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Abstract Usutu virus (USUV), an arbovirus from the Flaviviridae family, genus Flavivirus, has recently gained increasing attention because of its potential for emergence. After his discovery in South Africa, USUV spread to other African countries, then emerged in Europe where it was responsible for epizootics. The virus has recently been found in Asia. USUV infection in humans is considered to be most often asymptomatic or to cause mild clinical signs. However, a few cases of neurological complications such as encephalitis or meningo-encephalitis have been reported in both immunocompromised and immunocompetent patients. USUV natural life cycle involves Culex mosquitoes as its main vector, and multiple bird species as natural viral reservoirs or amplifying hosts, humans and horses can be incidental hosts. Phylogenetic studies carried out showed eight lineages, showing an increasing genetic diversity for USUV. This work describes the development and validation of a novel whole-genome amplicon-based sequencing approach to Usutu virus. This study was carried out on different strains from Senegal and Italy. The new approach showed good coverage using samples derived from several vertebrate hosts and may be valuable for Usutu virus genomic surveillance to better understand the dynamics of evolution and transmission of the virus.

Abstract Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19 +/− HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Abstract Background Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear. Methods Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated. Results Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary. Conclusions Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.

Abstract The long noncoding RNA (lncRNA)/Wingless (Wnt) axis is often dysregulated in digestive system tumors impacting critical cellular processes. Abnormal expression of specific Wnt-related lncRNAs such as LINC01606 (promotes motility), SLCO4A1-AS1 (promotes motility), and SH3BP5-AS1 (induces chemoresistance), plays a crucial role in these malignancies. These lncRNAs are promising targets for cancer diagnosis and therapy, offering new treatment perspectives. The lncRNAs, NEF and GASL1, differentially expressed in plasma show diagnostic potential for esophageal squamous cell carcinoma and gastric cancer, respectively. Additionally, Wnt pathway inhibitors like XAV-939 have demonstrated preclinical efficacy, underscoring their therapeutic potential. This review comprehensively analyzes the lncRNA/Wnt axis, highlighting its impact on cell proliferation, motility, and chemoresistance. By elucidating the complex molecular mechanisms of the lncRNA/Wnt axis, we aim to identify potential therapeutic targets for digestive system tumors to pave the way for the development of targeted treatment strategies.

Abstract Background NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. Methods Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. Results Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P

Abstract Background Hepatocellular carcinoma (HCC), a prevalent primary malignant tumor, is notorious for its high mortality rate. Despite advancements in HCC treatment, patient outcomes remain suboptimal. This study endeavors to assess the potential prognostic significance of POLH-AS1 in HCC. Methods In this research, we gathered RNA-Seq information from individuals with HCC in The Cancer Genome Atlas (TCGA). We analyzed the levels of POLH-AS1 expression in both HCC cells and tissues using statistical tests. Additionally, we examined various prognostic factors in HCC using advanced methodologies. Furthermore, we employed Spearman’s rank correlation analysis to examine the association between POLH-AS1 expression and the tumor’s immune microenvironment. Finally, the functional roles of POLH-AS1 in HCC were validated in two HCC cell lines (HEP3B and HEPG2). Results Our analysis revealed elevated POLH-AS1 expression across various cancers, including HCC, with heightened expression correlating with HCC progression. Notably, POLH-AS1 expression emerged as a potential biomarker for HCC patient survival and prognosis. Mechanistically, we identified the involvement of POLH-AS1 in tumorigenesis pathways such as herpes simplex virus 1 infection, interactions with neuroactive receptors, and the cAMP signaling pathway. Lastly, inhibition of POLH-AS1 was discovered to hinder the proliferation, invasion and migration of HEP3B and HEPG2 HCC cells. Conclusions POLH-AS1 emerges as a promising prognostic biomarker and therapeutic target for HCC, offering potential avenues for enhanced patient management and treatment strategies.

Abstract Probabilistic machine learning utilizes controllable sources of randomness to encode uncertainty and enable statistical modeling. Harnessing the pure randomness of quantum vacuum noise, which stems from fluctuating electromagnetic fields, has shown promise for high speed and energy-efficient stochastic photonic elements. Nevertheless, photonic computing hardware which can control these stochastic elements to program probabilistic machine learning algorithms has been limited. Here, we implement a photonic probabilistic computer consisting of a controllable stochastic photonic element – a photonic probabilistic neuron (PPN). Our PPN is implemented in a bistable optical parametric oscillator (OPO) with vacuum-level injected bias fields. We then program a measurement-and-feedback loop for time-multiplexed PPNs with electronic processors (FPGA or GPU) to solve certain probabilistic machine learning tasks. We showcase probabilistic inference and image generation of MNIST-handwritten digits, which are representative examples of discriminative and generative models. In both implementations, quantum vacuum noise is used as a random seed to encode classification uncertainty or probabilistic generation of samples. In addition, we propose a path towards an all-optical probabilistic computing platform, with an estimated sampling rate of ~1 Gbps and energy consumption of ~5 fJ/MAC. Our work paves the way for scalable, ultrafast, and energy-efficient probabilistic machine learning hardware.

Abstract Thermoelectrics converting heat and electricity directly attract broad attentions. To enhance the thermoelectric figure of merit, zT, one of the key points is to decouple the carrier-phonon transport. Here, we propose an entropy engineering strategy to realize the carrier-phonon decoupling in the typical SrTiO3-based perovskite thermoelectrics. By high-entropy design, the lattice thermal conductivity could be reduced nearly to the amorphous limit, 1.25 W m−1 K−1. Simultaneously, entropy engineering can tune the Ti displacement, improving the weighted mobility to 65 cm2 V−1 s−1. Such carrier-phonon decoupling behaviors enable the greatly enhanced μ W/κ L of ~5.2 × 103 cm3 K J−1 V−1. The measured maximum zT of 0.24 at 488 K and the estimated zT of ~0.8 at 1173 K in (Sr0.2Ba0.2Ca0.2Pb0.2La0.2)TiO3 film are among the best of n-type thermoelectric oxides. These results reveal that the entropy engineering may be a promising strategy to decouple the carrier-phonon transport and achieve higher zT in thermoelectrics.

Abstract To assess the efficacy of a novel 3D biomimetic hydrogel scaffold with immunomodulatory properties in promoting fracture healing. Immunomodulatory scaffolds were used in cell experiments, osteotomy mice treatment, and single-cell transcriptomic sequencing. In vitro, fluorescence tracing examined macrophage mitochondrial transfer and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Scaffold efficacy was assessed through alkaline phosphatase (ALP), Alizarin Red S (ARS) staining, and in vivo experiments. The scaffold demonstrated excellent biocompatibility and antioxidant-immune regulation. Single-cell sequencing revealed a shift in macrophage distribution towards the M2 phenotype. In vitro experiments showed that macrophage mitochondria promoted BMSCs’ osteogenic differentiation. In vivo experiments confirmed accelerated fracture healing. The GAD/Ag-pIO scaffold enhances osteogenic differentiation and fracture healing through immunomodulation and promotion of macrophage mitochondrial transfer.

Objective: To develop a deep learning model to predict lymph node (LN) status in clinical stage IA lung adenocarcinoma patients. Methods: This diagnostic study included 1,009 patients with pathologically confirmed clinical stage T1N0M0 lung adenocarcinoma from two independent datasets (699 from Cancer Hospital of Chinese Academy of Medical Sciences and 310 from PLA General Hospital) between January 2005 and December 2019. The Cancer Hospital dataset was randomly split into a training cohort (559 patients) and a validation cohort (140 patients) to train and tune a deep learning model based on a deep residual network (ResNet). The PLA Hospital dataset was used as a testing cohort to evaluate the generalization ability of the model. Thoracic radiologists manually segmented tumors and interpreted high-resolution computed tomography (HRCT) features for the model. The predictive performance was assessed by area under the curves (AUCs), accuracy, precision, recall, and F1 score. Subgroup analysis was performed to evaluate the potential bias of the study population. Results: A total of 1,009 patients were included in this study; 409 (40.5%) were male and 600 (59.5%) were female. The median age was 57.0 years (inter-quartile range, IQR: 50.0–64.0). The deep learning model achieved AUCs of 0.906 (95% CI: 0.873–0.938) and 0.893 (95% CI: 0.857–0.930) for predicting pN0 disease in the testing cohort and a non-pure ground glass nodule (non-pGGN) testing cohort, respectively. No significant difference was detected between the testing cohort and the non-pGGN testing cohort (P = 0.622). The precisions of this model for predicting pN0 disease were 0.979 (95% CI: 0.963–0.995) and 0.983 (95% CI: 0.967–0.998) in the testing cohort and the non-pGGN testing cohort, respectively. The deep learning model achieved AUCs of 0.848 (95% CI: 0.798–0.898) and 0.831 (95% CI: 0.776–0.887) for predicting pN2 disease in the testing cohort and the non-pGGN testing cohort, respectively. No significant difference was detected between the testing cohort and the non-pGGN testing cohort (P = 0.657). The recalls of this model for predicting pN2 disease were 0.903 (95% CI: 0.870–0.936) and 0.931 (95% CI: 0.901–0.961) in the testing cohort and the non-pGGN testing cohort, respectively. Conclusions: The superior performance of the deep learning model will help to target the extension of lymph node dissection and reduce the ineffective lymph node dissection in early-stage lung adenocarcinoma patients.

Objective: To analyze the impact of global population aging on cancer epidemiology, with a focus on the incidence and mortality rates among individuals aged 60 years and above. Methods: We utilized open-source data, retrieving population age estimates from the United Nations Population Division website. The GLOBOCAN 2020 database provided estimates for cancer cases and deaths in 2020 and 2040, while the Global Burden of Disease 2019 database supplied estimates of new cancer cases worldwide from 2000 to 2019. Inclusion criteria considered individuals aged 60 years and over, focusing on the top five deadliest cancers. The cohort-component method was employed for population prediction, with age-specific incidence and mortality rates estimated for 2020 used to forecast the cancer burden. Results: In 2021, the global population aged over 60 years accounted for 13.7%, with Europe/North America and Australia/New Zealand having the highest proportions. The older population is predicted to reach 19.2% by 2040. In 2020, of the 19.3 million new cancer cases worldwide, 64% occurred in individuals aged 60 and above, contributing to 71.3% of cancer-related deaths. The five most common cancer sites were the lung, colorectum, prostate, breast, and stomach. Cancer incidence and deaths are projected to rise significantly among older individuals, reaching 20.7 million new cases and 12.7 million deaths by 2040. Older age, tobacco use, dietary factors, alcohol consumption, and high body mass index (BMI) were identified as major risk factors for various cancers in this demographic. Conclusions: This study reveals a significant rise in cancer incidence and mortality among the elderly due to global population aging. The urgency for targeted interventions in cancer prevention, screening, and treatment for older individuals is emphasized. Despite acknowledged limitations, these findings contribute valuable insights to inform strategies for managing cancer in the elderly amidst evolving demographic trends.

AIM: To develop a deep learning-based model for automatic retinal vascular segmentation, analyzing and comparing parameters under diverse glucose metabolic status (normal, prediabetes, diabetes) and to assess the potential of artificial intelligence (AI) in image segmentation and retinal vascular parameters for predicting prediabetes and diabetes. METHODS: Retinal fundus photos from 200 normal individuals, 200 prediabetic patients, and 200 diabetic patients (600 eyes in total) were used. The U-Net network served as the foundational architecture for retinal artery-vein segmentation. An automatic segmentation and evaluation system for retinal vascular parameters was trained, encompassing 26 parameters. RESULTS: Significant differences were found in retinal vascular parameters across normal, prediabetes, and diabetes groups, including artery diameter (P=0.008), fractal dimension (P=0.000), vein curvature (P=0.003), C-zone artery branching vessel count (P=0.049), C-zone vein branching vessel count (P=0.041), artery branching angle (P=0.005), vein branching angle (P=0.001), artery angle asymmetry degree (P=0.003), vessel length density (P=0.000), and vessel area density (P=0.000), totaling 10 parameters. CONCLUSION: The deep learning-based model facilitates retinal vascular parameter identification and quantification, revealing significant differences. These parameters exhibit potential as biomarkers for prediabetes and diabetes.

Introduction: Cardiac hypertrophy is an important contributor of heart failure, and the mechanisms remain unclear. Leucine zipper protein 1 (LUZP1) is essential for the development and function of cardiovascular system; however, its role in cardiac hypertrophy is elusive. Objectives: This study aims to investigate the molecular basis of LUZP1 in cardiac hypertrophy and to provide a rational therapeutic approach. Methods: Cardiac-specific Luzp1 knockout (cKO) and transgenic mice were established, and transverse aortic constriction (TAC) was used to induce pressure overload-induced cardiac hypertrophy. The possible molecular basis of LUZP1 in regulating cardiac hypertrophy was determined by transcriptome analysis. Neonatal rat cardiomyocytes were cultured to elucidate the role and mechanism of LUZP1 in vitro. Results: LUZP1 expression was progressively increased in hypertrophic hearts after TAC surgery. Gain- and loss-of-function methods revealed that cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated pressure overload-elicited hypertrophic growth and cardiac dysfunction in vivo and in vitro. Mechanistically, the transcriptome data identified Stat3 pathway as a key downstream target of LUZP1 in regulating pathological cardiac hypertrophy. Cardiac-specific Stat3 deletion abolished the pro-hypertrophic role in LUZP1 cKO mice after TAC surgery. Further findings suggested that LUZP1 elevated the expression of Src homology region 2 domain-containing phosphatase 1 (SHP1) to inactivate Stat3 pathway, and SHP1 silence blocked the anti-hypertrophic effects of LUZP1 in vivo and in vitro. Conclusion: We demonstrate that LUZP1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling, and targeting LUZP1 may develop novel approaches to treat pathological cardiac hypertrophy.

ABSTRACT: Lactococcus lactis, widely used in the manufacture of dairy products, encounters various environmental stresses both in natural habitats and during industrial processes. It has evolved intricate machinery of stress sensing and defense to survive harsh stress conditions. Here, we identified a novel TetR/AcrR family transcription regulator, designated AcrR1, to be a repressor for acid and antibiotic tolerance that was derepressed in the presence of vancomycin or under acid stress. The survival rates of acrR1 deletion strain ΔAcrR1 under acid and vancomycin stresses were about 28.7-fold (pH 3.0, HCl), 8.57-fold (pH 4.0, lactic acid) and 2.73-fold (300 ng/mL vancomycin) greater than that of original strain F44. We also demonstrated that ΔAcrR1 was better able to maintain intracellular pH homeostasis and had a lower affinity to vancomycin. No evident effects of AcrR1 deletion on the growth and morphology of strain F44 were observed. Subsequently, we characterized that the transcription level of genes associated with amino acids biosynthesis, carbohydrate transport and metabolism, multidrug resistance, and DNA repair proteins significantly upregulated in ΔAcrR1 using transcriptome analysis and quantitative reverse transcription-PCR assays. Additionally, AcrR1 could repress the transcription of the nisin post-translational modification gene, nisC, leading to a 16.3% increase in nisin yield after AcrR1 deletion. Our results not only refined the knowledge of the regulatory mechanism of TetR/AcrR family regulator in L. lactis, but presented a potential strategy to enhance industrial production of nisin.

The high temperature oxidation behavior of Fe–36Ni Invar alloy in the forged billet stage and hot rolled rod stage in the compressed air atmosphere has been systematically studied. The results show that the oxide layer can be divided into the external oxide layer composed of Fe2O3, Fe3O4 and NiO, and the inner transition oxide layer composed of FeO, Fe2O3, Fe3O4 and NiO. In addition, hot rolled rod samples treated by solution and rolling have higher oxidation resistance. The mechanism of O diffusion during oxidation is analyzed, and it is found that the O atom adsorbed on the surface of the substrate diffuses into the grain along the grain boundary. The grain boundary is the optimal path for O diffusion to the interior of the material, which results in the degree of intergranular oxidation of the alloy being greater than the degree of intragranular oxidation. In summary, the oxidation resistance of Invar alloy can be improved by proper solution treatment and avoiding the formation of grain boundary cracks during production.

Objective: This article aimed to analyze the computed tomography (CT) imaging manifestations and clinical significance of scimitar syndrome to improve our understanding of the disease. Method: A total of 28 patients diagnosed with scimitar syndrome were enrolled in our hospital from January 2019 to January 2024, and their clinical and imaging data were retrospectively analyzed. Results: Among the 28 cases, there were 10 males and 18 females, with 15 and 13 cases of the infantile and adult types, respectively. The average age of patients with the infant type were (6.78±3.50) months, with 10 cases having total anomalous right pulmonary venous drainage. Among them, three cases had stenosis and obstruction at the site of ectopic drainage and two cases had concomitant atrial septal defect and pulmonary arterial hypertension; these five cases underwent surgical treatment. Five cases of partial anomalous right pulmonary venous drainage to the inferior vena cava were found during imaging examination owing to the presence of other deformities and pulmonary infections. The average age of patients with the adult type was (5.53±2.72) years old. Seven cases had total anomalous right pulmonary venous drainage to the inferior vena cava, with one case undergoing surgical treatment. Six cases had ectopic drainage from the right lower pulmonary vein to the inferior vena cava: two underwent elective surgery owing to a clear diagnosis for many years, and two underwent interventional treatment for systemic arterial blood supply owing to extralobar sequestration. Conclusion: There were significant differences in clinical manifestation between patients with infantile and adult types of scimitar syndrome. Using multiple imaging modes of CT examination combined with powerful reconstruction post-processing functions, children with scimitar syndrome can be evaluated comprehensively, providing a basis for the selection of clinical treatment methods and surgical plans.

Liver regeneration (LR) is a complex process encompassing three distinct phases: priming, proliferation phase and restoration, all influenced by various regulatory factors. After liver damage or partial resection, the liver tissue demonstrates remarkable restorative capacity, driven by cellular proliferation and repair mechanisms. The essential roles of non-coding RNAs (ncRNAs), predominantly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNA (circRNA), in regulating LR have been vastly studied. Additionally, the impact of ncRNAs on LR and their abnormal expression profiles during this process have been extensively documented. Mechanistic investigations have revealed that ncRNAs interact with genes involved in proliferation to regulate hepatocyte proliferation, apoptosis and differentiation, along with liver progenitor cell proliferation and migration. Given the significant role of ncRNAs in LR, an in-depth exploration of their involvement in the liver's self-repair capacity can reveal promising therapeutic strategies for LR and liver-related diseases. Moreover, understanding the unique regenerative potential of the adult liver and the mechanisms and regulatory factors of ncRNAs in LR are crucial for improving current treatment strategies and exploring new therapeutic approaches for various liver-related diseases. This review provides a brief overview of the LR process and the ncRNA expression profiles during this process. Furthermore, we also elaborate on the specific molecular mechanisms through which multiple key ncRNAs regulate the LR process. Finally, based on the expression characteristics of ncRNAs and their interactions with proliferation-associated genes, we explore their potential clinical application, such as developing predictive indicators reflecting liver regenerative activity and manipulating LR processes for therapeutic purposes.

Climate change has led to an increasing frequency and intensity of extreme climate events such as heat and drought extremes with considerable global public health burden. This systematic review collected 87 domestic and international studies from 2000 to 2023, considering the impacts of heat extremes, drought extremes, and compound hot-dry events on infectious diseases attributable to various transmission pathways such as waterborne, foodborne, insect-borne, airborne, and contact-transmitted diseases. Our results showed that high temperature was associated with increased transmission risks of waterborne and foodborne diseases including infectious diarrheal diseases (cholera, dysentery, typhoid, and paratyphoid) and infectious gastroenteritis; vector-borne diseases including dengue fever, Zika virus (ZIKV) disease, chikungunya fever, malaria, West Nile fever, and Rift Valley fever; airborne diseases including influenza-like diseases, influenza A, measles, and mumps; and contact-transmitted diseases including HIV/AIDS, schistosomiasis, and leptospirosis. Additionally, drought conditions also amplified the transmission risks of waterborne and foodborne diseases including cholera, Escherichia coli infection, rotavirus infection, and hepatitis E; vector-borne diseases such as scrub typhus, schistosomiasis, hemorrhagic fever with renal syndrome, and West Nile fever; airborne diseases including meningococcal meningitis, pertussis, measles, and upper respiratory infections; and contact-transmitted diseases such as HIV/AIDS. Along with global warming, the frequency of compound high temperature and drought events shows a considerably increasing trend, causing more adverse health effects than heat or drought alone. However, there is limited research quantifying their effects on infectious diseases. These associations may be mediated through temperature and precipitation on infectious disease pathogens, transmission vectors, population susceptibility, public health services, and behaviors. In the context of climate change, the increasing occurrence of compound events of high temperatures and droughts raises health concerns, and further studies are needed to enhance our understanding of the impacts of climate change on infectious diseases and improve human adaption to climate change.

Abstract The electromagnetic form factors G E and G M of the proton and neutron in the timelike region are extracted in a study of the processes e + e − → p ¯ p $$ \overline{p}p $$ and e + e − → n ¯ n $$ \overline{n}n $$ . The reaction amplitude is evaluated within the distorted wave Born approximation, with the interaction of the antinucleon-nucleon N ¯ N $$ \left(\overline{N}N\right) $$ pair taken into account. The latter is constructed within SU(3) chiral effective field theory up to next-to-leading order. An excellent description of the e + e − → N ¯ N $$ \overline{N}N $$ data in the energy region from the N ¯ N $$ \overline{N}N $$ threshold up to center-of-mass energies E cm = 2.2 GeV is achieved. Results for the electromagnetic form factors G E, G M, G E/G M, and the subtracted effective form factors, G osc, are provided. These can be helpful for further studies of the properties of the nucleons.

Abstract Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing to this resistance is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing. These modifications are pivotal in regulating RNA splicing, translation, transport, degradation, and stability. Governed by “writers,” “readers,” and “erasers,” RNA modifications impact numerous biological processes and cancer progression, including cell proliferation, stemness, autophagy, invasion, and apoptosis. Aberrant RNA modifications can lead to drug resistance and adverse outcomes in various cancers. Thus, targeting RNA modification regulators offers a promising strategy for overcoming drug resistance and enhancing treatment efficacy. This review consolidates recent research on the role of prevalent RNA modifications in cancer drug resistance, with a focus on m6A, m1A, m5C, m7G, Ψ, and A-to-I editing. Additionally, it examines the regulatory mechanisms of RNA modifications linked to drug resistance in cancer and underscores the existing limitations in this field.

Abstract This study aims to analyze the risk factors associated with delayed postoperative bleeding (DPPB) following colorectal polyp surgery, develop a dynamic nomogram and evaluate the model efficacy, provide a reference for clinicians to identify the patients at high risk of DPPB. Retrospective study was done on patients who underwent endoscopic colorectal polypectomy at the First Hospital of Lanzhou University from January 2020 to March 2023. Differences between the group with and without DPPB were compared, and independent risk factors for DPPB occurrence were identified through univariate analysis and combination LASSO and logistic regression. A dynamic nomogram was constructed based on multiple logistic regression to predict DPPB following colorectal polyp surgery. Model evaluation included receiver operating characteristic (ROC), Calibration curve, Decision curve analysis (DCA). DPPB occurred in 38 of the 1544 patients included. multivariate analysis showed that direct oral anticoagulants (DOACs), polyp location in the right hemi colon, polyp diameter, drink, and prophylactic hemoclips were the independent risk factors for DPPB and dynamic nomogram were established. Model validation indicated area under the ROC curve values of 0.936, 0.796, and 0.865 for the training set, validation set, and full set, respectively. The calibration curve demonstrated a strong alignment between the predictions of the column-line diagram model and actual observations. The decision curve analysis (DCA) displayed a significant net clinical benefit across the threshold probability range of 0–100%. The dynamic nomogram aids clinicians in identifying high-risk patients, enabling personalized diagnosis and treatment.

Abstract To date, the types of fuels used in pottery kilns during the Western Zhou Dynasty have not been adequately addressed. Samples from updraft kilns and semi-downdraft kilns at the Fengjing site, the capital in the late Western Zhou period, were selected for analysis. Through phytolith and wood charcoal analysis, various grasses mainly Panicoideae, Pooideae, and Eragrostidoideae, as well as millet, rice, and wheat crops were identified. Additionally, wood primarily from trees of the Quercus, Ulmus, and Liquidambar taxa was found. These findings suggest that different pottery kilns used similar fuels, demonstrating a broad-spectrum rather than specialized fuel utilization during the Zhou period.

Abstract In van der Waals heterostructures (vdWHs), the manipulation of interlayer stacking/coupling allows for the construction of customizable quantum systems exhibiting exotic physics. An illustrative example is the diverse range of states of matter achieved through varying the proximity coupling between two-dimensional (2D) quantum spin liquid (QSL) and superconductors within the TaS2 family. This study presents a demonstration of the intertwined physics of spontaneous rotational symmetry breaking, hidden magnetism, and Ising superconductivity (SC) in the three-fold rotationally symmetric, non-magnetic natural vdWHs 6R-TaS2. A distinctive phase emerges in 6R-TaS2 below a characteristic temperature (T *) of approximately 30 K, which is characterized by a remarkable set of features, including a giant extrinsic anomalous Hall effect (AHE), Kondo screening, magnetic field-tunable thermal hysteresis, and nematic magneto-resistance. At lower temperatures, a coexistence of nematicity and Kondo screening with Ising superconductivity is observed, providing compelling evidence of hidden magnetism within a superconductor. This research not only sheds light on unexpected emergent physics resulting from the coupling of itinerant electrons and localized/correlated electrons in natural vdWHs but also emphasizes the potential for tailoring exotic quantum states through the manipulation of interlayer interactions.

Abstract Significant research progress has been made in the field of protein structure and fitness prediction. Particularly, single-sequence-based structure prediction methods like ESMFold and OmegaFold achieve a balance between inference speed and prediction accuracy, showing promise for many downstream prediction tasks. Here, we propose SPIRED, a single-sequence-based structure prediction model that exhibits comparable performance to the state-of-the-art methods but with approximately 5-fold acceleration in inference and at least one order of magnitude reduction in training consumption. By integrating SPIRED with downstream neural networks, we compose an end-to-end framework named SPIRED-Fitness for the rapid prediction of both protein structure and fitness from single sequence with satisfactory accuracy. Moreover, SPIRED-Stab, the derivative of SPIRED-Fitness, achieves state-of-the-art performance in predicting the mutational effects on protein stability.

Abstract Background Diabetes mellitus (DM) and Helicobacter pylori infection (HPI) pose increasing public health challenges in aging societies, sharing common pathophysiological mechanisms, and linked to significant health risks. Our study examines their respective impacts on all-cause and cardiovascular mortalities in a comprehensive longitudinal population-based analysis. Methods The study analyzed data from the National Health and Nutrition Examination Survey (NHANES) database conducted between 1999 and 2019, which included information on Diabetes mellitus status and Helicobacter pylori infection status. Mortality data were obtained from the same database mentioned above. Results Among the 2719 participants, 1362 (50.1%) were free of both diabetes mellitus (DM) and Helicobacter pylori infection (HP) (DM −/HP −), 140 (5.1%) had DM alone (DM +/HP −), 1011 (37.2%) had HP alone (DM −/HP +), and 206 (7.6%) had both DM and HP (DM +/HP +). Compared to the DM −/HP − group, the DM +/HP − and DM + /HP + groups demonstrated increased all-cause mortality with adjusted hazard ratios (HRs) of 1.40 (95% [CI] 1.07–1.78) and 1.46 (95% CI 1.15–1.84), respectively. For diabetic mortality, DM +/HP– group and DM + /HP + group showed increased HR of 6.30 (95% CI 1.30–30.43) and 8.56 (95% CI 1.98–36.94), respectively. For cardiovascular mortality, the DM + /HP– group and DM + /HP + group exhibited increased HR of 1.75 (95% CI 1.14–2.69) and 1.98 (95% CI 1.40–2.79), respectively. The DM + /HP + cohort displayed the highest risk of overall mortality (p for trend = 0.003), diabetic mortality (p for trend

Abstract Background Ovarian cancer (OC) is the predominant primary tumor in the human reproductive system. Abnormal sialylation has a significant impact on tumor development, metastasis, immune evasion, angiogenesis, and treatment resistance. B4GALT5, a gene associated with sialylation, plays a crucial role in ovarian cancer, and may potentially affect clinicopathological characteristics and prognosis. Methods We conducted a comprehensive search across TIMER, GEPIA2, GeneMANIA, and Metascape to obtain transcription profiling data of ovarian cancer from The Cancer Genome Atlas (TCGA). The expression of B4GALT5 was test by immunohistochemistry. To investigate the impact of B4GALT5 on growth and programmed cell death in OC cells, we performed transwell assays and western blots. Results The presence of B4GALT5 was strongly associated with an unfavorable outcome in OC. B4GALT5 significantly promoted the proliferation of OC cells. Upon analyzing gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), it was discovered that B4GALT5 played a crucial role in the extracellular matrix, particularly in collagen-containing structures, and exhibited correlations with ECM-receptor interactions, transcriptional dysregulation in cancer, as well as the interleukin-1 receptor signaling pathway. Furthermore, there is a clear link between B4GALT5 and the tumor immune microenvironment in OC. Moreover, B4GALT5 exhibits favorable expression levels across various types of cancers, including CHOL, KIRC, STAD and UCES. Conclusion In conclusion, it is widely believed that B4GALT5 plays a pivotal role in the growth and progression of OC, with its heightened expression serving as an indicator of unfavorable outcomes. Moreover, B4GALT5 actively participates in shaping the cancer immune microenvironment within OC. This investigation has the potential to contribute significantly to a deeper understanding of the substantial involvement of B4GALT5 in human malignancies, particularly OCs.

Abstract Background Casein kinase 1α (CK1α), expressed in both ovarian germ and somatic cells, is involved in the initial meiosis and primordial follicle formation of mouse oocytes. Using in vitro and in vivo experiments in this study, we explored the function and mechanism of CK1α in estrogen synthesis in mice ovarian granulosa cells. Methods A CK1α knockout (cKO) mouse model, targeted specifically to ovarian granulosa cells (GCs), was employed to establish the influence of CK1α on in vivo estrogen synthesis. The influence of CK1α deficiency on GCs was determined in vivo and in vitro by immunofluorescence analysis and Western blot assay. Transcriptome profiling, differentially expressed genes and gene functional enrichment analyses, and computation protein–protein docking, were further employed to assess the CK1α pathway. Furthermore, wild-type female mice were treated with the CK1α antagonist D4476 to elucidate the CK1α's role in estrogen regulation. Results Ovarian GCs CK1α deficiency impaired fertility and superovulation of female mice; also, the average litter size and the estradiol (E2) level in the serum of cKO female mice were decreased by 57.3% and 87.4% vs. control mice, respectively. This deficiency disrupted the estrous cycle and enhanced the apoptosis in the GCs. We observed that CK1α mediated the secretion of estradiol in mouse ovarian GCs via the cytochrome P450 subfamily 19 member 1 (CYP19A1). Conclusions These findings improve the existing understanding of the regulation mechanism of female reproduction and estrogen synthesis. Trial registration Not applicable.

Abstract Drought is a major abiotic stress affecting crop yields. Mapping quantitative trait loci (QTLs) and mining genes for drought tolerance in rice are important for identifying gene functions and targets for molecular breeding. Here, we performed linkage analysis of drought tolerance using a recombinant inbred line population derived from Jileng 1 (drought sensitive) and Milyang 23 (drought tolerant). An ultra-high-density genetic map, previously constructed by our research team using genotype data from whole-genome sequencing, was used in combination with phenotypic data for rice grown under drought stress conditions in the field in 2017–2019. Thirty-nine QTLs related to leaf rolling index and leaf withering degree were identified, and QTLs were found on all chromosomes except chromosomes 6, 10, and 11. qLWD4-1 was detected after 32 days and 46 days of drought stress in 2017 and explained 7.07–8.19% of the phenotypic variation. Two loci, qLRI2-2 and qLWD4-2, were identified after 29, 42, and 57 days of drought stress in 2018. These loci explained 10.59–17.04% and 5.14–5.71% of the phenotypic variation, respectively. There were 281 genes within the QTL interval. Through gene functional annotation and expression analysis, two candidate genes, Os04g0574600 and OsCHR731, were found. Quantitative reverse transcription PCR analysis showed that the expression levels of these genes were significantly higher under drought stress than under normal conditions, indicating positive regulation. Notably, Os04g0574600 was a newly discovered drought tolerance gene. Haplotype analysis showed that the RIL population carried two haplotypes (Hap1 and Hap2) of both genes. Lines carrying Hap2 exhibited significantly or extremely stronger drought tolerance than those carrying Hap1, indicating that Hap2 is an excellent haplotype. Among rice germplasm resources, there were two and three haplotypes of Os04g0574600 and OsCHR731, respectively. A high proportion of local rice resources in Sichuan, Yunnan, Anhui, Guangdong and Fujian provinces had Hap of both genes. In wild rice, 50% of accessions contained Hap1 of Os04g0574600 and 50% carried Hap4; 13.51%, 59.46% and 27.03% of wild rice accessions contained Hap1, Hap2, and Hap3, respectively. Hap2 of Os04g0574600 was found in more indica rice resources than in japonica rice. Therefore, Hap2 has more potential for utilization in future drought tolerance breeding of japonica rice.

Abstract Lymph node metastasis (LNM) is a common invasive feature of hepatocellular carcinoma (HCC) associated with poor clinical outcomes. Through microarray profiling and bioinformatic analyses, we identified the circ-0044539-miR-29a-3p-VEGFA axis as a potential key factor in the progression of HCC LNM. In HCC cells and nude mice, circ-0044539 downregulation or miR-29a-3p upregulation was associated with small tumor size, PI3K-AKT-mTOR pathway inactivation, and downregulation of the key LNM factors (HIF-1α and CXCR4). Furthermore, circ-0044539 was also responsible for exosomal miR-29a-3p secretion. Exosomal miR-29a-3p was then observed to migrate to the LNs and downregulate High-mobility group box transcription factor 1 (Hbp1) in Polymorphonuclear Myeloid-derived suppressor cells (PMN-MDSCs), inducing the formation of a microenvironment suitable for tumor colonization. Overall, circ-0044539 promotes HCC cell LNM abilities and induces an immune-suppressive environment in LNs through exosomes, highlighting its potential as a target for HCC LNM and HCC immunotherapy.

Abstract Background The impact of weather on human health has been proven, but the impact of extreme weather events on cardiometabolic multimorbidity (CMM) needs to be urgently explored. Objectives Investigating the impact of extreme temperature, relative humidity (RH), and laboratory testing parameters at admission on adverse events in CMM hospitalizations. Designs Time-stratified case-crossover design. Methods A distributional lag nonlinear model with a time-stratified case-crossover design was used to explore the nonlinear lagged association between environmental factors and CMM. Subsequently, unbalanced data were processed by 1:2 propensity score matching (PSM) and conditional logistic regression was employed to analyze the association between laboratory indicators and unplanned readmissions for CMM. Finally, the previously identified environmental factors and relevant laboratory indicators were incorporated into different machine learning models to predict the risk of unplanned readmission for CMM. Results There are nonlinear associations and hysteresis effects between temperature, RH and hospital admissions for a variety of CMM. In addition, the risk of admission is higher under low temperature and high RH conditions with the addition of particulate matter (PM, PM2.5 and PM10) and O3_8h. The risk is greater for females and adults aged 65 and older. Compared with first quartile (Q1), the fourth quartile (Q4) had a higher association between serum calcium (HR = 1.3632, 95% CI: 1.0732 ~ 1.7334), serum creatinine (HR = 1.7987, 95% CI: 1.3528 ~ 2.3958), fasting plasma glucose (HR = 1.2579, 95% CI: 1.0839 ~ 1.4770), aspartate aminotransferase/ alanine aminotransferase ratio (HR = 2.3131, 95% CI: 1.9844 ~ 2.6418), alanine aminotransferase (HR = 1.7687, 95% CI: 1.2388 ~ 2.2986), and gamma-glutamyltransferase (HR = 1.4951, 95% CI: 1.2551 ~ 1.7351) were independently and positively associated with unplanned readmission for CMM. However, serum total bilirubin and High-Density Lipoprotein (HDL) showed negative correlations. After incorporating environmental factors and their lagged terms, eXtreme Gradient Boosting (XGBoost) demonstrated a more prominent predictive performance for unplanned readmission of CMM patients, with an average area under the receiver operating characteristic curve (AUC) of 0.767 (95% CI:0.7486 ~ 0.7854). Conclusions Extreme cold or wet weather is linked to worsened adverse health effects in female patients with CMM and in individuals aged 65 years and older. Moreover, meteorologic factors and environmental pollutants may elevate the likelihood of unplanned readmissions for CMM.

Abstract Background The encystation of Acanthamoeba castellanii has important ecological and medical significance. Blocking encystation is the key to preventing transmission and curing infections caused by A. castellanii. The formation of autophagosomes is one of the most important changes that occur during the encystation of Acanthamoeba. Our previous studies have shown that the heat shock protein 20 of A. castellanii (Ac-HSP20) is involved in its encystation. This study aimed to determine the role and mechanism of Ac-HSP20 in regulating autophagy involved in the encystation of A. castellanii. Methods Immunofluorescence assay, western blotting and transmission electron microscopy were used to analyze the dynamic changes in autophagy during the initiation and continuation of encystation. The knockdown of Ac-HSP20 was performed to clarify its regulation of encystation and autophagy and to elucidate the molecular mechanism by which Ac-HSP20 participates in autophagy to promote cyst maturation. Results The encystation rates and autophagosomes were significantly decreased by treatment with the autophagy inhibitor 3-MA. The autophagy marker LC3B and autophagic lysosomes increased with the induced duration of encystation and reached the maximum at 48 h. The encystation rate, LC3B expression and autophagosomes decreased when Ac-HSP20 was knocked down by siRNA transfection. In addition, the expression levels of Ac-HSP20 and LC3B increased and the expressions of p-AKT and p-mTOR decreased after 48 h of encystation without knockdown. However, the expressions of p-AKT and p-mTOR increased while the expression of LC3B decreased under the knockdown of Ac-HSP20. Furthermore, the protein expression of LC3B increased when the PI3K/AKT/mTOR signaling pathway was inhibited but decreased when the pathway was activated. Conclusions The results demonstrated that autophagy is positively correlated with the encystation of A. castellanii, and Ac-HSP20 regulates autophagy to maintain the homeostasis of A. castellanii by inhibiting the PI3K /AKT /mTOR signaling pathway, thus promoting the maturation and stability of encystation. Graphical Abstract

Abstract Background Alzheimer’s disease (AD) manifests with a higher rate of occurrence in women. Previous epidemiological studies have suggested a potential association between AD and gynecological cancers, but the causal relationship between them remains unclear. This study aims to explore the causal link between 12 types of gynecological cancers and AD using a bidirectional Mendelian randomization (MR) approach. Methods We obtained genetic correlation tools for AD using data from the most extensive genome-wide association study. Genetic correlation data for 12 types of gynecological cancers were also sourced from the Finnish Biobank. These cancers include breast cancer (BC), cervical adenocarcinoma (CA), cervical squamous cell carcinoma (CSCC), cervical cancer (CC), endometrial cancer (EC), ovarian endometrioid carcinoma (OEC), ovarian cancer (OC), ovarian serous carcinoma (OSC), breast carcinoma in situ (BCIS), cervical carcinoma in situ (CCIS), endometrial carcinoma in situ (ECIS), and vulvar carcinoma in situ (VCIS). We used the inverse-variance weighted (IVW) model for causal analysis and conducted horizontal pleiotropy tests, heterogeneity tests, MR-PRESSO tests, and leave-one-out analyses to ensure the robustness of our results. We also applied replication analysis and meta-analysis to further validate our experimental results. Results The study found that EC (P _IVW =0.037, OR [95% CI] = 1.032 [1.002, 1.064]) and CCIS (P _IVW = 0.046, OR [95% CI] = 1.032 [1.011, 1.064]) increase the risk of AD, whereas OC was negatively correlated with AD (P _IVW = 0.016, OR [95% CI] = 0.974[0.954, 0.995]). In reverse MR analysis, AD increased the risk of CC (P _IVW = 0.039, OR [95% CI] = 1.395 [1.017, 1.914]) and VCIS (P _IVW = 0.041, OR [95% CI] = 1.761 [1.027, 2.021]), but was negatively correlated with OEC (P _IVW = 0.034, OR [95% CI] = 0.634 [0.417, 0.966]). Sensitivity analysis results demonstrated robustness. These findings were further substantiated through replication and meta-analyses. Conclusions Our MR study supports a causal relationship between AD and gynecological cancers. This encourages further research into the incidence of gynecological cancers in female Alzheimer’s patients and the active prevention of AD.

Abstract Background Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT). Methods This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman’s rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test. Results Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p

Abstract Quantum chemical (QC) property prediction is crucial for computational materials and drug design, but relies on expensive electronic structure calculations like density functional theory (DFT). Recent deep learning methods accelerate this process using 1D SMILES or 2D graphs as inputs but struggle to achieve high accuracy as most QC properties depend on refined 3D molecular equilibrium conformations. We introduce Uni-Mol+, a deep learning approach that leverages 3D conformations for accurate QC property prediction. Uni-Mol+ first generates a raw 3D conformation using RDKit then iteratively refines it towards DFT equilibrium conformation using neural networks, which is finally used to predict the QC properties. To effectively learn this conformation update process, we introduce a two-track Transformer model backbone and a novel training approach. Our benchmarking results demonstrate that the proposed Uni-Mol+ significantly improves the accuracy of QC property prediction in various datasets.

Abstract Background Offspring consistently exhibit similar imaging features as their parents in cases of degenerative lumbar scoliosis (DLS). Nevertheless, the role of genetic factors in the pathogenesis of DLS remains uncertain. Methods A prospective analysis was conducted on 35 patients with DLS and their 36 offspring. Genomic DNA was extracted from 71 blood samples for gene mutation analysis using whole exome sequencin. Various demographic and imaging parameters were compared. Results In 11 pedigrees of the 35 family members with DLS, 13 suspected pathogenic genes were identified. Among the 35 DLS patients, 11/35(31.5%) exhibited susceptibility gene mutations (mutant group), while 24/35(68.5%) had no pathogenic gene mutations (non-mutant group). AVR was more severe in mutant group than that in no-mutant group (p

Abstract Dysregulation of splicing factor expression plays a crucial role in the progression of hepatocellular carcinoma (HCC). Our research found that the expression level of splicing factor ZMAT2 was increased in HCC, promoting the proliferation of HCC cells. RNAseq data indicated that the absence of ZMAT2 induced skipping exon of mRNA, while RIPseq data further revealed the mRNA binding motifs of ZMAT2. A comprehensive analysis of RNAseq and RIPseq data indicateed that ZMAT2 played a crucial role in the maturation process of TRIM28 mRNA. Knocking down of ZMAT2 led to the deletion of 25 bases in exon 11 of TRIM28, ultimately resulting in nonsense-mediated decay (NMD). Our data revealed that ZMAT2 could regulate TRIM28 to reduce the accumulation of ROS in HCC cells, thereby promoting their proliferation. Our research also discovered that ZMAT2 was capable of undergoing phase separation, resulting in the formation of liquid droplet condensates within HCC cells. Additionally, it was found that ZMAT2 was able to form protein-nucleic acid condensates with TRIM28 mRNA. In summary, this study is the first to reveal that ZMAT2 and TRIM28 mRNA form protein-nucleic acid condensates, thereby regulating the splicing of TRIM28 mRNA. The increased expression of ZMAT2 in HCC leads to upregulated TRIM28 expression and reduced ROS accumulation, ultimately accelerating the proliferation of HCC cells.

Abstract Background Chronic cough in children is closely related to gastroesophageal reflux (GER). However, this association has not been adequately studied due to a lack of diagnostic tools. Combined esophageal multichannel intraluminal impedance and pH (MII-pH) monitoring is considered the most accurate method for evaluating the association between symptoms and reflux, but data on its use in children with chronic cough are still lacking. We aimed to assess the association between chronic cough and GER in children through MII-pH monitoring. Methods Children with chronic cough (> 4 weeks) who were suspected gastroesophageal reflux disease(GERD) were selected to undergo 24 h MII-pH monitoring at our hospital. Patients were divided into groups according to their age, body position, reflux index (RI) or total reflux events, and the differences between the groups were analyzed. Then the significance and value of 24 h pH and impedance monitoring in chronic cough and the relationship between chronic cough and reflux were discussed. Results Overall, 426 patients were included. The median age was 12 months (interquartile range: 6–39.5 months), 129 (30.3%) patients had RI > 7% detected by pH-metry, and 290 (68.1%) patients had positive diagnosis based on the impedance data. GER predominantly occurred in the upright position and mostly involved weakly acidic reflux and mixed gas–liquid reflux. There were 14.1% of children in non-acid GER group were SAP positive showing no difference in acid GER group 13.2% (P = 0.88), whereas patients with SAP > 95% in MII positive group (47[16.2%]) is higher than in MII negative group (P

In the process of CO2-enhanced coalbed methane recovery, the behaviours of coal seam fractures significantly affect sequestration and extraction. To address the unclear impact of fracture roughness evolution on engineering efficiency under multi-physical field coupling effects, we developed an innovative interdisciplinary mathematical model. This model introduces a parameter to quantitatively describe coal seam fracture roughness and couples it with the gas flow control equations under multi-field effects in the coal seam. We investigated the thermo-hydro-mechanical (THM) coupling effects and fracture network characteristics in the coal seam gas extraction process. Results show that the mathematical model aligns well with field data and effectively characterizes coal seam fracture roughness. Fracture roughness significantly influences the residual gas pressure in the coal seam and the injection pressure of CO2. When the roughness parameter decreases from 0.24 to 0.18, the maximum methane content decreases by 32.5% and the maximum CO2 pressure increases by 26.7%, the maximum gas adsorption capacity of coal seam decreased by 31.7%, and the maximum CO2 adsorption capacity increased by 12.1%.

In order to predict the surface movement and deformation caused by coal seam mining, a mining subsidence estimation system is designed and developed with the help of C# language and ArcGIS Engine component tool library based on the probability integration method of polar coordinate system. The system is applicable to irregularly shaped mining workings, and is capable of predicting the subsidence, horizontal movement, horizontal deformation, tilt and curvature of various points on the surface of the mining area after different mining times, and post-process the prediction results to draw the surface movement and deformation cloud map. Taking 308 working face mining of a mine in Shaanxi Province as an example, the probability integral parameters are selected according to the mining conditions and formation lithology of the working face and are substituted into the system to predict the surface movement and deformation, and the results are compared with the measured surface movement and deformation. The results show that the relative error between the predicted surface subsidence value and the measured subsidence value is less than 10%, and the subsidence basin shape is basically consistent with the reality. The predicted result of the system is relatively reliable, and has certain applicability to the mining subsidence prediction.

ObjectiveTo investigate the mechanism and clinical significance of miR-18a-5p and retinoid acid receptor-related orphan receptor-α (RORA) in the proliferation and progression of colorectal cancer (CRC) cells. MethodsThe expressions of miR-18a-5p and RORA in CRC cells and tissues were detected via qRT-PCR, FISH, and IHC. Cell proliferation capability was detected through EdU and CFSE assay, cell apoptosis by flow cytometry assay, and cell migration and invasion abilities by cell scratch and Transwell invasion assays, respectively. The targeted regulation of miR-18a-5p on RORA was further verified via dual-luciferase reporter assay, cell function rescue test, RT-PCR, and Western blot assay. Finally, bioinformatics was used to explore the molecular mechanism of miR-18a-5p promoting malignant proliferation, invasion, and progression of CRC via regulating RORA. ResultsmiR-18a-5p exhibited a high expression in CRC tissues and cells (P

Abstract The realization and control of exchange bias (EB) are highly desirable for spintronic applications. All-oxide heterostructures comprised of ferromagnetic and antiferromagnetic/multiferroic oxides provide an ideal platform to enable the electric-field control of EB, promising for energy-efficient memory and logic devices. However, the low block temperature (TB) and small bias field (HEB) hinder further advances towards room-temperature applications. Here, we report an alternative approach to enhance the interface-induced EB by using ferrimagnetic double-perovskite with B-site cation ordering. In heterostructures comprised of double-perovskite Sr2FeReO6 (SFRO) and LaFeO3 (LFO), a high TB (about 250 K) and large HEB are observed, which is significantly larger than the counterparts with LFO and ferromagnetic oxides. Further analysis suggests that the cation-ordering and ferrimagnetic spin structure of the double-perovskite could contribute significantly to the enhanced exchanged bias when interfacing with G-type antiferromagnets. Our results open a new avenue for developing all-oxides heterostructures for future magnetic technologies.

Abstract Background Universal Health Coverage (UHC) is a common health policy objective outlined in the Sustainable Development Goals. With provincial governments taking the initiative, Pakistan has implemented and extended UHC program amid a complex public health landscape. In this context, we assess Pakistan’s progress toward achieving UHC at the national and subnational level. Methods We use data from the Demographic and Health Surveys and the Household Integrated Economic Survey to construct a UHC index at the national and subnational level for 2007, 2013, and 2018. Furthermore, we use Concentration Index (CI) and CI decomposition methodologies to assess the primary drivers of inequality in accessing medical services. Logistic regression and Sartori’s two-step model are applied to examine the key determinants of catastrophic health expenditure (CHE). Results Our analysis underscores Pakistan’s steady progress toward UHC, while revealing significant provincial disparities in UHC progress. Provinces with lower poverty rate achieve higher UHC index, which highlights the synergy of poverty alleviation and UHC expansion. Among the examined indicators, child immunization remains a key weakness that one third of the children are not fully vaccinated and one sixth of these not-fully-vaccinated children have never received any vaccination. Socioeconomic status emerges as a main contributor to disparities in accessing medical services, albeit with a declining trend over time. Household socioeconomic status is negatively correlated with CHE incidence, indicating that wealthier households are less susceptible to CHE. For individuals experiencing CHE, medicine expenditure takes the highest share of their health spending, registering a staggering 70% in 2018. Conclusion Pakistan’s progress toward UHC aligns closely with its economic development trajectory and policy efforts in expanding UHC program. However, economic underdevelopment and provincial disparities persist as significant hurdles on Pakistan’s journey toward UHC. We suggest continued efforts in UHC program expansion with a focus on policy consistency and fiscal support, combined with targeted interventions to alleviate poverty in the underdeveloped provinces.

Abstract We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752–0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer–Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

Abstract Qarhan Salt Lake, located in the Qaidam Basin on the Qinghai-Tibet Plateau in northwestern China, is the largest potash production base in China. The main potash deposit in Qarhan Salt Lake is a comprehensive deposit in which the liquid potassium resources dominated by potassium-rich and lithium-rich brine coexist with the low-grade solid potassium salt deposit composed of solid potash minerals (polyhalite, carnallite, sylvite). Polyhalite is one of the representative potassium minerals, widely distributed in the Bieletan area of Qarhan Salt Lake, coexisting with halite, and its deposition indicates that the paleo-temperature of brine in this area once fluctuated obviously. Twenty core samples from two boreholes in the Bieletan area of the Qarhan Salt Lake were subjected to fluid inclusions thermometry, and homogenization temperatures reflecting the brine temperatures during the precipitation of evaporite minerals in the Salt Lake were obtained, ranging from 12.4 to 28.9 °C and 9.2 to 19.8 °C, respectively. By scanning electron microscopy, acicular polyhalite and pompom-like aggregate of polyhalite have been identified in the sampling layer, indicating that evaporite deposition have reached the stage of potassium salt deposition. The temperature fluctuations of the fluid inclusions and the elemental chemical data are compared vertically, and the sections with significant temperature fluctuations are close to the layers where polyhalite were deposited. It shows that the paleo-temperature fluctuation impact the sedimentary environment of brine, and then affected the polyhalite deposition of Qarhan Salt Lake.

Abstract Industrial CO2 electrolysis via electrochemical CO2 reduction has achieved progress in alkaline solutions, while the same reaction in acidic solution remains challenging because of severe hydrogen evolution side reactions, acid corrosion, and low target product selectivity. Herein, an industrial acidic CO2 electrolysis to pure HCOOH system is realized in a proton-exchange-membrane electrolyzer using an acid-tolerant Bi-based metal-organic framework guided by a Pourbaix diagram. Significantly, the Faradaic efficiency of HCOOH synthesis reaches 95.10% at a large current density of 400 mA/cm2 with a high CO2 single-pass conversion efficiency of 64.91%. Moreover, the proton-exchange-membrane device also achieves an industrial-level current density of 250 mA/cm2 under a relatively low voltage of 3.5 V for up to 100 h with a Faradaic efficiency of 93.5% for HCOOH production, which corresponds to an energy consumption of 200.65 kWh/kmol, production rate of 12.1 mmol/m2/s, and an energy conversion efficiency of 38.2%. These results will greatly aid the contemporary research moving toward commercial implementation and success of CO2 electrolysis technology.

Abstract Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia’s severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.

Abstract Electrocatalytic CO2 reduction to multi-carbon products is a promising approach for achieving carbon-neutral economies. However, the energy efficiency of these processes remains low, particularly at high current densities. Herein, we demonstrate that the low energy efficiencies are, in part, sometimes significantly, attributed to the high concentration overpotential resulting from the instability (i.e., flooding) of catalyst-layer during electrolysis. To tackle this challenge, we develop copper/gallium bimetallic catalysts with reduced activation energies for the formation of multi-carbon products. Consequently, the reduced activation overpotential allows us to achieve practical-relevant current densities for CO2 reduction at low cathodic potentials, ensuring good stability of the catalyst-layer and thereby minimizing the undesired concentration overpotential. The optimized bimetallic catalyst achieves over 50% cathodic energy efficiency for multi-carbon production at a high current density of over $$1.0 \, {{\rm{A}}} \, {{\rm{cm}}}^{-2}$$ 1.0 A cm − 2 . Furthermore, we achieve current densities exceeding $$2.0 \, {{\rm{A}}} \, {{\rm{cm}}}^{-2}$$ 2.0 A cm − 2 in a zero-gap membrane-electrode-assembly reactor, with a full-cell energy efficiency surpassing 30%.

Abstract Background With orthopedic surgery increasing year on year, the main challenges in bone drilling are thermal damage, mechanical damage, and drill skid. The need for new orthopedic drills that improve the quality of surgery is becoming more and more urgent. Methods Here, we report the skidding mechanism of drills at a wide range of inclination angle and propose two crescent drills (CDTI and CDTII). The anti-skid performance and drilling damage of the crescent drills were analyzed for the first time. Inclined bone drilling experiments were carried out with crescent drills and twist drills and real-time drilling forces and temperatures were collected. Results The crescent drills are significantly better than the twist drill in terms of anti-skid, reducing skidding forces, thrust forces and temperature. The highest temperature is generated close to the upper surface of the workpiece rather than at the hole exit. Finally, the longer crescent edge with a small and negative polar angle increases the rake angle of the cutting edge and reduces thrust forces but increases skidding force and temperature. This study can promote the development of high-quality orthopedic surgery and the development of new bone drilling tools. Conclusion The crescent drills did not skid and caused little drilling damage. In comparison, the CDTI performs better in reducing the skidding force, while the CDTII performs better in reducing the thrust force.