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To further develop a protein-polysaccharide composite fat replacer in low-fat meat products, this used pumpkin seed protein (PSP) and carrageenan to prepare a composite emulsion fat replacer, and added it to myofibrillar protein (MP) to form heat induced gel. The effects of the composite emulsion formed by PSP and carrageenan at various additive amounts on the properties of MP gels were investigated through the determination of gel moisture distribution, textural properties, microstructure, rheological properties, and other indexes. The results showed that when PSP and carrageenan composite emulsion was added at 50%, the water-holding properties and strength of the gel significantly improved (P

Abstract As testicular mesenchymal stromal cells, stem Leydig cells (SLCs) show great promise in the treatment of male hypogonadism. The therapeutic functions of mesenchymal stromal cells are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs remain unclear. Here, we observe that SLCs transplantation restore male fertility and testosterone production in an ischemia‒reperfusion injury mouse model. SLCs prevent inflammatory cascades through mitochondrial transfer to macrophages. Reactive oxygen species (ROS) released from activated macrophages inducing mitochondrial transfer from SLCs to macrophages in a transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated manner. Notably, knockdown of TRPM7 in transplanted SLCs compromised therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. These findings reveal a new mechanism of SLCs transplantation that may contribute to preserve testis function in male patients with hypogonadism related to immune disorders.

PurposeThis meta-analysis was conducted to collect all available data and estimate the relationship between refractive error and the risk of diabetic retinopathy (DR) in patients with diabetes, and to assess whether vision-threatening DR (VTDR) is associated with refractive error.MethodsWe systematically searched several literature databases including PubMed, Embase, Cochrane Library, Web of Science, CNKI, CBM, Wan Fang Data, and VIP databases. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed or random effects models. Four models were developed to assess the relationship between refractive error and the risk and DR, VTDR: hyperopia and DR, VTDR; myopia and DR, VTDR; spherical equivalent (SE per D increase) and DR, VTDR; and axial length (AL per mm increase) and DR, VTDR. The included literature was meta-analyzed using Stata 12.0 software, and sensitivity analysis was performed. Publication bias in the literature was evaluated using a funnel plot, Begg's test, and Egger's test.ResultsA systematic search identified 3,198 articles, of which 21 (4 cohorts, 17 cross-sectional studies) were included in the meta-analysis. Meta-analysis showed that hyperopia was associated with an increased risk of VTDR (OR: 1.23; 95% CI: 1.08–1.39; P = 0.001), but not with DR (OR: 1.05; 95% CI: 0.94–1.17; P = 0.374). Myopia was associated with a reduced risk of DR (OR: 0.74; 95% CI: 0.61–0.90; P = 0.003), but not with VTDR (OR: 1.08; 95% CI: 0.85–1.38; P = 0.519). Every 1 diopter increase in spherical equivalent, there was a 1.08 increase in the odds ratio of DR (OR: 1.08; 95% CI: 1.05–1.10; P

Objective: The aim of this study was to enhance the polysaccharide yield from Stellariae Radix and evaluate its in vitro antioxidant activity. Methods: Ultrasonic-assisted extraction method was employed to extract polysaccharides from Stellariae Radix, the single-factor experiment was combined with the Box-Behnken response surface to optimize the parameters of the extraction process. Additionally, Sevag method was utilized for the removal of protein to obtain crude polysaccharide of Stellariae Radix, which was further analyzed for its antioxidant activity. Results: The optimized conditions for extracting polysaccharides from Stellariae Radix were an ultrasonic temperature of 50 ℃, a time of 3.20 h, and an extraction frequency of 2 times, resulting in a yield of 28.24%±0.10%. The content of polysaccharide was 59.13%. Notably, the crude polysaccharide demonstrated antioxidant activity with IC50 values of 5.47, 2.40 and 1.44 mg/mL for DPPH, OH, and ABTS+ radical scavenging activities, respectively. Conclusion: The optimized extraction process of polysaccharides from Stellariae Radix is feasible and can provide a theoretical foundation for the development and utilization of Stellariae Radix.

Male ageing is always accompanied by decreased fertility. The forkhead O (FOXO) transcription factor FOXO4 is reported to be highly expressed in senescent cells. Upon activation, it binds p53 in the nucleus, preventing senescent cell apoptosis and maintaining senescent cells in situ. Leydig cells play key roles in assisting spermatogenesis. Leydig cell senescence leads to deterioration of the microenvironment of the testes and impairs spermatogenesis. In this study, we observed that FOXO4-DRI, a specific FOXO4- p53 binding blocker, induced apoptosis in senescent Leydig cells, reduced the secretion of certain Senescence-Associated Secretory Phenotype and improved the proliferation of cocultured GC-1 SPG cells. In naturally aged mice, FOXO4-DRI-treated aged mice exhibited increased sperm quality and improved spermatogenesis.

Essential trace minerals play vital roles in maintaining human and animal health. However, an overdose of the existing inorganic trace minerals is prone to induce detrimental effects that outweigh positive benefits. In this study, an extracellular polymeric substances (EPS)-producing bacterium, identified as Bacillus licheniformis CCTCC M2020298, was isolated from marine using glutinous rice processing wastewater as enrichment medium. The EPS yield of Bacillus licheniformis CCTCC M2020298 could reach 8.62 g/L by using glutinous rice-processing wastewater containing medium. Furthermore, the potential of the EPS as a carrier for synthesizing EPS-iron (Fe) and EPS-copper (Cu) complex was explored. The results showed that the optimum condition for the synthesis EPS-Fe were the reaction temperature 70°C, pH 8.5–9.0 and mass ratio of EPS to trisodium citrate 2:1. The iron content of EPS-Fe reached 77.4 mg/g. Under the same condition, the copper content of EPS-Cu reached 90.7 mg/g. The elemental composition, functional groups and valence state of the mineral elements of EPS-Fe and EPS-Cu were well characterized. The EPS-Fe and EPS-Cu exhibited antioxidant activity in scavenging ·OH, DPPH and ·O2− free radicals, thereby leading to reduced oxidative stress and apoptosis levels in human colonic epithelial cells in vitro. They also inhibited the proliferation of mouse hepatocellular carcinoma H22 and the growth of intestinal pathogens in vitro. This study provided an effective avenue for EPS production from glutinous rice processing wastewater and proved the potential of EPS-Fe and EPS-Cu complexes as a new-type comprehensive essential trace mineral supplement.

Abstract Kaempferol has demonstrated notable positive effects on the osteogenic differentiation of mesenchymal stem cells (MSC) and osteoblasts. A substantial body of research has emphasized the role of dislodged titanium particles in aseptic loosening following joint replacement surgery. This study predominantly investigates the suppressive influence of Kaempferol on osteolysis induced by titanium (Ti) alloy particles. In vitro investigations disclosed that Kaempferol effectively enhanced mineralization and alkaline phosphatase (ALP) activity in bone-marrow mesenchymal stem cells exposed to Ti particles. In addition, we conducted a comprehensive analysis of osteogenic differentiation microarray data_sets (GSE37676, GSE79814, and GSE114474) to identify differentially expressed genes. Significantly, Kaempferol upregulated the expression of critical osteogenic markers, including Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), osterix/Sp-7, and β-catenin. In vivo experiments, including H&E staining and Immunohistochemistry, provided compelling evidence that Kaempferol exerted a robust inhibitory effect on periprosthetic osteolysis in mice, with particularly pronounced results at higher doses. Moreover, it elevated the expression levels of osteogenic factors and Wnt/β-catenin signaling components. These findings collectively indicate that Kaempferol mitigates the hindrance to osteogenesis posed by titanium particles by activating the Runx2 and Wnt/β-catenin signaling pathways. This research lays a solid foundation for the prospective utilization of Kaempferol in the management of aseptic loosening following arthroplasty, offering promising therapeutic potential.

Abstract Background Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD. Methods An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software. Results A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70–7.47), domperidone (OR: 2.29, 95%CI: 1.16–4.63), itopride(OR: 2.77, 95%CI: 1.41–5.59), acotiamide(OR: 2.63, OR: 1.33–5.36), and placebo(OR: 5.68, 95%CI: 2.98–11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75–3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16–4.14) and placebo (OR: 3.52, 95%CI: 2.01–6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics. Conclusions Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.

The long-standing fermented meat products were deeply popular with consumers due to the distinctive flavor and long storage life. From the point of protein degradation in the process of fermentation of meat products and based on the recent researches of fermented meat products, this paper discusses the factors affecting the muscle protein degradation including the function of microbial proteases and endogenous enzymes, and the protein hydrolysis activity of core microorganism. The structure changes of muscle protein during fermentation are analyzed, including secondary and tertiary structure and functional properties of protein. This paper furthermore summarizes how the muscle protein degradation during fermentation improving the texture properties and flavor of the fermented meat products, and deterioration of products due to excessive protein degradation. Finally, the perspectives of the future researches are listed in order to provide some meaningful ideas for the intensive study of the fermentation control of meat products.

Regulating the microstructure of powder metallurgy (P/M) nickel-based superalloys to achieve superior mechanical properties through heat treatment is a prevalent method in turbine disk design. However, in the case of dual-performance turbine disks, the complexity and non-uniformity of the heat treatment process present substantial challenges. The prediction of yield strength is typically derived from the analysis of microstructures under various heat treatment regimes. This method is time-consuming, expensive, and the accuracy often depends on the precision of microstructural characterization. This study successfully employed a coupled method of Artificial Neural Network (ANN) and finite element analysis (FEA) to reveal the relationship between the heat treatment process and yield strength. The coupled method accurately predicted the location specified and temperature-dependent yield strength based on the heat treatment parameters such as holding temperatures and cooling rates. The root mean square error (RMSE) and mean absolute percentage deviation (MAPD) for the training set are 50.37 and 3.77, respectively, while, for the testing set, they are 50.13 and 3.71, respectively. Furthermore, an integrated model of FEA and ANN is established using a Abaqus user subroutine. The integrated model can predict the yield strength based on temperature calculation results and automatically update material properties of the FEA model during the loading process simulation. This allows for an accurate calculation of the stress–strain state of the turbine disk during actual working conditions, aiding in locating areas of stress concentration, plastic deformation, and other critical regions, and provides a novel reliable reference for the rapid design of the turbine disk.

2-methylfuran is a significant organic chemical raw material which can be produced by hydrolysis, dehydration, and selective hydrogenation of biomass hemicellulose. 2-methylfuran can be converted into value-added chemicals and liquid fuels. This article reviews the latest progress in the synthesis of liquid fuel precursors through hydroxyalkylation/alkylation reactions of 2-methylfuran and biomass-derived carbonyl compounds in recent years. 2-methylfuran reacts with olefins through Diels–Alder reactions to produce chemicals, and 2-methylfuran reacts with anhydrides (or carboxylic acids) to produce acylated products. In the future application of 2-methylfuran, developing high value-added chemicals and high-density liquid fuels are two good research directions.

Colon cancer is increasing worldwide and is commonly regarded as hormone independent, yet recent reports have implicated sex hormones in its development. Nevertheless, the role of hormones from the hypothalamus–hypophysis axis in colitis-associated colorectal cancer (CAC) remains uncertain. In this study, we observed a significant reduction in the expression of the oxytocin receptor (OXTR) in colon samples from both patient with colitis and patient with CAC. To investigate further, we generated mice with an intestinal-epithelium-cell-specific knockout of OXTR. These mice exhibited markedly increased susceptibility to dextran-sulfate-sodium-induced colitis and dextran sulfate sodium/azoxymethane-induced CAC compared to wild-type mice. Our findings indicate that OXTR depletion impaired the inner mucus of the colon epithelium. Mechanistically, oxytocin was found to regulate Mucin 2 maturation through β1-3-N-acetylglucosaminyltransferase 7 (B3GNT7)-mediated fucosylation. Interestingly, we observed a positive correlation between B3GNT7 expression and OXTR expression in human colitis and CAC colon samples. Moreover, the simultaneous activations of OXTR and fucosylation by l-fucose significantly alleviated tumor burden. Hence, our study unveils oxytocin’s promising potential as an affordable and effective therapeutic intervention for individuals affected by colitis and CAC.

Abstract Antimicrobial peptides (AMPs) are important mediators of intestinal immune surveillance. However, the regional heterogeneity of AMPs and its regulatory mechanisms remain obscure. Here, we clarified the regional heterogeneity of intestinal AMPs at the single-cell level, and revealed a cross-lineages AMP regulation mechanism that bile acid dependent transcription factors (BATFs), NR1H4, NR1H3 and VDR, regulate AMPs through a ligand-independent manner. Bile acids regulate AMPs by perturbing cell differentiation rather than activating BATFs signaling. Chromatin accessibility determines the potential of BATFs to regulate AMPs at the pre-transcriptional level, thus shaping the regional heterogeneity of AMPs. The BATFs-AMPs axis also participates in the establishment of intestinal antimicrobial barriers of fetuses and the defects of antibacterial ability during Crohn’s disease. Overall, BATFs and chromatin accessibility play essential roles in shaping the regional heterogeneity of AMPs at pre- and postnatal stages, as well as in maintenance of antimicrobial immunity during homeostasis and disease.

Isoetes orientalis is an endangered hexaploidy species of Isoetaceae in China and the complete chloroplast genome of this species has not been reported. In the present study, a complete chloroplast genome of Isoetes orientalis (Isoetaceae) was assembled and annotated. This chloroplast genome has a circular structure of 145,504 bp in length, comprising a pair of inverted repeat (IR) regions of 13,207 bp each, a large single-copy (LSC) region of 91,864 bp, and a small single-copy (SSC) region of 27,226 bp. The chloroplast genome contains 136 genes, including 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis showed that I. orientalis was closely related to I. sinensis. These results provide additional resources for future studies on Isoetes from China and across the globe.

Nearly all modern life depends on artificial light; however, it does cause health problems. With certain restrictions of artificial light emitting technology, the influence of the light spectrum is inevitable. The most remarkable problem is its overload in the short wavelength component. Short wavelength artificial light has a wide range of influences from ocular development to mental problems. The visual neuronal pathway, as the primary light-sensing structure, may contain the fundamental mechanism of all light-induced abnormalities. However, how the artificial light spectrum shapes the visual neuronal pathway during development in mammals is poorly understood. We placed C57BL/6 mice in three different spectrum environments (full-spectrum white light: 400–750 nm; violet light: 400 ± 20 nm; green light: 510 ± 20 nm) beginning at eye opening, with a fixed light time of 7:00–19:00. During development, we assessed the ocular axial dimension, visual function and retinal neurons. After two weeks under short wavelength conditions, the ocular axial length (AL), anterior chamber depth (ACD) and length of lens thickness, real vitreous chamber depth and retinal thickness (LLVR) were shorter, visual acuity (VA) decreased, and retinal electrical activity was impaired. The density of S-cones in the dorsal and ventral retinas both decreased after one week under short wavelength conditions. In the ventral retina, it increased after three weeks. Retinal ganglion cell (RGC) density and axon thickness were not influenced; however, the axonal terminals in the lateral geniculate nucleus (LGN) were less clustered and sparse. Amacrine cells (ACs) were significantly more activated. Green light has few effects. The KEGG and GO enrichment analyses showed that many genes related to neural circuitry, synaptic formation and neurotransmitter function were differentially expressed in the short wavelength light group. In conclusion, exposure to short wavelength artificial light in the early stage of vision-dependent development in mice delayed the development of the visual pathway. The axon terminus structure and neurotransmitter function may be the major suffering.

Abstract The neutrophil-to-lymphocyte ratio is used to reflect body's inflammatory status with prognostic value in different cancers. We aimed to investigate the influence of preoperative NLR in the prognosis of CRLM patients receiving surgery using meta-analysis. Data in Cochrane Library, PubMed, Embase, and Web of Science databases created before October 2022 were recruited. Meta-analysis was carried out with RevMan 5.3 and Stata16 software, and the primary outcome indicators included overall survival (OS), and secondary outcome indicators included disease-free survival (DFS) and relapse-free survival (RFS). The pooled risk ratio (HR) and 95% confidence interval (CI) for each outcome indicator were determined using random-effects models or fixed-effects models. The pooled odds ratio (OR) and corresponding 95% confidence intervals (CI) for NLR and clinicopathological characteristics were determined with a fixed-effects model. 18 papers published between 2008 and 2022 (3184 patients in total) were included. The pooled analysis found that high preoperative NLR was correlated with poor OS (multivariate HR = 1.83, 95% CI = 1.61–2.08, p

In order to solve the problems that restrict the efficient development of coalbed methane resources under the conditions of soft and low permeability outburst coal seams in Huainan Mining Area, such as complex coal seam structure, multi-source gas emission, rapid decline of drainage flow, high rock roadway and drilling costs, and low (ultra-low) concentration coalbed methane utilization rate, six key technologies suitable for the coordinated development mode of coal and coalbed methane under the condition of coal seam group mining in Huainan mining area are put forward, namely: coalbed methane extraction technology of ground level staged fracturing wells, shield rapid construction technology of coalbed methane extraction roadways, enhanced extraction technology of underground soft coalbed methane, coalbed methane extraction technology of pressure relief in ground mining area, the construction technology of "replacing roadways with holes", and cascade utilization technology of low concentration coalbed methane. The application of supporting key technologies shows that staged fracturing technology and refined drainage and production technology of roof horizontal wells in broken and soft coal seam have effectively improved the pre pumping production of coalbed methane; The full face hard rock roadheader in deep coal mine roadway greatly improves the roadway excavation efficiency, realizing the automation and less humanization of hard rock excavation; Sand adding of hydraulic fracturing and ultra-high hydraulic slotting have realized pressure relief and permeability enhancement in large areas underground coal mine; Type III and IV surface mining area wells can replace the roof high drainage roadway in the treatment of pressure relief gas in coal seam group mining, and reduce the coalbed methane drainage intensity of other measures; The technology of "replacing roadways with holes" has significantly improved the quality of successful directional drilling at middle and high levels in complex roof; Cascade utilization technology of low concentration coalbed methane has greatly reduced the emission of coalbed methane. The six key technologies have guaranteed the safe production in Huainan mining area, and comprehensively improved the output of coal and coalbed methane and the utilization level of coalbed methane. Six key technologies ensure the safe production in Huainan mining area, and comprehensively improved the output of coal and coalbed methane and the utilization level of coalbed methane. Finally, in view of the problems such as high operation cost, low production, small scope of hydraulic fracturing coal reservoir reconstruction technology for surface horizontal wells, and the risk of breakage of mining wells, and small scale of cascade utilization of ultra-low concentration coalbed methane, the development direction of deep CBM precise geological guidance, super large scale efficient reservoir volume transformation, pumping effect evaluation technology, stable and continuous pumping technology of surface wells in mining areas, underground large area intelligent hydraulic enhanced permeability technology, "one well with multiple uses" collaborative pumping CBM technology, and full concentration CBM comprehensive utilization technology are proposed.

The one strain many compounds (OSMAC) strategy is an effective method for activating silent gene clusters by cultivating microorganisms under various conditions. The whole genome sequence of the marine-derived strain Streptomyces globisporus SCSIO LCY30 revealed that it contains 30 biosynthetic gene clusters (BGCs). By using the OSMAC strategy, three types of secondary metabolites were activated and identified, including three angucyclines, mayamycin A (1), mayamycin B (2), and rabolemycin (3); two streptophenazines (streptophenazin O (4) and M (5)); and a macrolide dimeric dinactin (6), respectively. The biosynthetic pathways of the secondary metabolites in these three families were proposed based on the gene function prediction and structural information. The bioactivity assays showed that angucycline compounds 1–3 exhibited potent antitumor activities against 11 human cancer cell lines and antibacterial activities against a series of Gram-positive bacteria. Mayamycin (1) selectively exhibited potent cytotoxicity activity against triple-negative breast cancer (TNBC) cell lines such as MDA-MB-231, MDA-MB-468, and Bt-549, with IC50 values of 0.60–2.22 μM.

FAM76B has been reported to be a nuclear speckle-localized protein with unknown function. In this study, FAM76B was first demonstrated to inhibit the NF-κB-mediated inflammatory pathway by affecting the translocation of hnRNPA2B1 in vitro. We further showed that FAM76B suppressed inflammation in vivo using a traumatic brain injury (TBI) mouse model. Lastly, FAM76B was shown to interact with hnRNPA2B1 in human tissues taken from patients with acute, organizing, and chronic TBI, and with different neurodegenerative diseases. The results suggested that FAM76B mediated neuroinflammation via influencing the translocation of hnRNPA2B1 in vivo during TBI repair and neurodegenerative diseases. In summary, we for the first time demonstrated the role of FAM76B in regulating inflammation and further showed that FAM76B could regulate the NF-κB-mediated inflammatory pathway by affecting hnRNPA2B1 translocation, which provides new information for studying the mechanism of inflammation regulation.

Protein post-translational modification (PTM) is a regulatory mechanism for protein activity modulation, localization, expression, and interactions with other cellular molecules. It involves the addition or removal of specific chemical groups on the amino acid residues of proteins. Its common forms include phosphorylation, ubiquitylation, methylation, and acetylation. Emerging research has highlighted lactylation, succinylation, and glycosylation. PTMs are involved in vital biological processes. The occurrence and development of diseases depends on protein abundance and is regulated by various PTMs. In addition, advancements in tumor immunotherapy have revealed that protein PTM is also involved in the proliferation, activation, and metabolic reprogramming of immune cells in tumor microenvironment. These PTMs play an important role in tumor immunotherapy. In this review, we comprehensively summarize the role of several types of PTMs in tumor immunotherapy. This review could provide new insights and future research directions for tumor immunotherapy.

Climate change is expected to result in more extreme rainfall regimes that are characterized by intensified rainfall events and prolonged dry intervals. However, to date, the response of the dryland ecosystems to changes in the rainfall regime has remained unresolved. To better understand the effects of individual dry intervals and extreme rainfall regimes on the aboveground/belowground net primary productivity (ANPP/BNPP) and species diversity of semi-arid sandy grassland, this study aimed to assess the influence of the timing and frequency of prolonged dry intervals on the function of a degraded sandy grassland under a constant total growing-season rainfall. A field rainfall manipulation experiment was carried out in northeast China. The results showed that the 30 day dry interval caused a significant decrease in ANPP and plant cover, except for April. The 30 day dry interval substantially increased the allocation of total net primary productivity (NPP) to BNPP in July, while decreasing the species richness in May and June. The extreme rainfall regimes with lower frequency and longer dry intervals significantly decreased the ANPP, BNPP, plant cover, species richness and species diversity index, while increasing the allocation of the NPP to BNPP and plant density. The mean duration of the dry interval exhibited significant negative correlations with the ANPP, plant cover, species richness, and Simpson index. Variability in dry interval’s mean length also had a negative correlation with ANPP, plant cover, and species richness. Our results suggest that annuals in the semiarid sandy land were highly responsive to changes in rainfall regime. Even if rainfall amount remained constant, increases in duration of the dry intervals and the frequency of extreme intervals were more likely to reduce net primary productivity and species diversity in semiarid sandy annual grasslands, and even contribute to desertification. The findings also provide new evidence for the vital roles of dry interval frequency, duration, and timing, as determinants of semiarid ecosystem function and structure.

Background Submucosal fibrosis is associated with adverse events of endoscopic submucosal dissection (ESD). The present study mainly aimed to establish a predictive model for submucosal fibrosis in patients with early gastric cancer (EGC) undergoing ESD.Methods Eligible patients with EGC, identified at Qilu Hospital of Shandong University from April 2013 to December 2023, were retrospectively included and randomly split into a training set and a validation set in a 7:3 ratio. Logistic regression analyses were used to pinpoint the risk factors for submucosal fibrosis. A nomogram was developed and confirmed using receiver operating characteristic (ROC) curves, calibration plots, Hosmer-Lemeshow (H-L) tests, and decision curve analysis (DCA) curves. Besides, a predictive model for severe submucosal fibrosis was further conducted and tested.Results A total of 516 cases in the training group and 220 cases in the validation group were recruited. The nomogram for submucosal fibrosis contained the following items: tumour location (long axis), tumour location (short axis), ulceration, and biopsy pathology. ROC curves showed high efficiency with an area under the ROC of 0.819 in the training group, and 0.812 in the validation group. Calibration curves and H-L tests indicated good consistency. DCA proved the nomogram to be clinically beneficial. Furthermore, the four items were also applicable for a nomogram predicting severe fibrosis, and the model performed well.Conclusion The predictive models, initially constructed in this study, were validated as convenient and feasible for endoscopists to predict submucosal fibrosis and severe fibrosis in patients with EGC undergoing ESD.

Abstract Major depressive disorder (MDD) is a severe brain disease associated with a significant risk of suicide. Identification of suicidality is sometimes life-saving for MDD patients. We aimed to explore the use of dynamic functional network connectivity (dFNC) for suicidality detection in MDD patients. A total of 173 MDD patients, including 48 without suicide risk (NS), 74 with suicide ideation (SI), and 51 having attempted suicide (SA), participated in the present study. Thirty-eight healthy controls were also recruited for comparison. A sliding window approach was used to derive the dFNC, and the K-means clustering method was used to cluster the windowed dFNC. A linear support vector machine was used for classification, and leave-one-out cross-validation was performed for validation. Other machine learning methods were also used for comparison. MDD patients had widespread hypoconnectivity in both the strongly connected states (states 2 and 5) and the weakly connected state (state 4), while the dysfunctional connectivity within the weakly connected state (state 4) was mainly driven by suicidal attempts. Furthermore, dFNC matrices, especially the weakly connected state, could be used to distinguish MDD from healthy controls (area under curve [AUC] = 82), and even to identify suicidality in MDD patients (AUC = 78 for NS vs. SI, AUC = 88 for NS vs. SA, and AUC = 74 for SA vs. SI), with vision-related and default-related inter-network connectivity serving as important features. Thus, the dFNC abnormalities observed in this study might further improve our understanding of the neural substrates of suicidality in MDD patients.

Abstract Purpose Stereotactic radiosurgery (SRS) has become a standard approach for the treatment of patients with few metastatic brain lesions. However, the optimal treatment approach for the use radiotherapy in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs) remain unclear. This study aimed to compare the survival outcomes and intracranial local control in NSCLC patients with 1–4 BMs who are treated with SRS using linear accelerators (LINAC-SRS), whole-brain radiotherapy (WBRT), or WBRT plus radiotherapy boost (WBRT + RTB). Materials and methods We retrospectively analyzed 156 NSCLC patients with 1–4 BMs who received LINAC-SRS, WBRT, and WBRT + RTB. The median overall survival (OS), intracranial progression-free survival (iPFS), and distant brain failure-free survival (DBF-FS) and related prognostic factors were analyzed. Results The median follow-up period was 31.6 months. The median OS times in the LINAC-SRS, WBRT, and WBRT + RTB groups were not reached, 33.3 months and 27.9 months, respectively. The difference in survival rate was non-significant (P = 0.909). The 2-year iPFS and DBF-FS rates in the LINAC-SRS, WBRT and WBRT + RTB groups were 51.6% and 37.5%; 42.0% and 50.4%; and 51.1% and 56.1%, respectively. There was no significant difference in 2-year iPFS or DBF-FS among the three groups (P = 0.572 for iPFS, P = 0.628 for DBF-FS). Multivariate analysis showed that the independent adverse prognostic factors for OS, iPFS, and DBF-FS were neurological symptoms, recursive partitioning analysis (RPA) class, and targeted therapy. Conclusion LINAC-SRS did not result in significantly superior survival times or intracranial local control compared to WBRT or WBRT + RTB in the treatment of NSCLC patients with 1–4 BMs.

Abstract Background Partial trisomy 13q is a less common chromosomal abnormality with a great clinical variability, among them, isolated partial trisomy 13q is extremely rare. Here, we report two new unrelated cases of partial trisomy 13q in Chinese families aiming to emphasize the genotype–phenotype correlation in partial trisomy 13q. Methods Enrolled in this study were two unrelated cases of partial 13q trisomy from two families in Quanzhou region South China. Karyotpe and single-nucleotide polymorphism (SNP) array analysis were employed to identify chromosome abnormalities and copy number variants in the families. Results A 72.9-Mb duplication in 13q14.11q34 region was identified using SNP array analysis in Patient 1 with an intellectual disability, developmental delay, seizures, gastric perforation, and other congenital malformations from a family with paternal inv(13)(p12q14.1). SNP array detection in Patient 2 revealed a 92.4-Mb duplication in 13q12.11q34 region combined with an 8.4-Mb deletion in Xq27.3q28 region with intellectual disability, developmental delay, cleft palate, and duplication of the cervix and the vagina. No chromosomal abnormality was elicited from the parents of Patient 2. Conclusions In this study, we presented two new unrelated cases of partial trisomy 13q with variable features in Chinese population, which may enrich the spectrum of the phenotypes partial trisomy 13q and further confirm the genotype–phenotype correlation.

Background and aimsCompared with self-prepared LRD, a prepackaged low-residue diet (LRD) can improve patient compliance, but whether it can further improve the quality of bowel preparation is uncertain. The study aimed to compare the application of the prepackaged formula LRD with self-prepared LRD in bowel preparation for colonoscopy.MethodsA multicenter randomized controlled trial was conducted in 15 centers. The eligible subjects were randomly assigned to one of two groups: the formula LRD group and the self-prepared LRD group. On the day before the colonoscopy, subjects in the self-prepared LRD group were instructed to consume a restricted LRD prepared by themselves, while subjects in the formula LRD group were given six bags of prepackaged formula LRD and instructed to consume them according to their individual need. The primary outcome was an adequate bowel preparation rate. Secondary outcomes mainly included Boston Bowel Preparation Scale (BBPS) scores, dietary restriction compliance rate, tolerance, satisfaction, adenoma detection rate (ADR), and adverse reactions. The trial was registered at ClinicalTrials.gov under the identifier NCT03943758.ResultsA total of 550 subjects were recruited. Compared with the self-prepared LRD group, the formula LRD group showed a higher adequate bowel preparation rate (94.5 vs. 80.4%; P < 0.01), BBPS scores (7.87 ± 1.13 vs. 6.75 ± 1.47; P < 0.01), dietary compliance rate (92.4 vs. 78.9%; P < 0.01), tolerance (P < 0.01 in degree of hunger, intensity of physical strength, and negative influence on daily activities), satisfaction (8.56 ± 1.61 vs. 7.20 ± 2.02; P < 0.01), and ADR (25.6 vs. 16.0%; P < 0.01). There was no significant difference in adverse reactions.ConclusionCompared with self-prepared LRD, the formula LRD showed similar safety and higher bowel preparation quality, compliance, and tolerance in bowel preparation. More formula LRDs could be designed according to different dietary habits and ethnic populations, and further researches are warranted to confirm their effect.Clinical trial registrationhttps://register.clinicaltrials.gov, identifier: NCT03943758.

Aldehyde dehydrogenase (ALDH), a common oxidoreductase in organisms, is an aldehyde scavenger involved in various metabolic processes. However, its function in different pathogenic fungi remains unknown. Fusarium graminearum causes Fusarium head blight in cereals, which reduces grain yield and quality and is an important global food security problem. To elucidate the pathogenic mechanism of F. graminearum, seven genes encoding ALDH were knocked out and then studied for their function. Single deletions of seven ALDH genes caused a decrease in spore production and weakened the pathogenicity. Furthermore, these deletions altered susceptibility to various abiotic stresses. FGSG_04194 is associated with a number of functions, including mycelial growth and development, stress sensitivity, pathogenicity, toxin production, and energy metabolism. FGSG_00139 and FGSG_11482 are involved in sporulation, pathogenicity, and SDH activity, while the other five genes are multifunctional. Notably, we found that FGSG_04194 has an inhibitory impact on ALDH activity, whereas FGSG_00979 has a positive impact. RNA sequencing and subcellular location analysis revealed that FGSG_04194 is responsible for biological process regulation, including glucose and lipid metabolism. Our results suggest that ALDH contributes to growth, stress responses, pathogenicity, deoxynivalenol synthesis, and mitochondrial energy metabolism in F. graminearum. Finally, ALDH presents a potential target and theoretical basis for fungicide development.

The plasticity of welded 441 ferritic stainless steel joints was controlled by varying the laser beam spot diameter during laser welding. A stainless steel plate thickness of 1.2 mm was used. The microstructures of the welded joints were analyzed for various spot diameters. The elongation of breaks and the reduced area of tensile specimens were analyzed to study the effects of spot diameter on plasticity of the welded joints. The results showed that the weld melt width and weld column crystal size increased with the spot diameter, but isometric crystals in the center of the weld were gradually reduced. Increasing spot diameter resulted in decreased tensile strength, elongation after breaks, and area reduction. So the parameter must be controlled during the laser welding.

Zinc (Zn)-enriched pears, which are derived from genetically related cultivars or crops fortified using agronomic methods, have the potential to partly satisfy the human demand for Zn nutrition and diversify consumer choices. However, a standard for the Zn fortification level in pears is lacking, and the disparity in literature-reported fruit Zn concentrations can vary by substantial amounts. Before investigating the Zn concentrations in fruits of the main pear cultivars in China, common sample preparation methods were compared. Among the pre-treatment methods tested, the freeze-dry technique had a greater degree of discrete variation, whereas oven drying (fresh weight) was the optimal method for determining fruit Zn concentrations. Based on the optimal method, no significant distribution patterns of fruit Zn concentration were found among the regions and strains examined. The averaged pulp Zn concentration in all 26 cultivars was 0.72 mg kg−1, with the Hongxiangsu, Jinfeng, and 420 cultivars having the highest concentrations. Combined with the findings from our previous field experiments on Zn-fortified pears, a Zn concentration of ≥0.90 mg kg−1 is the suggested standard for pear enrichment. These results help us to better understand pear Zn nutrition levels and facilitate the marketisation of the fortified fruit.

Abstract Phosphatidylinositol 3 kinase (PI3K)/AKT (also called protein kinase B, PKB) signalling regulates various cellular processes, such as apoptosis, cell proliferation, the cell cycle, protein synthesis, glucose metabolism, and telomere activity. Corneal epithelial cells (CECs) are the outermost cells of the cornea; they maintain good optical performance and act as a physical and immune barrier. Various growth factors, including epidermal growth factor receptor (EGFR) ligands, insulin-like growth factor 1 (IGF1), neurokinin 1 (NK-1), and insulin activate the PI3K/AKT signalling pathway by binding their receptors and promote antiapoptotic, anti-inflammatory, proliferative, and migratory functions and wound healing in the corneal epithelium (CE). Reactive oxygen species (ROS) regulate apoptosis and inflammation in CECs in a concentration-dependent manner. Extreme environments induce excess ROS accumulation, inhibit PI3K/AKT, and cause apoptosis and inflammation in CECs. However, at low or moderate levels, ROS activate PI3K/AKT signalling, inhibiting apoptosis and stimulating proliferation of healthy CECs. Diabetes-associated hyperglycaemia directly inhibit PI3K/AKT signalling by increasing ROS and endoplasmic reticulum (ER) stress levels or suppressing the expression of growth factors receptors and cause diabetic keratopathy (DK) in CECs. Similarly, hyperosmolarity and ROS accumulation suppress PI3K/AKT signalling in dry eye disease (DED). However, significant overactivation of the PI3K/AKT signalling pathway, which mediates inflammation in CECs, is observed in both infectious and noninfectious keratitis. Overall, upon activation by growth factors and NK-1, PI3K/AKT signalling promotes the proliferation, migration, and anti-apoptosis of CECs, and these processes can be regulated by ROS in a concentration-dependent manner. Moreover, PI3K/AKT signalling pathway is inhibited in CECs from individuals with DK and DED, but is overactivated by keratitis.

To improve the efficiency of coal seam water injection, the influence of nanofluids on coal surface wettability was studied based on the nano drag reduction and injection enhancement technology in the field of tertiary oil recovery. The composition optimization and performance evaluation of nanofluids with nano-silica and sodium lauryl sulfate as the main components were carried out, and the effects of the nanofluid with the optimal ratio on coal wettability were studied through spontaneous upward imbibition experiments. The results show that the composite nanofluid has a lower surface tension, and the lowest value of the interfacial tension is 15.79 mN/m. Therefore, the composite nanofluid can enhance the wettability of coal. However, its effects on coal samples with different metamorphic degrees is different, that is, low rank coal is the largest, middle rank coal is the second, and high rank coal is the least. In addition, a functional relationship between time and imbibition height is found for pulverized coal with different particle sizes. When the particle size of pulverized coal is 60–80 mesh, the wettability of nanofluid to coal is best. The findings in this paper provide a new perspective for improving the water injection efficiency for coal seams with low permeability.

Abstract Purpose Lung cancer is the leading cause of cancer-related mortality. STEAP1 and STEAP2 are overexpressed in various cancers. The purpose of this study was to evaluate the expression and prognostic value of STEAP1 and STEAP2 in patients with lung cancer. Methods The mRNA expression and protein expression of STEAP1 and STEAP2 and their prognostic characteristics were examined using Oncomine, GEPIA, and Kaplan-Meier (KM) plotters. The correlation analysis of STEAP1 and STEAP2 gene and protein levels was conducted using GeneMANIA and STRING. KEGG pathway analysis was used to explore the related signal pathways of STEAP 1 and STEAP2. Immunohistochemical methods were used to compare the expression of STEAP2 in normal lung and non-small cell lung cancer (NSCLC) tissues. Real-time quantitative polymerase chain reaction, western blotting, and immunocytochemistry were used to evaluate the expression of STEAP1 and STEAP2 in three lung cancer cell lines and normal lung epithelial cell lines. Results Analysis of the Oncomine database and GEPIA showed that STEAP1 was upregulated and STEAP2 was downregulated in lung cancer tissue, and both expressions were related to the clinical stage of lung cancer. Immunohistochemical analysis showed that STEAP1 protein expression was significantly upregulated in lung cancer compared to that in adjacent tissues. The expression of STEAP1 was positively correlated with the migration and invasion abilities of lung cancer cells. Compared with paracancer tissues, the expression of STEAP2 protein in lung cancer was significantly downregulated and was correlated with the histological grade of squamous cell carcinoma, pathological classification of adenocarcinoma, tumor, lymph node, and metastasis clinical stage, and lymph node metastasis. The expression of STEAP2 was negatively correlated with the migration and invasion abilities of lung cancer cells. The KM curve showed that the downregulation of STEAP1 expression and upregulation of STEAP2 expression were related to a good lung cancer prognosis. Conclusion STEAP1 and STEAP2 are expected to be potential diagnostic and prognostic markers for lung cancer, which may provide more accurate prognostic indicators for lung cancer.

ABSTRACT Men with nonobstructive azoospermia (NOA) face the dual problems of low sperm count and low sperm quality. Most men with NOA without a clear cause are classified as having idiopathic NOA (iNOA). Previous studies found that microbes exist in semen, and the semen microbes of NOA men are different from those of normal men. However, the relevant mechanism is not clear. In this study, we answered the three questions of “who is there,” “what is it doing,” and “who is doing it” by combining 16s rRNA, nontargeted metabolome detection and metabolite traceability analysis. We found that the composition and interaction of seminal plasma microbes in the iNOA group changed. Metabolite traceability analysis and metabolic pathway analysis revealed that microbial abnormalities in the NOA group were closely related to the decrease of microbial degradation of toluene and the increase of metabolism of fructose or mannose. In addition, the metabolic relationship between microbes and the host in male semen in iNOA revealed that such microbes can produce harmful metabolites that affect sperm quality, the microbes compete with sperm for essential nutrients, and their presence reduces sperm production of essential nutrients. IMPORTANCE Idiopathic nonobstructive azoospermia is one of the great challenges in assisted reproductive therapy. Although microdissection testicular sperm extraction technology is currently available, many men with iNOA still face the problem of poor sperm retrieval and poor sperm quality. The role of seminal plasma microbes in male disease has been continuously investigated since semen was demonstrated to harbor commensal microbes. To our knowledge, this is the first detailed description of the microbe-host relationship in iNOA semen. This study is an important complement to research on the treatment and etiology of iNOA and the rationale for our ongoing research.

In this paper, according to the one-dimensional heat transfer mechanism between fabric and human body, it is found that different thermal properties affect different heat transfer stages of fabric. Therefore, we used the maximum heat flux q max as the index to characterize the transient contact cool feeling of fabrics, and measured the thermal properties, various specifications and surface morphology of 40 kinds of summer fabrics. Firstly, we discussed the influence of the above properties on the transient cool feeling. Secondly, according to multivariate stepwise regression, the significant representative variables are selected, and the prediction model of transient coolness and fabric properties is established. Furthermore, the model was verified to explore the subjective and objective consistency. The results show that, in the transient heat transfer stage, the influencing factors that are significantly related to the cool feeling of fabric include fabric thickness, grammage, volumetric heat capacity, thermal conductivity, warp and weft density, and roughness. The main component representative variables of the cooling sensation regression equation are volumetric heat capacity and thickness, and other variables can be explained by these two variables. Changing them is the key to enhance the cooling sensation. The predicted value of coolness is in good agreement with the subjective evaluation of cooling sensation, which has a certain guiding effect on the actual human cool feeling. The purpose of this study is to find out the main factors that affect the cool feeling, and then apply the established cool feeling model to the development of fabrics in summer, so as to meet the thermal comfort requirements of human body’s fabrics.

IntroductionInflammatory bowel diseases (IBDs) are associated with both immune abnormalities and dysbiosis, characterized by a loss of Faecalibacterium prausnitzii (F. prausnitzii). However, the reason for F. prausnitzii deficiency remains unclear.Methods16S rDNA seque­ncing and IgA enzyme-linked immunosorbent assay (ELISA) were applied to identify bacterial community and IgA changes in ulcerative colitis (UC) patients. Forced immunization with F. prausnitzii in rabbits was conducted. To screen for potential IgA-reactive proteins in F. prausnitzii lysates, we performed western blotting and mass spectrometry analyses. Pyruvate: ferredoxin oxidoreductase (PFOR) was cloned and purified, then the immunoreactivity of PFOR was verified in peripheral blood mononuclear cells (PBMCs) through PCR, ELISpot assay and single-cell sequencing (scRNA-seq). Finally, the UC fecal dysbiosis was re-analyzed in the context of the phylogenetic tree of PFOR.ResultsF. prausnitzii was underrepresented in UC patients with elevated F. prausnitzii-reactive IgA in the fecal supernatant. Forced immunization with F. prausnitzii in rabbits led to high interferon-γ (IFN-γ) transcription in the colon, along with beta diversity disturbance and intestinal inflammation. PFOR was identified as an IgA-binding antigen of F. prausnitzii and the immunoreactivity was validated in PBMCs, which showed elevated expression of inflammatory cytokines. The scRNA-seq revealed enhanced signals in both T regulatory cells (Tregs) and monocytes after PFOR incubation. Furthermore, phylogenetic analysis revealed that PFOR was a common but conserved protein among the gut bacteria.DiscussionOur results collectively suggest that PFOR is a bioactive protein in the immune system and may contribute to host-microbial crosstalk. Conserved but bioactive microbial proteins, such as PFOR, warrant more attention in future host-microbial interaction studies.

PurposeWe performed this study to determine the relationship between serum vitamin D levels and refractive status in adolescents aged 12–19 years.MethodsCross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database from 2001 to 2006. We used weighted multivariate linear regression models to assess the association between serum vitamin levels and adolescent refractive status and then built a smooth curve fitting to investigate their internal non-linear relationships. Finally, subgroup analysis was performed according to gender, and the threshold effect of serum vitamin D levels on spherical equivalent degree was analyzed using a two-piecewise linear regression model.ResultA total of 5,901 adolescents aged 12 to 19 years were included in this study. After adjusting for all confounding factors, the multiple linear regression model showed no significant correlation between adolescent spherical equivalent degree and serum vitamin D [0.0019 (−0.0018, 0.0046)]. However, smooth curve fitting analysis showed an inverted U-shaped curve relationship between spherical equivalent degree and serum vitamin D levels in adolescents (turning point: 58.1 nmol/L). In analyses by gender subgroup, this inverted U-shaped relationship was found to be more pronounced in female adolescents (turning point: 61.6 nmol/L).ConclusionOur results suggest that the correlation between refractive status and serum vitamin D in adolescents differs by gender. When serum vitamin D concentrations were

Medullary thyroid carcinoma (MTC) is one of the common malignant endocrine tumors, which seriously affects human health. Although surgical resection offers a potentially curative therapeutic option to some MTC patients, most patients do not benefit from it due to the difficulty to access the tumors and tumor metastasis. The survival rate of MTC patients has improved with the recent advances in the research, which has improved our understanding of the molecular mechanism underlying MTC and enabled the development and approval of novel targeted drugs. In this article, we reviewed the molecular mechanisms related to MTC progression and the principle for the design of molecular targeted drugs, and proposed some future directions for prospective studies exploring targeted drugs for MTC.

Land Use/Land Cover (LULC) is a main factor that affects the hydrological process of catchments. A better understanding of its influence is of great significance to future land use planning and water resources management. Since 2011, the local government has implemented a land remediation plan, and the LULC in the Yanghe Reservoir Basin has undergone major changes. This paper uses The Soil and Water Assessment Tool (SWAT) model to study blue water (BW) and green water (GW) resources in three typical years (a wet year, dry year, and normal year) under two LULC scenarios in the basin in 2010 and 2017. The results show that from 2010 to 2017, the area of cultivated land and residential construction land increased by 227.28% and 269.23%, respectively; the area of unused land, woodland, and grassland decreased by 98.84%, 35.90% and 39.52%, respectively. Compared with the results of the 2010 LULC scenario, the average BW of the three typical years under the 2017 LULC scenario decreased by 11.66%, 52.32%, and 21.95%, respectively, and the average GW flow increased by 6.72%, 2.90%, and 6.83%, respectively, and the average GW reserves decreased by 14.80%, 11.39%, and 7.67%, respectively. Therefore, this study believes that changes of LULC have led to a significant decrease in runoff and an increase in evapotranspiration in the basin. HIGHLIGHTS A SWAT model was used to study the blue water and green water resources in three typical years under two LULC scenarios in 2010 and 2017 for the Yanghe Reservoir basin.; The increase in the area of arable land in the Yanghe Reservoir basin has led to an increase in the green water coefficient.;

Background and Objective: Colorectal cancer (CRC) bone metastasis (BM), particularly synchronous metastasis, is infrequent and has a poor prognosis. Radical surgery for CRC with BM is challenging, and chemotherapy is the standard treatment. However, it is unclear whether combining chemotherapy with primary tumor resection (PTR) yields greater survival benefits than chemotherapy alone, as no relevant reports exist. Material and Methods: The Surveillance, Epidemiology, and End Results (SEER) database provided data on 1662 CRC patients with bone metastasis between 2010 and 2018, who were divided into two groups: chemotherapy combined with PTR and chemotherapy alone. Survival distributions were compared using the log-rank test, and survival estimates were obtained using the Kaplan–Meier method. A Cox proportional multivariate regression analysis was conducted to estimate the survival benefit of chemotherapy combined with PTR while controlling for additional prognostic factors. Results: The chemotherapy only group consisted of 1277 patients (76.8%), while the chemotherapy combined with PTR group contained 385 patients (23.2%). Patients who received chemotherapy combined with PTR had a significantly higher 1-year survival rate (60.7%) and 2-year survival rate (32.7%) compared to those who only received chemotherapy (43.8% and 18.4%, respectively; p < 0.0001). Independent prognostic factors identified by Cox proportional analysis were age, location of the primary tumor, type of tumor, M stage, metastasectomy and PTR. Patients who received chemotherapy combined with PTR had a significantly improved prognosis (HR 0.586, 95% CI 0.497–0.691, p < 0.0001). All subgroups demonstrated a survival advantage for patients who received chemotherapy in combination with PTR. Conclusions: Our findings suggest that patients with BM from CRC may benefit from chemotherapy combined with PTR. Our analysis also identified age, location of the primary tumor, type of tumor, M stage, metastasectomy, and PTR as independent prognostic risk factors for CRC patients with synchronous BM.

The occurrence of gastroesophageal reflux disease (GERD) and symptom onset are closely associated with diet. We aimed to compare the dietary and lifestyle triggers between non-erosive reflux disease (NERD) and reflux esophagitis (RE) in Chinese patients and to provide evidence for development of practical dietary modifications for GERD. A multicenter cross-sectional survey was conducted. A total of 396 GERD patients with typical gastroesophageal reflux symptoms who received upper endoscopy in the previous month were enrolled, including 203 cases of NERD patients and 193 cases of RE patients. All participants completed questionnaires including demographic data, reflux symptoms, previous management, dietary and lifestyle habits, triggers of reflux symptoms, psychological status, and quality of life. There were no significant differences in GERD symptom scores between NERD and RE. RE patients had a higher male proportion and smoking/drinking and overeating rates than NERD patients. In the NERD group, more patients reported that fruits, dairy products, yogurt, bean products, cold food, and carbonated beverages sometimes and often induced reflux symptoms and had more triggers compared to RE patients. The number of triggers was positively correlated to GERD symptom score and GERD-HRQL score in both NERD and RE patients. However, 74.0% of GERD patients still often consumed the triggering foods, even those foods that sometimes and often induced their reflux symptoms, which might be related to the reflux relapse after PPI withdrawal considering NERD and RE patients had similar GERD symptom severity. There were some differences in terms of dietary habits, dietary and lifestyle triggers, and related quality of life between NERD and RE, and these results may provide evidence of different approaches toward the dietary modification of NERD and RE patients.

1,3-bis(cyclohexylmethyl)cyclopentane, a renewable high-density fuel, was first produced in a high overall carbon yield (79.5%) with vanillin and cyclopentanone, which can be derived from biomass. The synthetic route used in this work contains two steps. In the first step, 2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone was synthesized by aldol condensation of vanillin and cyclopentanone under the catalysis of sulphuric acid. Over the optimized condensation, a high carbon yield (82.6%) of 2,5-bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone was achieved at 80 ºC. In the second step, 2,5-bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone was hydrodeoxygenated over the Pd/HY catalyst in cyclohexane as solvent. High carbon yields of 1,3-bis(cyclohexylmethyl)cyclopentane (96.2%) was obtained. The polycycloalkane mixture as obtained has a density of 0.943 g mL−1 and a freezing point of −35 °C. It can be blended into conventional high-density fuels (e.g., JP-10) for rockets and missile propulsion as a potential application.

The original plant of Chinese medicine Stellariae Radix (Yin Chai Hu) is Stellaria dichotoma L. var. lanceolata Bge (abbreviated as SDL). SDL is a perennial herbaceous plant and a characteristic crop in Ningxia. Growth years are vital factors that affect the quality of perennial medicinal materials. This study aims to investigate the impact of growth years on SDL and screen for the optimal harvest age by comparing the medicinal material characteristics of SDL with different growth years. Additionally, metabolomics analysis using UHPLC-Q-TOF MS was employed to investigate the impact of growth years on the accumulation of metabolites in SDL. The results show that the characteristics of medicinal materials and the drying rate of SDL gradually increase with the increase in growth years. The fastest development period of SDL occurred during the first 3 years, after which the development slowed down. Medicinal materials characteristics of 3-year-old SDL exhibited mature qualities with a high drying rate, methanol extract content, and the highest content of total sterols and total flavonoids. A total of 1586 metabolites were identified, which were classified into 13 major classes with more than 50 sub-classes. Multivariate statistical analysis indicated significant differences in the diversity of metabolites of SDL in different growth years, with greater differences observed in metabolites as the growth years increased. Moreover, different highly expressed metabolites in SDL at different growth years were observed: 1–2 years old was beneficial to the accumulation of more lipids, while 3–5 years old was conducive to accumulating more alkaloids, benzenoids, etc. Furthermore, 12 metabolites accumulating with growth years and 20 metabolites decreasing with growth years were screened, and 17 significantly different metabolites were noted in 3-year-old SDL. In conclusion, growth years not only influenced medicinal material characteristics, drying rate, content of methanol extract, and total sterol and flavonoid contents, but also had a considerable effect on SDL metabolites and metabolic pathways. SDL planted for 3 years presented the optimum harvest time. The screened significantly different metabolites with biological activity, such as rutin, cucurbitacin e, isorhamnetin-3-o-glucoside, etc., can be utilized as potential quality markers of SDL. This research provides references for studying the growth and development of SDL medicinal materials, the accumulation of metabolites, and the selection of optimal harvest time.

Abstract Background Accumulating evidence supports the pivotal role of intestinal flora in irritable bowel syndrome (IBS). Serotonin synthesis by enterochromaffin (EC) cells is influenced by the gut microbiota and has been reported to have an interaction with IBS. The comparison between the microbiota of the caecal and colonic mucosa in IBS has rarely been studied. The aim of this study was to investigate the relationship between the gut microbiota, EC cells in caecum and descending colon, and diarrhoea-predominant IBS (IBS-D) symptoms. Results A total of 22 IBS-D patients and 22 healthy controls (HCs) were enrolled in our study. Hamilton anxiety (HAM-A) and Hamilton depression (HAM-D) grades increased significantly in IBS-D patients. In addition, the frequency of defecation in IBS-D patients was higher than that in HCs. Among the preponderant bacterial genera, the relative abundance of the Ruminococcus_torques_ group increased in IBS-D patients in caecum samples while Raoultella and Fusobacterium were less abundant. In the descending colon, the abundance of the Ruminococcus_torques_group and Dorea increased in IBS-D patients and Fusobacterium decreased. No difference was observed between the descending colon and caecum in regards to the mucosal-associated microbiota. The number of EC cells in the caecum of IBS-D patients was higher than in HCs and the expression of TPH1 was higher in IBS-D patients both in the caecum and in the descending colon both at the mRNA and protein level. Correlation analysis showed that the Ruminococcus_torques_group was positively associated with HAM-A, HAM-D, EC cell number, IBS-SSS, degree of abdominal pain, frequency of abdominal pain and frequency of defecation. The abundance of Dorea was positively associated with EC cell number, IBS-SSS, HAM-A, HAM-D and frequency of abdominal pain. Conclusions EC cell numbers increased in IBS-D patients and the expression of TPH1 was higher than in HCs. The Ruminococcus torques group and Dorea furthermore seem like promising targets for future research into the treatment of IBS-D patients.

Abstract Considering that the working temperature is much higher in high‐voltage direct‐current (HVDC) convert transformers than in conventional AC transformers, the combination of thermally upgraded paper and natural ester might be a better choice to withstand high temperature in long‐term operation. This study compares the chemical structure, DC breakdown voltage, space charge and trap distribution of thermally upgraded paper aged in natural esters and mineral oil. The relationship between DC breakdown and accumulated charges was analyzed. Results show that the thermally upgraded paper aged in natural ester (NEI‐TUP) has a higher volume resistivity and DC breakdown voltage than that aged in mineral oil (MOI‐TUP). The NEI‐TUP group has a larger deep trap density than the MOI‐TUP group due to the chemical structure of natural ester. The larger deep trap density could contribute to the lower charge accumulation quantity and higher DC breakdown voltage. The thermally upgraded paper immersed in natural ester presents better insulation capability under thermal and DC electrical stress than that immersed in conventional mineral oil. This research indicated that the combination of thermally upgraded paper and natural ester might be a potential alternative for the mineral oil immersed paper in the future.

Abstract Aβ42 is one of the most extensively studied blood and Cerebrospinal fluid (CSF) biomarkers for the diagnosis of symptomatic and prodromal Alzheimer’s disease (AD). Because of the heterogeneity and transient nature of Aβ42 oligomers (Aβ42Os), the development of technologies for dynamically detecting changes in the blood or CSF levels of Aβ42 monomers (Aβ42Ms) and Aβ42Os is essential for the accurate diagnosis of AD. The currently commonly used Aβ42 ELISA test kits usually mis-detected the elevated Aβ42Os, leading to incomplete analysis and underestimation of soluble Aβ42, resulting in a comprised performance in AD diagnosis. Herein, we developed a dual-target lateral flow immunoassay (dLFI) using anti-Aβ42 monoclonal antibodies 1F12 and 2C6 for the rapid and point-of-care detection of Aβ42Ms and Aβ42Os in blood samples within 30 min for AD diagnosis. By naked eye observation, the visual detection limit of Aβ42Ms or/and Aβ42Os in dLFI was 154 pg/mL. The test results for dLFI were similar to those observed in the enzyme-linked immunosorbent assay (ELISA). Therefore, this paper-based dLFI provides a practical and rapid method for the on-site detection of two biomarkers in blood or CSF samples without the need for additional expertise or equipment. Graphical Abstract

With the implementation of low impact development (LID) in urban areas, it is necessary to quantify the actual effectiveness of LID facilities. In this study, a coupled hydrology-hydrodynamic numerical model was utilized to investigate the runoff control effectiveness of permeable pavements in the city centre of Shijiazhuang, China. Two groups of designed rainfall events with the same duration but different rainfall amounts and peak rainfall intensity locations were presented, and the effectiveness of permeable pavement was demonstrated by the reduction in the total runoff volume, water depth, and inundated area. The results indicate that the rainfall amount is the main factor affecting the runoff control of permeable pavements, and their effectiveness decreases with increasing rainfall amounts and peak intensity coefficients. Moreover, permeable pavements are more effective in reducing the residential waterlogging area, and the proportion of the inundated area above a depth of 0.2 m is considerably diminished. This study reveals the response of the runoff control of permeable pavements to different rainfall patterns, which is essential for supporting the design and practical operation of permeable pavements. HIGHLIGHTS Simulation scenarios with different rainfall patterns were presented to investigate the runoff control effectiveness of permeable pavement.; A series of indicators, including runoff volume, water depth, and inundated area, were presented to illustrate the runoff control effectiveness.; The effect of the relationship between rainfall intensity and infiltration rate on runoff generation was analysed.;

Abstract Aims There is little knowledge about partial trisomy 4q and the genotype–phenotype correlation. In this study, we presented the detail of two Chinese families with partial distal 4q duplication in an attempt to clarify the correlation between the genotype and the phenotype. Methods Two pedigrees with distal 4q duplication were enrolled in this study. Karyotype analysis and single-nucleotide polymorphism (SNP) array detection were performed for prenatal diagnosis. Fluorescence in situ hybridization analysis. (FISH) was conducted to verify the copy number variants. Results Two families with partial trisomy 4q were identified. The fetus in pedigree 1 exhibited multiple ultrasound anomalies including intrauterine growth restriction and an atrioventricular septal defect who had a duplication of 4q28.3-qter associate with 6p25.2-p25.3 deletion, which resulted from balanced translocation carried by his father t(4;6)(q28.3;p25.2). The fetus in pedigree 2 had a distal 4q28.3-qter duplication combined with monosomy of Xp21.3-p22.3, and the karyotype was described as 46,X,der(X)t(X;4)(p21.3;q28.3)mat, which originally inherited from the pregnant woman who exhibited a mild clinical phenotype limited to short stature. Conclusions In our study, we for the first time identified the partial trisomy 4q associate with 6p or Xp deletion. In addition, our finding further strengthens that mild clinical phenotype in 4q duplication case may be due to the spreading of X inactivation to the autosomal in derivation of chromosome X.

Stellaria dichotoma L. var. lanceolata Bge. (SDL) is the original plant of the traditional Chinese medicine Yinchaihu (Stellaria Radix). It is mainly distributed in the arid desert areas of northwest China, which is the genuine medicinal material and characteristic cultivated crop in Ningxia. This study aims to analyze the effects of different origins on SDL metabolites and quality, as well as to screen the dominant habitat factors affecting SDL in different origins. In this study, metabolites of SDL from nine different production areas were analyzed by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF MS) based metabolomics. And field investigations were conducted to record thirteen habitat-related indicators. Results showed that 1586 metabolites were identified in different origins, which were classified as thirteen categories including lipids, organic acids and organic heterocyclic compounds derivatives. Multivariate statistical analysis showed that the metabonomic spectra of SDL from different origins had various characteristics. What’s more, co-expression network correlation analysis revealed that three metabolites modules (MEturquoise, MEbrown and MEblue) were more closely with the habitat factors and 104 hub metabolites were further screened out as the habitat-induced metabolite indicators. Besides, soil texture, soil pH value and soil total salt content were found as the dominant habitat factors which affect SDL metabolites. In conclusion, the study showed different habitat factors had various effects on SDL’s quality and established relationship between them, which provide reference for revealing SDL’s genuineness formation mechanism and guiding industrial crops practical production by habitat factors selection.

BackgroundCervical cancer (CC) is one of the most common cancers in women. This study aimed to investigate the clinical and non-clinical features that may affect the prognosis of patients with CC and to develop accurate prognostic models with respect to overall survival (OS) and cancer-specific survival (CSS).MethodsWe identified 11,148 patients with CC from the SEER (Surveillance, Epidemiology, and End Results) database from 2010 to 2016. Univariate and multivariate Cox regression models were used to identify potential predictors of patients’ survival outcomes (OS and CSS). We selected meaningful independent parameters and developed nomogram models for 1-, 3-, and 5-year OS and CSS via R tools. Model performance was evaluated by C-index and receiver operating characteristic curve. Furthermore, calibration curves were plotted to compare the predictions of nomograms with observed outcomes, and decision curve analysis (DCA) and clinical impact curves (CICs) were used to evaluate the clinical effectiveness of the nomograms.ResultsAll eligible patients (n=11148) were randomized at a 7:3 ratio into training (n=7803) and validation (n=3345) groups. Ten variables were identified as common independent predictors of OS and CSS: insurance status, grade, histology, chemotherapy, metastasis number, tumor size, regional nodes examined, International Federation of Obstetrics and Gynecology stage, lymph vascular space invasion (LVSI), and radiation. The C-index values for OS (0.831 and 0.824) and CSS (0.844 and 0.841) in the training cohorts and validation cohorts, respectively, indicated excellent discrimination performance of the nomograms. The internal and external calibration plots indicated excellent agreement between nomogram prediction and actual survival, and the DCA and CICs reflected favorable potential clinical effects.ConclusionsWe constructed nomograms that could predict 1-, 3-, and 5-year OS and CSS in patients with CC. These tools showed near-perfect accuracy and clinical utility; thus, they could lead to better patient counseling and personalized and tailored treatment to improve clinical prognosis.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) seriously affects the physical and mental health of approximately 90% of males. Due to its complex and unclear etiology, the treatment methods that are currently available for chronic prostatitis/chronic pelvic pain syndrome are controversial, and their efficacy is unsatisfactory. At present, most researchers believe that this kind of prostatitis is caused by autoimmune inflammation. Chinese herbs, which are the essence of traditional Chinese medicine (TCM), are emerging treatment options for inflammation and immune diseases. In this experiment, we investigated the effect of Ningmitai capsules (a kind of traditional Chinese medicine widely used to treat lower urinary tract inflammation and pain in males) on chronic prostatitis/chronic pelvic pain syndrome in a non-obese diabetes-experimental autoimmune prostatitis (NOD-EAP) mouse model. First, by using bioinformatics analysis of data from the Encyclopedia of Traditional Chinese Medicine (ETCM) database, we found that quercetin, which is one of the main components of Ningmitai capsules, could reduce the secretion of CCL2 by inhibiting the MAPK pathway. In animal experiments, it was found that after Ningmitai treatment, the inflammation in mouse prostates was alleviated, the expression of CCL2, which is related to pain, and MAPK pathway components were downregulated, and the activation of the inflammatory NF–κB and STAT3 pathways was reduced. Pelvic pain and inflammation were relieved in mice with EAP. Due to the presence of the blood–prostate barrier, the drug may not completely reach the prostate directly and take effect locally. However, we found that after Ningmitai treatment, the proportions of proinflammatory CD11b+Ly6Chigh immune cells in the spleen, bloodstream (systemic immunity), and prostate (local immunity) were reduced. The infiltration of CD11b+ immune cells into the spleen and prostate was decreased. These findings suggested that Ningmitai can treat chronic prostatitis/chronic pelvic pain syndrome by affecting systemic and local immunities through the CCL2–MAPK pathway.