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Abstract Obesity is an important risk factor for breast cancer in women before and after menopause. Adipocytes, key mediators in the tumor microenvironment, play a pivotal role in the relationship between obesity with cancer. However, the potential of dietary components in modulating this relationship remains underexplored. Genistein, a soy-derived isoflavone, has shown promise in reducing breast cancer risk, attenuating obesity-associated inflammation, and improving insulin resistance. However, there are no reports examining whether genistein has the ability to reduce the effects of obesity on breast tumor development. In this study, we constructed a mammary tumor model in ovariectomized obese mice and examined the effects of genistein on body condition and tumor growth. Moreover, the effects of genistein on the tumor microenvironment were examined via experimental observation of peritumoral adipocytes and macrophages. In addition, we further investigated the effect of genistein on adipocyte and breast cancer cell crosstalk via coculture experiments. Our findings indicate that dietary genistein significantly alleviates obesity, systemic inflammation, and metabolic disorders induced by a high-fat diet in ovariectomized mice. Notably, it also inhibits tumor growth in vivo. The impact of genistein extends to the tumor microenvironment, where it reduces the production of cancer-associated adipocytes (CAAs) and the recruitment of M2d-subtype macrophages. In vitro, genistein mitigates the transition of adipocytes into CAAs and inhibits the expression of inflammatory factors by activating PPAR-γ pathway and degrading nuclear NF-κB. Furthermore, it impedes the acquisition of invasive properties and epithelial‒mesenchymal transition in breast cancer cells under CAA-induced inflammation, disrupting the Wnt3a/β-catenin pathway. Intriguingly, the PPAR-γ inhibitor T0070907 counteracted the effects of genistein in the coculture system, underscoring the specificity of its action. Our study revealed that genistein can mitigate the adverse effects of obesity on breast cancer by modulating the tumor microenvironment. These findings provide new insights into how genistein intake and a soy-based diet can reduce breast cancer risk.

Abstract Depressive disorder is a significant public health problem worldwide, which adversely affects children and adolescents’ health. Impaired fasting blood glucose (IFG) is more common in depressive disorder, which becomes a clinical problem that needs to be focused on. The study purposed to determine the prevalence and related factors of IFG in Chinese children and adolescents with depressive disorder and the relationship between triglyceride and high-density lipoprotein cholesterol (TG/HDL-C) ratio and IFG. This research encompassed 756 individuals aged 8 to 18 with major depressive disorders, all diagnosed under DSM-5 criteria at the Third People’s Hospital of Fuyang from January 2020 to December 2021. We detected fasting blood glucose (FBG) and lipid levels and assessed the suicidal behaviors and depressive symptoms severity of each participant. The sociodemographic and included study variables were collected and analyzed. Our study employed multiple logistic regression to discern independent factors affecting IFG in conjunction with depressive disorders among children and adolescents. The prevalence of IFG was 6.5% (49/756). IFG was positively correlated with FBG, BMI, TG, TG/HDL-C, and was negatively correlated with gender and the type of antidepressant drug taken. Binary logistic analysis showed that male (OR = 2.57, 95% CI: 1.43–4.63, P = 0.002) and higher levels of TG (OR = 1.63, 95% CI: 1.11–2.38, P = 0.013) were independently associated with IFG in children and adolescents with depressive disorder. The incidence of IFG in children and adolescents with depressive disorder was high and was positively related to the TG/HDL-C ratio. The evaluation and management of IFG in pediatric depression should extend beyond pharmacological interventions. Comprehensive strategies in both assessment and management of IFG are essential to address this condition effectively in young patients facing depressive disorders.

Abstract Although Alzheimer’s disease (AD) and intracranial aneurysm (IA) were two different types of diseases that occurred in the brain, ruptured IA (RIA) survivors may experience varying degrees of cognitive dysfunction. Neither AD nor IA is easily recognizable by an early onset so that the incidence of adverse clinical outcomes would be on the rise. Therefore, we focused on the exploration of the shared genes and molecular mechanisms between AD and IA, which would be significant for the efficiency of co-screening and co-diagnosis. Two GEO datasets were selected for the weighted gene co-expression network analysis (WGCNA) and differentially expressed gene screening, obtaining 78 overlapped genes. Next, 9 hub genes were identified by the protein-protein interaction network, including PIK3CA, GAB1, IGF1R, PLCB1, PGR, PDGFRB, PLCE1, FGFR3, and SYNJ1. The interactions among the hub genes, miRNA, and TFs were also explored. Meanwhile, we performed GO and KEGG pathway enrichment analyses for the results of WGCNA and hub genes, which showed that the Ras signaling and Rap1 signaling were the main shared pathogenesis. In conclusion, the present bioinformatics analysis revealed that AD and IA had the shared genes and molecular mechanisms, and these outcomes were associated with inflammation and calcium homeostasis, which could provide research clues for further studies.

Abstract Cervical cancer (CCa) patients with lymph node (LN) metastasis face poor prognoses and have limited treatment options. Aberrant N6-methyladenosine (m6A) modification of RNAs are known to promote tumor metastasis, but their role in CCa remains unclear. Our study reveals that HNRNPC, an alternative splicing (AS) factor and m6A reader, increases tumor-related variants through m6A-dependent manner, thereby promoting lymphatic metastasis in CCa. We found that HNRNPC overexpression correlates with lymphatic metastasis and poorer prognoses in CCa patients. Functionally, knocking down HNRNPC markedly inhibited the migration and invasion of several CCa cell lines, while supplementing HNRNPC restored the malignant phenotypes of these cells. Mechanistically, HNRNPC regulates exon skipping of FOXM1 by binding to its m6A-modified motif. Mutating the m6A site on FOXM1 weakened the interaction between HNRNPC and FOXM1 pre-RNA, leading to a reduction in the metastasis-related FOXM1-S variant. In conclusion, our findings demonstrate that m6A-dependent alternative splicing mediated by HNRNPC is essential for lymphatic metastasis in CCa, potentially providing novel clinical markers and therapeutic strategies for patients with advanced CCa.

Abstract Elucidating the molecular dependencies behind the cancer-type specificity of driver mutations may reveal new therapeutic opportunities. We hypothesized that developmental programs would impact the transduction of oncogenic signaling activated by a driver mutation and shape its cancer-type specificity. Therefore, we designed a computational analysis framework by combining single-cell gene expression profiles during fetal organ development, latent factor discovery, and information theory-based differential network analysis to systematically identify transcription factors that selectively respond to driver mutations under the influence of organ-specific developmental programs. After applying this approach to VHL mutations, which are highly specific to clear cell renal cell carcinoma (ccRCC), we revealed important regulators downstream of VHL mutations in ccRCC and used their activities to cluster patients with ccRCC into three subtypes. This classification revealed a more significant difference in prognosis than the previous mRNA profile-based method and was validated in an independent cohort. Moreover, we found that EP300, a key epigenetic factor maintaining the regulatory network of the subtype with the worst prognosis, can be targeted by a small inhibitor, suggesting a potential treatment option for a subset of patients with ccRCC. This work demonstrated an intimate relationship between organ development and oncogenesis from the perspective of systems biology, and the method can be generalized to study the influence of other biological processes on cancer driver mutations.

Failure of oocyte activation, including polyspermy and defects in pronuclear (PN) formation, triggers early embryonic developmental arrest. Many studies have shown that phospholipase C zeta 1 (PLCZ1) mutations cause failure of PN formation following intracytoplasmic sperm injection (ICSI); however, whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization (IVF) remains unknown. Whole-exome sequencing (WES) was performed to identify candidate mutations in couples with primary infertility. Sanger sequencing was used to validate the mutations. Multiple PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced. Assisted oocyte activation (AOA) after ICSI was performed to overcome the failure of oocyte activation. We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles, including a novel missense mutation c.1154C>T, p.R385Q. PN formation failure was observed during the ICSI cycle. However, injection of multiple PLCZ1-mutated sperm induced PN formation, suggesting that the Ca2+ oscillations induced by the sperm exceeded the necessary threshold for PN formation. AOA after ICSI enabled normal fertilization, and all patients achieved successful pregnancies. These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy. Furthermore, this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal infectious disease caused by the SFTS virus (SFTSV), posing a significant public health threat. This study aimed to construct a dynamic model for the early identification of SFTS patients at high risk of disease progression. Methods All eligible patients enrolled between April 2014 and July 2023 were divided into training and validation sets. Thirty-four clinical variables in the training set underwent analysis using least absolute shrinkage and selection operator (LASSO) logistic regression. Selected variables were then input into the multivariate logistic regression model to construct a dynamic nomogram. The model’s performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) in both training and validation sets. Kaplan-Meier survival analysis was utilized to evaluate prognostic performance. Results 299 SFTS patients entered the final investigation, with 208 patients in the training set and 90 patients in the validation set. LASSO and the multivariate logistic regression identified six significant prediction factors: age (OR, 1.060; 95% CI, 1.017–1.109; P = 0.007), CREA (OR, 1.017; 95% CI, 1.003–1.031; P = 0.019), PT (OR, 1.765; 95% CI, 1.175–2.752; P = 0.008), D-dimer (OR, 1.039; 95% CI, 1.005–1.078; P = 0.032), nervous system symptoms (OR, 8.244; 95% CI, 3.035–26.858; P

Abstract Background Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection (LRTI) among children, has resurged in the form of endemic or even pandemic in many countries and areas after the easing of COVID-19 containment measures. This study aimed to investigate the differences in epidemiological and clinical characteristics of children hospitalized for RSV infection during pre- and post-COVID-19 eras in Yunnan, China. Methods A total of 2553 pediatric RSV inpatients from eight hospitals in Yunnan were retrospectively enrolled in this study, including 1451 patients admitted in 2018–2019 (pre-COVID-19 group) and 1102 patients admitted in 2023 (post-COVID-19 group). According to the presence or absence of severe LRTI (SLRTI), patients in the pre- and post-COVID-19 groups were further divided into the respective severe or non-severe subgroups, thus analyzing the risk factors for RSV-associated SLRTI in the two eras. Demographic, epidemiological, clinical, and laboratory data of the patients were collected for the final analysis. Results A shift in the seasonal pattern of RSV activity was observed between the pre-and post-COVID-19 groups. The peak period of RSV hospitalizations in the pre-COVID-19 group was during January–April and October–December in both 2018 and 2019, whereas that in the post-COVID-19 group was from April to September in 2023. Older age, more frequent clinical manifestations (fever, acute otitis media, seizures), and elevated laboratory indicators [neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP), interleukin 6 (IL-6), co-infection rate] were identified in the post-COVID-19 group than those in the pre-COVID-19 group (all P

Abstract Background Gastric cancer (GC), a molecularly heterogeneous disease, is the third leading cause of cancer death worldwide. The majority of GC cases worldwide occur in East Asia, predominantly China. Mutational Signature Framework offers an elegant approach to identify mutational processes present in tumors. Methods To identify mutational signature patterns, we conducted whole exome sequencing (WES) analysis in Chinese patients with GC. Mutect2 and MutsigCV were used to identify significantly mutated genes in 175 Chinese GC cases using paired tumor-normal tissues. We investigated mutational signatures using Catalogue of Somatic Mutations in Cancer (COSMIC) Version 2 (V2) and Version 3 (V3). Results We identified 104 mutated genes with P

[Introduction] The widespread adoption of electric vehicles (EVs) enhances environmental sustainability during travel, yet it simultaneously elevates strain on the mains supply. To assess the impact of EV charging on the power grid, a specialized charging load calculation method is developed for large EV cluster on the basis of the Monte Carlo method. [Method] In this approach, EVs were categorized into six groups based on their usage: private EVs, electric buses, electric taxis, online ride-hailing EVs, official EVs, and logistics EVs. Typical battery performance parameters for each group were identified, and probability models were established to characterize the variability in their travel and charging patterns. By integrating group scale forecasts, daily charging schedules for each group were simulated through random sampling. Subsequently, the daily charging load for each group was calculated, culminating in the total charging load for the EV cluster through an aggregation method. [Result] The EV cluster in a southern province in 2030 was taken as the simulation case. [Conclusion] The case analysis reveals that the proposed approach can provide the daily charging load of various EV groups and the entire EV cluster. Furthermore, among all types of EVs, electric buses have the highest peak charging load at 4 639.5 MW, followed by that of private EVs (not higher than 70% of the electric buses' peak load), and electric taxis have the lowest peak charging load. The charging peak of the entire EV cluster occurs between 19:00 and 23:00 at night, and the peak load can reach 10.0927 GW.

The processing body (P-Body) is a membrane-less organelle with stress-resistant functions. Under stress conditions, cells preferentially translate mRNA that favors the stress response, resulting in a large number of transcripts unfavorable to the stress response in the cytoplasm. These non-translating mRNAs aggregate with specific proteins to form P-Bodies, where they are either stored or degraded. The protein composition of P-Bodies varies depending on cell type, developmental stage, and external environmental conditions. This review primarily elucidates the protein composition in plants and the assembly of P-Bodies, and focuses on the mechanisms by which various proteins within the P-Bodies of plants regulate mRNA decapping, degradation, translational repression, and storage at the post-transcriptional level in response to ethylene signaling and abiotic stresses such as drought, high salinity, or extreme temperatures. This overview provides insights into the role of the P-Body in plant abiotic stress responses.

Artificial intelligence (AI)-enabled technology has the potential to expand access to high-quality health information and health care services. Learning how diverse users interact with technology enables improvements to the AI model and the user interface, maximizing its potential benefit for a greater number of people. This narrative describes how technology developers, academic researchers, and representatives from a community-based organization collaborated to conduct a community-centered project on emerging health technologies. Our project team comprised representatives from Stanford Medicine, Google, and Santa Clara Family Health Plan’s Blanca Alvarado Community Resource Center. We aimed to understand the usability and acceptability of an AI-driven dermatology tool among East San Jose, California, community members. Specifically, our objectives were as follows: to test a model for cross-sector research of AI-based health technology; to determine the utility of the tool in an ethnically and age-diverse population; to obtain in-depth user experience feedback from participants recruited during community events; to offer free skin health consultations; and to provide resources for receiving follow-up care. We describe a collaborative approach in which each party contributed expertise: knowledge of the community from the community health partner, clinical expertise from the academic research institution, and software and AI expertise from the technology company. Through an iterative process, we identified important community needs, including technological, language, and privacy support. Our approach allowed us to recruit and engage a diverse cohort of participants, over 70% of whom preferred a language other than English. We distill learnings from planning and executing this case study that may help other collaborators bridge the gap between academia, industry, and community in AI health care innovation.

This review explores the potential of including glutamine, a so-called non-essential amino acid, in the formulation of reduced-crude protein (CP) diets for broiler chickens. There is a precedent for benefits when including glycine and serine in reduced-CP diets. Fundamentally this is due to decreases in non-essential amino acid concentrations in reduced-CP diets — an unavoidable consequence of reducing CP without amino acid supplementation. The situation for glutamine is complicated because analysed dietary concentrations are very rarely provided as standard assays do not differentiate between glutamine and glutamate and are reported on a combined basis as glutamic acid. The dietary requirement for glutamic acid is approximately 36.3 g/kg but it is increasingly unlikely that this requirement will be met as dietary CP levels are progressively reduced. Glutamine is an abundant and versatile amino acid and constitutes 50.5 mg/g of whole-body chicken protein and is the dominant free amino acid in systemic plasma where it has been shown to provide 22.6% (139.9 of 620.3 μg/mL) of the total in birds offered 215 g/kg CP, wheat-based diets. In addition to dietary intakes, glutamine biosynthesis is derived mainly from the condensation of glutamate and ammonia (NH3) catalysed by glutamine synthetase, a reaction that is pivotal to NH3 detoxification. Glutamate and NH3 are converted to glutamine by phosphate-dependent glutaminase in the reciprocal reaction; thus, glutamine and glutamate are interchangeable amino acids. However, the rate of glutamine biosynthesis may not be adequate in rapidly growing broiler chickens and exogenous and endogenous glutamine levels are probably insufficient in birds offered reduced-CP diets. The many functional roles of glutamine, including NH3 detoxification and maintenance of acid-base homeostasis, then become relevant. Twenty feeding studies were identified where dietary glutamine supplementation, usually 10 g/kg, was evaluated in birds kept under thermoneutral conditions. On balance, the outcomes were positive, but the average dietary CP was 213 g/kg across the twenty feeding studies, which indicates that CP and, in turn, glutamine concentrations would have been adequate. This suggests that glutamine inclusions in reduced-CP diets hold potential and consideration is given to how this may be best confirmed.

With the large number of online courses currently available, learners may have difficulty choosing the appropriate course, so online education institutions have launched a free trial marketing approach. The factors influencing learners' continuous usage of online courses in the mode of course trial have become a prominent and meaningful topic. Online education platforms have also introduced a series of virtual management services for online learning through online communication media, but their effectiveness has not been fully studied. Based on the updated DeLone and McLean information systems success model (D&M model), this study investigated the impact of the online course content and learning platform on learners' continuous usage of online courses and the mediating mechanism, as well as explored the moderating role of virtual management. The empirical study (N = 371) showed that online course content matching (demand matching, ability matching) and perceived learning platform characteristics (perceived vividness, perceived ease of use) positively influenced continuous usage through satisfaction, and virtual management had a significant inverted U-shaped moderating effect.

Context The use of traditional Chinese medicine (TCM) for breast cancer patients inhibits tumor cell growth and proliferation, alleviates adverse reactions, and inhibits tumor recurrence and metastasis post-surgery. An assessment of its historical efficacy and an examination of the latest research trends are imperative to thoroughly leverage the potential of TCM for breast cancer treatment.Objective This study analyzes the published literature on TCM for breast cancer treatment using bibliometric analysis to determine the current state, identify hot spots, and discern trends, providing insight into research in this field.Methods TCM-based breast cancer treatment publications between 2003 and 2022 were retrieved from the Web of Science, China National Knowledge Infrastructure, Wanfang, and Duxiu databases. Visual analysis was performed using VOSviewer (V1.6.19) and CiteSpace (V6.3.R1) software. Examined metrics included the annual publication count, literature and journal, national and institutional contributions, author co-occurrence, keyword co-occurrence, keywords timeline, and keywords with citation bursts in this research field.Results and conclusion A total of 1080 English publications and 2617 Chinese publications were included in the analysis. China was the leading contributor of publications. High-frequency keywords such as ‘apoptosis’, ‘expression’, ‘in vivo’, ‘chemotherapy’, ‘triple-negative breast cancer’, and ‘lymphedema’ were identified from English and Chinese publications; ‘epithelial mesenchymal transition’ and ‘network pharmacology’ emerged as hotspots. The development of modern science, technology, and in-depth research can result in broader prospects for the research and application of TCM in breast cancer treatment, resulting in more effective solutions for the treatment of breast cancer and other malignant tumors.

In a single UAV-assisted mobile edge computing system, in order to enable the UAV to serve all user devices in a large area, the large area can be divided into a plurality of sub-areas and the UAV can be set to fly between the sub-areas with a fixed route to provide computing services for the user devices. Considering the scarcity of computational resources for user devices and the fact that users outside the coverage area of the UAV may choose to move to the coverage area for task offloading in order to maximize their own utility, the partial offloading problem of user devices can be transformed into the problem of maximizing the utility of each user device. The mixed-strategy game and the submodular game are used to determine the movement probability of user devices and the amount of offloaded data, so as to derive the optimal offloading strategy, and the existence of mixed-strategy Nash equilibrium and pure-strategy Nash equilibrium is proved, respectively. Simulation results show that the proposed scheme can effectively improve the utility of user device compared with classical schemes such as MBO (Binary Offloading Based on Mixed Strategy Game), and its convergence and stability are verified.

Abstract While KRAS mutation is the leading cause of low survival rates in lung cancer bone metastasis patients, effective treatments are still lacking. Here, we identified homeobox C10 (HOXC10) as a lynchpin in pan-KRAS-mutant lung cancer bone metastasis. Through RNA-seq approach and patient tissue studies, we demonstrated that HOXC10 expression was dramatically increased. Genetic depletion of HOXC10 preferentially impeded cell proliferation and migration in vitro. The bioluminescence imaging and micro-CT results demonstrated that inhibition of HOXC10 significantly reduced bone metastasis of KRAS-mutant lung cancer in vivo. Mechanistically, the transcription factor HOXC10 activated NOD1/ERK signaling pathway to reprogram epithelial-mesenchymal transition (EMT) and bone microenvironment by activating the NOD1 promoter. Strikingly, inhibition of HOXC10 in combination with STAT3 inhibitor was effective against KRAS-mutant lung cancer bone metastasis by triggering ferroptosis. Taken together, these findings reveal that HOXC10 effectively alleviates pan-KRAS-mutant lung cancer with bone metastasis in the NOD1/ERK axis-dependent manner, and support further development of an effective combinatorial strategy for this kind of disease.

Detecting relations between entities across multiple sentences in a document, referred to as document-level relation extraction, poses a challenge in natural language processing. Graph networks have gained widespread application for their ability to capture long-range contextual dependencies in documents. However, previous studies have often been limited to using only two to three types of nodes to construct document graphs. This leads to insufficient utilization of the rich information within the documents and inadequate aggregation of contextual information. Additionally, relevant relationship labels often co-occur in documents, yet existing methods rarely model the dependencies of relationship labels. In this paper, we propose the Interaction and Fusion of Rich Textual Information Network (IFRTIN) that simultaneously considers multiple types of nodes. First, we utilize the structural, syntactic, and discourse information in the document to construct a document graph, capturing global dependency relationships. Next, we design a regularizer to encourage the model to capture dependencies of relationship labels. Furthermore, we design an Adaptive Encouraging Loss, which encourages well-classified instances to contribute more to the overall loss, thereby enhancing the effectiveness of the model. Experimental results demonstrate that our approach achieves a significant improvement on three document-level relation extraction datasets. Specifically, IFRTIN outperforms existing models by achieving an F1 score improvement of 0.67% on Dataset DocRED, 1.2% on Dataset CDR, and 1.3% on Dataset GDA. These results highlight the effectiveness of our approach in leveraging rich textual information and modeling label dependencies for document-level relation extraction.

Abstract The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual’s genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner’s fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies.

Abstract Infections caused by pathogenic Escherichia coli are a serious threat to human health, while conventional antibiotic susceptibility tests (AST) have a long turn-around time, and rapid antibiotic susceptibility methods are urgently needed to save lives in the clinic, reduce antibiotic misuse and prevent emergence of antibiotic-resistant bacteria. We optimized and validated the feasibility of a novel rapid AST based on SYBR Green I and Propidium Iodide (SGPI-AST) for E. coli drug susceptibility test. A total of 112 clinical isolates of E. coli were collected and four antibiotics (ceftriaxone, cefoxitin, imipenem, meropenem) were selected for testing. Bacterial survival rate of E. coli was remarkably linearly correlated with S value at different OD600 values. After optimizing the antibiotic concentrations, the sensitivity and specificity of SGPI-AST reached 100%/100%, 97.8%/100%, 100%/100% and 98.4%/99% for ceftriaxone, cefoxitin, imipenem and meropenem, respectively, and the corresponding concordances of the SGPI-AST with conventional AST were 1.000, 0.980, 1.000 and 0.979, respectively. The SGPI-AST can rapidly and accurately determine the susceptibility of E. coli clinical isolates to multiple antibiotics in 60 min, and has the potential to be applied to guide the precise selection of antibiotics for clinical management of infections caused by pathogenic E. coli.

Abstract In recent years, research on organ-on-a-chip technology has been flourishing, particularly for drug screening and disease model development. Fibroblasts and vascular endothelial cells engage in crosstalk through paracrine signaling and direct cell–cell contact, which is essential for the normal development and function of the heart. Therefore, to faithfully recapitulate cardiac function, it is imperative to incorporate fibroblasts and vascular endothelial cells into a heart-on-a-chip model. Here, we report the development of a human heart-on-a-chip composed of induced pluripotent stem cell (iPSC)-derived cardiomyocytes, fibroblasts, and vascular endothelial cells. Vascular endothelial cells cultured on microfluidic channels responded to the flow of culture medium mimicking blood flow by orienting themselves parallel to the flow direction, akin to in vivo vascular alignment in response to blood flow. Furthermore, the flow of culture medium promoted integrity among vascular endothelial cells, as evidenced by CD31 staining and lower apparent permeability. The tri-culture condition of iPSC-derived cardiomyocytes, fibroblasts, and vascular endothelial cells resulted in higher expression of the ventricular cardiomyocyte marker IRX4 and increased contractility compared to the bi-culture condition with iPSC-derived cardiomyocytes and fibroblasts alone. Such tri-culture-derived cardiac tissues exhibited cardiac responses similar to in vivo hearts, including an increase in heart rate upon noradrenaline administration. In summary, we have achieved the development of a heart-on-a-chip composed of cardiomyocytes, fibroblasts, and vascular endothelial cells that mimics in vivo cardiac behavior.

Abstract Earthquake-induced rock landslides in the eastern mountains of the Tibetan Plateau, especially landslides with weak interlayers pose a significant threat to major construction projects. Prestressed anchor cable is one of the main reinforcement methods of rock slopes. This paper combines shaking table model tests and numerical simulation to study the reinforcement effect and dynamic response characteristics of prestressed anchor cables applied to rock slopes with weak interlayers under strong earthquakes. The research results show that prestressed anchor cables can effectively reinforce slopes with weak interlayers. A small cable inclination, a small spacing and a high prestress are recommended in the seismic reinforcement design of prestressed anchor cable. In addition, the characteristics of slope progressive damage and prestress loss under the earthquake are found by the shaking table test. The results have been applied in hazard prevention and control of rock slopes on the Chengdu-Lanzhou Railway at the eastern Qinghai-Tibet Plateau.

Abstract Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Abstract Multiple Sclerosis (MS) is a heterogeneous inflammatory and neurodegenerative disease with an unpredictable course towards progressive disability. Treating progressive MS is challenging due to limited insights into the underlying mechanisms. We examined the molecular changes associated with primary progressive MS (PPMS) using a cross-tissue (blood and post-mortem brain) and multilayered data (genetic, epigenetic, transcriptomic) from independent cohorts. In PPMS, we found hypermethylation of the 1q21.1 locus, controlled by PPMS-specific genetic variations and influencing the expression of proximal genes (CHD1L, PRKAB2) in the brain. Evidence from reporter assay and CRISPR/dCas9 experiments supports a causal link between methylation and expression and correlation network analysis further implicates these genes in PPMS brain processes. Knock-down of CHD1L in human iPSC-derived neurons and knock-out of chd1l in zebrafish led to developmental and functional deficits of neurons. Thus, several lines of evidence suggest a distinct genetic-epigenetic-transcriptional interplay in the 1q21.1 locus potentially contributing to PPMS pathogenesis.

Abstract Background Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain. Methods We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999–2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors. Results In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value

Camellia fascicularis has important ornamental, medicinal, and food value. It also has tremendous potential for exploiting bioactivities. However, the bioactivities of secondary metabolites in C. fascicularis have not been reported. The structures of compounds were determined by spectral analysis and nuclear magnetic resonance (NMR) combined with the available literature on secondary metabolites of C. fascicularis leaves. In this study, 15 compounds were identified, including 5 flavonoids (1–5), a galactosylglycerol derivative (6), a terpenoid (7), 4 lignans (8–11), and 4 phenolic acids (12–15). Compounds 6–7 and 9–12 were isolated from the genus Camellia for the first time. The remaining compounds were also isolated from C. fascicularis for the first time. Evaluation of antioxidant and antimicrobial activities revealed that compounds 5 and 8–11 exhibited stronger antioxidant activity than the positive drug ascorbic acid, while compounds 7, 13, and 15 showed similar activity to ascorbic acid. The minimum inhibitory concentration (MIC) of antibacterial activity for compounds 5, 7, 9, 11, and 13 against Pseudomonas aeruginosa was comparable to that of the positive control drug tetracycline at a concentration of 62.50 µg/mL; other secondary metabolites inhibited Escherichia coli and Staphylococcus aureus at concentrations ranging from 125–250 µg/mL.

Polyester-cotton fabrics (PTCO) have excellent properties and are ubiquitous in daily life, but their serious flammability brings great safety hazards to people's lives. This study used phenylphosphonic acid (PPOA) and urea as raw materials to prepare a flame retardant named POU. PTCO/POU was prepared by the pad-dry-cure technique, and the performance was compared with that of PTCO/PPOA, revealing many interesting phenomena. Based on the gas phase and condensed phase flame-retardant mechanism brought by P/N synergy, PTCO/POU had better flame retardancy than PTCO/PPOA did. The damaged length was 6.7 cm, and the limiting oxygen index (LOI) value was 30.1%. The char residues after burning were complete and denser with a higher degree of graphitization. Thermogravimetric analysis showed that POU can significantly reduce the Rmax of PTCO, and improve its thermal stability in high temperature zones. The CCT results showed that PTCO/POU had the longest time to ignition and the smallest fire growth index, which was of great significance for reducing fire risk. The TG-FTIR results showed that the volatile products of PTCO/POU were greatly reduced, and during the burning process, NH3 was produced to dilute the concentration of combustible gases. In addition, PTCO/POU also had better whiteness performance than PTCO/PPOA did. This work greatly improved the flame retardancy of PTCO in a simple way and expanded its application prospects.

Abstract In this study, a shaking table test was conducted on long-short composite anti-slide piles, the development process and dynamic response of cracks in a pile-supported slope were observed, and the failure mechanism of the slope was explored. The experiment showed that the failure of the pile-supported slope under an earthquake was a gradual process; cracks first occur at the top of the slope, where the support action of the piles was weak. As the input seismic action increased, cracks developed downwards along the slope. Owing to the support effect of the long-short anti-slide composite piles, the transmission path of the cracks changed, and the cracks developed along the top of the composite piles, ultimately leading to overtop failure. When cracks appeared on the slope or near final failure, the acceleration response law of the supported slope undergone a sudden change, which was an important indicator of slope instability. The distribution of dynamic soil stress on the pile body was greatly affected by the input peak ground acceleration, and the maximum bending moment of the long-short composite anti-slide piles was located near the weak interlayer.

Abstract Background Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. Results In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo. Conclusions In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.

Direct-to-smartphone, as a potential technological means for achieving the integration of space and ground in the future, has received widespread attention from industry and academia.Compared with traditional satellite mobile communication, there are many challenges in the current direct-to-smartphone technology.The current development status and system architecture of two direct-to-smartphone technology routes based on synchronous orbit satellites and asynchronous orbit satellites were introduced, and the technical challenges from the air-interface side, satellite side, network side, and terminal side were summarized.Several solutions were proposed, included satellite-terrestrial synchronization, satellite-borne ultra-large array antenna, and satellite-terrestrial heterogeneous network roaming, providing technical support for the development of direct-to-smartphone technology.Finally, a brief outlook were provided.

Abstract Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT.

Abstract Traditional quarter‐wavelength parallel‐line couplers (QWPLC) in microstrip form suffer heavily in low directivity because of unbalanced even‐mode and odd‐mode phase velocities. Related schemes to improve directivity lead to complex structures and large dimensions. This study derives and validates an iterative synthesis method to design a high‐directivity microstrip coupler adopting a symmetric stepped‐impedance microstrip coupled line (SSIMCL). Given that the even‐mode and odd‐mode effective dielectric constants (EDCs) vary with the characteristic impedances, the authors take the EDCs of traditional QWPLC as the initial values for an SSIMCL, and the characteristic impedances and EDCs can be computed and converged in several iterations, resulting in good phase delay balance and high coupler directivity. A 20‐dB microstrip coupler working at 1 GHz with high directivity is designed, fabricated, and measured. The obtained maximum directivity is 47 dB and approximately 1 GHz, while the relative bandwidth with a directivity higher than 20 dB and a return loss better than 20 dB is larger than 70%. The novel microstrip coupler also features a compact, simple structure shorter than λg/4.

Abstract Background Diabetes is a common chronic metabolic disease. The progression of the disease promotes vascular inflammation and the formation of atherosclerosis, leading to cardiovascular disease. The coronary artery perivascular adipose tissue attenuation index based on CCTA is a new noninvasive imaging biomarker that reflects the spatial changes in perivascular adipose tissue attenuation in CCTA images and the inflammation around the coronary arteries. In this study, a radiomics approach is proposed to extract a large number of image features from CCTA in a high-throughput manner and combined with clinical diagnostic data to explore the predictive ability of vascular perivascular adipose imaging data based on CCTA for coronary heart disease in diabetic patients. Methods R language was used for statistical analysis to screen the variables with significant differences. A presegmentation model was used for CCTA vessel segmentation, and the pericoronary adipose region was screened out. PyRadiomics was used to calculate the radiomics features of pericoronary adipose tissue, and SVM, DT and RF were used to model and analyze the clinical data and radiomics data. Model performance was evaluated using indicators such as PPV, FPR, AAC, and ROC. Results The results indicate that there are significant differences in age, blood pressure, and some biochemical indicators between diabetes patients with and without coronary heart disease. Among 1037 calculated radiomic parameters, 18.3% showed significant differences in imaging omics features. Three modeling methods were used to analyze different combinations of clinical information, internal vascular radiomics information and pericoronary vascular fat radiomics information. The results showed that the dataset of full data had the highest ACC values under different machine learning models. The support vector machine method showed the best specificity, sensitivity, and accuracy for this dataset. Conclusions In this study, the clinical data and pericoronary radiomics data of CCTA were fused to predict the occurrence of coronary heart disease in diabetic patients. This provides information for the early detection of coronary heart disease in patients with diabetes and allows for timely intervention and treatment.

BackgroundNumerous studies have established that probiotics or prebiotics can relieve the symptoms of allergic rhinitis (AR), but their mechanism of action remain underexplored. This study aimed to observe the clinical efficacy of probiotics combined with prebiotics in seasonal AR patients and explore their underlying mechanisms.MethodsWe conducted a prospective, randomized, double-blind, placebo-controlled clinical trial. The test group was given probiotics combined with prebiotics, whereas the placebo group was administered simulated preparation for 90 days. Outcome measures included total nasal symptom score (TNSS), visual analog scale, rhinitis quality of life questionnaire, fractional exhaled nitric oxide, and the rate and intensity of Loratadine use. Serum TNF-α, INF-γ, IL-4, IL-17, and IgE levels were measured by enzyme-linked immunosorbent assay. Intestinal microbiota was detected by 16S rRNA gene sequencing and quantitative PCR. Short-chain fatty acids were analyzed by gas chromatography-mass spectrometry.Results106 participants (N = 53 for both test group and placebo group) completed the study. From baseline to day 91, mean difference between groups (MDBG) in the reduction of TNSS was -1.1 (-2.2, -0.1) (P = 0.04); MDBG in the increment of TNF-α was 7.1 pg/ml (95% CI: 0.8, 13.4, P = 0.03); the INF-γ level was significantly increased (P = 0.01), whereas that of IL-17 (P = 0.005) was significantly decreased in the test group, whilst mean difference within groups was not statistically significant in the placebo group; MDBG in the increment of acetate was 12.4% (95% CI: 7.1%, 17.6%, P

ABSTRACT Purpose The vagal sensory nerve (VSN) is an essential interoceptive pathway that is connected to every level of the body. Its intricate genetic coding provides sustenance for physiological processes, including controlling blood pressure and respiration. Electroacupuncture (EA) is a proven surface stimulation therapy that can regulate vagal nerve activity, which can effectively prevent cardiovascular diseases. A growing number of studies have concentrated on the mapping of VSN codes, but little is known, and the physiological background of how EA influences interoceptive has not been fully explored. Method Here, we incorporate the hypothesized interaction among EA targets, VSNs, and the heart. This offers suggestions for using a versatile and focused EA strategy to modify vagal interoceptive awareness to enhance cardiovascular conditions. We first clarified the major role of vagal nerve in the control of cardiac activity. Additionally, we clarified the multidimensional coding pattern in the VSNs, revealing that the targeted control of multimodal interoceptive is the functional basis of the synchronization of cardiovascular system. Finding We propose a strategy in which EA of the VSNs is employed to activate the interoceptive loop and reduce the risk of cardiovascular disease.

Abstract The good combination of high strength and high toughness is a long‐standing challenge in the design of robust biomaterials. Meanwhile, robust biomaterials hardly perform fast and significant mechanical property changes under the trigger of light at room temperature. These limit the application of biomaterials in some specific areas. Here, photoresponsive alginate fibers are fabricated by using the designed azobenzene‐containing surfactant as flexible contact point for cross‐linking polysaccharide chains of alginate, which gain high mechanics through reinforced plastic strain and photo‐modulating mechanics through isomerization of azobenzene. By transferring molecular motion into macro‐scale mechanical property changes, such alginate fibers achieve reversible photo‐modulations on the mechanics. Their breaking strength and toughness can be photo‐modulated from 732 MPa and 112 MJ m−3 to 299 MPa and 27 MJ m−3, respectively, leading to record high mechanical changes among the developed smart biomaterials. With merits of good tolerance to pH and temperature, fast response to light, and good biocompatibility, the reported fibers will be suitable for working in various application scenarios as new smart biomaterials. This study provides a new design strategy for gaining highly‐strong and highly‐tough photoresponsive biomaterials.

Abstract Single‐drug therapies or monotherapies are often inadequate, particularly in the case of life‐threatening diseases like cancer. Consequently, combination therapies emerge as an attractive strategy. Cancer nanomedicines have many benefits in addressing the challenges faced by small molecule therapeutic drugs, such as low water solubility and bioavailability, high toxicity, etc. However, it remains a significant challenge in encapsulating two drugs in a nanoparticle. To address this issue, computational methodologies are employed to guide the rational design and synthesis of dual‐drug‐loaded polymer nanoparticles while achieving precise control over drug loading. Based on the sequential nanoprecipitation technology, five factors are identified that affect the formulation of drug candidates into dual‐drug loaded nanoparticles, and then screened 176 formulations under different experimental conditions. Based on these experimental data, machine learning methods are applied to pin down the key factors. The implementation of this methodology holds the potential to significantly mitigate the complexities associated with the synthesis of dual‐drug loaded nanoparticles, and the co‐assembly of these compounds into nanoparticulate systems demonstrates a promising avenue for combination therapy. This approach provides a new strategy for enabling the streamlined, high‐throughput screening and synthesis of new nanoscale drug‐loaded entities.

Abstract Novel phase of nano materials that break the traditional structural constraints are highly desirable, particularly in the field of mechanocatalysis, offering versatile applications ranging from energy to medical diagnosis and treatment. In this work, a distinct layered barium dititanate (BaTi2O5) nanocrystals using a pH‐modulated hydrothermal method is successfully synthesized. These nanocrystals exhibit outstanding hydrogen generation capability (1160 µmol g−1 h−1 in pure water) and demonstrate remarkable performance in organic dye degradation using ultrasonication. The crystal structure of this newly discovered BaTi2O5 phase, is determined by a combination of synchrotron Powder Diffraction refinement and X‐ray adsorption techniques, including X‐ray Absorption Near Edge Structure (XANES) and Extended X‐ray Absorption Fine Structure (EXAFS). Density Functional Theory calculations revealed that the newly‐discovered BaTi2O5 phase demonstrates dipole moments along the z‐axis, distributed in an antiparallel direction within a single unit cell. These inherent dipoles induce a surface polarization and a ferroelectric‐flexoelectric response under mechanical stimuli when the materials go to nano dimension. With a band alignment well‐suitable for hydrogen and reactive oxygen species generation, this BaTi2O5 phase demonstrates promising potential for Mechanocatalysis. The discovery of this distinct phase not only enriches the material candidates for mechanocatalysis but also provides valuable insights.

BackgroundFew studies have focused on the region-specific relationship between cardiovascular disease (CVD) and low temperature worldwide.ObjectiveWe aimed to provide an overview of trends in mortality and disability-adjusted life years (DALYs) for CVD and its subtypes attributable to low temperature over the past 30 years in 204 countries and regions, along with the associations of these trends with age, period, and birth cohorts.MethodsData on the estimated burden of CVDs (including ischemic heart disease, hypertensive heart disease, and stroke) attributable to low temperature were obtained from the Global Burden of Disease Study 2019. We utilized an age-period-cohort model to estimate overall annual percentage changes in mortality (net drifts), annual percentage changes from 15 ~ 19 to 81 ~ 85 years (local drifts), and period and cohort relative risk (period/cohort effects) between 1990 and 2019.ResultsAmong noncommunicable diseases, CVDs had the highest mortality rate and DALY loss attributable to low temperature worldwide and has increased from 65.7 to 67.3%, which is mainly attributed to the increase in East Asia and Pacific region. In terms of the level of economic and social development, an inverted U-shape was found in the age-standardized mortality rates (ASMR) due to low-temperature across different sociodemographic indices (SDI) regions. Both high CVD mortality (19.45, 95% CI [14.54, 24.17%]) and a decreasing mortality rate related to low temperature (from 1990 to 2019, net drift, −3.25% [−3.76, 2.73%] per year) was found in high SDI countries or territories, with opposite outcome found in low SDIs regions. The older adults (70+) and men share the highest rate of CVD ASMR and DALY attributed to low temperature across all regions, especially in North America and Europe and Central Asia.ConclusionMortality and DALY loss from CVD attributable to low temperature showed an overall decreasing trend globally except for East Asia and Pacific region. SDI, sex, age and geographic location contributed to the diversity of the CVD disease burden associated with low temperature worldwide. More attention should be given to the older adults, men, and low SDI regions.

BackgroundCarcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the predominant serum tumour markers (STMs) for predicting the prognosis of colorectal cancer (CRC). The objective of this research is to develop clinical prediction models based on preoperative and postoperative CEA and CA19-9 levels.Methods1,452 consecutive participants with stage I-III colorectal cancer were included. Kaplan-Meier method, log-rank test, and multivariate COX regression were used to evaluate the significance of preoperative and postoperative STMs. Patients were grouped into a discovery cohort (70%) and a validation cohort (30%). Variables for the nomograms were selected according to the Akaike information criterion (AIC). Subsequently, two clinical predictive models were constructed, evaluated, validated, and then compared with the AJCC 8th TNM stage.ResultsThe overall survival (OS) rate and disease-free survival(DFS) rate declined progressively as the number of positive tumour markers(NPTMs) before and after surgery increased. For both OS and DFS, age, sex, pN stage, and NPTMs before and after surgery were independent prognostic factors, and then clinical prediction models were developed. The Concordance index (C-index), Receiver operating characteristic (ROC) curve, calibration curve, Decision curve analysis (DCA), and risk score stratification all indicated that the models possessed robust predictive efficacy and clinical applicability. The Net reclassification index (NRI) and Integrated discrimination improvement (IDI) indicated that the performance of models was significantly superior to the TNM stage.ConclusionNomograms based on pre-and postoperative CEA and CA19-9 can accurately predict survival and recurrence for stage I-III CRC patients after radical surgery, and were significantly better than the AJCC 8th TNM stage.

Disinfection by-products (DBPs) generated from water treatment have serious adverse effects on human health and natural ecosystems. However, research on the mutagenicity of DBPs with different chemical structures is still limited. In the present study, we compared the mutagenicity of 8 typical DBPs in human-hamster hybrid (AL) cells and clarified the mechanisms involved. Our data displayed that the rank order for mutagenicity was as follows: iodoacetamide (IAcAm) > iodoacetonitrile (IAN) > iodoacetic acid (IAA) > bromoacetamide (BAcAm) ≈ bromoacetonitrile (BAN) > bromoacetic acid (BAA), which was confirmed by DNA double strand breaks and oxidative DNA damage. In contrast, bromoform (TBM) and iodoform (TIM) had minimal mutagenicity. The mutation spectrum analysis further revealed that IAN, IAcAm, and IAA could induce multilocus deletions in mammalian cells. Interestingly, nitrogenous DBPs (N-DBPs) and IAA were found to cause varying degrees of iron overload and lipid peroxidation, which was mediated by the activation of the Nrf2/HO-1 signaling pathway. Moreover, the presence of deferoxamine (DFO), an iron ion inhibitor, effectively reduced γ-H2AX and 8-OHdG induced by N-DBPs and IAA. These results indicated that the variations in genotoxicity among DBPs with different structures were associated with their ability to disrupt iron homeostasis. This study provided new insights into the mechanisms underlying the structure-dependent toxicity of DBPs and established a foundation for a more comprehensive understanding and intervention of the health risks associated with DBPs.

In the field of ophthalmology, orbital fat prolapse under the upper eyelid is less recognized than subconjunctival orbital fat prolapse. Despite its occasional occurrence in clinical practice, this condition is often inadequately understood and incorrectly classified due to its subtle manifestations and the limited number of focused studies. Typically affecting young patients, the prolapse is located subcutaneously in the mid-upper eyelid, resulting in a pseudo-occlusion. This study aims to investigate this specific ocular anomaly, we delineate the clinical presentations, surgical interventions, and differential diagnoses of this condition through three representative cases, proposing its classification as a distinct disease entity named Upper Eyelid Subcutaneous Orbital Fat Prolapse (UESOFP).

This paper studies how to integrate the smart charging of large-scale electric vehicles (EVs) into the generation and storage expansion planning (GSEP), while analyzing the impact of smart charging on the GSEP of a real power system in south China. For this purpose, a random simulation-based method is first developed to provide the tractable formulations of the adjustable charging load and reserve provision from EVs. This method avoids the unrealistic assumption that EVs drive and charge every day, which often exists in prior relevant approaches. Based on the random simulation, this paper proposes a novel GSEP optimization model which incorporates the weekly adjustable charging load of EVs. In the proposed model, the total charging load of EVs can be co-optimized with the investment and operational decisions of various generation and storage units. This GSEP model is applied to a provincial power system in south China. The numerical results show that the implementation of smart charging can significantly alter the decisions of GSEP. As the participation rate of smart charging improves from 0% to 90%, there is an additional 1,800 MW installation in wind and solar power, while the need to build new batteries is noticeably reduced; also, depending on the level of EV uptake, the annualized total system cost decreases by 5.11%–7.57%, and the curtailment of wind and solar power is reduced by 10.34%–19.64%. Besides, numerical tests reveal that the traditional assumption that EVs drive and charge every day can mislead the evaluation of adjustable charging load and overestimate the daily charging power peak by averagely 24.72%.

BackgroundCardiac lipid metabolism reprogramming is recognized as a critical pathological factor in the progression of chronic heart failure (CHF). The therapeutic potential of digilanid C and electroacupuncture stimulation (ES) in enhancing lipid metabolism and cardiac function has been established. However, the optimal synergistic regulatory strategies of these interventions on cardiac lipid metabolism have yet to be elucidated.MethodsThis study aimed to comprehensively evaluate the impact of a digilanid C-ES combination on cardiac steatosis remodeling in CHF. Assessments were conducted across various dimensions, including myocardial oxygen consumption, mitochondrial function, and lipid metabolism. Additionally, we sought to uncover the underlying neuromolecular mechanisms.ResultsOur findings, at both molecular and morphological levels, indicated that the synergistic application of digilanid C and ES significantly inhibited myocardial fibrosis and steatosis. This combination therapy facilitated the repair of cardiac neuro-vascular uncoupling and induced a reprogramming of lipid metabolism. Notably, the digilanid C-ES combination ameliorated cardiomyocyte apoptosis and enhanced mitochondrial biogenesis in CHF, leading to a restructured energy supply pattern. Cardiac immunofluorescence analyses revealed the aggregation of cardiac glial cells (CGCs) at sites of abnormal neurovascular coupling, a response to cardiac lipid degeneration. This was accompanied by a marked reduction in the abnormally elevated expression of interleukin 6 (IL-6) and glutamatergic signaling, which correlated with the severity of cardiac steatosis and the aberrant activation of CGCs. The combined therapy was found to activate the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) pathway, effectively attenuated lipid accumulation and over-recruitment of CGCs and deprivation of glutamatergic nerves.ConclusionThese findings underscore the potential of digilanid C and ES combination therapy as a novel approach to modulate the complex interplay between neurovascular dynamics and metabolic dysregulation in CHF.

ABSTRACT: Eggshell translucency is a widespread issue in the field of egg quality. Previous research has established that the heritability of eggshell translucency is relatively low or moderate. Scientists have also successfully identified SNP loci related to eggshell translucency on different chromosomes by using gene chips and single-variant GWAS. However, the specific impact of single or multiple genes on the trait of eggshell translucency remains unknown. In an effort to investigate this, we examined 170 SNPs associated with eggshell translucency obtained by our research group. We selected 966 half-sibling laying hens from 2 generations in 3 pure lines: Dwarf Layer-White, Rhode Island Red-White Strain, and Rhode Island Red. Eggs were collected from each hen over a period of 5 consecutive days, and eggshell translucency was measured using a grading method in which the hens were divided into 2 groups: an opaque group and a translucent group. We collected blood samples from the laying hens and extracted DNA. Time of flight mass spectrometry (TOF-MS) was used for genotyping to identify SNP loci that influence the trait of eggshell translucency. The results of our analysis revealed that using TOF-MS in 3 chicken strains, we were able to eliminate loci with low gene polymorphism, genetic effect contribution less than 1%, and deviation from Hardy-Weinberg equilibrium. Ultimately, 5 SNPs (Affx-50362599, rs15050262, rs312943734, rs316121113, and rs317389181) were identified on chromosomes 1, 5, and 19. Additionally, nine candidate genes (DCN, BTG1, ZFP92, POU2F1, NUCB2, FTL, GGNBP2, ACACA, and TADA2A) were found to be associated with these SNPs. No linkage disequilibrium relationship was observed between the 2 pairs of SNP loci on chromosomes 1 and 19. Based on previous studies on the formation mechanism of eggshell translucency, we hypothesize that NUCB2, FTL, and ACACA genes may be affecting the eggshell structure through different mechanisms, such as increase the water permeability or make thin of eggshell membrane, which promote moisture or part of other egg contents and ultimately lead to the formation of eggshell translucency. These findings validate and identify five SNP loci that regulate the translucency trait, and provide molecular markers for breeding non-translucent populations. Furthermore, this study serves as a reference for further investigation of the genetic regulatory mechanisms underlying eggshell translucency.