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This paper aimed to investigate the antioxidant activity of buckwheat bee pollen polysaccharides (BWPP) during the in vitro gastrointestinal digestion. The crude polysaccharides were purified using DEAE-52 cellulose column and their antioxidant activity during in vitro simulated gastric and intestinal digestion was studied. The results showed that after purification by DEAE-52 cellulose column chromatography, the highest total sugar content component BWPP-1 was obtained, which was mainly composed of Glc, Xyl, Ara, etc. The infrared spectrum showed that BWPP-1 had obvious polysaccharide characteristic absorption peaks. During the simulated in vitro gastrointestinal digestion, the ABTS+· scavenging rates of BWPP and BWPP-1 reached their maximum values at 60 minutes of simulated gastric juice digestion, which were 86.39%±1.28% and 90.38%±2.78%, respectively. There was a significant difference compared to other digestion times (P0.05). When simulating intestinal digestion, the maximum clearance rates of ABTS+· by BWPP and BWPP-1 reached 88.67%±0.40% and 91.82%±2.77% at 60 minutes, and the difference between the two was not significant (P>0.05). The DPPH· scavenging rates reached their peak values at 240 minutes of 57.11%±0.06% and 65.67%±3.67%, with significant difference (P

Abstract Background Herpes simplex virus type 1 (HSV-1) is a major cause of viral encephalitis, genital mucosal infections, and neonatal infections. Lactococcus lactis (L. lactis) has been proven to be an effective vehicle for delivering protein antigens and stimulating both mucosal and systemic immune responses. In this study, we constructed a recombinant L. lactis system expressing the protective antigen glycoprotein D (gD) of HSV-1. Results To improve the stability and persistence of antigen stimulation of the local mucosa, we inserted the immunologic adjuvant interleukin (IL)-2 and the Fc fragment of IgG into the expression system, and a recombinant L. lactis named NZ3900-gD-IL-2-Fc was constructed. By utilizing this recombinant L. lactis strain to elicit an immune response and evaluate the protective effect in mice, the recombinant L. lactis vaccine induced a significant increase in specific neutralizing antibodies, IgG, IgA, interferon-γ, and IL-4 levels in the serum of mice. Furthermore, in comparison to the mice in the control group, the vaccine also enhanced the proliferation levels of lymphocytes in response to gD. Moreover, recombinant L. lactis expressing gD significantly boosted nonspecific immune reactions in mice through the activation of immune-related genes. Furthermore, following the HSV-1 challenge of the murine lung mucosa, mice inoculated with the experimental vaccine exhibited less lung damage than control mice. Conclusion Our study presents a novel method for constructing a recombinant vaccine using the food-grade, non-pathogenic, and non-commercial bacterium L. lactis. The findings indicate that this recombinant vaccine shows promise in preventing HSV-1 infection in mice.

The global epidemic of metabolic diseases has led to the emergence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), which pose a significant threat to human health. Despite recent advances in research on the pathogenesis and treatment of MASLD/MASH, there is still a lack of more effective and targeted therapies. Extracellular vesicles (EVs) discovered in a wide range of tissues and body fluids encapsulate different activated biomolecules and mediate intercellular communication. Recent studies have shown that EVs derived from the liver and adipose tissue (AT) play vital roles in MASLD/MASH pathogenesis and therapeutics, depending on their sources and intervention types. Besides, adipose-derived stem cell (ADSC)-derived EVs appear to be more effective in mitigating MASLD/MASH. This review presents an overview of the definition, extraction strategies, and characterisation of EVs, with a particular focus on the biogenesis and release of exosomes. It also reviews the effects and potential molecular mechanisms of liver- and AT-derived EVs on MASLD/MASH, and emphasises the contribution and clinical therapeutic potential of ADSC-derived EVs. Furthermore, the future perspective of EV therapy in a clinical setting is discussed.

Abstract Background Herpes zoster is an infectious skin disease caused by the reactivation of the varicella zoster virus (VZV), which has been latent in the posterior root ganglia of the spinal cord or cranial ganglia for an extended period. Neurological complications caused by herpes zoster include aseptic meningitis, white matter disease, peripheral motor neuropathy, and Guillain-Barré syndrome. However, reduced unilateral sweating caused by the VZV is very rare. Case Presentation This article reports the case of a 34-year-old woman who was admitted to our hospital with sore throat, dizziness, and reduced sweating on the left side of her body. Physical examination found herpes lesions on the left upper lip and left external ear canal (scabbed) and reduced sweating on the left side of the body. Head magnetic resonance imaging (MRI) with contrast showed no abnormalities. After a lumbar puncture, the patient was diagnosed with viral meningitis by VZV infection. The electromyographic skin sympathetic reflex indicated damage to the left sympathetic nerve. Conclusions Secondary unilateral sweating reduction is a rare neurological complication of herpes zoster, caused by damage to the autonomic nervous system. Literature review and comprehensive examination indicated that the reduced unilateral sweating was due to the activation of latent herpes zoster virus in the autonomic ganglia which has damaged the autonomic nervous system. For patients who exhibit acute hemibody sweat reduction, doctors should consider the possibility of secondary autonomic nervous system damage caused by herpes zoster.

This study summarizes the significance of microRNA-134 (miRNA-134) in the pathophysiology, diagnosis, and treatment of depression, a disease still under investigation due to its complexity. miRNA-134 is an endogenous short non-coding RNA that can bind to the 3′ untranslated region (3′UTR) of miRNA-134, inhibiting gene translation and showing great potential in the regulation of mood, synaptic plasticity, and neuronal function. This study included 15 articles retrieved from four English-language databases: PubMed, Embase, The Cochrane Library, and Web of Science, and three Chinese literature databases: CNKI, Wanfang, and Chinese Science and Technology Periodical Database (VIP).We evaluated each of the 15 articles using the Critical Appraisal Skills Program (CASP) tool.The standard integrates analyzes of genomic, transcriptomic, neuroimaging, and behavioral data analyses related to miRNA-134 and depression. A multidimensional framework based on standardized criteria was used for quality assessment. The main findings indicate that miRNA-134 significantly affects synaptic plasticity and neurotransmitter regulation, in particular the synthesis and release of serotonin and dopamine. miRNA-134 shows high sensitivity and specificity as a biomarker for the diagnosis of depression and has therapeutic potential for the targeted treatment of depression. miRNA-134 plays a crucial role in the pathogenesis of depression, providing valuable insights for early diagnosis and the development of targeted therapeutic strategies. This work highlights the potential of miRNA-134 as a focal point for advancing personalized medicine approaches for depression.

Abstract Background To evaluate the hemodynamic characteristics of normal upper extremity arteries from the brachial artery to the fingertip arterioles. Methods We analyzed the characteristics and changes in the regularities of ultrasonic parameters in the upper extremity arteries of 104 healthy volunteers using color Doppler flow imaging and Angio Planewave UltraSensitive™ imaging. The measured ultrasonic parameters included the vessel diameter, blood-flow spectrum waveform, peak systolic velocity, end-diastolic velocity, resistance index, pulsatility index, ratio of PSV to EDV, blood-flow volume, along with systolic acceleration of each BA, radial artery, superficial palmar arch artery, palmar proper digital artery, and third-grade artery arch of the fingernail bed. Results From BA to FN3AA, the diameter, PSV, RI, S/D, VFlow, and slope of the artery significantly decreased (P

Abstract Background Tumor-associated macrophages (TAMs) significantly influence the progression, metastasis, and recurrence of esophageal squamous cell carcinoma (ESCC). The aberrant expression of long noncoding RNAs (lncRNAs) in ESCC has been established, yet the role of lncRNAs in TAM reprogramming during ESCC progression remains largely unexplored. Methods ESCC TAM-related lncRNAs were identified by intersecting differentially expressed lncRNAs with immune-related lncRNAs and performing immune cell infiltration analysis. The expression profile and clinical relevance of LINC00330 were examined using the TCGA database and clinical samples. The LINC00330 overexpression and interference sequences were constructed to evaluate the effect of LINC00330 on ESCC progression. Single-cell sequencing data, CIBERSORTx, and GEPIA were utilized to analyze immune cell infiltration within the ESCC tumor microenvironment and to assess the correlation between LINC00330 and TAM infiltration. ESCC-macrophage coculture experiments were conducted to investigate the influence of LINC00330 on TAM reprogramming and its subsequent effect on ESCC progression. The interaction between LINC00330 and C–C motif ligand 2 (CCL2) was confirmed through transcriptomic sequencing, subcellular localization analysis, RNA pulldown, silver staining, RNA immunoprecipitation, and other experiments. Results LINC00330 is significantly downregulated in ESCC tissues and strongly associated with poor patient outcomes. Overexpression of LINC00330 inhibits ESCC progression, including proliferation, invasion, epithelial–mesenchymal transition, and tumorigenicity in vivo. LINC00330 promotes TAM reprogramming, and LINC00330-mediated TAM reprogramming inhibits ESCC progression. LINC00330 binds to the CCL2 protein and inhibits the expression of CCL2 and downstream signaling pathways. CCL2 is critical for LINC00330-mediated TAM reprogramming and ESCC progression. Conclusions LINC00330 inhibited ESCC progression by disrupting the CCL2/CCR2 axis and its downstream signaling pathways in an autocrine fashion; and by impeding CCL2-mediated TAM reprogramming in a paracrine manner. The new mechanism of TAM reprogramming mediated by the LINC00330/CCL2 axis may provide potential strategies for targeted and immunocombination therapies for patients with ESCC. Graphical Abstract

Abstract Our preliminary investigation has identified the potential of serum fucosylated extracellular vesicles (EVs) miR-4732-5p in the early diagnosis of lung adenocarcinoma (LUAD) by a fucose-captured strategy utilizing lentil lectin (LCA)-magnetic beads and subsequent screening of high throughput sequencing and validation of real-time quantitative polymerase chain reaction (RT-qPCR). Considering the relatively complicated procedure, expensive equipment, and stringent laboratory condition, we have constructed an electrochemical biosensor assay for the detection of miR-4732-5p. miR-4732-5p is extremely low in serum, down to the fM level, so it needs to be detected by highly sensitive electrochemical methods based on the Mg2+-dependent DNAzyme splitting nucleic acid lock (NAL) cycle and hybridization chain reaction (HCR) signal amplification. In this study, signal amplification is achieved through the dual amplification reactions using NAL cycle in combination with HCR. In addition, hybridized DNA strands bind to a large number of methylene blue (MB) molecules to enhance signaling. Based on the above strategy, we further enhance our signal amplification strategies to improve detection sensitivity and accuracy. The implementation of this assay proceeded as follows: initially, miR-4732-5p was combined with NAL, and then Mg2+-dependent DNAzyme splitted NAL to release auxiliary DNA (S1) strands, which were subsequently captured by the immobilized capture probe DNA (C1) strands on the electrode surface. Following this, abundant quantities of DNA1 (H1) and DNA2 (H2) tandems were generated by HCR, and S1 strands then hybridized with the H1 and H2 tandems through base complementary pairing. Finally, MB was bonded to the H1 and H2 tandems through π–π stacking interaction, leading to the generation of a signal current upon the detection of a potential capable of inducing a redox change of MB by the electrode. Furthermore, we evaluated the performance of our developed electrochemical biosensor assay. The results demonstrated that our assay is a reliable approach, characterized by its high sensitivity (with a detection limit of 2.6 × 10−17 M), excellent specificity, good accuracy, reproducibility, and stability. Additionally, it is cost-effective, requires simple operation, and is portable, making it suitable for the detection of serum fucosylated extracellular vesicles miR-4732-5p. Ultimately, this development has the potential to enhance the diagnostic efficiency for patients with early-stage LUAD.

Abstract Background Aberrant fucosylation observed in cancer cells contributes to an augmented release of fucosylated exosomes into the bloodstream, where miRNAs including miR-4732-3p hold promise as potential tumor biomarkers in our pilot study. However, the mechanisms underlying the sorting of miR-4732-3p into fucosylated exosomes during lung cancer progression remain poorly understood. Methods A fucose-captured strategy based on lentil lectin-magnetic beads was utilized to isolate fucosylated exosomes and evaluate the efficiency for capturing tumor-derived exosomes using nanoparticle tracking analysis (NTA). Fluorescence in situ hybridization (FISH) and qRT-PCR were performed to determine the levels of miR-4732-3p in non-small cell lung cancer (NSCLC) tissue samples. A co-culture system was established to assess the release of miRNA via exosomes from NSCLC cells. RNA immunoprecipitation (RIP) and miRNA pull-down were applied to validate the interaction between miR-4732-3p and heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein. Cell functional assays, cell derived xenograft, dual-luciferase reporter experiments, and western blot were applied to examine the effects of miR-4732-3p on MFSD12 and its downstream signaling pathways, and the impact of hnRNPK in NSCLC. Results We enriched exosomes derived from NSCLC cells using the fucose-captured strategy and detected a significant upregulation of miR-4732-3p in fucosylated exosomes present in the serum, while its expression declined in NSCLC tissues. miR-4732-3p functioned as a tumor suppressor in NSCLC by targeting 3'UTR of MFSD12, thereby inhibiting AKT/p21 signaling pathway to induce cell cycle arrest in G2/M phase. NSCLC cells preferentially released miR-4732-3p via exosomes instead of retaining them intracellularly, which was facilitated by the interaction of miR-4732-3p with hnRNPK protein for selective sorting into fucosylated exosomes. Moreover, knockdown of hnRNPK suppressed NSCLC cell proliferation, with the elevated levels of miR-4732-3p in NSCLC tissues but the decreased expression in serum fucosylated exosomes. Conclusions NSCLC cells escape suppressive effects of miR-4732-3p through hnRNPK-mediated sorting of them into fucosylated exosomes, thus supporting cell malignant properties and promoting NSCLC progression. Our study provides a promising biomarker for NSCLC and opens a novel avenue for NSCLC therapy by targeting hnRNPK to prevent the "exosome escape" of tumor-suppressive miR-4732-3p from NSCLC cells.

Herpes simplex virus type 1 (HSV-1) is a globally widespread virus that causes and associates with a wide range of diseases, including herpes simplex encephalitis, herpes simplex keratitis, and herpes labialis. The interaction between HSV-1 and the host involves complex immune response mechanisms, including recognition of viral invasion, maintenance of latent infection, and triggering of reactivation. Antiviral therapy is the core treatment for HSV-1 infections. Meanwhile, vaccine development employs different strategies and methods, and several promising vaccine types have emerged, such as live attenuated, protein subunit, and nucleic acid vaccines, offering new possibilities for the prevention of HSV-1 infection. Moreover, HSV-1 can be modified into a therapeutic vector for gene therapy and tumour immunotherapy. This review provides an in-depth summary of HSV-1 infection-associated innate and adaptive immune responses, disease pathogenesis, current therapeutic approaches, recent advances in vaccine development, and vector therapy applications for cancer treatment. Through a systematic review of multiple aspects of HSV-1, this study aims to provide a comprehensive and detailed reference for the public on the prevention, control, and treatment of HSV-1.

Over the past decade, the attrition rate of Chinese medical graduates has remained high, and the COVID-19 pandemic has exacerbated this situation. Medicine specialty students are the main force of the future healthcare industry. The career choices and career confidence of those entering the healthcare industry will have a huge influence on the quality of future healthcare provision. Considering the possible emergence of public health emergencies such as COVID-19 in the future, helping students develop good career adaptability will contribute to their future career development. However, the relationship between career adaptability, career coping styles and career decision-making self-efficacy remains unclear during the COVID-19. This study aims to examine the interconnections amongst career coping styles, career adaptability and career decision-making self-efficacy among Chinese medicine specialty students and the mediating role of career decision-making self-efficacy. Questionnaire survey was conducted on 747 medicine specialty students from China. The results showed that positive coping style has a significant positive correlation with career decision-making self-efficacy, career adaptability, and their sub-dimensions. There was a partial mediating effect of career decision self-efficacy between the predictor variable positive coping style and the outcome variable career adaptability. By promoting the level of positive coping style or career decision-making self-efficacy among medicine specialty students, the career adaptability can be directly or indirectly enhanced. This survey will help to guide future medical education decisions during a similar pandemic to prevent further loss of healthcare professionals in the medical service.

Objective Most patients with colorectal cancer (CRC) show no early symptoms, and tumor markers have low sensitivity and specificity. We therefore investigated the ability of serum fibrin degradation complex DR-70 plus traditional tumor markers to diagnose CRC. Methods We retrospectively screened patients with CRC or non-malignant colorectal diseases, as well as healthy individuals, for inclusion in this study. The individuals’ clinical characteristics were recorded, and serum samples were collected. Expression levels of DR-70 and conventional tumor markers were measured by enzyme-linked immunosorbent assay and electrochemiluminescence. Results DR-70 levels differed significantly among patients with CRC, patients with benign colorectal diseases, and healthy individuals. Receiver operating characteristic curve analysis identified DR-70 as a conventional tumor marker with the highest sensitivity and the second-highest specificity after carcinoembryonic antigen. Conclusions This study identified DR-70 as a reliable marker for the detection, differentiation, and progression of CRC, with good sensitivity and specificity. DR-70 measurement could greatly improve the efficacy of CRC diagnosis when used together with other tumor markers.

Polycyclic aromatic hydrocarbons (PAHs) and dioxins are potential causes of multiple diseases by activating the aryl hydrocarbon receptor (AhR) pathway. Health risk assessment of chemicals primarily relies on the relative potency factor (RPF), although its accuracy may be limited when solely using EC50 values. The induction of cytochrome P4501A1 (CYP1A1) serves as a biomarker for AhR activation and is an integrator of dioxin-like toxicity. Here, we present a method for evaluating the risks associated with AhR activation using mathematical models of dose-CYP1A1 induction. The dose-effect curves for certain PAHs and dioxins, including Ant, BghiP, 1,2,3,4,7,8-HxCDD, and others, exhibited a non-classical S-shaped form. The toxic equivalent factor (TEF) profiles revealed a broad range of toxic equivalent factor values. The TEFs for PAHs ranged from approximately 0.01 to 6, with higher values being observed when the concentration was less than 10−10 M, with the exceptions of Ace, Phe, and BghiP. Most congeners of dioxins got the lowest TEF value at around 10−10 M, ranging from 0.04 to 1.00. The binding affinity of AhR to ligands did not display a strong correlation with the EC50 of CYP1A1 expression, suggesting that the AhR-mediated effects of PAHs and dioxins are not fixed but instead fluctuate with the dose. Air samples acquired from a parking area were used to compare the proficiency of RPF and our current approach. In the current method, naphthalene and chrysene were the primary contributors of PAHs to AhR-mediated risks in parking lots air samples, respectively. However, the contributions of naphthalene and chrysene could be disregarded in the RPF approach.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent liver diseases worldwide, and its occurrence is strongly associated with obesity, insulin resistance (IR), genetics, and metabolic stress. Ranging from simple fatty liver to metabolic dysfunction-associated steatohepatitis (MASH), even to severe complications such as liver fibrosis and advanced cirrhosis or hepatocellular carcinoma, the underlying mechanisms of MASLD progression are complex and involve multiple cellular mediators and related signaling pathways. Pattern recognition receptors (PRRs) from the innate immune system, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), RIG-like receptors (RLRs), and DNA receptors, have been demonstrated to potentially contribute to the pathogenesis for MASLD. Their signaling pathways can induce inflammation, mediate oxidative stress, and affect the gut microbiota balance, ultimately resulting in hepatic steatosis, inflammatory injury and fibrosis. Here we review the available literature regarding the involvement of PRR-associated signals in the pathogenic and clinical features of MASLD, in vitro and in animal models of MASLD. We also discuss the emerging targets from PRRs for drug developments that involved agent therapies intended to arrest or reverse disease progression, thus enabling the refinement of therapeutic targets that can accelerate drug development.

AbstractDrought has historically represented the greatest abiotic stress to adversely affect the stability of soybean (Glycine max (L.) Merr.) yields in non-irrigated field conditions. To investigate the genetic basis underlying drought tolerance in soybean, we screened the seed yield per plant (YP) in a natural diversity panel of 149 accessions under both water deficit (drought-stressed; YP-S) and well-watered (full irrigation; YP-W) conditions in field and greenhouse trials and calculated a drought susceptibility index (DSI) based on the differences in yield between treatments within each accession. A total of 19 quantitative trait loci (QTLs) were identified: eight were significantly associated with YP-W, 10 were associated with YP-S, 2 were associated with DSI and one QTL was associated with both YP-S and DSI. We then compared QTLs identified here with previously reported markers and found that these loci were located in regions associated with yield-related and other agronomic traits. In particular, YP-S-associated single nucleotide polymorphism (SNP) ss246509299 in chromosome (Chr.) 8, and YP-W-associated ss249310678 on Chr. 17 were both previously correlated with canopy wilt. Eight significant QTLs were located within eight genes. Glyma.18g092200, contained ss249600231 and annotated as GmWRKY168, is reportedly responsive to cadmium. This study helps to resolve which loci contribute to yield under drought stress in soybean, and can potentially serve as markers for selection of elite, high-yield and drought tolerant varieties.

This comprehensive review delves into the complex interplay between mitochondrial gene defects and pancreatic cancer pathogenesis through a multiomics approach. By amalgamating data from genomic, transcriptomic, proteomic, and metabolomic studies, we dissected the mechanisms by which mitochondrial genetic variations dictate cancer progression. Emphasis has been placed on the roles of these genes in altering cellular metabolic processes, signal transduction pathways, and immune system interactions. We further explored how these findings could refine therapeutic interventions, with a particular focus on precision medicine applications. This analysis not only fills pivotal knowledge gaps about mitochondrial anomalies in pancreatic cancer but also paves the way for future investigations into personalized therapy options. This finding underscores the crucial nexus between mitochondrial genetics and oncological immunology, opening new avenues for targeted cancer treatment strategies.

Abstract: The COVID-19 pandemic caused substantial stress to healthcare workers (HCW) worldwide. This study examined the mental health of frontline Chinese HCW through their dream experience during the COVID-19 pandemic and their subjective perception of reported dreams. Using semistructured interviews, we evaluated 45 dreams from 28 HCW from various hospital departments. Six themes emerged after a thematic analysis of these dreams: warning, escape, alienation of HCW, gender inequality, archetypal-mythological dreams, and negative emotions. The findings indicate a close relationship between the participants’ mental health state and their dreams, which contributes a new insight into understanding the COVID-19 pandemic and its impact on frontline HCW. It allows us to provide them with better psychological support in a global public health crisis. In the conclusion to this article, we discuss future research directions for the dreams of frontline HCW.

To reduce the significant losses caused by slope failures and landslides, it is of great significance to detect and predict these disasters scientifically. This study focused on Huangdao District of Qingdao City in Shandong Province, using the improved Faster R-CNN network to detect slope failures and landslides. This study introduced a multi-scale feature enhancement module into the Faster R-CNN model. The module enhances the network’s perception of different scales of slope failures and landslides by deeply fusing high-resolution weak semantic features with low-resolution strong semantic features. Our experiments show that the improved Faster R-CNN model outperformed the traditional version, and that ResNet50 performed better than VGG16 with an AP value of 90.68%, F1 value of 0.94, recall value of 90.68%, and precision value of 98.17%. While the targets predicted by VGG16 were more dispersed and the false detection rate was higher than that of ResNet50, VGG16 was shown to have an advantage in predicting small-scale slope failures and landslides. The trained Faster R-CNN network model detected geological hazards of slope failure and landslide in Huangdao District, missing only two landslides, thereby demonstrating high detection accuracy. This method can provide an effective technical means for slope failures and landslides target detection and has practical implications.

Traditional studies on the carrying capacity of groundwater resources mainly focus on a comprehensive evaluation, and this paper provides quantitative prediction and early warning on the carrying capacity of groundwater resources, which is important for groundwater management and protection. This study constructed an early warning indicator system for the carrying capacity of groundwater resources, established an early warning method on the carrying capacity of groundwater resources, determined the early warning grades of Henan Province and various cities from 2023 to 2025, and analyzed the spatial distribution pattern. The results showed that the early warning grades of Henan Province from 2023 to 2025 were mild warnings. In the subsystems, the early warning grades of the groundwater resources and economic society systems were mild warnings, while the early warning grades of the ecological environment system were moderate warnings. The early warning grades of the carrying capacity of groundwater resources in all cities were basically mild or moderate warnings, showing a downward trend. This study establishes an early warning method on the carrying capacity of groundwater resources that includes the selection of early warning indicators, prediction of indicators, and determination of the early warning grades which can be a reference for other regions. HIGHLIGHTS Consider groundwater, economic society, and ecological environment as a GEE system.; An evaluation indicator system covering the GEE system is constructed.; An early warning method on the carrying capacity of groundwater resources is established.; The method is applied in Henan to quantitatively predict and early warn.;

The traditional groundwater overexploitation restoration only considers the impact on groundwater, on the basis of which, this paper also comprehensively considers the impact on economic society and the ecological environment. Based on analyzing the effect of groundwater overexploitation restoration on the groundwater–economic society–ecological environment (GESEE) system, an evaluation indicator system covering the GESEE system was constructed, an evaluation method for the effect of groundwater overexploitation restoration was established, and the effects were evaluated for Hebei Province, China, from 2014 to 2019. The results showed that the effect of groundwater overexploitation restoration in Hebei Province was obvious, and the grade of the groundwater overexploitation restoration effect improved from fair to good. The grade of the groundwater overexploitation restoration effect in most cities was improved to good. The measures that most affected the effect of groundwater overexploitation restoration in Hebei Province are strict control of extraction and reduction of consumption, while measures such as the replacement of water sources also play a significant role. An evaluation indicator system constructed in this paper can help to promote sophisticated effect evaluation of groundwater overexploitation restoration and improve the understanding and management of groundwater overexploitation restoration. HIGHLIGHTS An evaluation indicator system covering the groundwater–economic society–ecological environment system is constructed.; An evaluation method for the effect of groundwater overexploitation restoration is established.; The evaluation method is applied at both provincial and municipal levels in Hebei Province, one of the most severe groundwater overexploitation areas in the world.;

The traditional drought field studies are inadequate to study drought field characteristics from the perspective of trend and periodicity at the same time, especially to compare the interannual and interdecadal variations of different drought types in the drought field to reveal their similarity and difference patterns. The drought field in Pearl River Basin (PRB) was determined in this paper using the standardized precipitation evapotranspiration index (SPEI) and the empirical orthogonal function (EOF)/rotated empirical orthogonal function (REOF). Periodic characteristics and trend features of the drought field were recognized by extreme-point symmetric mode decomposition (ESMD) and other methods. The results showed that from the perspective of regional characteristics five different spatial modes may be used to categorize the interannual drought field of the PRB; there were interannual cycles associated with the southwest-type drought and the northwest-type drought. The central-south-, north-central- and eastern-type droughts had both interannual and interdecadal cycles; during the study period, the PRB's five types of drought revealed a changing tendency as opposed to a straightforward linear trend; from the interannual variation, the southwest-type drought was consistent with the northwest-type drought prior to 2000, and the north-central-type drought was consistent with the eastern-type drought before 2010. HIGHLIGHTS The spatial characteristics and periodic properties of the watershed were identified.; There are five spatial modes in the Pearl River Basin.; Southwestern and northwestern droughts have interannual cycles.; Five types of droughts in the Pearl River Basin showed a fluctuating trend.; The interannual similarity and variability of the five droughts were studied.;

Abstract Background Neurobrucellosis (NB) presents a challenge for rapid and specific diagnosis. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has showed power in detection of causative pathogens, even some infrequent and unexpected pathogens. In this study, we presented 8 cases of NB diagnosed by the NGS of CSF. Methods Between August 1, 2018 and September 30, 2020, NGS was used to detect causative pathogens in clinically suspected central nervous system (CNS) infections. Data on demographics, clinical features, and laboratory tests, imaging results and NGS results were collected and reviewed. Results Among the presented 8 patients, Brucella was rapidly detected using NGS of CSF within 1–4 days, despite those eight patients had variable medical history, disease course, clinical manifestations, laboratory tests and imaging findings. NGS showed the sequence reads corresponded to Brucella species were 8 to 448, with genomic coverage of 0.02 to 0.87%. The relative abundance was 0.13% to 82.40% and sequencing depth was 1.06 to 1.24. Consequently, patients were administered with 3 to 6 months of doxycycline, ceftriaxone and rifampicin, double or triple combination, supplemented with symptomatic therapy and were fully recovered except for case 1. Conclusion NGS of CSF provides a powerful tool in detection of Brucella in a prompt and specific manner, and can be considered for first-line diagnostic use in practice.

The intricate interplay among water, energy, food, and ecology underscores the paramount importance of investigating water–energy–food–ecology (WEFE) systems to foster regional sustainable development. In this study, a dynamic simulation model for the WEFE system was formulated using system dynamics, probing alterations in resource supply, demand dynamics, and ecosystem responses to resource shifts. Utilizing Henan Province as a case study and factoring in resource scarcity and environmental pollution, five scenarios were crafted to forecast WEFE system developmental trajectories from 2005 to 2035. The findings revealed the following key insights: (1) Within each subsystem, the food supply–demand balance ratio maintained a robust level of approximately 4.0. Conversely, the water and energy supply–demand balance ratio remained below 1.0 throughout the study period, indicating a worsening trend in the annual misalignment between supply and demand. Carbon dioxide (CO2) emissions are projected to surge by 103%, posing challenges for future CO2 emission reduction efforts. (2) Among the various scenarios, the Green Development (GD) scenario emerged as pivotal for fostering a coordinated development of the WEFE system. Implementation of the GD scenario showcased a notable 38.1% improvement in the resource supply–demand ratio and a 26% reduction in CO2 emissions. (3) Addressing ecosystem feedback, the reduction of carbon emissions emerges as a focal point for future ecological environment enhancement initiatives in Henan Province. Strategic emphasis should be placed on adjusting energy consumption and its structure to propel the healthy development of the ecological environment. This study serves as a guide for managing regional WEFE systems effectively.

Introduction: Sepsis-mediated acute lung injury (ALI) is a critical clinical condition. Artesunate (AS) is a sesquiterpene lactone endoperoxide that was discovered in Artemisia annua, which is a traditional Chinese herb. AS has a broad set of biological and pharmacological actions; however, its protective effect on lipopolysaccharide (LPS)-induced ALI remains unclear. Methods: LPS-mediated ALI was induced in rats through bronchial LPS inhalation. Then NR8383 cells were treated with LPS to establish an in vitro model. Further, we administered different AS doses in vivo and in vitro. Results: AS administration significantly decreased LPS-mediated pulmonary cell death and inhibited pulmonary neutrophil infiltration. Additionally, AS administration increased SIRT1 expression in pulmonary sections. Administration of a biological antagonist or shRNA-induced reduction of SIRT1 expression significantly inhibited the protective effect of AS against LPS-induced cellular injury, pulmonary dysfunction, neutrophil infiltration, and apoptosis. This demonstrates that enhanced SIRT1 expression is crucially involved in the observed protective effects. Conclusion: Our findings could suggest the use of AS for treating lung disorders through a mechanism involving SIRT1 expression.

Abstract Background The ubiquitin–proteasome and autophagy-lysosomal systems collaborate in regulating the levels of intracellular proteins. Dysregulation of protein homeostasis is a central feature of malignancy. The gene encoding 26S proteasome non-ATPase regulatory subunit 2 (PSMD2) of the ubiquitin–proteasome system is an oncogene in various types of cancer. However, the detailed role of PSMD2 in autophagy and its relationship to tumorigenesis in esophageal squamous cell carcinoma (ESCC) remain unknown. In the present study, we have investigated the tumor-promoting roles of PSMD2 in the context of autophagy in ESCC. Methods Molecular approaches including DAPgreen staining, 5-Ethynyl-2ʹ-deoxyuridine (EdU), cell counting kit 8 (CCK8), colony formation, transwell assays, and cell transfection, xenograft model, immunoblotting and Immunohistochemical analysis were used to investigate the roles of PSMD2 in ESCC cells. Data-independent acquisition (DIA) quantification proteomics analysis and rescue experiments were used to study the roles of PSMD2 in ESCC cells. Results We demonstrate that the overexpression of PSMD2 promotes ESCC cell growth by inhibiting autophagy and is correlated with tumor progression and poor prognosis of ESCC patients. DIA quantification proteomics analysis shows a significant positive correlation between argininosuccinate synthase 1 (ASS1) and PSMD2 levels in ESCC tumors. Further studies indicate that PSMD2 activates the mTOR pathway by upregulating ASS1 to inhibit autophagy. Conclusions PSMD2 plays an important role in repressing autophagy in ESCC, and represents a promising biomarker to predict prognosis and a therapeutic target of ESCC patients.

Abstract Background TP53 mutations are frequent in non‐small cell lung cancer (NSCLC). Different categories of TP53 mutations may be associated with survival in advanced NSCLC, but their effect on prognosis is diverse. To date, a comprehensive comparison of the relationship between different classes of TP53 alterations and survival in advanced NSCLC has rarely been performed. Moreover, the prognostic significance of a novel approach called the evolutionary action of TP53 (EAp53) in advanced NSCLC is unclear. Methods A total of 210 patients with NSCLC harboring TP53 mutation data were enrolled. Genomic and clinical data for the Memorial Sloan Kettering Cancer Center (MSKCC) cohort with advanced NSCLC were obtained from cBioPortal. Relationship between clinical characteristics and TP53 mutations was performed by Fisher's exact test or χ2 test. Overall survival (OS) analysis was evaluated using Kaplan–Meier method and Cox proportional hazards regression model. Results TP53 mutations were identified in 51.4% of NSCLC patients and were mainly located in exons 5, 7, and 8. The distribution patterns of missense and truncating mutations of TP53 were remarkably different. Among patients with advanced NSCLC who never received immune checkpoint inhibitor treatments, EAp53 high‐risk mutations were significantly associated with poor OS in both our cohort and the MSKCC cohort. Moreover, marked differences were observed in the mutational landscape between patients with EAp53 high‐risk mutations (HR group) and other patients (OT group). The HR group displayed higher mutation frequencies in the RTK, cell cycle, and DNA damage repair (DDR) pathways than the OT group. In addition, the tumor mutation burden in the HR group was significantly higher than that in the OT group. Conclusions This study provided important insights into the molecular‐clinical profile of TP53‐mutated NSCLC patients. Moreover, the data revealed that EAp53 high‐risk mutations were an independent prognostic factor for worse OS in advanced NSCLC.

Anthocyanins are prone to degradation and color fading after sterilization. This work examined the potential of wheat protein hydrolysates (WPHs, 40 g/L) in improving the stability of purple sweet potato anthocyanins (PSPAs) under a pH of 6.8 after sterilization at 121 °C followed by storage. Results showed that WPHs increased the thermal degradation half-life of PSPAs 1.65 times after sterilization. Compared to PSPAs alone, after being stored at 37 °C and 45 °C for 7 days, the retention concentration of PSPAs with WPHs was 5.4 and 32.2 times higher, and the color change of PSPAs with WPHs decreased from 6.19 and 10.46 to 0.29 and 0.77, respectively. AFM data, fluorescence and UV spectrograms indicated the formation of complexes between PSPAs and WPHs by hydrophobic attraction confirmed by zeta-potential data. PSPAs with WPHs had stable particle size and zeta potential, which may also significantly increase the concentrations after digestion and antioxidant power of PSPAs. This work indicated that the assembled PSPAs composite structure by WPHs significantly reduced the degradation of PSPAs at a pH of 6.8 after sterilization at 121 °C followed by long-term storage.

Background: Persistent HPV infection can easily lead to the occurrence and development of cervical cancer and its precancerous lesions. Many studies have shown that Simiao Decoction may be effective in treating HPV infection, but the efficacy and safety of Simiao Decoction for HPV infection have never been systematically evaluated. Purpose: To evaluate the efficacy and safety of Simiao Decoction in the treatment of cervical HPV infection. Study design: A systematic review and meta-analysis of all randomized clinical trials (RCTs) comparing Simiao Decoction versus conventional treatment. Materials and methods: Seven databases were searched from their inception until May 14, 2023. All the RCTs comparing the efficacy and safety of Simiao Decoction versus conventional treatment were selected. Analyses were performed using Review Manager 5.3. HPV negative conversion rate (NCR) was defined as the primary endpoint, and treatment response rate (TRR), and adverse reaction (AR) were defined as the secondary endpoints. The quality of each endpoint was assessed by The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. Results: Ten RCTs recruiting 799 patients with HPV infection were included. The results showed that compared with conventional treatment, Simiao Decoction improved NCR (RR = 1.45, 95 % CI 1.31, 1.61, P

Orbital meningioma is a rare type of orbital tumor with high invasiveness and recurrence rates, making it extremely challenging to treat. Due to the special location of the disease, surgery often cannot completely remove the tumor, requiring postoperative radiation therapy. Here, we report a case of an elderly male patient with right-sided proptosis, visual impairment, and diplopia. Imaging diagnosis revealed a space-occupying lesion in the extraconal space of the right orbit. Pathological and immunohistochemical examination of the resected tumor confirmed it as a grade 3 anaplastic meningioma. Two months after surgery, the patient complained of right eye swelling and a magnetic resonance imaging (MRI) scan showed a recurrence of the tumor. The patient received helical tomotherapy (TOMO) in the postoperative tumor bed and high-risk areas within the orbit with a total dose of 48Gy. However, there was no significant improvement in the patient’s right eye swelling, and the size of the recurrent lesion showed no significant change on imaging. Gamma knife multifractionated stereotactic radiosurgery (MF-SRS) was then given to the recurrent lesion with 50% prescription dose 13.5Gy/3f, once every other day. An imaging diagnosis performed 45 days later showed that the tumor had disappeared completely. The patient’s vision remained unchanged, but diplopia was significantly relieved after MF-SRS. We propose a new hybrid treatment model for recurrent orbital meningioma, where conventional radiation therapy ensures local control of high-risk areas around the postoperative cavity, and MF-SRS maximizes the radiation dose to recurrent lesion areas while protecting surrounding tissues and organs.

Background The prevalence of sleep deprivation among college students is increasing and has a few associated factors. Methods The present study analyzed 2,142 college students from 28 provinces in China. The Chinese version of the Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep duration. Binary logistic regression was conducted to explore the sleep deprivation related factors. Age and gender were controlled as covariates. Results Among the 2,142 college students (27.7% male, 72.3% female), 1,620 (75.6%) reported the average sleep duration was below 7 h per day for one month, 49.3% (1,055/2,142) slept 6∼7 h (contains 6 h), 21.0% (449/2,142) slept 5∼6 h (contains 5 h), and 5.4% (116/2,142) slept

Abstract Background microRNAs (miRNAs) and N6‐methyladenosine (m6A) play important roles in ovarian cancer (OvCa). However, the mechanisms by which miRNAs regulate m6A in OvCa have not been elucidated so far. Methods To screen m6A‐related miRNAs, Pearson's correlation analysis of miRNAs and m6A regulators was implemented using The Cancer Genome Atlas database (TCGA). To determine the level of m6A, RNA m6A quantitative assays were used. Then, colony formation assays, EdU assays, wound healing assays, and Transwell assays were performed. The dual‐luciferase reporter assay was used to confirm the miRNA target genes. Protein–protein interaction (PPI) analysis of the target genes was performed, and hub genes were discovered using the cytoHubba/Cytoscape software. The underlying molecular mechanisms were explored by bioinformatics and RNA stability assays. Results A total of 126 miRNAs were identified as m6A‐related miRNAs by Pearson's correlation analysis. Among them, the high level of miR‐30c‐5p was associated with good prognosis in OvCa patients. In vitro, the miR‐30c‐5p agomir lowered the m6A level and inhibited OvCa cell proliferation, migration, and invasion. The hub target genes of miR‐30c‐5p were identified as (i) XPO1, (ii) AGO1, (iii) HNRNPA2B1, of which m6A reader HNRNPA2B1 was highly expressed in OvCa tissues and related with poor prognosis. In vitro, knockdown of HNRNPA2B1 significantly reduced m6A level and hampered the proliferation and migration of OvCa cells. The inhibition of m6A reader HNRNPA2B1 attenuated the suppression of proliferation and migration and the low m6A level induced by the miR‐30c‐5p downregulation. Mechanistically, m6A reader HNRNPA2B1 might regulate CDK19 mRNA stability to alter m6A level. Conclusions miR‐30c‐5p inhibits OvCa progression and reduces the m6A level by inhibiting m6A reader HNRNPA2B1, thus providing new insights into the m6A regulatory mechanism in OvCa.

The Haihe River basin is the main grain production base and the highland of economic strategic development in China. Based on daily meteorological data during 1960–2020, the characteristics of drought evolution in the Haihe River basin were analyzed by the standardized precipitation evapotranspiration index (SPEI). Pearson correlation method and cross-wavelet analysis were used to explore the correlation between the SPEI and climate factors (global warming, sunspots, and atmospheric circulation indices). Global warming has led to a trend of increasing drought in the basin, and there is an obvious zonality in the change of the trend, with the strongest impact on the central region of the basin (112°E–120°E, 38°N–41°N). The SPEI was negatively correlated with the number of sunspots. The more sunspots there were, the more severe the drought in the basin. The drought was most susceptible to the El Niño-Southern Oscillation (ENSO) and the Atlantic Multidecadal Oscillation (AMO), followed by the Arctic Oscillation (AO) and the Pacific Decadal Oscillation (PDO). The North Atlantic Oscillation (NAO), the Pacific North America index (PNA), and the Western Pacific index (WP) were the least associated with the drought in the basin. HIGHLIGHTS The drought trend and the relationship between drought and climatic factors were analyzed.; The drought trend is obviously aggravated in the Haihe River basin.; Drought caused by global warming has an obvious zonal trend.; The more sunspots there were, the more severe the drought.; The drought is mainly affected by the ENSO and AMO.;

Abstract Background A new technique for analgesia called pectoral nerve block is widely used in surgeries of breast cancer. Pectoral nerve block type II (Pecs II) block has less influence on immunity when compared with general anesthesia method. The purpose of this research is to demonstrate whether Pecs II block has influence on the recurrence of breast cancer after surgical operation. Methods 526 breast cancer patients were recruited in this research and randomized into general anesthesia group and general anesthesia with Pecs II block group. Recurrence-free survival (RFS), distant recurrence-free survival (DRFS), and overall survival (OS) were evaluated for the two groups. Results Based on the statistical data, only the consumption of remifentanil was dramatically reduced by the performance of Pecs II block when compared with general anesthesia method. The performance of Pecs II block had no significant influence on OS, RFS, and DRFS of breast cancer patients after surgery. ASA physical status III, TNM stage 2 + 3, and mastectomy were proved to have association with lower recurrence-free survival. Conclusion In conclusion, the performance of Pecs II block declined the remifentanil consumption during surgery of breast cancer. Meanwhile, the performance of Pecs II block had no significant influence on the OS, RFS, and DRFS of breast cancer patients after surgical resection.

The effects of different UV absorbents and preservatives on the weatherability of modified waterborne polyurethane (WPU) printed laminated bamboo were investigated. Three types of UV absorbents including 2-hydroxy-4-n-octoxy-benzophenone (UV-531), 2-(2 H-benzotriazol-2-yl)-4-(1,1,3,3 tetramethylbutyl) phenol (UV-329), and nano-TiO2, and four types of preservatives including boric acid (BA), borax (BX), ammonium polyphosphate (APP), and disodium octaborate tetrahydrate (DOT) were selected to modify WPU coatings. The printed laminated bamboo was tested to evaluate the coating physical and chemical properties and dimensional stability. Thirteen coating types were tested. The results showed that the 0 (20% WPU), 5 (UV-531-BA/BX), 6 (UV-531-BA/BX/APP), 7 (UV-531-BA/BX/DOT), 8 (UV-531-BA/BX/APP/DOT), and 9 (nano-TiO2/BA/BX) samples performed well in adhesion, abrasion resistance, hardness, and temperature denaturation. Fourier transform infrared (FT-IR) spectra analyses and dimensional stability analysis were carried out on the six kinds of coatings screened out. FT-IR spectra analyses showed the successful introduction of UV light absorbers and flame retardants, whereas test results of hygroscopicity showed that the coated test material improved the dimensional stability performance. Test material 8(UV-531-BA/BX/APP/DOT) had the best dimensional stability performance.

Rubin’s variance estimator of the multiple imputation estimator for a domain mean is not asymptotically unbiased. Kim et al. derived the closed-form bias for Rubin’s variance estimator. In addition, they proposed an asymptotically unbiased variance estimator for the multiple imputation estimator when the imputed values can be written as a linear function of the observed values. However, this needs the assumption that the covariance of the imputed values in the same imputed dataset is twice that in the different imputed datasets. In this study, we proposed a bootstrap variance estimator that does not need this assumption. Both theoretical argument and simulation studies show that it was unbiased and asymptotically valid. The new method was applied to the Hox pupil popularity data for illustration.

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent health issues. The improvement of NAFLD is related to the activation of the farnesoid X receptor (FXR). Typhaneoside (TYP) is the main component of Typha orientalis Presl, which plays a positive role in the resistance of glucose and lipid metabolism disorders. This study aims to investigate the alleviative effect and the underlying mechanism of TYP on OAPA-induced cells and high-fat-diet (HFD)-induced mice with disorders of glucose and lipid metabolism, inflammation, oxidative stress and lower thermogenesis through FXR signaling. All the serum lipid, body weight, oxidative stress and inflammatory levels of WT mice were significantly increased after HFD administration. These mice were presented with pathological injury, liver tissue attenuation, energy expenditure, insulin resistance, and impaired glucose tolerance. These above-mentioned changes in HFD-induced mice were remarkably reversed by TYP, which improved HFD-induced energy expenditure, oxidative stress, inflammation, insulin resistance, and lipid accumulation in a dose-dependent manner by activating the expression of FXR. Furthermore, using a high throughput drug screening strategy based on fluorescent reporter genes, we found that TYP functions as a natural agonist of FXR.TYP-mediated FXR activation also significantly repressed TG hyperaccumulation in mouse primary Hepatocytes (MPHs). However, these beneficial effects of TYP were not observed in FXR-/- MPHs. Overall, activation of the FXR pathway by TYP is related to the improvement of metabolic parameters, such as blood glucose, lipid accumulation, insulin resistance, inflammation, oxidative stress and energy expenditure in vitro and in vivo.

Few studies have considered the impacts of sample size and sample ratio of presence and absence points on the results of random forest (RF) testing. We applied this technique for the prediction of the spatial distribution of snail habitats based on a total of 15,000 sample points (5,000 presence samples and 10,000 control points). RF models were built using seven different sample ratios (1:1, 1:2, 1:3, 1:4, 2:1, 3:1, and 4:1) and the optimal ratio was identified via the Area Under the Curve (AUC) statistic. The impact of sample size was compared by RF models under the optimal ratio and the optimal sample size. When the sample size was small, the sampling ratios of 1:1, 1:2 and 1:3 were significantly better than the sample ratios of 4:1 and 3:1 at all four levels of sample sizes (p0.05). The sample ratio of 1:2 appeared to be optimal for a relatively large sample size with the lowest quartile deviation. In addition, increasing the sample size produced a higher AUC and a smaller slope and the most suitable sample size found in this study was 2400 (AUC=0.96). This study provides a feasible idea to select an appropriate sample size and sample ratio for ecological niche modelling (ENM) and also provides a scientific basis for the selection of samples to accurately identify and predict snail habitat distributions.

Accurate reconstruction of species trees often relies on the quality of input gene trees estimated from molecular sequences. Previous studies suggested that if the sequence length is fixed, the maximum likelihood may produce biased gene trees which subsequently mislead inference of species trees. Two key questions need to be answered in this context: what are the scenarios that may result in consistently biased gene trees? and for those scenarios, are there any remedies that may remove or at least reduce the misleading effects of consistently biased gene trees? In this article, we establish a theoretical framework to address these questions. Considering a scenario where the true gene tree is a 4-taxon star tree T∗=(S1,S2,S3,S4) with two short branches leading to the species S1 and S2, we demonstrate that maximum likelihood significantly favors the wrong bifurcating tree [(S1, S2), S3, S4] grouping the two species S1 and S2 with short branches. We name this inconsistent behavior short branch attraction, which may occur in real-world data involving a 4-taxon bifurcating gene tree with a short internal branch. If no mutation occurs along the internal branch, which is likely if the internal branch is short, the 4-taxon bifurcating tree is equivalent to the 4-taxon star tree and thus will suffer the same misleading effect of short branch attraction. Theoretical and simulation results further demonstrate that short branch attraction may occur in gene trees and species trees of arbitrary size. Moreover, short branch attraction is primarily caused by a lack of phylogenetic information in sequence data, suggesting that converting short internal branches to polytomies in the estimated gene trees can significantly reduce artifacts induced by short branch attraction.

DAPB, a new molecule including danshensu, borneol, and a mother nucleus of ACEI (Angiotensin-converting enzyme inhibitors), is being developed as an antihypertensive candidate compound. A rapid, accurate, and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was established and validated for the determination of DAPB in rat plasma. Chromatographic separation was performed on an Agilent SB-C18 column after protein precipitation by acetonitrile with a mobile phase consisting of acetonitrile and deionized water with 0.02% formic acid and 5 mM NH4F (v/v) at a flow rate of 0.2 mL/min. Quantification was performed using electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The method was linear over the range of 2–1000 ng/mL. The intra- and inter-day precision was within 12%, with accuracies less than 7%. Stability was within the acceptable limits under various storage and processing conditions. No apparent matrix effect was detected. The validated method was applied to the pre-clinical pharmacokinetic study of DAPB after oral administration of 30 mg/kg and intravenous administration of 6 mg/kg in rats.

BackgroundMenopausal women may experience menopausal syndrome and long-term effects caused by low estrogen levels, such as senile dementia and osteoporosis in the elderly. Most menopausal women may have misconceptions about menopause and low use of pharmacological interventions. These misconceptions may damage the quality of life and miss the critical period for preventing senile diseases. Thus, enhancing the awareness of menopausal women regarding psychosocial and physical changes through health education programs was a way to improve positive attitudes toward menopause and make further treatment options.ObjectivesThis study aimed to evaluate the effect of multidisciplinary health education based on lifestyle medicine on menopausal syndrome and lifestyle behaviors of menopausal women.MethodsThe study was conducted in several hospitals in Chongqing, China. The two groups were from different hospitals with similar medical levels in order to reduce information contamination. It was designed as a clinical controlled trial in which the intervention group (n = 100) and control group (n = 87) were matched for age, age at menarche, menopausal symptoms and drug use status at enrollment. Women in the intervention group received multidisciplinary health education based on lifestyle medicine for 2 months while those in the control group received routine outpatient health guidance. Menopausal syndrome, physical activity and dietary status of participants were assessed before and after the intervention. Paired t-tests and Independent-sample t-tests were adopted for comparison within and between groups, respectively, in the normal variables. Wilcoxon signed-rank tests and Mann-Whitney U tests were adopted for comparison within and between group, respectively, in the abnormal variables. Categorical variables were tested using Pearson's χ2. P-value < 0.05 was statistically significant in statistical tests.ResultsPost intervention testing indicated that menopausal syndrome of participants was significantly improved in the intervention group compared to the control group (P < 0.001). Between-group comparison showed a significant improvement of weekly energy expenditure of total physical activity (P = 0.001) and participation in exercise (P < 0.001) in the intervention group compared to the control group after the intervention. The dietary status of participants was significantly improved in the intervention group compared to the control group (P < 0.001). In the intervention group, the menopausal syndrome of participants improved more in the hormone drug group than in the non-hormone group (P = 0.007), as did the control group (P = 0.02). In the hormone drug group, the physical activity (P = 0.003) and dietary status (P = 0.001) mproved more in the intervention group than in the control group.ConclusionsThe multidisciplinary health education based on lifestyle medicine was effective in improving the menopausal syndrome and healthy lifestyle behaviors of menopausal women. Studies with extended observation period and larger sample size are in need to evaluate the long-term scale-up effects of the multidisciplinary health education.

The inflammasome is a protein complex composed of a variety of proteins in cells and which participates in the innate immune response of the body. It can be activated by upstream signal regulation and plays an important role in pyroptosis, apoptosis, inflammation, tumor regulation, etc. In recent years, the number of metabolic syndrome patients with insulin resistance (IR) has increased year by year, and the inflammasome is closely related to the occurrence and development of metabolic diseases. The inflammasome can directly or indirectly affect conduction of the insulin signaling pathway, involvement the occurrence of IR and type 2 diabetes mellitus (T2DM). Moreover, various therapeutic agents also work through the inflammasome to treat with diabetes. This review focuses on the role of inflammasome on IR and T2DM, pointing out the association and utility value. Briefly, we have discussed the main inflammasomes, including NLRP1, NLRP3, NLRC4, NLRP6 and AIM2, as well as their structure, activation and regulation in IR were described in detail. Finally, we discussed the current therapeutic options-associated with inflammasome for the treatment of T2DM. Specially, the NLRP3-related therapeutic agents and options are widely developed. In summary, this article reviews the role of and research progress on the inflammasome in IR and T2DM.

N6-methyladenosine (m6A) modification has been demonstrated to exhibit a crucial prognostic effect on colorectal cancer (CRC). Nonetheless, potential mechanism of m6A in survival rate and immunotherapeutic response remains unknown. Here we investigated the genes associated with m6A regulators and developed a risk score for predicting the overall survival (OS) of CRC patients. RNA-seq transcriptomic profiling data of COAD/READ samples were obtained from The Cancer Genome Atlas (TCGA) database. Absolute Shrinkage and Selection Operator (LASSO)- Cox regression analysis was conducted to identify the m6A-related gene expression signatures and the selected genes were inputted into stepwise regression to develop a prognostic risk score in TCGA, and its predictive performance of CRC survival was further validated in Gene Expression Omnibus (GEO) datasets. According to our results, the risk score comprising 18 m6A-related mRNAs was significantly associated with CRC survival in both TCGA and GEO datasets. And the stratified analysis also confirmed that high-risk score acted as a poor factor in different age, sex, T stage, and tumour, node, metastasis (TNM) stages. The m6A-related prognostic score in combination with clinical characteristics yielded time-dependent area under the receiver operating characteristic curve (AUCs) of 0.85 (95%CI: 0.79–0.91), 0.84 (95%CI: 0.79–0.90) and 0.80 (95%CI: 0.71–0.88) for the prediction of the 1-, 3-, 5-year OS of CRC in TCGA cohort. Furthermore, mutation of oncogenes occurred more frequently in the high-risk group and the composition of immune cells in tumour microenvironment (TME) was significantly distinct between the low- and high-risk groups. The low-risk group had a lower microsatellite instability (MSI) score, T-cell exclusion score and dysfunction score, implying that low-risk patients may have a better immunotherapy response than high-risk patients. In summary, a prognostic risk score derived from m6A-related gene expression signatures could serve as a potential prognostic predictor for CRC survival and indicator for predicting immunotherapy response in CRC patients.

Background: The activation of alveolar macrophages (AMs) modulated via leucine-rich repeat (NLR) pyrin domain containing 3 (NLRP3) inflammasome activation is key to the progression of renal ischemia/reperfusion (rI/R)-mediated acute lung injury (ALI). Sirtuin-1 (SIRT1) can attenuate NLRP3 inflammasome activation during I/R stress and may be an important mechanism underlying ALI pathogenesis. Penehyclidine hydrochloride (PHC), an anticholinergic drug, exerts protective effects against rI/R-mediated ALI. This study aimed to decipher the effects of PHC on SIRT1 activation and the underlying mechanism of the protective activity of PHC against rI/R-mediated ALI.Materials and methods: We used an ALI rat model and the rat AMs cell line NR8383 to assess the degree of lung injury in vivo and in vitro.Results: The results show that PHC attenuates rI/R-mediated lung injury indices, myeloperoxidase, and apoptosis in vivo. It decreases the rI/R-mediated release of prostaglandin E2 and nitric oxide, mitochondrial reactive oxygen species production, and the activity of NADPH oxidase-4 in vitro. PHC ameliorates the rI/R-induced activation of the thioredoxin-interacting protein, caspase 1 (P10 unit), and NLRP3 inflammasome, along with reduced activation of interleukin-1β and interleukin-18 in vitro. We show that PHC alleviates the rI/R-induced reduction of SIRT1 and the depletion of SIRT1 eliminates the ameliorating activity of PHC on the NLRP3 inflammasome activation in vitro. Conclusions: In summary, the findings suggest that PHC ameliorates the rI/R-mediated ALI through the SIRT1-mediated NLRP3 inflammasome activation.

Introduction: Penehyclidine hydrochloride (PHC) is an anticholinergic with anti-inflammatory and anti-oxidation activities. PHC displayed protectivity against renal ischemia reperfusion (RIR) injury. Nevertheless, the precise protectivity of PHC on RIR-induced lung injury remains unknown. Methods: We examined the effects of PHC on RIR-induced lung injury and investigated the underlying mechanism. We induced RIR in mice and administrated PHC to RIR mice. Kidney function was monitored by measuring the blood urea nitrogen (BUN) and creatinine level in serum. We evaluated the lung injury, myeloperoxidase (MPO) activity in lung, pro-inflammatory cytokine level, and oxidative markers in serum and lung tissues. We tested the expression level of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) in lung of RIR mice after PHC treatment. Finally, we evaluated the effects of PHC in RIR Nrf2-/- mice. Results: PHC greatly downregulated the serum levels of BUN, creatinine, IL-6, NO, malondialdehyde (MDA), and matrix metalloproteinase-2. PHC also ameliorated the lung injury, decreased the MPO activity, and suppressed production of IL-6, TNF-α, IFN-γ, MDA, and O2-, while it promoted production of superoxide dismutase (SOD) and catalase (CAT) in lung. PHC improved the production of Nrf2 and HO-1. Conclusion: The protectivity of PHC was absent in Nrf2-/- mice. PHC ameliorated RIR-induced lung injury through Nrf2 pathway.

Based on the ray acoustic model, a new relationship between the radiation force and the acoustic power is studied for a rectangular weakly focusing transducer. The effect of pressure reflection coefficient on this model is discussed. For a totally absorbing target, an approximate closed-form expression is also derived and the performance of this model is compared with that of the far-field integration model. The numerical results show that the agreement is excellent with these two models, which can be both used for correction of measured results, but the formula based on the ray acoustic model can be applied more widely in practice because of its simpler expression. The experimental results show further the effectiveness of the relationship between radiation force and acoustic power for rectangular weakly focusing transducer based on the ray acoustic model. The results presented in this paper are important for application of ultrasound transducers in therapy.

The transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-κB) is expressed in brown adipocytes, but its role remains largely unknown in the cells. This issue was addressed in current study by examining NF-κB in brown adipocytes in vitro and in vivo. NF-κB activity was increased by differentiation of brown adipocytes through elevation of p65 (RelA) expression. The transcriptional activity of NF-κB was induced by the cold stimulation with an elevation in S276 phosphorylation of p65 protein. Inactivation of NF-κB in brown adipocytes made the knockout mice [uncoupling protein 1 (Ucp1)–CreER–p65f/f, U-p65-KO] intolerant to the cold environment. The brown adipocytes exhibited an increase in apoptosis, a decrease in cristae density and uncoupling activity in the interscapular brown adipose tissue (iBAT) of p65-KO mice. The alterations became severer after cold exposure of the KO mice. The brown adipocytes of mice with NF-κB activation (p65 overexpression, p65-OE) exhibited a set of opposite alterations with a reduction in apoptosis, an increase in cristae density and uncoupling activity. In mechanism, NF-κB inhibited expression of the adenine nucleotide translocase 2 (ANT2) in the control of apoptosis. Data suggest that NF-κB activity is increased in brown adipocytes by differentiation and cold stimulation to protect the cells from apoptosis through down-regulation of ANT2 expression.

Background: Lung cancer is the main cause of cancer-related death, with epithelial-mesenchymal transition (EMT) playing an important role in the development of this disease. The EMT-related genes Polypeptide N-Acetylgalactosaminyltransferase 3 (GALNT3) and 2′-5′-Oligoadenylate Synthetase 1 (OAS1) are involved in numerous tumor processes. Although these genes have been extensively studied in cancer, they have yet to be analyzed by multi-omics in lung adenocarcinoma (LUAD). Methods: EMT-related genes were identified by R and Venn diagram. Cox regression and Kaplan-Meier analysis were performed to evaluate patient survival, and the Gene Expression Profiling Interactive Analysis (GEPIA) database was used for correlation analysis. GeneCards and R packages were used to explore gene characterization and functional annotation. The Tumor Immune Estimation Resource (TIMER), Human Protein Atlas (HPA), University of Alabama at Birmingham Cancer (UALCAN), and The Cancer Genome Atlas (TCGA) databases were used to investigate gene expression, which was then confirmed by RT-PCR. Clinicopathological analysis was carried out using the UALCAN database. Functional mechanisms and multi-omics analysis were performed using DNA Methylation Interactive Visualization Database (DNMIVD), Targetscan, TIMER, Tumor–immune System Interactions Database (TISIDB) and cBioportal. Diagnostic values were calculated using ROC curve analysis. Results: A total of 320 EMT-related genes were identified in LUAD. Their characteristics were confirmed in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database by the intersection of 855 and 3600 different genes from the Gene Expression Omnibus (GEO) and EMTome databases, respectively. Expression of the EMT-related genes GALNT3 and OAS1 was associated with the prognosis of LUAD patients. A positive correlation was observed between the expression of GALNT3 and OAS1, and their expression was higher in LUAD tissue than in normal lung tissue. This was confirmed using RT-PCR. Multi-omics analysis revealed that GALNT3 and OAS1 expression was associated with gene mutation and methylation, cellular immune infiltration, and several immune subtypes. A miRNA-GALNT3/OAS1 regulatory network was also found. Receiver operating characteristic (ROC) curve analysis found that GALNT3 and OAS1 expression combined had superior diagnostic value to that of each marker alone. Conclusions: GALNT3 and OAS1 expression are associated with immune cell infiltration and poor prognosis in LUAD. Their combined expression has high diagnostic value; hence, GALNT3 and OAS1 may be valuable biomarkers for the early detection of LUAD.

Airborne laser scanning (ALS) point cloud segmentation is an essential procedure for 3D data understanding and applications. This task is challenging due to the unstructured, disordered, and sparse distribution of the point cloud. PointNet++ is a well known end-to-end learning network for point cloud segmentation without fully exploring the local and contextual features, which are less efficient and accurate in capturing the complexity of point clouds. On this basis, we design a novel encoder-decoder network architecture to obtain the semantic features of the ALS point cloud at different levels and achieve a better segmentation effect. The improved local feature aggregation module can merge the deep feature of the point cloud, combining local and global self-attention convolutional networks. It can adaptively explore the inherent semantics feature of points and capture more extensive context information of ALS point cloud, termed DSPNet++. Finally, the conditional random field optimization model can be used to refine the segmentation results. We evaluated the performance of our method on the Vaihingen dataset of the International Society for Photogrammetry and Remote Sensing (ISPRS) and the GML(B) 3D dataset. Experimental results show that our method fully exploits the semantic feature of the ALS point cloud and can achieve higher accuracy. A comparative study with established deep learning models also confirms that our proposed method has outstanding performance in the ALS point cloud segmentation task.