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Abstract Research on the potential association between life-ever gallstones and depressive symptoms is limited. This study aims to evaluate whether the presence of gallstone disease is associated with depressive symptoms. In this cross-sectional study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 cycles. The presence of depressive symptoms and gallstone disease was assessed using questionnaire responses. Adjusted odds ratios (OR) were calculated using a multivariate logistic regression model, with adjustments made for age, sex, race, body mass index, history of cardiovascular disease, hypertension, arthritis, and pulmonary disease across different models. Subgroup and sensitivity analyses were conducted to ensure the stability of the results. This study included 6201 adults aged 20 years and above, with 539(8.7%) experiencing depressive symptoms. After adjusting for age, sex, race, body mass index, CVD history, hypertension, arthritis, pulmonary disease, depressive symptoms were possibly associated with life-ever gallstones (OR 1.37, 95% CI 0.91–2.08).When depressive symptoms were categorized as mild, moderate, moderately severe, and severe,life-ever gallstones was possibly associated with mild depressive symptoms (OR 1.12, 95% CI 0.81–1.56), moderate depressive symptoms (OR 1.37, 95% CI 0.89–2.12), moderately severe depressive symptoms (OR 1.93, 95% CI 0.93–3.99), and severe depressive symptoms (OR 0.67, 95% CI 0.16–2.88).As a continuous variable, life-ever gallstones was associated with the PHQ-9 score (OR 0.42, 95% CI 0.02–0.83). The results remained stable after multiple imputation for all missing data. This cross-sectional study demonstrates no significant association between life-ever gallstones and depressive symptoms in US adults.

Abstract Objectives To apply cardiac magnetic resonance imaging (CMR) for detailed myocardial characterization in uremic cardiomyopathy (UC), hypertensive cardiomyopathy (HTN), and hypertrophic cardiomyopathy (HCM) aiming to enrich the understanding of UC’s etiology and further support the development of therapeutic strategies. Methods A total of 152 patients (age: 49.2 ± 9.9 years; 65.8% male) underwent routine CMR from June 2016 to March 2023. Retrospectively, 53 patients with UC, 39 patients with HTN, 30 patients with HCM, and 30 healthy controls were included. Functional analysis, feature tracking of the left ventricle and left atrium, and myocardial T1, T2, and T2* mapping were performed. Statistical analysis included Pearson correlation and ROC analysis to define correlations and discriminators between groups. Results UC patients demonstrated significantly higher native T1 (p

PurposeThis study aimed to characterize the safety profiles of rivaroxaban-associated suspected adverse events by mining the Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsA disproportionality analysis of spontaneously reported suspected adverse drug reactions (ADRs) was conducted. The reports in FAERS from 2014 to 2024 were compiled. Frequentist and Bayesian statistics were both applied to calculate drug-AE combinations in system organ classes and preferred-term levels. Reporting odds ratio (ROR), proportional reporting ratio (PRR), the Medicines and Healthcare products Regulatory Agency (MHRA), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) methods were analyzed and used to compare the suspected AEs.ResultsOf 77,384 ADR reports, 66,705 (86.20%) were serious rivaroxaban AE reports. The most common age group was above 65 years. The suspected adverse effects of rivaroxaban emerging for system organ classes (SOCs) primarily included “Gastrointestinal disorders”; “Injury, poisoning, and procedural complications”, “Nervous system disorders” and “Vascular disorders”. Ranked by EBGM, the top signal strength of suspected AE signals of rivaroxaban under ROR algorithm at the preferred-term (PT) level were “Haemorrhagic arteriovenous malformation” (N = 571, ROR = 756.520, PRR = 754.029, Information Component (IC) = 7.197, Empirical Bayesian Geometric Mean (EBGM) = 146.725), “Gastrointestinal vascular malformation haemorrhagic” (N = 197, ROR = 211.138, PRR = 210.950, IC = 6.614, EBGM = 97.923), and “Diverticulum intestinal haemorrhagic” (N = 722, ROR = 169.898, PRR = 169.210, IC = 6.458, EBGM = 97.920). Moreover, uncommon but significantly suspected AE signals, such as “Coagulation factor X level increased”, “Basal ganglia haematoma”, and “Proctitis haemorrhagic” were observed. Notably, “Gastrointestinal haemorrhage” (N = 13,436, ROR = 80.477, PRR = 74.460, IC = 5.729, EBGM = 53.042), “Upper gastrointestinal haemorrhage”(N = 2,872, ROR = 73.978, PRR = 72.797, IC = 5.706, EBGM = 52.198) and “Internal haemorrhage” (N = 2,368, ROR = 91.979, PRR = 80.899, IC = 5.813, EBGM = 56.212) exhibited relatively high occurrence rates and signal strengths. From 2014 to 2024, the IC values of rivaroxaban-associated suspected AEs for “Surgical and medical procedures” and “Cardiac disorders” showed an annual increasing trend in the time-span analysis. Based on the various visulization plots, a key discovery is that “Gastrointestinal hemorrhage” emerged as the most significant suspected AE across five algorithms. The exciting finding was that the MGPS algorithm revealed a higher risk of suspected AEs under the “Investigations” category. However, the results of the analyses of the other algorithms at the SOC level were not akin to this. Moreover, the results of signal mining for the three main types of indication populations with adverse drug reactions (ADRs), including Atrial fibrillation, Cerebrovascular accident prophylaxis, and Deep vein thrombosis were shown that “Gastrointestinal haemorrhage”, “Epistaxis”, “Haematuria”, “Rectal haemorrhage”, and “Upper gastrointestinal haemorrhage” were detected as the most common and significant signals of suspected adverse events.ConclusionRivaroxaban has risks of various suspected adverse reactions while providing therapeutic effects and being used widely. Our pharmacovigilance study may provide valuable hints that practitioners should closely monitor occurrences of “Gastrointestinal disorders”, “Injury, poisoning, and procedural complications” and “Nervous system disorders”, and other events in clinical applications. Consequently, it remains to persist in monitoring rivaroxaban, assessing the associated risks in the future.

Diabetic nephropathy(DN) is the primary factor leading to the advancement of end-stage renal disease.Tubulointerstitial fibrosis(TIF) is a crucial element that impacts renal function in DN.When exposed to high levels of glucose,the activation of inflammasomes can trigger cell death pathways,including pyroptosis.This can potentially lead to TIF,which in turn causes the decline of renal function.This article focuses on the pathogenic mechanisms of TIF resulting from DN.This study reviews the potential of blocking pyroptosis to slow down the course of DN,providing a new and promising target for therapeutic intervention in the treatment of DN.

Abstract Linkage maps are essential for genetic mapping of phenotypic traits, gene map-based cloning, and marker-assisted selection in breeding applications. Construction of a high-quality saturated map requires high-quality genotypic data on a large number of molecular markers. Errors in genotyping cannot be completely avoided, no matter what platform is used. When genotyping error reaches a threshold level, it will seriously affect the accuracy of the constructed map and the reliability of consequent genetic studies. In this study, repeated genotyping of two recombinant inbred line (RIL) populations derived from crosses Yangxiaomai × Zhongyou 9507 and Jingshuang 16 × Bainong 64 was used to investigate the effect of genotyping errors on linkage map construction. Inconsistent data points between the two replications were regarded as genotyping errors, which were classified into three types. Genotyping errors were treated as missing values, and therefore the non-erroneous data set was generated. Firstly, linkage maps were constructed using the two replicates as well as the non-erroneous data set. Secondly, error correction methods implemented in software packages QTL IciMapping (EC) and Genotype-Corrector (GC) were applied to the two replicates. Linkage maps were therefore constructed based on the corrected genotypes and then compared with those from the non-erroneous data set. Simulation study was performed by considering different levels of genotyping errors to investigate the impact of errors and the accuracy of error correction methods. Results indicated that map length and marker order differed among the two replicates and the non-erroneous data sets in both RIL populations. For both actual and simulated populations, map length was expanded as the increase in error rate, and the correlation coefficient between linkage and physical maps became lower. Map quality can be improved by repeated genotyping and error correction algorithm. When it is impossible to genotype the whole mapping population repeatedly, 30% would be recommended in repeated genotyping. The EC method had a much lower false positive rate than did the GC method under different error rates. This study systematically expounded the impact of genotyping errors on linkage analysis, providing potential guidelines for improving the accuracy of linkage maps in the presence of genotyping errors.

Abstract Brainbow is a genetic cell-labeling technique that allows random colorization of multiple cells and real-time visualization of cell fate within a tissue, providing valuable insights into understanding complex biological processes. However, fluorescent proteins (FPs) in Brainbow have distinct excitation spectra with peak difference greater than 35 nm, which requires sequential imaging under multiple excitations and thus leads to long acquisition times. In addition, they are not easily used together with other fluorophores due to severe spectral bleed-through. Here, we report the development of a single-wavelength excitable Brainbow, UFObow, incorporating three newly developed blue-excitable FPs. We have demonstrated that UFObow enables not only tracking the growth dynamics of tumor cells in vivo but also mapping spatial distribution of immune cells within a sub-cubic centimeter tissue, revealing cell heterogeneity. This provides a powerful means to explore complex biology in a simultaneous imaging manner at a single-cell resolution in organs or in vivo.

Abstract Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment. We used Microwell-seq3 to profile chromatin accessibility in more than 200,000 single nuclei and the full-length transcriptome in ~50,000 nuclei from multiple adult mouse tissues. Compared with the existing polyadenylated transcript capture methods, integrative analysis of cell type-specific regulatory elements and total RNA expression uncovered comprehensive cell type heterogeneity in the brain. Gene regulatory networks based on chromatin accessibility profiling provided an improved cell type communication model. Finally, we demonstrated that Microwell-seq3 can identify malignant cells and their specific regulons in spontaneous lung tumors of aged mice. We envision a broad application of Microwell-seq3 in many areas of research.

ABSTRACT Infection with Mycobacterium bovis precipitates a spectrum of pathologies in bovines, notably necrotic pneumonia, mastitis, and arthritis, impinging upon the health and nutritional assimilation of these animals. A pivotal factor, lipocalin 2 (Lcn2), is responsive to microbial invasion, inflammatory processes, and tissue damage, the extent of which Lcn2 modulates the gut environment, however, remains unclear in response to M. bovis-induced alterations. To explore the role of Lcn2 in shaping the gut milieu of mice during a 5-week period post-M. bovis infection, Lcn2 knockout Lcn2−/− mice were scrutinized for changes in the gut microbiota and metabolomic profiles. Results showed that Lcn2−/− mice infected with M. bovis exhibited notable shifts in the operational taxonomic units (OTUs) of gut microbiota, alongside significant disparities in α and β diversity. Concomitantly, a marked increase was observed during the 5-week period in the abundance of Akkermansia, Oscillospira, and Bacteroides, coupled with a substantial decrease in Ruminococcus within the microbiome of Lcn2 knockout mice. Notably, Akkermansia muciniphila was significantly enriched in the gut flora of Lcn2−/− mice. Furthermore, the absence of Lcn2 significantly altered the gut metabolomic landscape, evidenced by elevated levels of metabolites such as taurodeoxycholic acid, 10-undecenoic acid, azelaic acid, and dodecanedioic acid in Lcn2−/− mice. Our findings demonstrated that the lack of Lcn2 in the context of M. bovis infection profoundly affected the regulation of gut microbiota and metabolomic components, culminating in a transformed gut environment. Our results revealed that Lcn2 may regulate gut microbiota and metabolome components, changing the intestinal environment, thereby affecting the infection status of M. bovis.IMPORTANCEOur study addresses the critical knowledge gap regarding the specific influence of lipocalin 2 (LCN2) in the context of Mycobacterium bovis infection, particularly focusing on its role in the gut environment. Utilizing LCN2 knockout (Lcn2−/−) mice, we meticulously assessed changes in the gut microbiota and metabolic components following M. bovis infection. Our findings reveal alterations in the gut microbial community, emphasizing the potentially crucial role of LCN2 in maintaining stability. Furthermore, we observed significant shifts in specific microbial communities, including the enrichment of Akkermansia muciniphila, known for its positive impact on intestinal health and immune regulation. The implications of our study extend beyond understanding the dynamics of the gut microbiome, offering insights into the potential therapeutic strategies for gut-related health conditions and microbial dysbiosis.

AimsVitamin D deficiency (VDD) is prevalent in the population, with inadequate intake, impaired absorption and metabolism as the main causative factors. VDD increases the risk of developing chronic diseases such as type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), but the molecular mechanisms underlying this phenomenon are not known. The aim of this study was to investigate the association and potential mechanisms of vitamin D levels with the progression of DN by analyzing general clinical data and using bioinformatics methods.MethodsThe study included 567 diabetes mellitus type 2 (T2DM) patients from the Rocket Force Characteristic Medical Center as the case group and 221 healthy examinees as the normal control group. T2DM patients were categorized into T2DM, early diabetic nephropathy (EDN), and advanced diabetic nephropathy (ADN) based on the progression of diabetic nephropathy. The renal RNA-seq and scRNA-seq data of patients with DN were mined from public databases, and the differential expression of vitamin D-related genes in normal-EDN-ADN was analyzed by bioinformatics method, protein interaction network was constructed, immune infiltration was evaluated, single cell map was drawn, and potential mechanisms of VD and DN interaction were explored.ResultsChi-square test showed that vitamin D level was significantly negatively correlated with DN progression (p

Mobile edge computing (MEC) supported by unmanned aerial vehicle (UAV) and intelligent reflecting surface (IRS) can provide ubiquitous communication and computing services for internet of things (IoT) devices, particularly in remote areas and emergency situations caused by natural disasters. Additionally, integrating IRS and UAV can enhance the network’s secure service performance to address the significant challenges posed by colluding eavesdroppers in the system. To address the contradiction between high-security communication rate and low energy consumption, this paper introduces security energy efficiency as a performance metric for the system. To improve the security energy efficiency of the system, we propose an IRS-assisted UAV-MEC system for the joint optimization of computing resources, IRS phase shift, and UAV trajectory to maximize system’s performance. The optimization problem is a non-convex fraction problem, and complex coupling relations exist among the physical variables. We propose an iterative algorithm with a double-loop structure to solve the problem, in which the outer loop is based on the Dinkelbach method, and the inner loop is based on the block coordinate descent (BCD) algorithm to decompose the total problem. Finally, numerical simulations show that our proposed algorithm improves the system’s security energy efficiency compared with benchmark schemes, obtains a good trade-off between the security communication rate and energy consumption of the system, and improves the security communication performance of the system in the presence of colluding eavesdroppers.

Abstract Effective disinfection of contaminated surfaces is essential for preventing the transmission of pathogens. In this study, we investigated the UV irradiance and wavelength distribution of a 222-nm ultraviolet C (UVC) excimer lamp and its disinfection efficacy against microorganisms in laboratory conditions. By using a carrier quantitative germicidal test with stainless steel sheets as carriers, we examined the disinfection effect of the 222-nm UVC lamp on three standard strains-Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. We tested the disinfection efficacy under different conditions by adjusting irradiation time, as well as the state and temperature of the stainless steel carriers. Our results indicated that a bacterial suspension in PBS and not-dried stainless steel carriers yielded better disinfection than in TSB and dried carriers. Additionally, carrier temperature had no significant impact on disinfection efficacy. When utilizing a bacterial suspension in PBS and non-dried carriers at a temperature of 20 °C, the three bacteria were eliminated by 222-nm UVC excimer lamp irradiation in just 15 s. In contrast, when using a bacterial suspension in TSB and dried carriers at temperatures of 20 °C, 4 °C, or − 20 °C, the three bacteria were eradicated by 222-nm UVC excimer lamp irradiation in 60 s. Comparatively, the LPM lamp required more than 10 min to achieve the same disinfection effect. Our data demonstrate that the 222-nm UVC excimer lamp has higher irradiance and a more potent microbial disinfection effect than the LPM lamp, requiring significantly less irradiation time to achieve the same disinfection effect under identical conditions. Furthermore, the 222-nm UVC excimer lamp exhibited a substantial disinfection effect on bacterial propagules at low temperatures. Our findings support the optimization of “tunnel-type” cold-chain goods disinfection devices, providing an alternative, highly efficient, and practical tool to combat the spread of SARS-CoV-2 through cold-chain systems. Graphical Abstract

Both melatonin and hydrogen sulfide (H2S) mitigate chromium (Cr) toxicity in plants, but the specific interaction between melatonin and H2S in Cr detoxification remains unclear. In this study, the interaction between melatonin and H2S in Cr detoxification was elucidated by measuring cell wall polysaccharide metabolism and antioxidant enzyme activity in maize. The findings revealed that exposure to Cr stress (100 μM K2Cr2O7) resulted in the upregulation of L-/D-cysteine desulfhydrase (LCD/DCD) gene expression, leading to a 77.8% and 27.3% increase in endogenous H2S levels in maize leaves and roots, respectively. Similarly, the endogenous melatonin system is activated in response to Cr stress. We found that melatonin had a significant impact on the relative expression of LCD/DCD, leading to a 103.3% and 116.7% increase in endogenous H2S levels in maize leaves and roots, respectively. In contrast, NaHS had minimal effects on the relative mRNA expression of serotonin-Nacetyltransferase (SNAT) and endogenous melatonin levels. The production of H2S induced by melatonin is accompanied by an increase in Cr tolerance, as evidenced by elevated gene expression, elevated cell wall polysaccharide content, increased pectin methylesterase activity, and improved antioxidant enzyme activity. The scavenging of H2S decreases the melatonin-induced Cr tolerance, while the inhibitor of melatonin synthesis, p-chlorophenylalanine (p-CPA), has minimal impact on H2S-induced Cr tolerance. In conclusion, our findings suggest that H2S serves as a downstream signaling molecule involved in melatonin-induced Cr tolerance in maize.

Abstract A healthy intestine plays an important role in the growth and development of farm animals. In small intestine, Paneth cells are well known for their regulation of intestinal microbiota and intestinal stem cells (ISCs). Although there has been a lot of studies and reviews on human and murine Paneth cells under intestinal homeostasis or disorders, little is known about Paneth cells in farm animals. Most farm animals possess Paneth cells in their small intestine, as identified by various staining methods, and Paneth cells of various livestock species exhibit noticeable differences in cell shape, granule number, and intestinal distribution. Paneth cells in farm animals and their antimicrobial peptides (AMPs) are susceptible to multiple factors such as dietary nutrients and intestinal infection. Thus, the comprehensive understanding of Paneth cells in different livestock species will contribute to the improvement of intestinal health. This review first summarizes the current status of Paneth cells in pig, cattle, sheep, horse, chicken and rabbit, and points out future directions for the investigation of Paneth cells in the reviewed animals.

Background and objective: Osteosarcoma is a common primary malignant tumor of bone, and doxorubicin is one of the most widely used therapeutic drugs. While the problem of doxorubicin resistance limits the long-term treatment benefits in osteosarcoma patients. The role of miRNAs and their target genes in osteosarcoma have become increasingly prominent. Currently, there is no report on miR-506-3p reversing doxorubicin resistance by targeting STAT3 in osteosarcoma. The purpose of this study was to investigate the molecular mechanism that overexpression of miR-506-3p reverses doxorubicin resistance in drug-resistant osteosarcoma cells.Methods: Doxorubicin-resistant osteosarcoma cells (U-2OS/Dox) were constructed by intermittent stepwise increasing stoichiometry. The target genes of miR-506-3p were predicted by bioinformatics approach and the targeting relationship between miR-506-3p and STAT3 was detected using dual luciferase reporter assay. U-2OS/Dox cells were treated with miR-506-3p overexpression and STAT3 silencing respectively. Then Western blot and RT-qPCR were used to detect the protein and mRNA expression levels of JAK2/STAT3 signaling pathway, drug-resistant and apoptotic associated molecules. The migration and invasion were assessed by cell scratch assay and transwell assay. The cell proliferative viability and apoptosis were investigated by CCK8 assay and flow cytometry assay.Results: U-2OS/Dox cells were successfully constructed with a 14.4-fold resistance. MiR-506-3p is directly bound to the 3′-UTR of STAT3 mRNA. Compared with U-2OS cells, the mRNA expression of miR-506-3p was reduced in U-2OS/Dox cells. Overexpression of miR-506-3p decreased the mRNA expression levels of JAK2, STAT3, MDR1/ABCB1, MRP1/ABCC1, Survivin and Bcl-2, and decreased the protein expression levels of p-JAK2, STAT3, MDR1/ABCB1, MRP1/ABCC1, Survivin and Bcl-2, and conversely increased Bax expression. It also inhibited the proliferation, migration and invasion of U-2OS/Dox cells and promoted cells apoptosis. The results of STAT3 silencing experiments in the above indicators were consistent with that of miR-506-3p overexpression.Conclusion: Overexpression of miR-506-3p could inhibit the JAK2/STAT3 pathway and the malignant biological behaviors, then further reverse doxorubicin resistance in drug-resistant osteosarcoma cells. The study reported a new molecular mechanism for reversing the resistance of osteosarcoma to doxorubicin chemotherapy and provided theoretical support for solving the clinical problems of doxorubicin resistance in osteosarcoma.

BackgroundUrinary incontinence (UI) might be linked to suicidal ideation, but we do not yet have all the relevant details. This study aimed to dig deeper into the connection between UI and suicidal ideation using data from the National Health and Nutrition Examination Survey (NHANES).MethodsWe examined 31,891 participants aged ≥ 20 years from NHANES 2005-2018 who provided complete information. We used standardized surveys to check for UI and signs of suicidal ideation. To better understand this relationship, we used statistical tools such as multivariable logistic regression, subgroup analysis, and sensitivity analyses.ResultsAmong the 31,891 participants, 28.9% reported UI and 10.7% reported suicidal ideation. Those with UI exhibited a significantly greater incidence of suicidal ideation (15.5%) than did those without UI (8.8%, P < 0.001). After adjusting for various factors, including age, sex, marital status, socioeconomic status, educational level, lifestyle factors, and chronic comorbidities, UI remained significantly associated with suicidal ideation (OR:1.54, 95% CI = 1.39-1.7, P < 0.001). Among all types of UI, MUI participants were more likely to experience suicidal ideation. Compared with no UI, higher odds of suicidal ideation suffered from MUI (OR:2.11, 95%CI:1.83-2.44, P < 0.001), SUI (OR:1.4, 95%CI:1.19-1.65, P < 0.001), UUI(OR:1.37,95%CI:1.16-1.62, P < 0.001) after full adjustment. With the exception of individuals living with a partner, the remaining subgroups exhibited a positive correlation between urinary incontinence and suicidal ideation, considering that factors such as age, sex, and prevalent comorbidities such as hypertension, depression, and diabetes did not reveal any statistically significant interactions (all P > 0.05). Sensitivity analyses, incorporating imputed missing covariates, did not substantially alter the results (OR: 1.53, 95% CI: 1.4-1.68, P < 0.001).ConclusionUrinary incontinence may correlate with increased suicidal ideation risk, priority screening for suicidal ideation and timely intervention are essential for individuals with urinary incontinence, but prospective studies are needed to verify the results.

In this study, lightweight strain hardening cementitious composites (LW-SHCC) was developed through mix proportion design and experimental tests. The modified Andreasen and Andersen (A&A) model was applied for dry materials mixture proportioning and micromechanics for the fiber-reinforced composites were applied for designing the materials achieving multiple cracking and strain hardening characteristics. Four types of 3M™ glass microbubbles were considered as lightweight aggregates to achieve the lightweight of the composites. The designed SHCC mixes were tested in the lad, including tensile test and compressive test, to optimize the mixture design of the SHCC. Results showed the developed LW-SHCC exhibited tensile strain capacities of 3.05–4.07 % at the densities of 1.20–1.44 g/cm3. A numerical simulation was conducted to predict the tensile behavior of LW-SHCC based on the micromechanics model, which can simulate the initial and peak values of stress and strain of SHCC materials. Simulation results indicated that the tensile response could be reasonably predicted using the proposed numerical model and glass microbubbles acting as artificial flaws were an ideal material to develop the tensile strain hardening and multiple cracking behavior of the composites.

Abstract Background Caloric restriction (CR) has been known to promote health by reprogramming metabolism, yet little is known about how the epigenome and microbiome respond during metabolic adaptation to CR. Results We investigate chromatin modifications, gene expression, as well as alterations in microbiota in a CR mouse model. Collectively, short-term CR leads to altered gut microbial diversity and bile acid metabolism, improving energy expenditure. CR remodels the hepatic enhancer landscape at genomic loci that are enriched for binding sites for signal-responsive transcription factors, including HNF4α. These alterations reflect a dramatic reprogramming of the liver transcriptional network, including genes involved in bile acid metabolism. Transferring CR gut microbiota into mice fed with an obesogenic diet recapitulates the features of CR-related bile acid metabolism along with attenuated fatty liver. Conclusions These findings suggest that CR-induced microbiota shapes the hepatic epigenome followed by altered expression of genes responsible for bile acid metabolism.

Abstract Using the wire beam electrode technique, electrochemical impedance spectroscopy, energy-dispersive X-ray spectroscopy, the formation of calcareous deposits in a tidal zone and its effects on the corrosion and protection of Q235 steel under cathodic protection were studied. Results showed that the production of aragonite CaCO3 crystals significantly reduced from the immersion zone to the high-tide zone, the protective performance of the deposited layer weakened, and the corrosion of the metal intensified. In the immersion zone, the cathodic protection current density decreased, and the potential shifted negatively, indicating that the protection performance of the deposited layer was enhanced and the metal was effectively protected. In the tidal zone, the deposited layer was stratified, and the porosity of the deposited layer increased by dry-wet cycling. During flood tide, the cathodic reaction is accelerated near the waterline, which promotes the corrosion of the metal and the loss of the sacrificial anode under water.

In order to prepare biomass-derived carbon materials with high specific capacitance at a low activation temperature (≤700 °C), nanoporous carbon materials were prepared from zanthoxylum bungeanum peels and seeds via the pyrolysis and KOH-activation processes. The results show that the optimal activation temperatures are 700 °C and 600 °C for peels and seeds. Benefiting from the hierarchical pore structure (micropores, mesopores, and macropores), the abundant heteroatoms (N, S, and O) containing functional groups, and plentiful electrochemical active sites, the PAC-700 and SAC-600 derive the large capacities of ~211.0 and ~219.7 F g−1 at 1.0 A g−1 in 6 M KOH within the three-electrode configuration. Furthermore, the symmetrical supercapacitors display a high energy density of 22.9 and 22.4 Wh kg−1 at 7500 W kg−1 assembled with PAC-700 and SAC-600, along with exceptional capacitance retention of 99.1% and 93.4% over 10,000 cycles at 1.0 A g−1. More significantly, the contribution here will stimulate the extensive development of low-temperature activation processes and nanoporous carbon materials for electrochemical energy storage and beyond.

Hydrogen sulfide (H2S), a novel gas signaling molecule, has been shown to enhance plant resistance to various abiotic stresses. Here, we investigated the effect of sodium hydrosulfide (NaHS, a H2S donor) on the growth, photosynthetic parameters, and enzyme activities related to carbon and nitrogen metabolism, as well as the levels of carbohydrates and nitrogen metabolites in foxtail millet seedlings subjected to drought stress conditions in pots. The findings revealed that drought stress led to a significant 41.2% decline in the total dry weight (DW) after 12 days of treatment, whereas plants treated with NaHS showed a lesser reduction of 18.7% in total DW. Under drought stress, exogenous NaHS was found to enhance carbon metabolism in foxtail millet seedlings by significantly enhancing photosynthetic capacity, starch, and sucrose content. Additionally, exogenous NaHS was observed to improve nitrogen metabolism by substantially increasing soluble protein content, nitrogen assimilate activity, and synthesis of nitrogen-containing compounds in foxtail millet seedlings. In summary, the exogenous application of NaHS stimulated seedling growth and enhanced drought resistance in foxtail millet by modulating carbon and nitrogen metabolism processes affected by drought stress.

Deoxynivalenol (DON) is a common toxin in grains and feeds, and DON exposure triggers severe small intestinal injury and inflammation, which harms the health of humans and livestock. DON treatment leads to a decrease in Paneth cells, whereas the role of Paneth cells in DON-induced intestinal injury is poorly understood. We utilized dithizone (40 mg/kg) to keep murine Paneth cell number at a low level. The results showed that dithizone-mediated long-term disruption of Paneth cells aggravated intestinal injury, intestinal stem cell (ISC) loss, and microbiota disorder in DON (2 mg/kg)-treated mice. Unexpectedly, the number of goblet cells and proliferative cells was boosted in mice treated with dithizone and DON. After dithizone and DON treatments, the Firmicutes/Bacteroidetes (F/B) ratio was reduced, and the increased abundance of Dubosiella and the decreased abundance of Lactobacillus were observed in mice. The functional recovery of Paneth cells by lysozyme (200 U/day) supplementation improved intestinal injury and ISC loss in mice after DON challenge. In addition, lysozyme also promoted the growth and ISC activity of intestinal organoids. Taken together, these results demonstrate the protective role of Paneth cells in DON-induced intestinal injury. Our study raises a novel target, Paneth cell, for the treatment of DON exposure.

Particulate matter (PM2.5, PM10) in urban subway stations can significantly impact passengers' health. The particle concentration in subway stations is influenced by many factors. However, few existing studies have explored the impact of environmental control systems in-depth, especially under different outdoor pollution conditions. To address this research gap, this study focused on measuring and comparing the characteristics of PM2.5 and PM10 at subway stations with three control systems (open, closed, and screen door) under varying pollution conditions in Beijing. Particle concentrations from platforms, carriages, and outdoors were monitored and analyzed using statistical methods. The results showed that the particle concentration in the closed system was generally 20–40 μg/m3 higher than that in the screen system at the platform, which might be attributed to the piston wind, as the air from the tunnel with a lot of dirt. The pollution in the carriage was more severe for the open system than that of the screen system. The PM2.5/PM10 ratio in the carriage was 91%, 90%, and 83.84% for the closed, open, and screen systems, respectively. This indicates that the screen door could reduce the particle concentration in the platform to 10%–50%. The particle concentration varied among subway stations with different environmental control systems, suggesting that the prevention and control strategies for particulate matter pollution should be different for stations with different systems.

Abstract Background Monochasma savatieri Franch. ex Maxim is a medicinally valuable herb. However, the collection and protection of the wild germplasm resources of M. savatieri are still insufficient, and their genetic diversity and population structure have been poorly studied. Results We collected and examined 46 M. savatieri individuals from Fujian, Hunan, Jiangxi, and Zhejiang provinces for genetic diversity and population structure, using 33 newly developed expressed sequence tag-simple sequence repeat (EST-SSR) markers. Applying these markers, we detected a total of 208 alleles, with an average of 6.303 alleles per locus. The polymorphic information content varied from 0.138 to 0.884 (average: 0.668), indicating a high level of polymorphism. At the population level, there was a low degree of genetic diversity among populations (I = 0.535, He = 0.342), with Zhejiang individuals showing the highest genetic diversity among the four populations (Fst = 0.497), which indicated little gene flow within the M. savatieri populations (Nm = 0.253). Mantel test analysis revealed a significant positive correlation between geographical and genetic distance among populations (R 2 = 0.3304, p

Abstract Background Studies have investigated the association between serum lipids level or apolipoprotein levels and breast cancer (BC) risk. However, the relationship between serum lipids level and apolipoprotein levels and histological type of breast cancer remains unclear. This study was aimed to explore the association between serum lipids level and the histological type of BC, particularly to estrogen receptor (ER) and progesterone receptor (PR) positive BC. Materials and methods 220 cases of pathology-confirmed BC were retrospectively collected in this study. Patients’ demographic information, clinical data, and pathological features were obtained from medical records. Serum levels including high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), ApoB, ApoE and lipoprotein a(LP(a)) were collected before treatment. Logistic regression analyses were used to show the association between serum lipids and subtypes of BC. Receiver operating characteristic (ROC) curves were generated to analyze the predictive performance. Results There were 70 ER-negative and 73 PR-negative BC. Patients with ER-negative BC had higher HDL-c, higher LDL-c, and higher LP(a) than those in ER-positive one (p

The Mexican axolotl is a well-established tetrapod model for regeneration and development. Here the authors report a scRNA-seq method to profile neotenic, metamorphic and limb development stages, highlighting unique perturbation patterns of cell type-related gene expression throughout metamorphosis.

Single-cell RNA sequencing technology offers a unique opportunity to dissect cell heterogeneity of animals. Here, the authors construct a Xenopus cell landscape including larval and adult organs to dissect cell heterogeneity of the amphibian.

Abstract Background The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. Methods One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. Results The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12–0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12–5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02–0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06–0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79–0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70–0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08–0.99). Conclusion Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis.

ObjectiveThis study aimed to analyze the changes in structure and function in amygdala sub-regions in patients with postpartum depression (PPD) before and after acupuncture.MethodsA total of 52 patients with PPD (All-PPD group) were included in this trial, 22 of which completed 8 weeks of acupuncture treatment (Acu-PPD group). An age-matched control group of 24 healthy postpartum women (HPW) from the hospital and community were also included. Results from the 17-Hamilton Depression Scale (17-HAMD) and the Edinburgh Postnatal Depression Scale (EPDS) were evaluated, and resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed at baseline and after the acupuncture treatment. Sub-regions of the amygdala were used as seed regions to measure gray matter volume (GMV) and analyzed for resting-state functional connectivity (RSFC) values separately. Finally, correlation analyses were performed on all patients with PPD to evaluate association values between the clinical scale scores, GMV, and RSFC values, while controlling for age and education. Pearson's correlation analyses were conducted to investigate the relevance between GMV and RSFC values of brain regions that differed before and after acupuncture treatment and clinical scale scores in Acu-PPD patients.ResultsThe HAMD scores for Acu-PPD were reduced after acupuncture treatment (P < 0.05), suggesting the positive effects of acupuncture on depression symptoms. Structurally, the All-PPD group showed significantly decreased GMV in the left lateral part of the amygdala (lAMG.L) and the right lateral part of the amygdala (lAMG.R) compared to the HPW group (P < 0.05). In addition, the GMV of lAMG.R was marginally increased in the Acu-PPD group after acupuncture (P < 0.05). Functionally, the Acu-PPD group showed a significantly enhanced RSFC between the left medial part of the amygdala (mAMG.L) and the left vermis_6, an increased RSFC between the right medial part of the amygdala (mAMG.R) and left vermis_6, and an increased RSFC between the lAMG.R and left cerebelum_crus1 (P < 0.05). Moreover, correlation studies revealed that the GMV in the lAMG.R was significantly related to the EPDS scores in the All-PPD group (P < 0.05).ConclusionOur findings demonstrated that the structure of amygdala sub-regions is impaired in patients with PPD. Acupuncture may improve depressive symptoms in patients with PPD, and the mechanism may be attributed to changes in the amygdala sub-region structure and the functional connections of brain areas linked to the processing of negative emotions. The fMRI-based technique can provide comprehensive neuroimaging evidence to visualize the central mechanism of action of acupuncture in PPD.

Occult hepatitis B virus (HBV) infection (OBI) is a condition in which replication-competent viral DNA is detected in the liver (with detectable or undetectable HBV DNA in serum) of individual testing negative for HBV surface antigen (HBsAg). It is a risk factor for transfusion or transplant transmission, reactivation after immunosuppression or chemotherapy, and progression of chronic liver disease and hepatocarcinogenesis. The long-term stable presence of covalently closed circular DNA (cccDNA), which is fully replicative in the nucleus of infected hepatocytes is the molecular basis for the formation of OBI. HBV genome in liver tissue, HBV DNA and anti-HBc test in serum are the gold standard, common method and alternative markers for OBI diagnosis, respectively. Due to the stability of covalently closed circular DNA (cccDNA) and the long half-life of hepatocytes, the existence of OBI is extensive and prolonged. The low and/or intermittent replication of HBV in OBI patients, the limitations of the sensitivity of serological tests, and the non-standardized and invasive nature of liver histology render the “commonly used” serological tests are unreliable and the “gold standard” liver histology is impractical, thus the findings from studies on the formation, diagnosis and transplantation or transfusion transmission of HBV in OBI strongly suggest that the “alternative” marker, the anti-HBc test, may be the most reliable and practical approach for OBI diagnosis.

As the largest internal organ of the human body, the liver has an extremely complex vascular network and multiple types of immune cells. It plays an important role in blood circulation, material metabolism, and immune response. Optical imaging is an effective tool for studying fine vascular structure and immunocyte distribution of the liver. Here, we provide an overview of the structure and composition of liver vessels, the three-dimensional (3D) imaging of the liver, and the spatial distribution and immune function of various cell components of the liver. Especially, we emphasize the 3D imaging methods for visualizing fine structure in the liver. Finally, we summarize and prospect the development of 3D imaging of liver vessels and immune cells.

From 2018, several foodborne diseases caused by the consumption of wet rice noodles contaminated with microorganisms have attracted the attention of consumers and surveillance departments. We explored the crucial risk factors for the contamination of Bacillus cereus during the various steps of the wet rice noodles production chain (from raw material to marketing phase). A total of 273 samples were collected in each corresponding production phase. The contamination level was quantitatively detected in the samples, and the corresponding temperature and time were recorded and analyzed using @Risk software. The quantitative detection results of raw material were determined as the initial contamination level in the model to predict the final contamination level and assess the key risk factors for B. cereus contamination in wet rice noodles. The model predicted that the final contamination level of B. cereus was in the range of −3.55 to 4.34 log CFU/g in 95% wet rice noodles at the marketing phase. The highest predicted contamination level was 6.28 log CFU/g, and the risk of exceeding the threshold was 0.80%. The model was verified to be valid for R2 > 0.96, and the predicted results could be used for reference. Moreover, the sensitivity analysis revealed that in addition to raw material, the key control factors were buffering temperature in the packaging delivery phase, transporting temperature and time from factory to marketing phase; their correlation coefficients (r) were 0.18, 0.16, and 0.15, respectively. Therefore, manufacturers need to adjust the current predelivery buffering and transporting mode. It is recommended to reduce the predelivery buffering temperature, and refrigerated trucks are preferred to control the proliferation of B. cereus in transported food, thus reducing the occurrence of foodborne diseases and improving the safety of food.

Serving as the guardians of small intestine, Paneth cells (PCs) play an important role in intestinal homeostasis maintenance. Although PCs uniquely exist in intestine under homeostasis, the dysfunction of PCs is involved in various diseases not only in intestine but also in extraintestinal organs, suggesting the systemic importance of PCs. The mechanisms under the participation of PCs in these diseases are multiple as well. The involvements of PCs are mostly characterized by limiting intestinal bacterial translocation in necrotizing enterocolitis, liver disease, acute pancreatitis and graft-vs-host disease. Risk genes in PCs render intestine susceptible to Crohn’s disease. In intestinal infection, different pathogens induce varied responses in PCs, and toll-like receptor ligands on bacterial surface trigger the degranulation of PCs. The increased level of bile acid dramatically impairs PCs in obesity. PCs can inhibit virus entry and promote intestinal regeneration to alleviate COVID-19. On the contrary, abundant IL-17A in PCs aggravates multi-organ injury in ischemia/reperfusion. The pro-angiogenic effect of PCs aggravates the severity of portal hypertension. Therapeutic strategies targeting PCs mainly include PC protection, PC-derived inflammatory cytokine elimination, and substituting AMP treatment. In this review, we discuss the influence and importance of Paneth cells in both intestinal and extraintestinal diseases as reported so far, as well as the potential therapeutic strategies targeting PCs.

Construction healthy city is a global strategy advocated by the WHO to address the social and environmental problems brought about by urbanization worldwide, and is also an important grip for China to promote the strategy of Beautiful China and Healthy China in the new era. This study constructed an evaluation system for health development efficiency (HDE) of Chinese cities from an input–output perspective, evaluated the HDE of 284 prefecture-level and above cities in China from 2009 to 2019 using the super-efficient SBM model, and further explored the dynamic transfer characteristics, spatial spillover effects, and future development trends of urban HDE in depth using Markov chain model and spatial Markov chain model. The main findings were as follows. (1) From 2009 to 2019, the average level of HDE in Chinese cities generally showed a “W-shaped” fluctuating upward trend, increasing from 0.6106 to 0.6538, an overall increase of 7 %. However, the overall input–output efficiency was still relatively low, with only 27.11 % of cities in a high efficiency state in 2019. (2) The spatial distribution pattern of HDE of cities nationwide showed a gradually decreasing pattern with the urban cluster cities as the core, specifically “eastern cities > western cities > central cities” and “mega cities > super cities > large cities > medium cities > small cities”. (3) There was a significant spatial spillover effect on the HDE of Chinese cities. When a city was adjacent to a region with low HDE, the probability of its HDE type shifting downward increased, and when it was adjacent to a region with high HDE, the probability of its HDE type shifting upward increased. (4) In the long term, the distribution of urban HDE in China gradually shifted from intermediate (ML and MH) to high (H) or low (L) state over time, with the greatest possibility (27.40 %) of dynamic shift to high (H) states. After further classification and prediction based on spatial neighborhood states, heterogeneity in the future evolutionary impact of different neighborhood contexts on urban HDE was found. These findings can provide references for improving the quality of healthy cities work and optimizing healthy cities guidance policies.

Abstract Aim This study aimed to assess advance care planning readiness among patients with chronic diseases and identify its relationship to patients’ coping styles. Design A cross‐sectional study. Methods Patients with chronic diseases (N = 168) were recruited from community health service centres. We used a self‐designed and validated “advance care planning readiness questionnaire” to measure the patients’ advance care planning readiness and a "simplified coping style questionnaire” to measure the patients’ coping styles. Results Multiple linear regression analyses observed a positive relationship between “active coping style” (p = .002, 95%CI: 1.788, 7.599) with ACP readiness and a negative relationship between “passive coping style” (p

Abstract Background Several studies have suggested adverse effects of particulate matter (PM) exposure on male reproductive health; few have investigated the association between PM exposure and semen quality in a large population of fertile men. Methods We evaluated 14 parameters of semen quality in 1554 fertile men in Nanjing from 2014 to 2016. Individual exposure to particular matter ≤10 μm in diameter (PM10) and ≤ 2.5 μm in diameter (PM2.5) during key periods of sperm development (0-90, 0-9, 10-14, 15-69, and 70-90 days before semen collection) were estimated by inverse distance weighting interpolation. Associations between PM exposure and semen quality were estimated using multivariable linear regression. Results Higher 90-days average PM2.5 was in association with decreased sperm motility (2.21% for total motility, 1.93% for progressive motility per 10 μg/m3 increase, P

Abstract Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide and is accompanied by low diagnosis and survival rates. The molecular mechanism of GC must be elucidated to improve treatment strategies. Recent research has shown that the expression of myelin and lymphocyte (MAL) protein is reduced in a variety of adenocarcinomas and has the function of suppressing tumor growth. However, the mechanism by which MAL regulates the epithelial-mesenchymal transition (EMT) in GC remains unclear. Here, we showed that MAL expression was downregulated in specimens from patients with GC and was negatively correlated with the clinical stage. Gain- and loss-of function assays showed that interference with MAL significantly increased tumor cell proliferation, metastasis, invasion and the EMT. Overexpression of MAL significantly inhibited the malignant behavior of GC cells. Moreover, MAL suppressed the malignant behavior of GC cells by inhibiting STAT3 phosphorylation in vitro and in vivo. Our data indicate that MAL suppresses the malignant behavior of GC cells via the STAT3/EMT axis. This study also provides insights into the pathophysiological process of GC and a reference for diagnosis and treatment.

Lignin, the most abundant source of renewable aromatic compounds on the planet, is attracting more scholarly attention due to its possibility of replacing petroleum-based chemicals and products. However, it remains underutilized because of the heterogeneity of its multi-level structure that prevents homogenization and standardization of derived products. The key to solving these problems lies in finding a general preparation method to achieve the integrated utilization of lignin molecules at all levels. The assembly-mediated granulation methods provide a significant means for the integrated value-added utilization of lignin, and for biomass productization applications, it is significant to understand the molecular mechanisms of lignin nano-colloids (LNCs) formation thus accurately guiding their functionalization. Therefore, a thorough understanding of the assembly morphology and behavior of lignin in different solutions towards colloids is of great scientific importance. In this minireview, we focus on the assembly behavior of lignin in different solvents, specifically in mono-solvent and multi-solvent, and in particular, we review various methods for preparing lignin composite colloids and concentrate on the applications in therapy, cosmetics and emulsification, which are important for guiding the preparation and efficient utilization of LNCs.

Abstract Background Peroxisome proliferator-activated receptor alpha (PPARα) is associated with diabetic retinopathy (DR), and the underlying mechanism is still unclear. Aim of this work was to investigate the mechanism of PPARα in DR. Methods Human retinal capillary pericytes (HRCPs) were treated with high glucose (HG) to induce DR cell model. DR mouse model was established by streptozotocin injection, and then received 5-Aza-2-deoxycytidine (DAC; DNA methyltransferase inhibitor) treatment. Hematoxylin–eosin staining was performed to assess retinal tissue damage. PPARα methylation was examined by Methylation-Specific PCR. Flow cytometry and DCFH-DA fluorescent probe was used to estimate apoptosis and reactive oxygen species (ROS). The interaction between DNA methyltransferase-1 (DNMT1) and PPARα promoter was examined by Chromatin Immunoprecipitation. Quantitative real-time PCR and western blot were performed to assess gene and protein expression. Results HG treatment enhanced the methylation levels of PPARα, and repressed PPARα expression in HRCPs. The levels of apoptotic cells and ROS were significantly increased in HRCPs in the presence of HG. Moreover, DNMT1 was highly expressed in HG-treated HRCPs, and DNMT1 interacted with PPARα promoter. PPARα overexpression suppressed apoptosis and ROS levels of HRCPs, which was rescued by DNMT1 up-regulation. In DR mice, DAC treatment inhibited PPARα methylation and reduced damage of retinal tissues. Conclusion DNMT1-mediated PPARα methylation promotes apoptosis and ROS levels of HRCPs and aggravates damage of retinal tissues in DR mice. Thus, this study may highlight novel insights into DR pathogenesis.

Abstract Background Intraductal papillary mucinous neoplasms (IPMNs) can potentially undergo malignant transformation. Studies have shown that high-density lipoprotein cholesterol (HDL-c) was associated with the risk of cancer. In this study, the association between HDL-c and the incidence of malignancy in IPMNs was investigated. Materials and methods 226 patients with histologically proven IPMNs who underwent surgery were included in the present study. Patients were assigned to a training group (n = 151) and validation group (n = 75). Patients’ demographic information, clinical data, and histopathological evaluation findings were obtained from medical records. Malignant IPMNs were defined as lesions that showed high grade dysplasia and invasive carcinoma. Logistic regression analyses were used to show the association between HDL-c and malignant IPMNs. Receiver operating characteristic (ROC) curves were generated to analyze predictive performance. Results The prevalence of low HDL-c levels was higher in patients with malignant IPMNs than in those with non-malignant IPMNs (P

Unexplained recurrent pregnancy loss (URPL) is a significant reproductive health issue, affecting approximately 5% of pregnancies. Enhancer RNAs (eRNAs) have been reported to play important roles during embryo development and may be related to URPL. To investigate whether and how eRNAs are involved in URPL, we performed RNA sequencing in decidual tissue. Through comprehensive screening and validation, we identified a decidua-enriched eRNA long noncoding-CES1-1 (lnc-CES1-1) enriched in URPL patients and studied its function in decidua-associated cell lines (DACs). Higher expression of lnc-CES1-1 increased the level of inflammatory factors tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) and impaired the cell migration ability, which was attenuated by downregulating peroxisome proliferators-activated receptor γ (PPARγ). Upon activation by signal transduction and activation of transcription 4 (STAT4), lnc-CES1-1 interacted with the transcription factor fused in sarcoma (FUS) to upregulate the expression of PPARγ and affected cell migration. Taken together, these findings provide novel insights into the biological functions of decidua-associated lnc-CES1-1 and the molecular mechanisms underlying URPL. Our findings indicated that lnc-CES1-1 might be a potential candidate biomarker for URPL diagnosis and treatment.

Since the outbreak of the COVID-19 epidemic, it has spread on a large scale around the world, seriously affecting people’s physical and mental health. In China, almost all schools have postponed semesters, suspended offline classes, and implemented closed-off management, which has brought significant challenges to the study and life of college students. The study aimed to explore the relationship between risk perception, perceived stress, perceived control, and mental health among Chinese college students. This cross-sectional study was conducted among 1,856 college students. The results showed that risk perception was positively correlated with mental health. After adding the mediating variable of perceived stress, risk perception still significantly predicted mental health. In addition, the interaction term of perceived stress and perceived control significantly negatively predicted mental health. Specifically, perceived stress significantly affected mental health in the low-perceived control group. In contrast, in the high-perceived control group, the predictive effect of perceived stress on mental health disappeared. The present study showed that perceived stress partially mediated the relationship between risk perception and mental health; perceived control moderated the relationship between perceived stress and mental health, and high perceived control could buffer the effect of perceived stress on mental health.

Alkylphenol ethoxylates (APEOs) represent a non-ionic surfactant widely used as adjuvants in pesticide formulation, which is considered to cause an endocrine-disrupting effect. In the current study, we established a detection method for the APEOs residue in tea based on solid-phase extraction (SPE) for the simultaneous analysis of nonylphenol ethoxylates (NPEOs) and octylphenol ethoxylates (OPEOs) by UPLC–MS/MS. In the spiked concentrations from 0.024 to 125.38 μg/kg for 36 monomers of APEOs (nEO = 3–20), the recoveries of APEOs range from 70.3–110.7% with RSD ≤ 16.9%, except for OPEO20 (61.8%) and NPEO20 (62.9%). The LOQs of OPEOs and NPEOs are 0.024–6.27 and 0.16–5.01 μg/kg, respectively. OPEOs and NPEOs are detected in 50 marketed tea samples with a total concentration of 0.057–12.94 and 0.30–215.89 µg/kg, respectively. The detection rate and the range of the monomers of NPEOs are generally higher than those of OPEOs. The current study provides a theoretical basis for the rational use of APEOs as adjuvants in commercial pesticide production.

Abstract Obstacles to widespread deployments of direct air capture of CO2 (DAC) lie in high material and energy costs. By grafting quaternary ammonium (QA) functional group to mesoporous polymers with high surface area, a unique DAC adsorbent with moisture swing adsorption (MSA) ability and ultra-high kinetics was developed in this work. Functionalization is designed for efficient delivery of QA group through mesopores to active substitution sites. This achieved ultra-high kinetics adsorbent with half time of 2.9 min under atmospheric environment, is the highest kinetics value reported among DAC adsorbents. A cyclic adsorption capacity of 0.26 mmol g−1 is obtained during MSA process. Through adsorption thermodynamics, it is revealed that adsorbent with uniform cylindrical pore structure has higher functional group efficiency and CO2 capacity. Pore structure can also tune the MSA ability of adsorbent through capillary condensation of water inside its mesopores. The successful functionalization of mesoporous polymers with superb CO2 adsorption kinetics opens the door to facilitate DAC adsorbents for large-scale carbon capture deployments.

Our study aims to explore the active components and mechanisms of the Danshen-Guizhi drug pair in treating ovarian cancer by network pharmacology and in vitro experiment. The “component-target-pathway” diagram of the Danshen-Guizhi drug pair was established by network pharmacology, and the effective active components, important targets as well as potential mechanisms of the Danshen-Guizhi drug pair were analyzed. The predicted results were verified by molecular docking and in vitro experiments. The main active components of the Danshen-Guizhi drug pair in the treatment of ovarian cancer are salviolone, luteolin, β-sitosterol and tanshinone IIA. The main core target is PTGS2. The pathways involved mainly include the cancer pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. The molecular docking results showed that salviolone and tanshinone IIA had good binding ability to the target. The expression of PTGS2 mRNA and PGE2 in ovarian cells were significantly inhibited by salviolone. The mechanism of the Danshen-Guizhi drug pair in the treatment of ovarian cancer may be regulating cell proliferation, apoptosis and tumor immunity. This provides a theoretical basis for the clinical development and application of the Danshen-Guizhi drug pair.

Benzophenone-3 (BP-3) is widely used in a variety of cosmetics and is prevalent in drinking water or food, and women were under notable high exposure burden of BP-3. Reports show the associations between prenatal exposure to BP-3 and the risk of fetal loss, but its underlying mechanism remains largely unknown. Pregnant ICR mice were gavaged with BP-3 from gestational day (GD) 0 to GD 6 at doses of 0.1, 10 and 1000 mg/kg/day. The samples were collected on GD 12. Ultra-performance liquid chromatography coupled with mass spectrometry-based metabolomics was used to detect metabolome changes in fetal mice, the uterus and the placenta to identify the underlying mechanism. The results showed that the body weight and relative organ weights of the liver, brain and uterus of pregnant mice were not significantly changed between the control group and the treatment group. BP-3 increased fetal loss, and induced placental thrombosis and tissue necrosis with enhancement of platelet aggregation. Metabolomic analysis revealed that fructose and mannose metabolism, the TCA cycle, arginine and proline metabolism in the fetus, arginine and proline metabolism and biotin metabolism in the uterus, and arginine biosynthesis and pyrimidine metabolism in the placenta were the key changed pathways involved in the above changes. Our study indicates that exposure to BP-3 can induce placental thrombosis and fetal loss via the disruption of maternal and fetal metabolism in mice, providing novel insights into the influence of BP-3 toxicity on the female reproductive system.

Background Obesity has become one of the most serious issues threatening the health of humankind, and we conducted this study to examine whether and how celastrol protects against obesity. Methods We fed male Sprague-Dawley rats a high-fat diet and administered celastrol to obese rats for 3 weeks. By recording body weight (BW) and other measures, we identified the effective dose of celastrol for obesity treatment. Feces were collected to perform 16S rRNA sequencing, and hypothalami were extracted for transcriptome sequencing. We then treated leptin knockout rats with celastrol and explored the changes in energy metabolism. Male Institute of Cancer Research (ICR) mice were used to test the acute toxicity of celastrol. Results We observed that celastrol reduced BW and promoted energy expenditure at a dose of 500 µg/kg BW but that food intake was not changed after administration. The diversity of the gut microbiota was improved, with an increased ratio of Bacteroidetes to Firmicutes, and the gut microbiota played an important role in the anti-obesity effects of celastrol. Hypothalamic transcriptome analysis showed a significant enrichment of the leptin signaling pathway, and we found that celastrol significantly enhanced energy expenditure, which was mediated by the leptin signaling pathway. Acute lethal toxicity of celastrol was not observed at doses ranging from 0 to 62.5 mg/kg BW. Conclusion Our study revealed that celastrol decreased the BW of obese rats by enhancing energy expenditure but not by suppressing food intake and that this effect was mediated by the improvement of the gut microbiota and the activation of the hypothalamic leptin signaling pathway.

Abstract Background Successful implantation and delivery require both the functional embryo and receptive endometrium in assisted reproductive technology (ART) cycles. However, little is known about embryo-endometrial interaction on live-birth. We aimed to investigate the independent effect and interaction of endometrial thickness (EMT) and embryo quality on live-birth in fresh embryo transfer (ET) cycles. Methods We conducted a retrospective cohort study including 15,012 ART cycles between 2013 and 2016 in three centers in China. Poisson regression with generalized estimating equations was employed to calculate relative risks (RRs) and 95% confidence intervals (CIs). We estimated the interaction of embryo quality and EMT on live-birth rate (LBR). Results The LBR per cycle was 42.8% overall. LBR increased with increasing EMT and reached a plateau (50.6 to 54.2%) when EMT was 11 mm or thicker. Embryo quality represented by cumulative score was associated with LBR independently of number of embryos transferred and EMT. LBR was not increased with thicker EMT when only Q1 cleavage-stage embryo transferred (aRR 0.95, 95%CI 0.61–1.46). LBR was not increased significantly with thicker EMT with transfer of two good-quality cleavage-stage embryos and any blastocyst combination except Q1 group. There was significant interaction between EMT and embryo quality on LBR for cleavage-stage ETs (P=0.023). Conclusions This study demonstrated the nonlinear EMT-LBR association and the EMT cut-off value of 11 mm which may be of more clinical significance for predicting live-birth. Embryo quality is an independent prognostic tool for LBR. Our finding of significant embryo-endometrial interaction indicates combination of EMT and embryos quality might improve the prognostic value in clinical practice for live-birth in patients undergoing transfer of 1–2 fresh cleavage-stage embryos.

Abstract Background Heat shock protein 27 (HSP27) has been proposed as a vital protective factor in atherosclerosis. The objective of the present study was to evaluate the association between circulating HSP27 and carotid intima–media thickness (IMT) in individuals with type 2 diabetes and to determine whether HSP27 represents an independent marker of subclinical atherosclerosis in this patient population. Methods We performed a cross-sectional community-based study in 186 Chinese subjects with a median duration of type 2 diabetes of 8.2 years who underwent ultrasound carotid IMT measurement. Serum HSP27 levels were assessed by ELISA. Results Serum HSP27 levels were significantly higher in the IMT (+, > 1.0 mm) group than in the IMT (−, ≤1.0 mm) group, with the median values of 8.80 ng/mL (5.62–12.25) and 6.93 ng/mL (4.23–9.60), respectively (P = 0.006). The discriminative value of HSP27 to evaluate IMT was 7.16 ng/mL and the area under the curve was 0.72 (95%CI = 0.64–0.80, P = 0.0065). Spearman’s rank correlation analysis demonstrated that the concentrations of circulating HSP27 were positively associated with carotid IMT (r = 0.198, P = 0.007) and blood urea nitrogen (r = 0.170, P