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Abstract Background Empathy fatigue refers to the excessive empathy required of medical staff in the process of helping patients, which can produce traumatic experiences and emotional exhaustion. Severe empathy fatigue can even lead to medical disputes and errors, exacerbating increasingly tense doctor–patient relationships. Most studies on empathy fatigue focus on nurses, with few studies on physicians. Methods A cross-sectional questionnaire was used to assess empathy fatigue among physicians in public tertiary general hospitals in southwest China using convenience sampling. Results A total of 562 physicians participated in the survey; average empathy satisfaction scores were 32.1 ± 6.85, 28.2 ± 5.30, and 26.2 ± 6.04 for empathy satisfaction disorder, job burnout, and secondary traumatic stress domains, respectively. We identified 291 (51.8%) physicians with severe empathy fatigue. Working two or three night shifts per week was associated with severe empathy fatigue. In total, 424 (75.4%) physicians had thoughts of resigning. Weekly rest time, empathic satisfaction disorder, job burnout, and secondary traumatic stress disorder influenced thoughts of resigning. Conclusions The majority of hospital physicians experience empathy fatigue and have considered resigning; this study provides reference data that demonstrate the extent of this issue. Efforts are urgently needed to address empathy fatigue in physicians and, therefore, increase physician retention.

Abstract This study aimed to explore the potential association between Endothelin type A receptor (EDNRA) genetic polymorphisms and susceptibility to large artery atherosclerotic stroke (LAA), as well as the involvement of inflammation mechanisms. We recruited Han Chinese patients with LAA and age- and sex-matched controls. The distribution of alleles and genotypes for 16 single nucleotide polymorphisms (SNPs) in EDNRA was analyzed using dominant, recessive, and co-dominant genetic models between cases and controls. We quantified the mRNA and protein levels of EDNRA and NLRP3 genes, and concentrations of inflammatory factors (TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, and CCL18) in peripheral blood samples randomly selected from cases and controls. We also investigated the relationship between these SNPs, gene expression patterns and inflammatory factor levels. A total of 428 LAA cases and 434 controls were enrolled in this study. The results showed that rs5343 TT genotype of EDNRA was significantly associated with an increased risk of LAA (OR = 3.243, 95%CI = 1.608–6.542, P = 0.001). It also demonstrated a significant upregulation level of NLRP3 as well as higher concentrations of IL-10, IL-18, and CCL-18 in cases compared to controls. Besides, we discovered that the EDNRA polymorphisms were linked to NLRP3, IL-6, IL-10, and IL-18 levels in cases. There existed a positive correlation between EDNRA transcription levels and both NLRP3 transcript levels (r = 0.437, p

Abstract Despite the broad potential applications of C-glycosides, facile synthetic methods remain scarce. Transforming glycosyltransferases with promiscuous or natural O-specific chemoselectivity to C-glycosyltransferases is challenging. Here, we employ rational directed evolution of the glycosyltransferase MiCGT to generate MiCGT-QDP and MiCGT-ATD mutants which either enhance C-glycosylation or switch to O-glycosylation, respectively. Structural analysis and computational simulations reveal that substrate binding mode govern C-/O-glycosylation selectivity. Notably, directed evolution and mechanism analysis pinpoint the crucial residues dictating the binding mode, enabling the rational design of four enzymes with superior non-inherent chemoselectivity, despite limited sequence homology. Moreover, our best mutants undergo testing with 34 substrates, demonstrating superb chemoselectivities, regioselectivities, and activities. Remarkably, three C-glycosides and an O-glycoside are produced on a gram scale, demonstrating practical utility. This work establishes a highly selective platform for diverse glycosides, and offers a practical strategy for creating various types of glycosylation platforms to access pharmaceutically and medicinally interesting products.

Abstract Understanding the distribution of cutting force provides a foundation for the design and optimization of cutterhead layout. The simulation of rotary cutting with a large cutting radius remains a challenge for laboratory tests. In this study, taking the driving condition of the Mawan Tunnel located in the Guangdong-Hong Kong-Macao Greater Bay Area as a case study, a full-scale rotary cutting platform with large cutting radius was used to investigate the rock-breaking effects. Rotary cutting with cutting depths of 1–8 mm and cutting radii of 200–1400 mm were carried out on the granite testing platform using a 19-in disc cutter. The normal force, rolling force, and side force during the cutting process were systematically monitored. Moreover, the time–frequency characteristics of the rock breaking process and the effects of cutting depth, cutting radius and stress state on the average and peak loads were investigated. The results show that the average normal force and rolling force increased with increasing cutting depth, while the side force was less affected by cutting depth through the Boltzman model analysis. The average normal force and rolling force were not significantly affected by the cutting radius, but the average side force decreased as a power function with increasing cutting radius, and showed a stable side force when the installation radius exceeded 1000 mm. The dominant frequency of the cutting force was 0–1.2 Hz, exhibiting notable low-frequency characteristics. Additionally, the ratio of peak to average (RPA) with respect to triaxial cutting force demonstrated an increase with the growth of cutting depth, while RPA in terms of side force exhibited a corresponding growth with the increasing cutting radius. In particular, the cutting force characteristics of the cutterhead obtained in this study can inform the layout of disc cutters and real-life TBM operations, thereby avoiding severe overloading of internal disc cutters.

Abstract The advancement of microcomb sources, which serve as a versatile and powerful platform for various time–frequency measurements, have spurred widespread interest across disciplines. Their uses span coherent optical and microwave communications, atomic clocks, high-precision LiDARs, spectrometers, and frequency synthesizers. Recent breakthroughs in fabricating optical micro-cavities, along with the excitation and control of microcombs, have broadened their applications, bridging the gap between physical exploration and practical engineering systems. These developments pave the way for pioneering approaches in both classical and quantum information sciences. In this review article, we conduct a thorough examination of the latest strategies related to microcombs, their enhancement and functionalization schemes, and cutting-edge applications that cover signal generation, data transmission, quantum analysis, and information gathering, processing and computation. Additionally, we provide in-depth evaluations of microcomb-based methodologies tailored for a variety of applications. To conclude, we consider the current state of research and suggest a prospective roadmap that could transition microcomb technology from laboratory settings to broader real-world applications.

Extracellular vesicles from skin-derived precursor Schwann cells (SKP-SC-EVs) promote neurite outgrowth in culture and enhance peripheral nerve regeneration in rats. This study aimed at expanding the application of SKP-SC-EVs in nerve grafting by creating a chitosan/PLGA-based, SKP-SC-EVs-containing tissue engineered nerve graft (TENG) to bridge a 40-mm long sciatic nerve defect in dogs. SKP-SC-EVs contained in TENGs significantly accelerated the recovery of hind limb motor and electrophysiological functions, supported the outgrowth and myelination of regenerated axons, and alleviated the denervation-induced atrophy of target muscles in dogs. To clarify the underlying molecular mechanism, we observed that SKP-SC-EVs were rich in a variety of miRNAs linked to the axon growth of neurons, and miR-30b-5p was the most important among others. We further noted that miR-30b-5p contained within SKP-SC-EVs exerted nerve regeneration-promoting effects by targeting the Sin3a/HDAC complex and activating the phosphorylation of ERK, STAT3 or CREB. Our findings suggested that SKP-SC-EVs-incorporating TENGs represent a novel type of bioactive material with potential application for peripheral nerve repair in the clinic.

Abstract Background Intraoperative hypothermia is a common complication during cesarean section (C-section) and associated with the high maternal mortality and morbidity. This study aimed to explore the risk factors associated with the incidence of intraoperative hypothermia in women who underwent emergency C-section deliveries. Methods We retrospectively enrolled women who underwent emergency cesarean deliveries from August 2022 to Dec 2023 at Suzhou Municipal Hospital of Anhui Province. Baseline characteristics, thermal status, and perioperative information were extracted. Hypothermia was defined as the onset of a core temperature below 36 °C. Data were compared between patients with and without a hypothermia during surgery. Logistic regression analyses were performed to determine the risk factors for low-temperature-status. Results Overall, 87 patients were included, and 30 underwent hypothermia during surgery. For women with a normal temperature status, women in the hypothermia group had a lower incidence of receiving active warming methods (52.6% vs. 30%, P = 0.044). In the logistic regression model involving core temperature, a pre-surgery core temperature

Objective Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Abstract Protein Disulfide-Isomerase A2 (PDIA2) is a gene that encodes proteins, responsible for protein folding and modification within cells. The development and course of many disorders are intimately linked to the aberrant expression of PDIA2. Nevertheless, more research is necessary to fully understand PDIA2’s biological significance in pan-cancer, notably in prostate cancer (PCa). PDIA2 expression is elevated in various tumors and closely related to patient prognosis. Patients with prostate cancer who express PDIA2 high in particular have a bad prognosis in terms of progression-free survival. In addition, the upregulation of PDIA2 expression in prostate cancer patients is accompanied by higher Gleason scores, advanced tumor staging, lymph node metastasis, and elevated PSA levels. Detailed experiments further demonstrate that PDIA2 is a carcinogenic gene affecting prostate cancer cells’ response to dasatinib therapy. For patients with prostate cancer, there is a clear positive connection between the expression level of PDIA2 and a bad prognosis. The prostate cancer treatment efficacy of dasatinib is hampered by PDIA2, which is intimately linked to the growth, invasion, and metastasis of PCa cells. In summary, our research highlights the potential of PDIA2 as a biomarker for the diagnosis and management of PCa.

Abstract Background Sleep and physical activity (PA) are thought to be interconnected with the development of rheumatoid arthritis (RA). However, the precise nature and extent of these relationships have yet to be fully quantified. This study aimed to quantify the longitudinal effects of sleep behaviors, PA, and genetic susceptibility on the incidence of RA and to estimate the combined effects and interactions among these exposures. Methods A total of 363,211 adults were derived from a large European cohort. We incorporated five sleep behaviors (sleep duration, insomnia, snoring, chronotype, and daytime sleepiness) to generate sleep patterns, which were defined based on healthy sleep scores. Multivariate-adjusted Cox proportional hazard models were conducted to assess the individual and combined associations of sleep patterns, PA, and genetic susceptibility with the risk of RA occurrence. Multiplicative and additive interactions were estimated by P interaction and relative excess risk due to interaction (RERI) between each of the two exposures. Results During a follow-up of 12.5 years, 4262 RA cases were ascertained. A healthy sleep pattern was associated with a decreased risk of RA in a dose-response manner, with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI] = 0.75–0.84), independent of traditional risk factors and genetic predisposition. Under the restricted cubic splines model, a non-linear association was detected for PA and RA risk. Participants in the intermediate quintile 3 showed the lowest risk for developing RA, with a HR 95% CI of 0.84 (0.76–0.92). Moreover, there was an additive interaction effect of intermediate sleep pattern and PA, with a 0.45 (95% CI = 0.02–0.87) RERI of developing RA. Additionally, individuals at high genetic risk had the greatest 10-year absolute risk reduction (10.58 per 1000 person-years) when adopting both favorable behaviors. Conclusions A healthy sleep pattern and moderate PA were associated with a reduced risk of developing RA, which can offset the deleterious effects of predisposing genetic components. Implementing these modifiable lifestyle factors into public health practices is beneficial for RA prevention.

Abstract In contrast to conventional cognitive training paradigms, where learning effects are specific to trained parameters, playing action video games has been shown to produce broad enhancements in many cognitive functions. These remarkable generalizations challenge the conventional theory of generalization that learned knowledge can be immediately applied to novel situations (i.e., immediate generalization). Instead, a new “learning to learn” theory has recently been proposed, suggesting that these broad generalizations are attained because action video game players (AVGPs) can quickly acquire the statistical regularities of novel tasks in order to increase the learning rate and ultimately achieve better performance. Although enhanced learning rate has been found for several tasks, it remains unclear whether AVGPs efficiently learn task statistics and use learned task knowledge to guide learning. To address this question, we tested 34 AVGPs and 36 non-video game players (NVGPs) on a cue-response associative learning task. Importantly, unlike conventional cognitive tasks with fixed task statistics, in this task, cue-response associations either remain stable or change rapidly (i.e., are volatile) in different blocks. To complete the task, participants should not only learn the lower-level cue-response associations through explicit feedback but also actively estimate the high-level task statistics (i.e., volatility) to dynamically guide lower-level learning. Such a dual learning system is modelled using a hierarchical Bayesian learning framework, and we found that AVGPs indeed quickly extract the volatility information and use the estimated higher volatility to accelerate learning of the cue-response associations. These results provide strong evidence for the “learning to learn” theory of generalization in AVGPs. Taken together, our work highlights enhanced hierarchical learning of both task statistics and cognitive abilities as a mechanism underlying the broad enhancements associated with action video game play.

Abstract Objective The underlying mechanisms of Overactive Bladder (OAB) remain unclear. This research is designed to investigate the correlation between the intake of dietary live microorganisms and OAB. Methods This analysis encompasses a cross-sectional study of broad population information gathered from the National Health and Nutrition Examination Surveys (NHANES) spanning the years 2007 to 2018. Participants were categorized into three groups—low, medium, and high—according to their consumption of dietary live microorganisms, as per the Sanders Dietary Active Microbiota Classification System. We utilized a weighted logistic regression model, restricted cubic spline (RCS), and subgroup analyses to investigate the relationship between dietary live microorganism intake and OAB. Results This research encompassed 16,795 subjects. The incidence of OAB was reduced in the group consuming a high amount of live dietary microbes compared to the groups with low and medium intake of such microbes. After detailed adjustments for covariates, analysis revealed that participants in the high live dietary microbe group had notably reduced odds of OAB compared to those in the low live dietary microbe group (OR: 0.84, 95% CI: 0.71–0.99, p = 0.03). RCS analysis indicated a nonlinear correlation between high dietary active microbiota intake and the incidence of OAB. Conclusion This research emphasizes the potential advantages of a high dietary intake of active microbiota for preventing OAB. These findings support incorporating active microbiota into dietary guidelines, demonstrating their connection with a decreased incidence of OAB.

Abstract. Background:. Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid (GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods:. We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 (E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results:. GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions:. GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

The timely and accurate recognition of multi-type structural surface damage (e.g., cracks, spalling, corrosion, etc.) is vital for ensuring the structural safety and service performance of civil infrastructure and for accomplishing the intelligent maintenance of smart cities. Deep learning and computer vision have made profound impacts on automatic structural damage recognition using nondestructive test techniques, especially non-contact vision-based algorithms. However, the recognition accuracy highly depends on the training data volume and damage completeness in the conventional supervised learning pipeline, which significantly limits the model performance under actual application scenarios; the model performance and stability for multi-type structural damage categories are still challenging. To address the above issues, this study proposes a dual-stage optimization-based few-shot learning segmentation method using only a few images with supervised information for multi-type structural damage recognition. A dual-stage optimization paradigm is established encompassing an internal network optimization based on meta-task and an external meta-learning machine optimization based on meta-batch. The underlying image features pertinent to various structural damage types are learned as prior knowledge to expedite adaptability across diverse damage categories via only a few samples. Furthermore, a mathematical framework of optimization-based few-shot learning is formulated to intuitively express the perception mechanism. Comparative experiments are conducted to verify the effectiveness and necessity of the proposed method on a small-scale multi-type structural damage image set. The results show that the proposed method could achieve higher segmentation accuracies for various types of structural damage than directly training the original image segmentation network. In addition, the generalization ability for the unseen structural damage category is also validated. The proposed method provides an effective solution to achieve image-based structural damage recognition with high accuracy and robustness for bridges and buildings, which assists the unmanned intelligent inspection of civil infrastructure using drones and robotics in smart cities.

A 61-kb biosynthetic gene cluster (BGC), which is accountable for the biosynthesis of hibarimicin (HBM) B from Microbispora rosea subsp. hibaria TP-A0121, was heterologously expressed in Streptomyces coelicolor M1154, which generated a trace of the target products but accumulated a large amount of shunt products. Based on rational analysis of the relevant secondary metabolism, directed engineering of the biosynthetic pathways resulted in the high production of HBM B, as well as new HBM derivates with improved antitumor activity. These results not only establish a biosynthetic system to effectively synthesize HBMs—a class of the largest and most complex Type-II polyketides, with a unique pseudo-dimeric structure—but also set the stage for further engineering and deep investigation of this complex biosynthetic pathway toward potent anticancer drugs.

Abstract Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

Abstract In the context of globalization, the integration of cultural elements into scientific research, particularly through the incorporation of traditional Chinese cultural motifs in scientific illustrations, represents a novel frontier in enhancing the universality and appeal of scientific discoveries. This paper explores the innovative practice of embedding traditional Chinese cultural elements into scientific paper illustrations, highlighting its significant role in augmenting the global appeal of research findings, promoting diversity and innovation in scientific inquiry, and facilitating cross-cultural understanding. Through a series of case studies, including symbolic representations of ancient myths and the use of traditional themes to elucidate complex scientific phenomena, we demonstrate how this cultural integration not only makes scientific content more accessible and engaging but also fosters a deeper appreciation of Chinese heritage among international audiences. This approach not only bridges the gap between science and culture but also contributes to a more inclusive and interconnected global scientific community, underscoring the importance of cultural diversity in enriching scientific exploration and communication.

Abstract Cracks in tunnel lining structures constitute a common and serious problem that jeopardizes the safety of traffic and the durability of the tunnel. The similarity between lining seams and cracks in terms of strength and morphological characteristics renders the detection of cracks in tunnel lining structures challenging. To address this issue, a new deep learning-based method for crack detection in tunnel lining structures is proposed. First, an improved attention mechanism is introduced for the morphological features of lining seams, which not only aggregates global spatial information but also features along two dimensions, height and width, to mine more long-distance feature information. Furthermore, a mixed strip convolution module leveraging four different directions of strip convolution is proposed. This module captures remote contextual information from various angles to avoid interference from background pixels. To evaluate the proposed approach, the two modules are integrated into a U-shaped network, and experiments are conducted on Tunnel200, a tunnel lining crack dataset, as well as the publicly available crack datasets Crack500 and DeepCrack. The results show that the approach outperforms existing methods and achieves superior performance on these datasets.

The increasing utilization of transparent ceramics in laser systems, particularly the magnesium aluminate spinel (MgAl2O4) transparent ceramic, has positioned it as the primary candidate for high energy laser system exit windows. Nevertheless, the increased energy and power of laser output necessitate higher standards for the laser-induced damage threshold in transparent ceramics. Residual micropores within transparent ceramics pose a potential source of damage. In this study, we employed the post-annealing process to effectively modulate the density and size of micropores. We first established the relationship between the density and size of micropores and laser damage threshold, which described the damage morphology of transparent ceramic in detail. Subsequently, we developed a multi-physical field coupled kinetic model of laser damage in micropores, providing a quantitative analysis of how factors such as micropore size and density influence the damage morphology of transparent ceramic surfaces when subjected to laser irradiation. Using time-resolved pumping and probing technology, we conducted in situ detection of laser damage caused by micropores, enabling detailed examination of damage kinetic behavior. Ultimately, this study elucidated the physical mechanism behind micropore-induced transparent ceramic damage. This has significant implications for enhancing the anti-laser damage performance of transparent ceramics in high-intensity laser systems.

Abstract Background Jasmonate ZIM-domain (JAZ) proteins, which act as negative regulators in the jasmonic acid (JA) signalling pathway, have significant implications for plant development and response to abiotic stress. Results Through a comprehensive genome-wide analysis, a total of 20 members of the JAZ gene family specific to alfalfa were identified in its genome. Phylogenetic analysis divided these 20 MsJAZ genes into five subgroups. Gene structure analysis, protein motif analysis, and 3D protein structure analysis revealed that alfalfa JAZ genes in the same evolutionary branch share similar exon‒intron, motif, and 3D structure compositions. Eight segmental duplication events were identified among these 20 MsJAZ genes through collinearity analysis. Among the 32 chromosomes of the autotetraploid cultivated alfalfa, there were 20 MsJAZ genes distributed on 17 chromosomes. Extensive stress-related cis-acting elements were detected in the upstream sequences of MsJAZ genes, suggesting that their response to stress has an underlying function. Furthermore, the expression levels of MsJAZ genes were examined across various tissues and under the influence of salt stress conditions, revealing tissue-specific expression and regulation by salt stress. Through RT‒qPCR experiments, it was discovered that the relative expression levels of these six MsJAZ genes increased under salt stress. Conclusions In summary, our study represents the first comprehensive identification and analysis of the JAZ gene family in alfalfa. These results provide important information for exploring the mechanism of JAZ genes in alfalfa salt tolerance and identifying candidate genes for improving the salt tolerance of autotetraploid cultivated alfalfa via genetic engineering in the future.

Background Immune checkpoint inhibitors (ICIs) are therapeutically effective for hepatocellular carcinoma (HCC) but are individually selective. This study examined the role of specific common fragile sites (CFSs) related gene in HCC immunotherapy.Methods We analyzed HCC tissues using next-generation sequencing and flow cytometry via time-of-flight technology. A humanized orthotopic HCC mouse model, an in vitro co-culture system, untargeted metabolomics and a DNA pulldown assay were used to examine the function and mechanism of WWOX in the tumor immune response.Results WWOX was the most upregulated CFS-related gene in HCC patients responsive to ICIs. WWOX deficiency renders HCC resistant to PD-1 treatment in humanized orthotopic HCC mouse model. Macrophage infiltration is increased and CD8 T-cell subset infiltration is decreased in WWOX-deficient HCC patients. HCC-derived oleic acid (OA) promotes macrophage conversion to an immunosuppressive phenotype. Mechanistically, WWOX deficiency promoted OA synthesis primarily via competitive binding of NME2 with KAT1, which promoted acetylation of NME2 at site 31 and inhibited NME2 binding to the SCD5 promoter region. Pharmacological blockade of SCD5 enhanced the antitumor effects of anti-PD-1 therapy.Conclusions WWOX is a key factor for immune escape in HCC patients, which suggests its use as a biomarker for stratified treatment with ICIs in clinical HCC patients.

ABSTRACT Although coronavirus disease 2019 (COVID-19) has not been considered a public health emergency of international concern since last year, intermittent regional impacts still persist, and accurate testing remains crucial. Ribonuclease P protein subunit P30 (RPP30) RNA, known for its broad and stable expression in tissue cells, was used to evaluate samples from 10 hospitals with over 3,000 negative nucleic acid tests. The results revealed that the overall pass rate for the collected samples was consistently low and exhibited significant heterogeneity. After reassessing the evaluative effectiveness of RPP30 RNA Ct values from the samples of 132 positive individuals under quarantine observation, it was used to identify factors affecting sampling quality. These factors included different stages ranging from sample collection to PCR processing, various characteristics of both samplers and individuals being sampled, as well as sampling season and location. The results indicated that post-sampling handling had minimal impact, winter and fever clinic samples showed higher quality, whereas children’s samples had lower quality. The key finding was that the characteristics of samplers were closely related to sampling quality, emphasizing the role of subjectivity. Quality control warnings led to substantial improvements, confirming this finding. Consequently, although there are various factors during the testing process, the most critical aspect is to improve, supervise, and maintain standardized practices among sampling staff.IMPORTANCEThis study further confirmed the reliability of internal references (IRs) in assessing sample quality, and utilized a large sample IR data to comprehensively and multidimensionally identify significant interference factors in nucleic acid test results. By further reminding and intervening in the subjective practices of specimen collectors, good results could be achieved.

Large-volume presses (LVPs) providing large volumes, liquid media, deformation capability, jump compression, and in situ measurements are in great demand for high-pressure research, particularly in the fields of geoscience, condensed matter physics, material science, chemistry, and biology. A high-pressure and high-temperature (HPHT) platform with different LVP subsystems, both solid-state and liquid environments, and nonequilibrium subsystems, has been constructed at the Synergetic Extreme Condition User Facility, Jilin University. This article describes the construction of the different subsystems and provides an overview of the capabilities and characteristics of the different HPHT subsystems. A large sample volume (1000 mm3) at 20 GPa is achieved through the use of a belt-type apparatus in the solid-state subsystem. HPHT conditions (1.8 GPa and 1000 K) are realized in the liquid subsystem through the use of a piston–cylinder-type LVP with optical diamond windows for in situ spectroscopic measurements. A maximum pressure jump to 10.2 GPa can be reached within 20 ms in the nonequilibrium subsystem with the use of an improved bladder-pressurization jump press. Some typical results obtained with different LVPs are briefly reviewed to illustrate the applications and advantages of these presses. In summary, the platform described here has the potential to contribute greatly to high-pressure research and to innovations in high-pressure technology.

IntroductionThis study explored the effects of task-switching type and sex on the task-switching ability of methamphetamine abstainers, as well as the differences in brain mechanisms under drug cravings under drug cravings using near-infrared spectroscopy.MethodsCraving-inducing videos were used to arouse 20 methamphetamine abstainers (including 10 men), whose switching ability was then assessed using voluntary and cued task-switching exercises.ResultsDuring task-switching under methamphetamine cravings, the activation of the premotor cortex (PMC), supplementary motor area (SMA), frontal eye field (FEF), and dorsolateral prefrontal cortex (DLPFC) in women was significantly stronger than in men, while the activation of FEF in men was significantly stronger than in women. Voluntary task-switching induced stronger FEF activation than cued task-switching. During the latter, women exhibited stronger activation in the anterior prefrontal cortex (aPFC) than men.DiscussionBoth men and women showed brain lateralization during task-switching under methamphetamine cravings. Men tended to adopt proactive control and use a top-down dominant strategy to start a new task. Women, however, tend to use a bottom-up strategy focusing on inhibiting old tasks and emotional switching. Moreover, in cued task-switching, the result shows women paid more attention to emotional processing than did men, which suggests that different task-switching training programs should be developed according to sex.

Abstract The escalating demands for smart biomedical systems ignite a significantly growing influence of three‐dimensional (3D) printing technology. Recognized as a revolutionary and potent fabrication tool, 3D printing possesses unparalleled capabilities for generating customized functional devices boasting intricate and meticulously controlled architectures while enabling the integration of multiple functional materials. These distinctive advantages arouse a growing inclination toward customization and miniaturization, thereby facilitating the development of cutting‐edge biomedical systems. In this comprehensive review, the prevalent 3D printing technologies employed in biomedical applications are presented. Moreover, focused attention is paid to the latest advancements in harnessing 3D printing to fabricate smart biomedical systems, with specific emphasis on exemplary ongoing research encompassing biomedical examination systems, biomedical treatment systems, as well as veterinary medicine. In addition to illuminating the promising potential inherent in 3D printing for this rapidly evolving field, the prevailing challenges impeding its further progression are also discussed. By shedding light on recent achievements and persisting obstacles, this review aims to inspire future breakthroughs in the realm of smart biomedical systems.

IntroductionAntitumor medications such as Avastin, Berubicin, and Temozolomide have fundamentally transformed the treatment landscape for gliomas by exhibiting potent pharmacological effects on both high-grade and low-grade gliomas. This study aims to determine which anti-glioma medication presents the lowest risk for personalized use in clinical patients by assessing the adverse drug reactions (ADRs) associated with these medications as reported in the World Health Organization (WHO) VigiAcess database, and by comparing the characteristics of adverse responses among the three drugs.MethodsThis investigation employs a retrospective descriptive analysis method. We compiled ADR reports for three commercially available anti-glioma medications from WHO-VigiAccess, gathering data on the disease systems and symptoms associated with ADRs, as well as the age, gender, and geographic characteristics of the patients represented in the reports. To provide a reference for clinical treatment, we analyzed the similarities and differences in the adverse reactions of the three medications by calculating the proportion of adverse reactions recorded for each drug.ResultsA total of 132,471 adverse events (AEs) associated with three anti-glioma drugs were reported in VigiAccess. The analysis revealed that the ten most frequently reported AEs included bone marrow suppression, myalgia, leukopenia, thrombocytopenia, nausea, vomiting, death, rhabdomyolysis, disease progression, and a decrease in neutrophil count. The five most common categories of AEs related to anti-glioma drugs were blood and lymphatic system diseases (20,233 cases, 15.2%), general disorders and administration site conditions (26,973 cases, 20.3%), gastrointestinal dysfunction (22,061 cases, 16.7%), necessitating further investigations (18,285 cases, 13.8%), and musculoskeletal and connective tissue diseases (30,695 cases, 23.1%). Notably, the adverse events associated with Avastin were more pronounced in the category of musculoskeletal and connective tissue diseases compared to the other two drugs. Furthermore, Berubicin exhibited a particularly high proportion of blood and lymphatic system disease AEs, reaching 45.6%, which was significantly greater than those observed for the other two drugs.ConclusionThere is limited correlation between antineoplastic medications and ADRs. Current comparative observational studies indicate that these inhibitors are associated with both common and specific adverse effects documented in the ADR reports submitted to the World Health Organization (WHO).

IntroductionAccurate in-hospital mortality prediction following percutaneous coronary intervention (PCI) is crucial for clinical decision-making. Machine Learning (ML) and Data Mining methods have shown promise in improving medical prognosis accuracy.MethodsWe analyzed a dataset of 4,677 patients from the Regional Vascular Center of Primorsky Regional Clinical Hospital No. 1 in Vladivostok, collected between 2015 and 2021. We utilized Extreme Gradient Boosting, Histogram Gradient Boosting, Light Gradient Boosting, and Stochastic Gradient Boosting for mortality risk prediction after primary PCI in patients with acute ST-elevation myocardial infarction. Model selection was performed using Monte Carlo Cross-validation. Feature selection was enhanced through Recursive Feature Elimination (RFE) and Shapley Additive Explanations (SHAP). We further developed hybrid models using Augmented Grey Wolf Optimizer (AGWO), Bald Eagle Search Optimization (BES), Golden Jackal Optimizer (GJO), and Puma Optimizer (PO), integrating features selected by these methods with the traditional GRACE score.ResultsThe hybrid models demonstrated superior prediction accuracy. In scenario (1), utilizing GRACE scale features, the Light Gradient Boosting Machine (LGBM) and Extreme Gradient Boosting (XGB) models optimized with BES achieved Recall values of 0.944 and 0.954, respectively. In scenarios (2) and (3), employing SHAP and RFE-selected features, the LGB models attained Recall values of 0.963 and 0.977, while the XGB models achieved 0.978 and 0.99.DiscussionThe study indicates that ML models, particularly the XGB optimized with BES, can outperform the conventional GRACE score in predicting in-hospital mortality. The hybrid models' enhanced accuracy presents a significant step forward in risk assessment for patients post-PCI, offering a potential alternative to existing clinical tools. These findings underscore the potential of ML in optimizing patient care and outcomes in cardiovascular medicine.

Background and aimsThe relationship between the ABCA7 gene and Alzheimer’s disease (AD) has been widely studied across various populations. However, the results have been inconsistent. This meta-analysis aimed to evaluate the association of ABCA7 polymorphisms with AD risk, including specific subtypes such as late-onset Alzheimer’s disease (LOAD).MethodsRelevant studies were identified through comprehensive database searches, and the quality of each study was assessed using the Newcastle-Ottawa Scale (NOS). Allele and genotype frequencies were extracted from the included studies. The pooled odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models. Multiple testing corrections were conducted using the false discovery rate (FDR) method. The Cochran Q statistic and I2 metric were used to evaluate heterogeneity between studies, while Egger’s test and funnel plots were employed to assess publication bias.ResultsA total of 36 studies, covering 21 polymorphisms and involving 31,809 AD cases and 44,994 controls, were included in this meta-analysis. NOS scores ranged from 7 to 9, indicating high-quality studies. A total of 11 SNPs (rs3764650, rs3752246, rs4147929, rs3752232, rs3752243, rs3764645, rs4147934, rs200538373, rs4147914, rs4147915, and rs115550680) in ABCA7 were significantly associated with AD risk. Among these SNPs, two (rs3764650 and rs3752246) were also found to be related to the late-onset AD (LOAD) subtype. In addition, two SNPs (rs4147929 and rs4147934) were associated with the susceptibility to AD only in non-Hispanic White populations. A total of 10 SNPs (rs3764647, rs3752229, rs3752237, rs4147932, rs113809142, rs3745842, rs3752239, rs4147918, rs74176364, and rs117187003) showed no significant relationship with AD risk. Sensitivity analyses confirmed the reliability of the original results, and heterogeneity was largely attributed to deviations from Hardy–Weinberg equilibrium, ethnicity, and variations between individual studies.ConclusionThe available evidence suggests that specific ABCA7 SNPs may be associated with AD risk. Future studies with larger sample sizes will be necessary to confirm these results.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42024540539.

ABSTRACT The number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and to provide evidence for the prevention and control strategies of M. pneumoniae in children in this region. A total of 66,488 pediatric patients with respiratory tract infection were enrolled from January 2015 to November 2023 in this study. The results of this study exhibited that M. pneumoniae infection in the Anhui region was characterized by a high positive rate during 2021–2023, especially this year is considered a year of pandemic for M. pneumoniae infection. Moreover, the positive rate of M. pneumoniae in female children is significantly higher than in male children, and the infection rate of M. pneumoniae in children increases significantly with age, particularly in school-aged children.IMPORTANCEThe number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and provide evidence for the prevention and control strategies of M. pneumoniae in children in this region.

IntroductionDNA methylation inhibitors (azacitidine, decitabine) have revolutionized the treatment dilemma of myelodysplastic syndromes (MDS), a group of malignant hematopoietic disorders. This study evaluates the adverse drug reactions (ADRs) following the use of DNA methylation inhibitors in the World Health Organization (WHO) VigiAccess database and compares the characteristics of ADRs between the two drugs to select the drug with the minimum individualized risk for patients.MethodsThis study employed a retrospective descriptive analysis method. We compiled ADR reports for two marketed DNA methylation inhibitors for the treatment of MDS from WHO-VigiAccess. Data collected included demographic data such as age groups, gender, and regions of global patients covered by ADR reports, as well as data on the disease systems and symptoms caused by ADRs recorded in the annual reports and reports received by WHO. By calculating the proportion of ADRs reported for each drug, we compared the similarities and differences in ADRs between the two drugs.ResultsOverall, 23,763 adverse events (AEs) related to the two DNA methylation inhibitors were reported in VigiAccess. The results showed that the top 10 most common AEs were febrile neutropenia, bone marrow suppression, neutropenia, anemia, pancytopenia, leukopenia, thrombocytopenia, bone marrow failure, agranulocytosis, and hematotoxicity. The top five common types of DNA methylation inhibitor AEs were blood and lymphatic system disorders (11,178 cases, 47.0%), cardiac organ diseases (1,488 cases, 6.3%), various congenital familial genetic diseases (49 cases, 0.2%), ear and labyrinth diseases (100, 4.2%), and endocrine system diseases (57, 2.4%).ConclusionThere is no Strong correlation between DNA methylation inhibitors and ADRs. Current comparative observational studies of these inhibitors show that there are common and specific adverse reactions in the ADR reports received by WHO for these drugs. Clinicians should improve the rational use of these drugs based on the characteristics of ADRs.

Silicosis is a systemic disease caused by long-term exposure to high concentrations of free silica dust particles in the workplace. It is characterized by a persistent inflammatory response, fibroblast proliferation, and excessive collagen deposition, leading to pulmonary interstitial fibrosis. Epithelial interstitial transformation (EMT) can cause epithelial cells to lose their tight junctions, cell polarity, and epithelial properties, thereby enhancing the properties of interstitial cells, which can lead to the progression of fibrosis and the formation of scar tissue. Integrin 1 (ITGB1) is considered an important factor for promoting EMT and tumor invasion in a variety of tumors and also plays an important role in the progression of fibrotic diseases. Therefore, ITGB1 can be used as a potential target for the treatment of silicosis. In this study, we found that silica exposure induced epithelial-mesenchymal transformation in rats and that the expression of integrin ITGB1 was elevated along with the EMT. We used CRISPR/Cas9 technology to construct integrin ITGB1 knockdown cell lines for in vitro experiments. We compared the expression of the EMT key proteins E-cadherin and vimentin in the ITGB1 knockdown cells and wild-type cells simultaneously stimulated by silica and detected the aggregation point distribution of E-cadherin and vimentin in the cells using laser confocal microscopy. Our results showed that ITGB1 knockout inhibited the ITGB1/ILK/Snail signaling pathway and attenuated the EMT occurrence compared to control cells. These results suggested that ITGB1 is associated with silica-induced EMT and may be a potential target for the treatment of silicosis.

Currently, there is a scarcity of studies exploring the safe operating parameters for coal-fired power units at loads below 30%.To accurately understand the operating characteristics of coal-fired units under low load conditions, and to provide a design basis for flexibility modifications, a simulation model coupled with boiler and turbine was established, which includes the flue gas and air system, steam and water system, steam turbine, and steam extraction heat recovery system, and the iterative calculation strategy for low load conditions was proposed. The simulation calculation was performed on a 350 MW supercritical coal-fired unit, with the model results showing a high degree of alignment with the unit’s design and operational parameters. Under the condition of 269MW, the maximum calculation error between the model’s predicted exit flue gas temperature of the air preheater and the actual operational results was 8.84%. This discrepancy was due to a sudden increase in the operating flue gas temperature, which may be associated with a blockage in the air preheater. And the simulation results under low load conditions indicate that when the unit load is below 20%, the furnace total airflow is controlled to no less than 30% of the airflow at Maximum Continuous Rating (BMCR) and the minimum feedwater flow rate can be reduced to 20% of that in Turbine Heat Acceptance (THA) load, and the unit switches to wet state operation around 20% load. As the unit load decreases, the coal consumption rate for power generation and steam turbine heat consumption rate both increase significantly. The coal consumption rate for power generation at 30% load is increased by 13.3% compared to BMCR load, and it is increased by 32.5% at 15% load which is operated in wet state. Under low load conditions, the coal consumption rate of the unit can be reduced by decreasing the oxygen content in the flue gas, reducing the minimum feedwater flow rate, and implementing boiler water recirculation.

The recent years have witnessed a great leap for near-infrared (NIR) spectroscopy technology in multifunctional application fields. In this study, a double-perovskite structured Cr3+-doped Cs2KScF6 fluoride NIR phosphor with peak location at 778 nm and full-width at half maximum (FWHM) of 95 nm was synthesized by a co-precipitation method. The integral emission intensity at 423 K retains 70 % of that at room temperature (RT), showing good luminescent thermal stability. Combining the obtained phosphor in an NIR phosphor converted light-emitting diode (NIR pc-LED) device, the output power and photoelectric conversion efficiency can reach 72.28 mW and 6.83 % at 320 mA. By virtue of the good optical performance, clear structural images of different fruits were visualized by using the NIR pc-LED as light source, suggesting the potential of Cs2KScF6:Cr3+ phosphor to be used in high-power LED devices.

Government data identification is a fundamental work in building a national integrated government big data system.This article reviewed the research progress of data identification technology, compared the similarities and differences in coding rules of different data identification technologies, and further reviewed the progress of government data identification and its applications.Based on the clear rights and responsibilities, high security requirements, and strong compatibility requirements of government data, the next generation government data identification system Gcode was proposed.Gcode consists of three parts: external code, internal code, and security code.Among them, the external code was compatible with the Code for Unified Social Information, the internal code established an association relationship of ＆quot;institution-departmentsystem-data＆quot;, and the security code achieved anti-counterfeiting verification by introducing blockchain technology.Gcode has clear rights and responsibilities, strong compatibility and high security, and can support cross-level, cross-region, crosssystem, cross-department, and cross-business sharing of government data, effectively promoting the implementation of＆quot;one data, one source＆quot; of government data.

Abstract Medullary Carcinoma of the Colon (MCC) is a rare histological subtype of colon cancer, and there is currently no recognized optimal treatment plan for it, with its prognosis remaining unclear. The aim of this study is to analyze the independent prognostic factors for MCC patients and develop and validate nomograms to predict overall survival (OS). A total of 760 patients newly diagnosed with MCC from 2004 to 2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly allocated to a training group and a validation group in a 7:3 ratio. Univariate and multivariable Cox regression analyses were conducted to identify prognostic factors and construct nomograms. The nomogram prediction model was evaluated and validated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The study found that elderly women are more susceptible to MCC, and the ascending colon and cecum are the most common sites of involvement. MCC is poorly differentiated, with stages II and III being the most common. Surgery is the primary treatment for MCC. The prognosis for patients with stage IV MCC is poor, with a median survival time of only 10 months. Independent prognostic factors for MCC include age, N stage, M stage, surgery, chemotherapy, and tumor size. Among them, age 7 cm (HR = 1.66, 95%CI 1.20–2.30) were risk factors for colon medullary carcinoma. The results of ROC, AUC, calibration curves, and DCA demonstrate that the nomogram prediction model exhibits good predictive performance. We have updated the demographic characteristics of colon medullary carcinoma and identified age, N staging, M staging, surgery, chemotherapy and tumor size as independent prognostic factors for colon medullary carcinoma. Additionally, we have established nomograms for prognostic prediction. These nomograms can provide personalized predictions and serve as valuable references for clinical decision-making.

Abstract The Jishishan Ms 6.2 earthquake occurred at 23:59 on December 18, 2023 in Gansu Province, China. We conducted a field survey to assess the hazards and damages caused by the earthquake and its associated geo-activities. Subsequently, we organized a seminar to discuss the possible causes of the destruction of a prehistoric site—Lajia Settlement—dated back to four thousand years B.P. and located only several kilometers away from the epicenter of the Jishishan earthquake. The Jishishan earthquake was unique for its hazard and disaster process, which featured ground shaking and a series of complex geological and geomorphological activities: sediment and soil spray piles, liquefaction, collapse, landslide, and mudflow along water channels. We define this phenomenon as the Jishishan earthquake ripple hazard (JERH). The most recent evidence from the JERH suggests that a prehistoric earthquake similar to the JERH, instead of riverine floods or earthquake-induced landslide dam outburst flood, as previously hypothesized, destroyed the Lajia Settlement.

Abstract Due to global warming and the disturbance of the interannual variability of precipitation, the frequency of extreme drought events has increased. The impact of global climate change on water resources is becoming increasingly apparent, then it is particularly necessary to explore the carrying capacity of water ecological environment under extreme drought conditions, which can guarantee the ecological water security in river basins. This study takes the Guanzhong area of the Wei River Basin as an example, calculating the water environment carrying capacity of 40 areas in the Weihe Guanzhong area in different levels of years under extreme drought conditions by comprehensive evaluation model of carrying capacity and using geographic information system GIS to display the spatial distribution of water environment carrying capacity in 40 regions. According to the results of the spatial distribution of water environmental bearing capacity, four different schemes are designed to improve the bearing capacity. The first plan reduces the industrial water consumption and irrigation quota by 5%, the second plan increases the industrial water and sewage treatment rate on this basis. the third plan further improves the development and utilization rate of surface and groundwater, and the fourth plan, on the basis of the first three plans, supplies 600 million cubic meters of industrial and agricultural water to Guanzhong region. Through comparative analysis, without taking any measures, under the extreme drought conditions, the water environment carrying capacity of the 40 areas in Guanzhong is all in an unbearable state. Overall, plan 4 has the most significant improvement in the water environment-carrying capacity, especially the Dong zhuang Reservoir of the Jing River which has played a very important role in enhancing the water ecological environment carrying capacity of the downstream water of the Wei River.

Abstract The LAT1-4F2hc complex (SLC7A5-SLC3A2) facilitates uptake of essential amino acids, hormones and drugs. Its dysfunction is associated with many cancers and immune/neurological disorders. Here, we apply native mass spectrometry (MS)-based approaches to provide evidence of super-dimer formation (LAT1-4F2hc)2. When combined with lipidomics, and site-directed mutagenesis, we discover four endogenous phosphatidylethanolamine (PE) molecules at the interface and C-terminus of both LAT1 subunits. We find that interfacial PE binding is regulated by 4F2hc-R183 and is critical for regulation of palmitoylation on neighbouring LAT1-C187. Combining native MS with mass photometry (MP), we reveal that super-dimerization is sensitive to pH, and modulated by complex N-glycans on the 4F2hc subunit. We further validate the dynamic assemblies of LAT1-4F2hc on plasma membrane and in the lysosome. Together our results link PTM and lipid binding with regulation and localisation of the LAT1-4F2hc super-dimer.

Abstract Background This study aimed to investigate the impact of self-consciousness on depression of college students, and mainly focus on confirming the mediator role of life meaningful and self-efficacy, as well as the moderator role of social support. Methods In the present study, convenient sampling method was adopted, 583 college students were recruited from Harbin city and Wenzhou city in China. All students were assessed using self-assessment scales, including self-consciousness scale, life meaningful scale, self-efficacy scale, social support scale, and self-rating depression scale. Descriptive statistical analysis and correlation analysis, structural equation model analysis were conducted by SPSS 25.0 and M-plus. Results Results showed that self-consciousness was negatively related to depression, life meaningful and self-efficacy partially mediated the relation between self-consciousness and depression. Moderated mediation analysis further indicated that the relation between self-efficacy and depression were moderated bu social support. Compare with college students who had high social support, depression in those with low social support was more susceptible to the effect of self-efficacy. Conclusion These findings imply that college students with low levels of self-consciousness are more easy to be depressive, enhancing their sense of life meaning and self-efficacy can effectively alleviate depression, and college student with high social support can benefit more from self-efficacy. Therefore we should pay more attention to the mental health problems of low levels self-consciousness college students in university.

SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv)2 form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC50 lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.

Coronary microcirculation dysfunction (CMD) is one of the main causes of cardiovascular disease. Traditional treatment methods lack specificity, making it difficult to fully consider the differences in patient conditions and achieve effective treatment and intervention. The complexity and diversity of CMD require more standardized diagnosis and treatment plans to clarify the best treatment strategy and long-term outcomes. The existing treatment measures mainly focus on symptom management, including medication treatment, lifestyle intervention, and psychological therapy. However, the efficacy of these methods is not consistent for all patients, and the long-term efficacy is not yet clear. GSEA is a bioinformatics method used to interpret gene expression data, particularly for identifying the enrichment of predefined gene sets in gene expression data. In order to achieve personalized treatment and improve the quality and effectiveness of interventions, this article combined GSEA (Gene Set Enrichment Analysis) technology to conduct in-depth research on potential drug targets and their interaction networks in coronary microcirculation dysfunctions. This article first utilized the Coremine medical database, GeneCards, and DrugBank public databases to collect gene data. Then, filtering methods were used to preprocess the data, and GSEA was used to analyze the preprocessed gene expression data to identify and calculate pathways and enrichment scores related to CMD. Finally, protein sequence features were extracted through the calculation of autocorrelation features. To verify the effectiveness of GSEA, this article conducted experimental analysis from four aspects: precision, receiver operating characteristic (ROC) curve, correlation, and potential drug targets, and compared them with Gene Regulatory Networks (GRN) and Random Forest (RF) methods. The results showed that compared to the GRN and RF methods, the average precision of GSEA improved by 0.11. The conclusion indicated that GSEA helped identify and explore potential drug targets and their interaction networks, providing new ideas for personalized quality of CMD.

BackgroundCancer immunotherapy has made significant progress in recent years, with numerous studies worldwide. Immunotherapy has had a transformative impact on oncology and autoimmune diseases. In the biomedical arena, hydrogels with good properties are widely used in cancer immunotherapy. Our study used bibliometrics to analyze the changing trends in using hydrogels for cancer immunotherapy.MethodsFrom 2013 to 2023, a systematic search was conducted in the Web of Science Core Collection database to identify reviews and articles discussing the applications of hydrogels in cancer immunotherapy. The software CiteSpace was used to visually perform the bibliometric analysis in terms of research trends, countries, institutions, authors, journals, and keywords. Individual authors’ productivity was assessed with the Lotka’s law. The most relevant publication sources were identified by Bradford’s law.ResultsA total of 422 English-language publications related to hydrogels in cancer immunotherapy were collected. The number of annual publications increased rapidly after 2021 and remained constant for the past two years. China published the most articles in this field. The institution with the maximum number of published articles was the Chinese Academy of Sciences in China. Chen. Q was the most prolific author, and Liu. Z was the second most published author. In terms of journal contributions, the journal “Biomaterials” had the highest number of publications (n = 30). Biomaterials, Advanced Functional Materials and Journal of Controlled Release were the most influential journals. Keyword analysis revealed that cancer immunotherapy, drug delivery, immunogenic cell death, tumor microenvironment, injectable hydrogels, and immune checkpoint blockade were the primary research hotspots. In recent 3 years, adoptive T-cell therapy, black phosphorus, cell capture, adaptive cell therapy, tumor microenvironment, photodynamic therapy, and sustained release were the research hotspots in this field. Our study summarizes the objective of hydrogels in cancer immunotherapy in recent years, providing a reference for potential researchers in related field.ConclusionThis bibliometric analysis shows the progress and trend of research on hydrogels in cancer immunotherapy. This study provides a significant avenue for future investigation into current concerns and trends in research within this field.

Human exposure to per- and polyfluoroalkyl substances (PFASs) has received considerable attention, particularly in pregnant women because of their dramatic changes in physiological status and dietary patterns. Predicting internal PFAS exposure in pregnant women, based on external and relevant parameters, has not been investigated. Here, machine learning (ML) models were developed to predict the serum concentrations of PFOA and PFOS in a large population of 588 pregnant participants. Dietary exposure characteristics, demographic parameters, and in particular, serum fatty acid (FA) data were used for the model development. The fitting results showed that the inclusion of FAs as covariates significantly improved the performance of the ML models, with the random forest (RF) model having the best predictive performance for PFOA (R2 = 0.33, MAE = 1.51 ng/mL, and RMSE = 1.89 ng/mL) and PFOS (R2 = 0.12, MAE = 2.65 ng/mL, and RMSE = 3.37 ng/mL). The feature importance analysis revealed that serum FAs greatly affected PFOA concentration in the pregnant women, with saturated FAs being associated with decreased PFOA levels and unsaturated FAs with increased levels. Comparison with one-compartment pharmacokinetic model further demonstrated the advantage of the ML models in predicting PFAS exposure in pregnant women. Our models correlate for the first time blood chemical concentrations with human FA status using ML, introducing a novel perspective on predicting PFAS levels in pregnant women. This study provides valuable insights concerning internal exposure of PFASs generated from external exposure, and contributes to risk assessment and management in pregnant populations.

Background: Silicosis, characterized by interstitial lung inflammation and fibrosis, poses a significant health threat. ATII cells play a crucial role in alveolar epithelial repair and structural integrity maintenance. Inhibiting ATII cell senescence has shown promise in silicosis treatment.However, the mechanism behind silica-induced senescence remains elusive. Methods: The study employed male C57BL/6 N mice and A549 human alveolar epithelial cells to investigate silicosis and its potential treatment. Silicosis was induced in mice via intratracheal instillation of crystalline silica particles, with honokiol administered intraperitoneally for 14 days. Silica-induced senescence in A549 cells was confirmed, and SIRT3 knockout and overexpression cell lines were generated. Various analyses were conducted, including immunoblotting, qRT-PCR, histology, and transmission electron microscopy. Statistical significance was determined using one-way ANOVA with Tukey's post-hoc test. Results: This study elucidates how silica induces ATII cell senescence, emphasizing mtDNA damage. Notably, honokiol (HKL) emerges as a promising anti-senescence and anti-fibrosis agent, acting through sirt3. honokiol effectively attenuated senescence in ATII cells, dependent on sirt3 expression, while mitigating mtDNA damage. Sirt3, a class III histone deacetylase, regulates senescence and mitochondrial stress. HKL activates sirt3, protecting against pulmonary fibrosis and mitochondrial damage. Additionally, HKL downregulated cGAS expression in senescent ATII cells induced by silica, suggesting sirt3's role as an upstream regulator of the cGAS/STING signaling pathway. Moreover, honokiol treatment inhibited the activation of the NF-κB signaling pathway, associated with reduced oxidative stress and mtDNA damage. Notably, HKL enhanced the activity of SOD2, crucial for mitochondrial function, through sirt3-mediated deacetylation. Additionally, HKL promoted the deacetylation activity of sirt3, further safeguarding mtDNA integrity. Conclusions: This study uncovers a natural compound, HKL, with significant anti-fibrotic properties through activating sirt3, shedding light on silicosis pathogenesis and treatment avenues.

Ultrahigh-temperature–pressure experiments are crucial for understanding the physical and chemical properties of matter. The recent development of boron-doped diamond (BDD) heaters has made such melting experiments possible in large-volume presses. However, estimates of temperatures above 2600 K and of the temperature distributions inside BDD heaters are not well constrained, owing to the lack of a suitable thermometer. Here, we establish a three-dimensional finite element model as a virtual thermometer to estimate the temperature and temperature field above 2600 K. The advantage of this virtual thermometer over those proposed in previous studies is that it considers both alternating and direct current heating modes, the actual sizes of cell assemblies after compression, the effects of the electrode, thermocouple and anvil, and the heat dissipation by the pressure-transmitting medium. The virtual thermometer reproduces the power–temperature relationships of ultrahigh-temperature–pressure experiments below 2600 K at press loads of 2.8–7.9 MN (∼19 to 28 GPa) within experimental uncertainties. The temperatures above 2600 K predicted by our virtual thermometer are within the uncertainty of those extrapolated from power–temperature relationships below 2600 K. Furthermore, our model shows that the temperature distribution inside a BDD heater (19–26 K/mm along the radial direction and

Abstract Boulenophrys sangzhiensis and Boulenophrys tuberogranulata, two narrow‐distributed toad species within the Megophryidae family in southern China, are experiencing population declines due to habitat loss and degradation. Despite their critical conservation status, the two species remain largely overlooked in public and scientific spheres. This study presented the first sequencing, assembly, and annotation of the complete mitogenomes of both species using next‐generation sequencing. The mitogenome of B. sangzhiensis was 16,950 bp, while that of B. tuberogranulata was 16,841 bp, each comprising 13 protein‐coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and a noncoding control region (D‐loop). The gene content, nucleotide composition, and evolutionary rates of each mitogenome were analyzed. Both mitogenomes exhibited negative AT skew and GC skew with high A + T content. ATP8 exhibited the highest evolutionary rate, while COI had the lowest. A phylogenetic analysis based on 28 mitogenomes revealed two major clades of Megophryidae, supporting the classification of two subfamilies, Megophryinae and Leptobrachiinae. Within the subfamily Megophryinae, the genus Boulenophrys was divided into two species groups. Intriguingly, despite coexisting in Zhangjiajie City, B. sangzhiensis and B. tuberogranulata exhibited distinct origins from the two different species groups, underscoring the unique role of the coexisting area Zhangjiajie in driving their speciation and preserving their current populations. A parallel pattern was also identified in the Leptobrachiinae genus Leptobrachium within the same region. This study provided valuable data references and enhanced our understanding of the molecular characteristics of these threatened amphibian species.

ObjectiveTo determine the efficacy of mechanical thrombectomy combined with prolonged mild hypothermia compared with conventional treatment in managing acute middle cerebral artery occlusion, and to explore whether extending the duration of hypothermia can improve neurological function.MethodFrom 2018 to June 2023, a retrospective analysis was conducted on 45 patients with acute middle cerebral artery occlusion treated at the NICU of Suzhou Kowloon Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. After thrombectomy, patients were admitted to the neurological intensive care unit (NICU) for targeted temperature management. Patients were divided into two groups: the mild hypothermia group (34.5–35.9°C) receiving 5–7 days of treatment, and the normothermia group (control group) whose body temperature was kept between 36 and 37.5°C using pharmacological and physical cooling methods. Baseline characteristics and temperature changes were compared between the two groups of patients. The primary outcome was the modified Rankin Scale (mRS) score at 3 month after surgery, and the secondary outcomes were related complications and mortality rate. Prognostic risk factors were investigated using both univariate and multivariate logistic regression analyses.ResultsAmong 45 patients, 21 underwent prolonged mild hypothermia, and 24 received normothermia, with no significant differences in baseline characteristics between the two groups. The duration of mild hypothermia ranged from 5 to 7 days. The incidence of chills (33.3% vs. 8.3%, p = 0.031) and constipation (57.1% vs. 20.8%, p = 0.028) was significantly higher in the mild hypothermia group compared with the control group. There was no significant difference in mortality rates between the mild hypothermia and the control group (4.76% vs. 8.33%, p = 1.000, OR = 1.75, 95% CI, 0.171–17.949). At 3 month, there was no significant difference in the modified mRS (0–3) score between the mild hypothermia and control groups (52.4% vs. 25%, p = 0.114, OR = 0.477, 95% CI, 0.214–1.066). Infarct core volume was an independent risk factor for adverse neurological outcomes.ConclusionProlonged mild hypothermia following mechanical thrombectomy had no severe complications and shows a trend to improve the prognosis of neurological function. The Infarct core volume on CTP was an independent risk factor for predicting neurological function.

Pattern-illuminated Fourier ptychography (piFP) is an elegant combination of structured illumination imaging and a Fourier ptychographic algorithm with the ability to image beyond the diffraction limit of the employed optics. Artifact-free piFP super-resolution reconstruction requires a high level of stability in the illumination pattern. However, unpredictable pattern variation occurs in the presence of environment perturbation, intensity fluctuation, and pointing instability at the source, leading to declines in image reconstruction quality. To address this issue, we present an efficient and robust piFP algorithm based on low-rank approximation (LRA-piFP), which relaxes the requirement for the stability of illumination patterns. This LRA-piFP method can model frame-wise pattern variation during a full scan, thus improve the reconstruction quality significantly. We take numerical simulations and proof-of-principle experiments with both long-range imaging and microscopy for demonstrations. Results show that the LRA-piFP method can handle different kinds of pattern variation and outperforms other state-of-the-art techniques in terms of reconstruction quality and resolution improvement. Our method provides effective experimental robustness to piFP with a natural algorithmic extension, paving the way for its application in both macroscopic and microscopic imaging.