determined using the Vector Diopteric Distance method, and the completeness of exams was assessed against national standards. Multiple regressions were conducted to estimate the impact of no eyeglasses sales on the accuracy of the final prescription of local refractionists, as well as the completeness of examinations. Results Among 226 eye exams (73 in public hospitals, 153 in private optical shops), 133 (58.8%) were randomized to control group and 93 (41.2%) to no eyeglasses sales group. The inaccuracy rate of final prescriptions provided by local refractionists (≥ 1.0 D, experts’ final prescription as the reference) was 25.6% in control group, while 36.6% in no-sale group (P = 0.077). The likelihood of providing inaccurate final prescriptions was significantly higher in no-sale group compared to control group (OR = 1.607; 95% CI: 1.030 to 2.508; P = 0.037). This was particularly evident in private optical shops (OR = 2.433; 95% CI: 1.386 to 4.309; P = 0.002). In terms of process quality, the no-sale group performed significantly less subjective refraction (OR = 0.488; 95% CI: 0.253 to 0.940; P = 0.032) and less testing SP’s own eyeglasses (OR = 0.424; 95% CI: 0.201 to 0.897; P = 0.025). The duration of eye exams was 3.917 min shorter (95% CI: -6.798 to -1.036; P = 0.008) in no-sale group. Conclusions Separating eyeglasses sales from optical care could lead to worse quality of eye care. Policy makers should carefully consider the role of economic incentives in healthcare reform.

Abstract Background In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold‑inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). Methods CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. Results Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)‑like population. Moreover, hyperthermia substantially improved the sensitivity of radiation‑resistant NPC cells and CSC‑like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti‑tumor‑killing activity of hyperthermia against NPC cells and CSC‑like cells, whereas ectopic expression of Cirbp compromised tumor‑killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC‑like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. Conclusion Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Abstract Growing evidence suggests that hypertensive individuals have a greater risk of developing depression, and depression can also increase the incidence of hypertension. In the hypertensive population, the association between triglyceride glucose (TyG) index and depression remains unclear. This study aimed to assess the association between TyG index and depression in hypertensive people through the cross‐sectional study of the National Health and Nutrition Examination Survey (2007–2018). To assess the relationship between TyG index and depression in hypertensive population, we conducted weighted multiple logistic regression models and used a generalized additive model to probe for nonlinear correlations. In addition, we employed a recursive algorithm to determine the inflection point and established a two‐piece linear regression model. This study enrolled 5897 individuals. In the model adjusted for all covariates, the ORs (95% CI) for the relationship between TyG index and depression in hypertensive population were 1.32 (1.12–1.54). A nonlinear association was found between TyG index and depression, with an inflection point at 8.7. After the inflection point, the ORs (95% CI) were 1.44 (1.15–1.79). Only the interaction with the obese population was statistically significant. Our study highlighted a nonlinear association between TyG index and depression in American hypertensive adults.

In response to the situation in the Huanghuai region, where corn fertilization and pesticide application primarily rely on manual methods such as hand broadcasting fertilizer and using manual backpack sprayers, resulting in low levels of mechanization, this study designed an electric integrated work vehicle in line with the trend of developing new energy. The vehicle is powered by six 12 V, 100 Ah lead-acid batteries and integrates the functions of fertilization and pesticide spraying. It can achieve precise hole-fertilization, applying fertilizer to a depth of 100 to 150 mm near the roots of corn, and can also perform multi-row pesticide spraying. The vehicle’s electronic control system is divided into two functional areas: 220 V and 24 V. The walking system uses a 220 V, 2 kW AC servo motor, which is driven by converting the voltage of the 72 V battery group into a 220 V sine wave AC through an inverter, and the motor speed can be adjusted. The working width is adjusted by two fixed electric cylinders at the top of the rear wheel frame. The user can preset the width through the control panel, and during operation, the electric cylinders can be automatically controlled to the optimal working width via a whisker-type limit switch. Analysis using ADAMS software shows that when the vehicle speed is 2, 3, and 5 km per hour, the opening angles of the duckbill controller are 66°, 58°, and 48°, respectively, indicating that the higher the speed, the smaller the opening angle. This shortens the fertilization interval time and makes the fertilization spacing more stable. The maximum opening angle of the adjacent duckbill is 25°, indicating that the fertilization amount remains stable. When the vehicle is moving in reverse, the duckbill always remains closed, and at different speeds, the opening angle change curve of the duckbill controller is smooth and regular. This vehicle significantly improves the efficiency and precision of corn planting. However, improvements are still needed in battery technology, control system optimization, and the high cost of electric agricultural machinery to promote the widespread application of agricultural mechanization.

This study proposes a risk measurement approach to assess collision risks in mixed traffic flow, focusing on the integrated behavior of car-following and lane-changing. A new surrogate safety measure (SSM), denoted as Rtotal, is developed to provide a comprehensive risk assessment. Numerical analysis is used to determine the weights of parameters within Rtotal, and its validity is substantiated using an empirical dataset, with a risk threshold of 0.49 established when the time to collision (TTC) is set to 2 s. The study incorporates scenarios of connected and automated vehicle (CAV) degradation and evaluates the influence of penetration rates, perception–reaction time (PRT), and lane-changing modes on risk levels. Simulation results reveal that a CAV penetration rate between 0.4 and 0.6 represents a critical range where collision risks significantly increase, reflecting safety dynamics under CAV degradation. Furthermore, in scenarios involving lane-changing, the degradation of the following vehicle in the target lane poses the highest risk. At lower PRTs, the penetration rate exerts a more significant influence on collision risks. Rtotal has been validated across various scenarios, showing strong applicability and more sensitive trends than other SSMs, making it well-suited for assessing long-term comprehensive traffic flow risks. These findings offer practical guidance for traffic management to establish real-time risk prediction and warning systems for identifying high-risk car-following and lane-changing behaviors. Future research can explore the applicability of the proposed risk index in more complex traffic scenarios and its effectiveness across different levels of vehicle automation and connectivity.

In complex marine environments, extracting target features from acoustic signal is very difficult, making the targets hard to be recognized. Therefore, it is necessary to perform denoising method on the acoustic signal to highlight the target features. However, training deep learning denoising models requires a large mount of acoustic data with labels and obtaining labels with real measured data is also extremely difficult. In this paper, an enhanced simulation algorithm, which considers integrating features of target line spectrum and ocean environmental noise, is proposed to construct a large-scale training sample set. Additionally, a deep convolutional denoising model is presented, which is first train on simulated data and directly applied to real measured data for denoising, enabling line spectrum to be significantly displayed in the time-frequency spectrogram. The results on simulation experiments and sea trials demonstrate that the proposed method can significantly reduce ocean noise while preserving the characteristics of target line spectrum. Furthermore, the experiments demonstrate that the proposed convolutional denoising model has transferability and generalization, making it suitable for denoising underwater acoustic signal in different marine areas.

Deep learning techniques have been widely investigated as an effective method for signal measurement in recent years. However, most existing deep learning-based methods still face difficulty in deploying on embedded platforms and perform poorly in real-time applications. To address this, this paper develops two accelerators, as the core of the signal measurement system, for intelligent signal processing. Firstly, by introducing the idea of automated framework, we propose a simplest deep neural network (DNN)-based hardware structure, which automatically maps algorithms to hardware modules, supports configurable parameters, and has the advantage of low latency, with an average inference time of only 3.5 μs. Subsequently, another accelerator is designed with the efficient hardware structure of the long short-term memory (LSTM) + DNN model, demonstrating outstanding performance with a classification accuracy of 98.82%, mean absolute error (MAE) of 0.27°, and root mean square errors (RMSE) of 0.392° after model compression. Moreover, parallel optimization strategies are exploited to further reduce latency and support simultaneous frequency and direction measurement tasks. Finally, we test the actual collected signal data on the XCVU13P field programmable gate array (FPGA). The results show that the time of inference saves 28–31% for the DNN model and 71–73% for the LSTM + DNN model compared to running on graphic processing unit (GPU). In addition, the parallel strategies further decrease the delay by 23.9% and 37.5% when processing continuous data. The FPGA-based and deep learning-assisted hardware accelerators significantly improve real-time performance and provide a promising solution for signal measurement.

To address the problems of missed and false detections caused by target occlusion and lighting variations, this paper proposes a recognition model based on YOLOv5 with bi-level routing attention to achieve precise real-time small object recognition, using the problem of tailhook recognition for carrier-based aircraft as a representative application. Firstly, a module called D_C3, which combines deformable convolution, was integrated into the backbone network to enhance the model’s learning ability and adaptability in specific scenes. Secondly, a bi-level routing attention mechanism was employed to dynamically focus on the regions of the feature map that are more likely to contain the target, leading to more accurate target localization and classification. Additionally, the loss function was optimized to accelerate the bounding box regression process. The experimental results on the self-constructed CATHR-DET and the public VOC dataset demonstrate that the proposed method outperforms the baselines in overall performance.

Antarctic krill oil has been proven to be able to promote the ovarian development of crustaceans, but its optimal application dose and potential regulatory mechanism in Macrobrachium rosenbergii are still unclear. In this study, five isonitrogenous and isolipidic diets with gradient additions of Antarctic krill oil (0%, 1.5%, 3%, 4.5%, and 6%) were served exposed to 8 weeks of feeding. The results show that 3–4.5% Antarctic krill oil supplementation significantly increases the weight gain rate and specific growth rate of M. rosenbergii (p < 0.05). In addition, 3–4.5% Antarctic krill oil supplementation significantly increased the content of hemolymph vitellogenin (VTG) and the levels of reproductive hormones, including methyl farnesoate (MF), estradiol (E2), and progesterone (P4) (p < 0.05). The differences in ovarian index, oocyte volume, yolk granule deposition in oocytes, and the transcription levels of VTG genes in hepatopancreas and ovarian tissues demonstrated that the addition of Antarctic krill oil significantly promoted ovarian development and vitellogenesis, especially at the 4.5% addition level. In terms of molecular signaling, this study confirms that the retinol metabolic signaling pathway, MF signaling pathway, steroid hormone signaling pathway, and ecdysone signaling pathway, along with their specific molecules, such as Farnesoic acid-O-methyltransferase (FAMeT), retinoid x receptor (RXR), ecdysone receptor (EcR), and estrogen-related receptor (ERR), are involved in the regulation of the ovarian development of M. rosenbergii by adding Antarctic krill oil at appropriate doses. The findings indicate that the supplementation of 4.5% Antarctic krill oil in the diet is optimal for stimulating the secretion of reproductive hormones in female M. rosenbergii, thereby promoting vitellogenesis and ovarian development.

The rake angles on both sides of the cutting edges of the hourglass worm gear hob significantly influence its cutting performance, which, in turn, plays a decisive role in the surface quality of the machined worm wheel. To balance the rake angles along the tooth height direction of each hob tooth and enhance the overall cutting performance of the hob, this paper proposes a method that utilizes a rotating paraboloid surface to generate the helical rake face of the hourglass worm gear hob. First, the conjugate condition equations for the rake face generated by the rotating paraboloid surface are derived. A mathematical model for the helical rake face of planar double-enveloping hourglass worm gear hob is established. This study explores the influence of two machining parameters on the rake angle, specifically the milling drive ratio coefficient k and the geometric parameter of a parabolic milling cutter p. Through a systematic analysis of the variations in rake angle at the dividing toroidal surface and along the tooth height direction, the optimal parameter values were identified as k = 0.9115 and p = 0.6834. The results show that, after optimization, the hob rake angle range is around ±4.7°, with a maximum rake angle difference of 6.3072° along the tooth height direction, and the rake angles on both sides of the teeth are more balanced. The structure of the rake face is more reasonable, reflecting the feasibility of rotating paraboloid tools for forming tools in the machining of complex surfaces.

Abstract Janzen–Connell (JC) effects, hypothesized to be partially driven by negative plant–soil feedbacks (PSFs), are considered to be a key mechanism that regulates tropical forest plant diversity and coexistence. However, intraspecific variation in JC effects may weaken this mechanism, with the strength of PSFs being a potentially key variable process. We conducted a manipulated experiment with seedlings from two populations of Pometia pinnata (Sapindaceae), a tropical tree species in southwest China. We aimed to measure the intraspecific difference in PSF magnitude caused by inoculating the soil from different P. pinnata source populations and growing seedlings under differing light intensity and water availability treatments, and at varying plant densities. We found negative PSFs for both populations with the inoculum soil originating from the same sites, but PSFs differed significantly with the inoculum soil from different sites. PSF strength responded differently to biotic and abiotic drivers; PSF strength was weaker in low moisture and high light treatments than in high moisture and low light treatments. Our study documents intraspecific variation in JC effects: specifically, P. pinnata have less defenses to their natively‐sourced soil, but are more defensive to the soil feedbacks from soil sourced from other populations. Our results imply that drought and light intensity tended to weaken JC effects, which may result in loss of species diversity with climate change.

Abstract Objective This study was based on a retrospective clinical observational cohort study of a two‐center application of nusinersen in China to evaluate the clinical efficacy and adverse effects of nusinersen in the treatment of SMA (spinal muscular atrophy) Types 1–3. Methods Clinical data from children with clinically and genetically confirmed 5qSMA from a double center in western China (the Second Affiliated Hospital of Xi'an Jiaotong University and the Second Hospital of West China of Sichuan University). All children were younger than 18 years of age. Patients were assessed for motor function and underwent blood and fluid tests before each nusinersen injection. Results At 14‐month follow‐up, 100% of children had improved their HFMSE (Hammersmith Functional Motor Scale Expanded) score, 83.6% had improved their CHOP INTEND (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders) score, and 66.6% had improved their RULM (Revised Upper Limb Module) score by ≥3 points from baseline, and their 6MWT (6‐min walk test) was 216.00 ± 52.08 m longer than at baseline. The age of the child at the start of treatment was negatively correlated with the clinical efficacy of nusinersen; the younger the child, the better the response to treatment. No significant adverse effects affecting the treatment and quality of life of the child were observed during the treatment of SMA with nusinersen. Conclusion This study concluded that nusinersen is clinically beneficial for children with SMA in western China, with mild adverse effects.

BackgroundMetastasis remains the leading cause of mortality among colorectal cancer (CRC) patients. Identification of new metastasis-related genes are critical to improve colorectal cancer prognosis.MethodsData on mRNA expression in metastatic and primary CRC was obtained from the Gene Expression Omnibus (GEO) database, including GSE81986, GSE41568, GSE71222, GSE21510, and GSE14333. Additionally, data concerning mRNA expression in colon cancer (COAD) and adjacent normal tissues were acquired from The Cancer Genome Atlas (TCGA) database. Hub genes were identified by weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis. Moreover, we assessed the impact of hub gene expression on both overall survival (OS) and disease-free survival (DFS) in patients and identified ZG16 as a potential target. We generated CRC cell lines transfected with lentivirus OE-ZG16 to investigate proliferation, invasion, and migration in vitro. To further elucidate the involvement of ZG16, we utilized gene set enrichment analysis (GSEA) to identify enriched pathways, which were subsequently validated via Western blot analysis.ResultsFive datasets containing primary and metastatic CRC samples from GEO database and CRC samples from TCGA database were included in this study and 29 hub genes were identified by WGCNA and differentially expressed gene (DEG) analysis. Low expression of the hub genes (CLCA1 and ZG16) was associated with poor DFS and OS. We confirmed the low expression of ZG16 in CRC using external database and IHC analysis at both transcriptional and protein levels. In addition, the expression of ZG16 was notably elevated in NCM460 cells in comparison to CRC cell lines. The overexpression of ZG16 in CRC cells has been shown to inhibit the proliferation, invasion, and migration of CRC cells. Furthermore, the overexpression of ZG16 has been found to suppress the activation of the epithelial-mesenchymal transition (EMT) and Wnt/β-catenin signaling pathways in CRC.ConclusionZG16 may serve as a promising therapeutic target for metastatic CRC treatment.

ObjectiveThis meta-analysis aims to examine differences in biochemical markers of bone metabolism between individuals with type 2 diabetes (T2DM) and non-T2DM control groups.Materials and methodsTwo independent evaluators searched five databases: PubMed, EMBASE, EBSCOhost, Web of Science, and the Cochrane Library. We aimed to identify observational studies investigating the impact of T2DM on biochemical markers of bone metabolism. Literature retrieval covered the period from the establishment of the databases up to November 2022. Studies were included if they assessed differences in biochemical markers of bone metabolism between T2DM patients and non-T2DM control groups using cross-sectional, cohort, or case-control study designs.ResultsFourteen studies were included in the analysis, comprising 12 cross-sectional studies and 2 cohort studies. Compared to the non-T2DM control group, T2DM patients showed reduced levels of Osteocalcin and P1NP, which are markers of bone formation. Conversely, levels of Alkaline phosphatase and Bone-specific alkaline phosphatase, other bone formation markers, increased. The bone resorption marker CTX showed decreased levels, while TRACP showed no significant difference.ConclusionIn individuals with T2DM, most bone turnover markers indicated a reduced rate of bone turnover. This reduction can lead to increased bone fragility despite higher bone mineral density, potentially increasing the risk of osteoporosis.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php? identifier CRD42022366430.

Abstract The development of gene editing tools has been a significant area of research in the life sciences for nearly 30 years. These tools have been widely utilized in disease detection and mechanism research. In the new century, they have shown potential in addressing various scientific challenges and saving lives through gene editing therapies, particularly in combating cardiovascular disease (CVD). The rapid advancement of gene editing therapies has provided optimism for CVD patients. The progress of gene editing therapy for CVDs is a comprehensive reflection of the practical implementation of gene editing technology in both clinical and basic research settings, as well as the steady advancement of research and treatment of CVDs. This article provides an overview of the commonly utilized DNA‐targeted gene editing tools developed thus far, with a specific focus on the application of these tools, particularly the clustered regularly interspaced short palindromic repeat/CRISPR‐associated genes (Cas) (CRISPR/Cas) system, in CVD gene editing therapy. It also delves into the challenges and limitations of current gene editing therapies, while summarizing ongoing research and clinical trials related to CVD. The aim is to facilitate further exploration by relevant researchers by summarizing the successful applications of gene editing tools in the field of CVD.

Background: 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods: The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H&E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result: Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF-α, and IL-1β), and inhibits epithelial cell apoptosis in 5-Fu-treated mice without compromising 5-Fu's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion: This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.

Addressing the threats of climate change, pollution, and overfishing to marine ecosystems necessitates a deeper understanding of coastal and oceanic fluid dynamics. Within this context, Lagrangian Coherent Structures (LCS) emerge as essential tools for elucidating the complexities of marine fluid dynamics. Methods used to detect LCS include geometric, probabilistic, cluster-based and braid-based approaches. Advancements have been made to employ Finite-time Lyapunov Exponents (FTLE) to detect LCS due to its high efficacy, reliability and simplicity. It has been proven that the FTLE approach has provided invaluable insights into complex oceanic phenomena like shear, confluence, eddy formations, and oceanic fronts, which also enhanced the understanding of tidal-/wind-driven processes. Additionally, FTLE-based LCS were crucial in identifying barriers to contaminant dispersion and assessing pollutant distribution, aiding environmental protection and marine pollution management. FTLE-based LCS has also contributed significantly to understanding ecological interactions and biodiversity in response to environmental issues. This review identifies pressing challenges and future directions of FTLE-based LCS. Among these are the influences of external factors such as river discharges, ice formations, and human activities on ocean currents, which complicate the analysis of ocean fluid dynamics. While 2D FTLE methods have proven effective, their limitations in capturing the full scope of oceanic phenomena, especially in 3D environments, are evident. The advent of 3D LCS analysis has marked progress, yet computational demands and data quality requirements pose significant hurdles. Moreover, LCS extracted from FTLE fields involves establishing an empirical threshold that introduces considerable variability due to human judgement. Future efforts should focus on enhancing computational techniques for 3D analyses, integrating FTLE and LCS into broader environmental models, and leveraging machine learning to standardize LCS detection.

Background Disruptions in calcium homeostasis are associated with a wide range of diseases, and play a pivotal role in the development of cancer. However, the construction of prognostic models using calcium extrusion-related genes in colon adenocarcinoma (COAD) has not been well studied. We aimed to identify whether calcium extrusion-related genes serve as a potential prognostic biomarker in the COAD progression. Methods We constructed a prognostic model based on the expression of calcium extrusion-related genes (SLC8A1, SLC8A2, SLC8A3, SLC8B1, SLC24A2, SLC24A3 and SLC24A4) in COAD. Subsequently, we evaluated the associations between the risk score calculated by calcium extrusion-related genes and mutation signature, immune cell infiltration, and immune checkpoint molecules. Then we calculated the immune score, stromal score, tumor purity and estimate score using the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm. The response to immunotherapy was assessed using tumor immune dysfunction and exclusion (TIDE). Finally, colorectal cancer cells migration, growth and colony formation assays were performed in RKO cells with the overexpression or knockdown SLC8A3, SLC24A2, SLC24A3, or SLC24A4. Results We found that patients with high risk score of calcium extrusion-related genes tend to have a poorer prognosis than those in the low-risk group. Additionally, patients in high-risk group had higher rates of KRAS mutations and lower MUC16 mutations, implying a strong correlation between KRAS and MUC16 mutations and calcium homeostasis in COAD. Moreover, the high-risk group showed a higher infiltration of regulatory T cells (Tregs) in the tumor microenvironment. Finally, our study identified two previously unreported model genes (SLC8A3 and SLC24A4) that contribute to the growth and migration of colorectal cancer RKO cells. Conclusions Altogether, we developed a prognostic risk model for predicting the prognosis of COAD patients based on the expression profiles of calcium extrusion-related genes, Furthermore, we validated two previously unreported tumor suppressor genes (SLC8A3 and SLC24A4) involved in colorectal cancer progression.

Summary: Methicillin-resistant Staphylococcus aureus (MRSA) infection, a major cause of hospital- and community-acquired pneumonia, still has a high mortality rate. Extracellular vesicles (EVs), as crucial mediators of intercellular communication, have a significant impact on infectious diseases. However, the role of EVs from alveolar macrophages (AMs) in MRSA pneumonia remains unclear. We report that AMs phagocytose MRSA and release more EVs in mice with MRSA pneumonia. EVs from AMs harboring phagocytosed MRSA exhibit significant proinflammatory effects and induce necroptosis by delivering tumor necrosis factor α (TNF-α) and miR-146a-5p. Mechanically, the upregulated miR-146a-5p in these EVs enhances the phosphorylation of RIPK1, RIPK3, and MLKL by targeting TNF receptor-associated factor 6 (TRAF6), thereby promoting TNF-α-induced necroptosis. The combination of a TNF-α antagonist and an miR-146a-5p antagomir effectively improves the outcomes of mice with MRSA pneumonia. Overall, we reveal the pronecrotic effect of EVs from MRSA-infected AMs and provide a promising target for the prevention and treatment of MRSA pneumonia.

Abstract The redox mediated photoelectrochemical (PEC) or electrochemical (EC) alkene oxidation process is a promising method to produce high value‐added epoxides. However, due to the competitive reaction of water oxidation and overoxidation of the mediator, the utilization of the electricity is far below the ideal value, where the loss of epoxidation's faradaic efficiency (FE) is ≈50%. In this study, a Br−/HOBr‐mediated method is developed to achieve a near‐quantitative selectivity and ≈100% FE of styrene oxide on α‐Fe2O3, in which low concentration of Br− as mediator and locally generated acidic micro‐environment work together to produce the higher active HOBr species. A variety of styrene derivatives are investigated with satisfied epoxidation performance. Based on the analysis of local pH‐dependent epoxidation FE and products distribution, the study further verified that HOBr serves as the true active mediator to generate the bromohydrin intermediate. It is believed that this strategy can greatly overcome the limitation of epoxidation FE to enable future industrial applications.