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Abstract Objectives Predictions regarding the on-going burden of SARS-CoV-2, and vaccine recommendations, require an understanding of infection-associated immune protection. We assessed whether early COVID-19 provided protection against Omicron infection. Methods We enrolled a cohort of adults in Ontario, Canada, with COVID-19 prior to October 2020 (early infection, EI), and a matched cohort with COVID-19 testing and a negative PCR (non-EI). Participants completed baseline surveys then surveys every two weeks until January 2023. Multivariable Cox regression was used to assess factors associated with COVID-19 infection during the first 14 months of Omicron. Results Overall, 624 EI (70%) and 175 (77%) non-EI participants met criteria for analysis; 590 (95%) EI and 164 (94%) non-EI had received at least 2 COVID-19 vaccine doses prior to Omicron. Of 624 EI, 175 (28%) had one SARS-CoV-2 re-infection and 8 (1.3%) had two, compared to 84 (48%) non-EI participants with one, 5 (2.9%) with two and 1 (0.6%) with 3 infections (P

Abstract Tick-borne encephalitis (TBE) is an increasing health threat in Sweden and elsewhere in Europe. TBE vaccination is commonly recommended in Sweden, but limited data are available on uptake, effectiveness, and impact of TBE vaccination. General population surveys conducted in 2019–2022 were used to estimated TBE vaccine uptake. TBE vaccine effectiveness (VE) was estimated using the screening method utilizing the surveys and public health TBE surveillance data, which predominately includes hospitalized TBE cases, from 2018 to 2022. Impact of TBE vaccination was calculated based on disease incidence and observed VE. In 2018–2022, 2,015 TBE cases were reported in Sweden; 82.8% (1,564/1,890) of cases with known TBE vaccination history were unvaccinated. Among persons surveyed from the general population with known vaccination history, 52.0% (11,562/22,247) were unvaccinated. Three dose VE against TBE was 89.0% (95% confidence interval 84.3–92.4). When stratified by age group, VE was 86.0% (55.7–95.6) in 1–15 years-of-age and 93.8% (87.5–96.9) in 16–49 years-of-age. In a conservative estimate, despite suboptimal compliance with TBE vaccination recommendations, vaccination averted an estimated thousand TBE cases, most resulting in hospitalization, in Sweden from 2018 to 2022. To prevent additional TBE cases in Sweden, enhanced efforts to increase TBE vaccine uptake and compliance to the TBE vaccination schedule are needed.

Abstract The involvement of B lymphocytes in the pathogenesis of rheumatoid arthritis (RA) is well-established, with their early and aberrant activation being a crucial factor. However, the mechanisms underlying this abnormal activation in RA remain incompletely understood. In this study, we identified a significant reduction in MAPK4 expression in both RA patients and collagen-induced arthritis (CIA) mouse models, which correlates with disrupted B cell activation. Using MAPK4 knockout (KO) mice, we demonstrated that MAPK4 intrinsically promotes the differentiation of marginal zone (MZ) B cells. Loss of MAPK4 in KO mice enhances proximal BCR signaling and activates the PI3K-AKT-mTOR pathway, leading to heightened B cell proliferation. Notably, B cells from MAPK4 KO mice produce significantly higher levels of IL-6, a key pro-inflammatory cytokine in RA. Furthermore, MAPK4 KO mice exhibit impaired T cell-independent humoral immune responses. Mechanistically, MAPK4 inhibits the activation of the PI3K signaling pathway in B cells by activating the IRF4-SHIP1 pathway. Treatment with the MAPK4 agonist Vacquinol-1 enhances MZ B cell differentiation in WT mice and reduces IL-6 secretion in CIA mouse models. In summary, this study reveals the diverse roles of MAPK4 in regulating of B cell functions, with potential implications for developing therapeutic strategies for RA and related autoimmune diseases.

Abstract The total polysaccharides extracted from Laetiporus sulphureus fruiting bodies by ultrasound-assisted complex enzyme method were separated by freeze–thaw combined with fehling reagent to prepare purified polysaccharide (LSPS1). The results of monosaccharide composition and molecular weight distribution demonstrated that LSPS1 contained galactose (51.83%), mannose (26.89%), fucose (16.13%) and glucose (5.15%), and the molecular weight was around 17.3 kDa. Methylation analysis indicated that the backbone of LSPS1 consisted of 1,6-Galp residues, branched at O-2 of Galp with t-Manp, t-Fucp and t-Glcp residues as side chains. In addition, LSPS1 was used for the synthesis of SeNPs based on the redox system of sodium selenite and ascorbic acid. The L. sulphureus polysaccharide selenium nanoparticles (LSPS1–SeNPs) were characterized by UV, FT-IR, ICP-MS, EDX, DLS and SEM, inferring that LSPS1–SeNPs were stabilized with spherical and granular surface structure as well as a mean particle size of 96.72 ± 1.12 nm. Both of LSPS1 and LSPS1–SeNPs possessed strong antioxidant and hypoglycemic activities while the effects of LSPS1–SeNPs were superior to LSPS1. The findings provided valuable structural information for L. sulphureus polysaccharide, and will promote the application of SeNPs by L. sulphureus polysaccharide in potential antioxidant agent and hypoglycemic candidate. Graphical Abstract

The main pathological features of Parkinson’s disease (PD) are the loss of dopaminergic neurons and the formation of Lewy bodies in the basal ganglia, but its exact etiology remained unknown. A large number of studies have shown that neuroinflammation is closely associated with the development and progression of PD, and the research on inflammation-related mechanisms may help to provide new targets for the prevention and control of PD and search for new treatment strategies. Repetitive transcranial magnetic stimulation (rTMS) can effectively improve the symptoms of PD patients and alleviate neuroinflammation, but further studies are needed to clarify its detailed mechanism. This article summarizes the association of neuroinflammation with the development and progression of PD, analyzes the role of rTMS in the treatment of neuroinflammation in PD, and proposes the future research directions.

Abstract Background Congenital heart disease (CHD) is a heterogeneous collection of structural abnormalities of the heart or great vessels that are present at birth. These birth defects are one of the leading causes of infant mortality and morbidity worldwide. The etiology and pathogenesis of CHD are unclear and largely considered to be multifactorial in nature. Since the chromosomal profile of CHD has not been analyzed in a large sample size, we aimed to summarize the clinical features, cytogenetics findings, and pregnancy outcomes of CHD to provide a clinical reference for prenatal diagnosis. Methods Among 21,152 pregnant women, 471 (2.23%) showed fetal CHD on cordocentesis or amniocentesis. The number of cases showing simple CHD, simple CHD with concomitant extracardiac structural abnormalities, complex CHD, and complex CHD with concomitant extracardiac structural abnormalities was 128, 124, 89, and 130, respectively. For prenatal genetic diagnosis, karyotyping was performed with single-nucleotide polymorphism array(SNP-array)-based chromosomal microarrays, fluorescence in situ hybridization (FISH), copy number variation sequencing (CNV-seq), and BACs-on-Beads™ (BoBs) analyses. The results of ultrasonography examinations, genetic analyses, and pregnancy outcomes were recorded in detail. Results Ventricular septal defects (VSDs) were observed in 245 (52.02%) cases of fetal CHD. Among the 471 cases of CHD, 258 (54.78%) showed other ultrasound abnormalities. The most common ultrasound abnormalities were abnormalities of the central nervous system. The 471 cases included 93 (19.75%) cases showing chromosomal abnormalities, and the incidence of these abnormalities increased with advanced maternal age or the presence of other ultrasound abnormalities. In eight cases, karyotype analysis showed normal results while SNP-array or CNV-seq results were abnormal. Among the 453 cases that were followed up, 166 (36.64%) involved pregnancy termination, 273 (60.26%) involved live births, 7 (1.55%) involved fetal death in utero, and 7 (1.55%) involved neonatal death after birth. Conclusions Fetuses with CHD showed higher rates of chromosomal abnormalities. In cases diagnosed with fetal CHD during fetal ultrasonic examination, the mothers should undergo a careful and comprehensive fetal ultrasound scan as well as prenatal genetic testing, including karyotype analysis and SNP-array or CNV-sequencing. The prognosis for simple fetal CHD is good, while the prognosis for complex fetal CHD and extracardiac anomalies is poor.

Abstract Background Systemic lupus erythematosus (SLE) is linked to host gut dysbiosis. Here we performed faecal gut microbiome sequencing to investigate SLE-pathogenic gut microbes and their potential mechanisms. Methods There were 134 healthy controls (HCs) and 114 SLE cases for 16 S ribosomal RNA (rRNA) sequencing and 97 HCs and 124 SLE cases for shotgun metagenomics. Faecal microbial changes and associations with clinical phenotypes were evaluated, and SLE-associated microbial genera were identified in amplicon analysis. Next, metagenomic sequencing was applied for accurate identification of microbial species and discovery of their metabolic pathways and immunogenic peptides both relevant to SLE. Finally, contribution of specific taxa to disease development was confirmed by oral gavage into lupus-prone MRL/lpr mice. Results SLE patients had gut microbiota richness reduction and composition alteration, particularly lupus nephritis and active patients. Proteobacteria/Bacteroidetes (P/B) ratio was remarkably up-regulated, and Escherichia was identified as the dominantly expanded genus in SLE, followed by metagenomics accurately located Escherichia coli and Escherichia unclassified species. Significant associations primarily appeared among Escherichia coli, metabolic pathways of purine nucleotide salvage or peptidoglycan maturation and SLE disease activity index (SLEDAI), and between multiple epitopes from Escherichia coli and disease activity or renal involvement phenotype. Finally, gavage with faecal Escherichia revealed that it upregulated lupus-associated serum traits and aggravated glomerular lesions in MRL/lpr mice. Conclusion We characterize a novel SLE exacerbating Escherichia outgrowth and suggest its contribution to SLE procession may be partially associated with metabolite changes and cross-reactivity of gut microbiota-associated epitopes and host autoantigens. The findings could provide a deeper insight into gut Escherichia in the procession of SLE.

Abstract The olfactory sensory system of Drosophila has several advantages, including low power consumption, high rapidity and high accuracy. Here, we present a biomimetic intelligent olfactory sensing system based on the integration of an 18-channel microelectromechanical system (MEMS) sensor array (16 gas sensors, 1 humidity sensor and 1 temperature sensor), a complementary metal‒oxide‒semiconductor (CMOS) circuit and an olfactory lightweight machine-learning algorithm inspired by Drosophila. This system is an artificial version of the biological olfactory perception system with the capabilities of environmental sensing, multi-signal processing, and odor recognition. The olfactory data are processed and reconstructed by the combination of a shallow neural network and a residual neural network, with the aim to determine the noxious gas information in challenging environments such as high humidity scenarios and partially damaged sensor units. As a result, our electronic olfactory sensing system is capable of achieving comprehensive gas recognition by qualitatively identifying 7 types of gases with an accuracy of 98.5%, reducing the number of parameters and the difficulty of calculation, and quantitatively predicting each gas of 3–5 concentration gradients with an accuracy of 93.2%; thus, these results show superiority of our system in supporting alarm systems in emergency rescue scenarios.

BackgroundUnderstanding children's eating behaviors is crucial for elucidating the etiology of childhood obesity. However, the relationship between these behaviors and abdominal fat accumulation remains poorly understood. This study aims to investigate this association in primary school children.MethodsThis study included 1,475 children aged 8–10 years in Ningbo, China. Body composition was measured both at baseline (September 2022) and after 9 months of follow-up (June 2023). Primary caregivers completed the Children's Eating Behavior Questionnaire (CEBQ). A mixed-effects linear model was applied to analyze the relationships between children's eating behaviors and body composition.ResultsGreater visceral fat area (VFA) was associated with greater slowness in eating [β = 0.25 (0.02, 0.49)], greater food responsiveness [β = 0.29 (0.14, 0.43)], increased emotional undereating [β = 0.35 (0.17, 0.54)], and more emotional overeating [β = 0.21 (0.02, 0.39)]. Children with greater trunk fat mass (TrFM) tended to have greater food responsiveness [β = 0.02 (0.01, 0.03)] and greater enjoyment of food [β = 0.01 (0.00, 0.03)], increased emotional undereating [β = 0.02 (0.01, 0.03)] and emotional overeating [β = 0.02 (0.00, 0.03)]. Prospectively, positive correlations were observed between VFA and food responsiveness [β = 0.18 (0.02, 0.35)], as were emotional undereating [β = 0.31 (0.10, 0.52)] and emotional overeating [β = 0.24 (0.03, 0.46)]. Similarly, TrFM was positively correlated with food responsiveness [β = 0.02 (0.00, 0.03)], enjoyment of food [β = 0.02 (0.00, 0.04)], emotional undereating [β = 0.02 (0.01, 0.04)] and emotional overeating [β = 0.02 (0.01, 0.04)].ConclusionsOur findings suggest that eating behaviors are significantly associated with abdominal fat accumulation in primary school children. Addressing specific eating behaviors may be crucial in mitigating abdominal fat and its related health risks.

Abstract Progranulin (PGRN) plays a critical role in bronchial asthma and the function of various immune cells. However, the mechanisms by which PGRN influences B‐cell receptor (BCR) signaling and immunoglobulin E(IgE) production are not fully understood. The study aimed to elucidate the molecular mechanisms through which PGRN affects BCR signaling, B‐cell differentiation, and IgE production. A PGRN knockout mouse model, along with techniques including flow cytometry, the creation of a bone marrow chimeric mouse model, total internal reflection fluorescence (TIRF), and Western blot (WB) analysis is employed, to investigate the link between PGRN and various aspects of B‐cell biology. It is discovered that the absence of PGRN in mice alters peripheral B‐cell subpopulations, promotes IgE class switching in a cell‐intrinsic manner, and affects B‐cell subpopulations. Additionally, PGRN modulates B‐cell functions by regulating BCR signaling pathways, metabolic processes, and the actin cytoskeleton during early B‐cell activation. Significantly, PGRN deficiency results in diminished production of NP‐specific antibodies. Moreover, it is found that PGRN inhibits B‐cell activation and IgE production through the PGRN‐IFITM3‐STAT1 signaling pathway. The findings provide new strategies for the targeted treatment of bronchial asthma, highlighting the crucial role of PGRN in B‐cell signaling and IgE production.

Cancer remains a major global health challenge. Immunotherapy has revolutionized the management of cancer, yet only a limited number of patients respond to such treatments. This is largely attributed to the immunosuppressive tumor microenvironment, which diminishes the effectiveness of immunotherapy. Recent studies have underscored the potential of naturally derived caerin 1 peptides, particularly caerin 1.1 and caerin 1.9, which exhibit strong antitumor effects and enhance the efficacy of immunotherapies in animal models. This review encapsulates the current research aimed at augmenting the effectiveness of immunotherapy, focusing on the role of caerin 1.1 and caerin 1.9 in boosting immunotherapeutic outcomes, elucidating possible mechanisms, and discussing their limitations and challenges.

Geological hazards along mountain highways affect the transportation and safety of residents in mountainous towns. Risk assessment comprehensively analyzes the contributing characteristics of the geological hazard-prone environment and triggering factors, which is crucial for highway disaster prevention and mitigation. Taking the lower section of the provincial highway Zhutoukengzi - Dukanxia road (S223) in Jiangxi Province as an example, four types of geologic hazard evaluation models were constructed based on frequency ratio (FR), coupled entropy index (EI), hierarchical analysis method (AHP) and the combination of the two (EI- AHP). For the development characteristics of the geological environment and geologic hazards along the highway, the natural slopes were selected and the geologic hazards are evaluated. AHP), to construct four kinds of geohazard risk evaluation models. For the geological environment and geohazard development characteristics along the highway, eight evaluation factors, such as natural slope, slope direction, topographic relief, slope morphology, slope cutting height, slope cutting gradient, stratigraphic lithology, and the relationship between faults and slopes were selected as the risk evaluation indexes, and the slope units were selected as the evaluation unit, and FR was used to quantify the evaluation factors, and AHP and EI were combined to calculate the evaluation factors. AHP and EI were used to calculate the subjective and objective weights of the evaluation factors, and the multi-coupling model based on FR was obtained by relying on the ArcGIS platform, and the geohazard hazard zoning maps along the highway with different evaluation models were drawn. The results show that the AUC values of the four evaluation models, FR, EI-FR, AHP-FR and EI-AHP-FR, are 0.746, 0.811, 0.836, 0.833, respectively, indicating that the AHP-FR evaluation model has the highest prediction accuracy and can effectively evaluate the risk of geologic hazards along the highway. The areas classified as high-risk, relatively high-risk, moderate-risk, relatively low-risk, and low-risk zones for the lower section of the Zhutoukengzi-Qukan road in Jiangxi Province were 0.295 km2, 0.570 km2, 1.509 km2, 0.354 km2, and 1.732 km2, respectively, accounting for 6.66%, 12.79%, 33.86%, 7.97%, and 38.71% of the total area. This study provided a comprehensive zoning of potential geological hazards along the S223 road, offering scientific geological reference for the safe construction and operation of roads.

Abstract Soil hydraulic parameters are vital for precisely characterizing soil hydrological processes, which are critical indicators for regulating climate change effects on terrestrial ecosystems and governing feedbacks between water, energy, and carbon–nitrogen cycles. Although many studies have integrated comprehensive soil datasets, data quality and cost challenges result in data completeness deficiencies, especially for deep soil information. These gaps not only impede methodological endeavours but also constrain soil parameter-based ecosystem process studies spanning from local profiles to global earth system models. We established a soil dataset across the entire Yellow River Basin (YRB) (795,000 km2) using high-density in situ field sampling. This observation-based dataset contains records of soil texture (2924), bulk density (2798), saturated hydraulic conductivity (2782), and water retention curve parameters (1035) down to a maximum depth of 5 m. This dataset, which extends the recorded data range for deep soil hydraulic parameters, is valuable as a direct data resource for environmental, agronomical and hydrological studies in the YRB and regions with similar pedological and geological backgrounds around the world.

Abstract The regulation of circadian rhythms and the sleep–wake states involves in multiple neural circuits. The suprachiasmatic nucleus (SCN) is a circadian pacemaker that controls the rhythmic oscillation of mammalian behaviors. The basal forebrain (BF) is a critical brain region of sleep–wake regulation, which is the downstream of the SCN. Retrograde tracing of cholera toxin subunit B showed a direct projection from the SCN to the horizontal limbs of diagonal band (HDB), a subregion of the BF. However, the underlying function of the SCN–HDB pathway remains poorly understood. Herein, activation of this pathway significantly increased non–rapid eye movement (NREM) sleep during the dark phase by using optogenetic recordings. Moreover, activation of this pathway significantly induced NREM sleep during the dark phase for first 4 h by using chemogenetic methods. Taken together, these findings reveal that the SCN–HDB pathway participates in NREM sleep regulation and provides direct evidence of a novel SCN-related pathway involved in sleep–wake states regulation.

Some properties of the constant in asymptotic expansion of iterates of a cubic function were investigated. This paper analyzed the monotonicity, differentiability of the constant with respect to the initial value and the functional equation that is satisfied.

Abstract Wheat is one of the major food crops worldwide. Stripe rust can cause a great loss of wheat yield, especially when the disease is prevalent. Chemical control not only causes the loss of resistance to stripe rust but also has a serious impact on the human body and environment. Therefore, the most economical measure to control wheat stripe rust is to cultivate resistant varieties. Rapid variation of stripe rust races often leads to rapid "loss" of resistance to stripe rust disease; therefore, breeders and researchers have to continuously explore new stripe rust resistance genes to provide new resistance sources for the rapid variation of stripe rust races. Previous studies have confirmed that PI660076, a spring wheat line, showed stripe rust resistance under natural conditions at the adult stage, which has great value in breeding programs. In this study, a recombinant inbred lines (RIL) population was constructed by crossing the wheat line PI660076 with the stripe rust-susceptible line AvS. Genotyping of the population was performed using a wheat 15 K SNP array. Three QTLs were identified using phenotypic data over four years across three environments. The resistance type of each QTL was determined by inoculating the RIL lines with single and homozygous QTL during the seedling and adult stages under controlled conditions. The all-stage resistance (ASR) QTL, QYr076.jaas-2A (flanked by SNP marker AX-11048464 and Kompetitive Allele-Specific PCR (KASP) marker KASP_4940) explained 7.13–16.58% and 6.95–7.25% of infection type (IT) and disease severity (DS), respectively. The adult-plant resistance (APR) resistance QTL, QYr076.jaas-4D.1 (flanked by KASP marker KASP_0795 and SNP marker AX-111567243,) explained 6.85–12.70% and 7.94–17.26% of IT and DS, respectively. The APR resistance QTL, QYr076.jaas-4D.2 flanked by KASP markers KASP_9130 and KASP_6535, explained 7.97–39.19% and 8.77–20.55% of the phenotypic variation in IT and DS, respectively. All the three QTLs are likely to be new. The obtained results lay a foundation for further utilization of the stripe rust-resistant line PI660076, as well as for fine mapping and molecular marker-assisted selection breeding. Graphical Abstract

Streptococcus pneumoniae is an important cause of community-acquired pneumonia (CAP) in Japan. Here, we report the serotype distribution and antimicrobial susceptibility of cultured pneumococcal isolates from Japanese adults aged ≥18 years with CAP. This was a prospective, population-based, active surveillance study conducted in Goto City, Japan from December 2015 to November 2020. Pneumococcal isolates from sterile sites (blood and pleural fluid) and non-sterile sites (sputum and bronchoalveolar lavage) were cultured as part of the standard of care. S. pneumoniae were serotyped using the Quellung reaction. Antimicrobial susceptibility was tested using microdilution and interpreted according to the Clinical and Laboratory Standards Institute criteria. Isolates resistant to erythromycin were phenotyped using the triple-risk test and genotyped by polymerase chain reaction. A total of 156 pneumococcal isolates were collected (138 from sputum, 15 from blood, and 3 from bronchoalveolar lavage) from 1992 patients. Of these, 142 were non-duplicate isolates from unique patients and were included in the analyses. Serotypes contained within the 13-valent pneumococcal conjugate vaccine (PCV13) (including 6C), PCV15 (including 6C), and PCV20 (including 6C and 15C) were detected in 39 (27%), 45 (32%), and 80 (56%) of 142 isolates, respectively. The most common serotypes were 35B (12%), 11A (11%), and 3 (11%). Multidrug resistance (MDR) was detected in 96/142 (68%) isolates. Of the 96 MDR isolates, 31, 32, and 59% were PCV13, PCV15, and PCV20 serotypes, respectively; the most common MDR serotypes were 35B (16%), 6C, 10A, and 15A (9% each), and 3 and 11A (8% each). A total of 119 isolates were resistant to macrolides; 41 (35%) had an M phenotype, 53 (45%) had an iMcLS phenotype, and 25 (21%) had a cMLS phenotype. In conclusion, pneumococcal serotypes 35B, 11A and 3 were most frequently associated with pneumonia and antimicrobial resistance was common among pneumococcal isolates from adults with CAP in Goto City, Japan. Implementing higher-valency PCVs May help reduce vaccine-type CAP among Japanese adults.

Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with favorable effects on fatty and glucose metabolism, has been considered the leading candidate drug for nonalcoholic steatohepatitis (NASH) treatment. However, its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major drawback. Ferroptosis, a newly recognized form of cell death characterized by uncontrolled lipid peroxidation, is involved in the progression of NASH. Nitric oxide (NO) is a versatile biological molecule that can degrade extracellular matrix. In this study, we developed a PEGylated thiolated hollow mesoporous silica nanoparticles (MSN) loaded with OCA, as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol (ONL@MSN). Biochemical analyses, histology, multiplexed flow cytometry, bulk-tissue RNA sequencing, and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle (ONL@MSN) in a mouse NASH model. Compared with the OCA-loaded nanoparticles (O@MSN), ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ferroptosis. ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis, inhibition of immune response/lipid peroxidation, and correction of microbiota dysbiosis. These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR, ferroptosis, and fibrosis.

Abstract It is metabolic and signaling crosstalk between stromal cells and tumors in the tumor microenvironment, which influences several aspects of tumor formation and drug resistance, including metabolic reprogramming. Despite considerable findings linking lncRNAs in HIF-1-related regulatory networks to cancer cell, little emphasis has been given to the role in communication between cancer-associated fibroblasts (CAFs) and tumor cells. Previously, we observed that NNT-AS1 was substantially expressed in CAFs cells and CAFs exosomes, and subsequently investigated the influence of CAFs exosomal NNT-AS1 on glucose metabolism, proliferation, and metastasis of pancreatic ductal adenocarcinoma (PDAC) cells. Transmission electron microscopy was used to examine exosomes secreted by PDAC patient-derived CAFs. qRT-PCR was used to evaluate the expression of NNT-AS1, miR-889-3p, and HIF-1. The role of CAFs-derived exosomal NNT-AS1 in PDAC cell progression and metabolism have been identified. Dual luciferase reporter assays examined the binding between NNT-AS1, miR-889-3p, and HIF-1. After PDAC cells co-culture exosomes secreted by CAFs, we found that they alter glucose metabolism, proliferation, and metastasis. In PDAC cells, CAF-derived exosomal lncRNA NNT-AS1 acted as a molecular sponge for miR-889-3p. Furthermore, HIF-1 could be targeted by miR-889-3p and was controlled by NNT-AS1. This study explores the mechanism by which NNT-AS1 influences the interaction of CAFs on glycolytic remodeling, proliferation, and metastasis of tumor cells through regulating miR-889-3p/HIF-1α, which also helps discover new clinical treatment targets for PDAC.

Summary: Background: The prevalence of metabolic-associated steatotic liver disease (MASLD) is rising precipitously among children, particularly in regions or countries burdened with high prevalence of obesity. However, identifying those at high risk remains a significant challenge, as the majority do not exhibit distinct symptoms of MASLD. There is an urgent need for a widely accepted non-invasive predictor to facilitate early disease diagnosis and management of the disease. Our study aims to 1) evaluate and compare existing predictors of MASLD, and 2) develop a practical screening strategy for children, tailored to local prevalence of obesity. Methods: We utilized a school-based cross-sectional survey in Beijing as the training dataset to establish predictive models for screening MASLD in children. An independent school-based study in Ningbo was used to validate the models. We selected the optimal non-invasive MASLD predictor by comparing logistic regression model, random forest model, decision tree model, and support vector machine model using both the Beijing and Ningbo datasets. This was followed by serial testing using the best performance index we identified and indices from previous studies. Finally, we calculated the potential MASLD screening recommendation categories and corresponding profits based on national and subnational obesity prevalence, and applied those three categories to 200 countries according to their obesity prevalence from 1990 to 2022. Findings: A total of 1018 children were included (NBeijing = 596, NNingbo = 422). The logistic regression model demonstrated the best performance, identifying the waist-to-height ratio (WHtR, cutoff value ≥0.48) as the optimal noninvasive index for predicting MASLD, with strong performance in both training and validation set. Additionally, the combination of WHtR and lipid accumulation product (LAP) was selected as an optimal serial test to improve the positive predictive value, with a LAP cutoff value of ≥668.22 cm × mg/dL. Based on the obesity prevalence among 30 provinces, three MASLD screening recommendations were proposed: 1) “Population-screening-recommended”: For regions with an obesity prevalence ≥12.0%, where MASLD prevalence ranged from 5.0% to 21.5%; 2) “Resources-permitted”: For regions with an obesity prevalence between 8.4% and 12.0%, where MASLD prevalence ranged from 2.3% to 4.4%; 3) “Population-screening-not-recommended”: For regions with an obesity prevalence

Background With the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth weight percentile curves for singletons and twins in EPIs from China and the USA and compare the differences between them.Methods In China, EPIs were from 31 provinces, from 2010 to 2021. The collected information was sex, gestational age, birth weight, singletons and twins. We used the generalised additive models for location scale and shape method to construct the birth weight percentile curves by gestational age and sex for EPIs. The National Vital Statistics System database from 2016 to 2021 was also analysed. We compared the differences between the 50th birth weight percentile curves of the two databases.Results We identified 8768 neonates in China (5536 singletons and 3232 twins) and 121 933 neonates in the USA (97 329 singletons and 24 604 twins). We established the 3rd, 10th, 25th, 50th, 75th, 90th and 97th birth weight reference curves for China and the USA. The results showed that males had higher birth weights than females. In China, for the same gestational age and sex, birth weights in singletons and twins were found to be similar, though singleton males born in China had slightly higher birth weights than male twins. In the USA, birth weights were also similar for females and males, with the same gestational age in singletons and twins.Conclusion We established birth weight reference percentile curves by gestational age and sex for singletons and twins among EPIs in China and the USA.

Chemokines regulate the trophoblast dysfunction involved in the occurrence and development of pathological pregnancy, including missed abortions. In particular, CXC chemokine receptor type 5 mediates cell proliferation, migration, and inflammation; nonetheless, its role in missed abortions remains unclear. This study aimed to examine the expression of CXC chemokine receptor type 5 in missed abortions and to investigate the effects of CXC chemokine receptor type 5 on the biological behaviour of trophoblasts, as well as the underlying mechanisms. Our results indicated that CXC chemokine receptor type 5 was upregulated in the villi of women who experienced unexplained missed abortions, as compared with those who had normal pregnancies. CXC chemokine receptor type 5 inhibited the proliferation and migration of human first-trimester trophoblast/simian virus cells but promoted cell apoptosis. With respect to its mechanisms, CXC chemokine receptor type 5 activated the extracellular signal-regulated protein kinase 1/2 signalling pathway and upregulated the secretion of interleukin-6; however, it had no effect on the secretion of tumour necrosis factor-α. In conclusion, our findings suggest that CXC chemokine receptor type 5 induces trophoblast dysfunction and participates in the processes of unexplained missed abortions, wherein p-ERK and interleukin-6 may be involved.

Abstract To study the evolution rules and behaviors of heat transport in a sandstone geothermal reservoir caused by cooled water reinjection, this research focuses on the quantitative relationship among reinjection parameters and the thermal breakthrough time of production wells. The permeation, tracer, and reinjection tests were conducted in a simulation model using a large sand tank in conjunction with the numerical simulation method based on COMSOL Multiphysics. Subsequently, sensitivity analysis and nonlinear fitting were performed to investigate the effects of fluid viscosity and density on the reinjection process, and to analyze the impact of reinjection parameters on the thermal breakthrough time of production wells, along with their underlying mechanisms and law. The results indicate that the migration velocity of reinjection water is greater in coarse sand layer compared to that in medium sand layer, and the thermal breakthrough time t is linearly correlated with reinjection rate (Q) raised to the power of − 0.85, temperature difference (ΔT) raised to the power of − 0.21, and spacing between the production and reinjection wells (R) raised to the power of 1.4. The correlation equation and analysis show that when the temperature difference between production and reinjection ΔT is more than 30 ℃, the influence of ΔT on the thermal breakthrough time of production well becomes weak, because ΔT exerts an effect on the thermal breakthrough time of production well t by influencing the relative position of the 18.5 ℃ isotherm in the temperature transition region. The error in reinjecting high-temperature fluid into low-temperature fluid may be corrected by introducing a viscosity correction coefficient α μ.

When focusing on biodiversity maintenance, ecological security pattern (ESP) planning gradually becomes a multi-objective planning strategy for sustainable development; wildlife conservation and ecosystem health maintenance should be balanced with local economic development and people’s livelihood enhancement goals. This study focuses on ESP mapping in the Qinling-Daba Mountain area, which is an ecologically significant and socioeconomically underdeveloped area. The tradeoff between conservation and development is made by varying the area of ecological sources and incorporating ecosystem service tradeoffs into ecological source identification through multi-scenario designation. ESPs under six scenarios were generated based on the minimum resistance model, and the important ecological corridors and strategic points in each scenario were identified and compared. The results show the following: (1) The scenario that sets around 30 percent of the study area as ecological sources maintains the integrity of natural ecosystems and leaves space for food and material supply to residents. (2) In this scenario, the ecological sources are connected by 60 corridors that cross 137 townships with high population densities (>100 people/km2) and intersect with major traffic lines at 71 points. Engineering, management, or education strategies must be taken in these townships or intersections to avoid human–wildlife conflicts. (3) The study area needs to construct both short (north–south) corridors linking proximate ecological sources for species’ daily movement and long (west–east) corridors connecting large and distant sources for species’ seasonal migration and gene flow. (4) The multi-scenario approach turns out to be an effective strategy for ESP planning with considerations for development–conservation tradeoffs.

Abstract Metastasis has emerged as a major impediment to achieve successful therapeutic outcomes in hepatocellular carcinoma (HCC). Nonetheless, the intricate molecular mechanisms governing the progression of HCC remain elusive. Herein, we present evidence highlighting the influence exerted by insulin-like growth factor-binding protein 2 (IGFBP2) as a potent oncogene driving the malignant phenotype. Our investigation reveals a marked elevation of IGFBP2 expression in primary tumors, concomitant with the presence of mesenchymal biomarkers in HCC. Through in vitro and in vivo experimentation, we demonstrate that the overexpression of IGFBP2 expedites the progression of epithelial-mesenchymal transition (EMT) and facilitates the metastatic potential of HCC cells, chiefly mediated by the Wnt/β-catenin signaling pathway. Notably, knockdown of IGFBP2 significantly decreased the expression of total and nuclear β-catenin, N-cadherin and vimentin in the treatment of the specific activator of Wnt/β-catenin CHIR-99021. Collectively, our findings identify IGFBP2 as a pivotal regulator within the HCC EMT axis, whereby its overexpression confers the distinctly aggressive clinical features characteristic of the disease.