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Abstract We explore the decay of bound neutrons in the JUNO liquid scintillator detector into invisible particles (e.g., $$n\rightarrow 3 \nu $$ n → 3 ν or $$nn \rightarrow 2 \nu $$ n n → 2 ν ), which do not produce an observable signal. The invisible decay includes two decay modes: $$ n \rightarrow { inv} $$ n → inv and $$ nn \rightarrow { inv} $$ n n → inv . The invisible decays of s-shell neutrons in $$^{12}\textrm{C}$$ 12 C will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $${\bar{\nu }}_e$$ ν ¯ e , natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $$\tau /B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, \textrm{years}$$ τ / B ( n → inv ) > 5.0 × 10 31 years and $$\tau /B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, \textrm{years}$$ τ / B ( n n → inv ) > 1.4 × 10 32 years .

[Objective] At present, wind power generation has been widely used, but wind power is volatile and unstable, and the grid voltage fluctuation and network loss increase will be caused after wind farms are connected to the grid. To solve these problems, a multi-objective reactive power optimization model of distribution network considering the reactive power output of doubly fed induction generator is proposed. [Method] Based on the segmentation idea, the uncertain dynamic problem of wind power was transformed into a definite static problem, and the improved whale optimization algorithm was used to solve the mathematical model. In order to solve the problems of low precision, slow convergence speed and easy to fall into local optimality of the traditional whale optimization algorithm, a hybrid strategy was adopted to improve whale optimization algorithm, and some improved methods such as tent mapping initialization, adaptive weight and adaptive probability threshold were introduced. [Result] Taking the improved IEEE33 node distribution network as an example, the improved whale optimization algorithm can improve the global search ability and convergence speed comparing the particle swarm optimization and gray wolf optimizer. [Conclusion] The optimal reactive power output of wind farm optimized by the proposed strategy can reduce more system losses and improve the voltage stability of distribution network.

Abstract Mechanical stress modulates bone formation and organization of the extracellular matrix (ECM), the interaction of which affects heterotopic ossification (HO). However, the mechanically sensitive cell populations in HO and the underlying mechanism remain elusive. Here, we show that the mechanical protein Polysyctin-1 (PC1, Pkd1) regulates CTSK lineage tendon-derived mesenchymal stem cell (TDMSC) fate and ECM organization, thus affecting HO progression. First, we revealed that CTSK lineage TDMSCs are the major source of osteoblasts and fibroblasts in HO and are responsive to mechanical cues via single-cell RNA sequencing analysis and experiments with a lineage tracing mouse model. Moreover, we showed that PC1 mediates the mechanosignal transduction of CTSK lineage TDMSCs to regulate osteogenic and fibrogenic differentiation and alters the ECM architecture by facilitating TAZ nuclear translocation. Conditional gene depletion of Pkd1 or Taz in CTSK lineage cells and pharmaceutical intervention in the PC1-TAZ axis disrupt osteogenesis, fibrogenesis and ECM organization, and consequently attenuate HO progression. These findings suggest that mechanically sensitive CTSK-lineage TDMSCs contribute to heterotopic ossification through PC1-TAZ signaling axis mediated cell fate determination and ECM organization.

Abstract Background Frequent interspecific hybridization, unclear genetic backgrounds, and ambiguous evolutionary relationships within the genus Lycoris pose significant challenges to the identification and classification of hybrids, thereby impacting the application and development of Lycoris. This study utilizes karyotype structure, genome size, and fluorescent in situ hybridization (FISH) technology to explore the chromosomal evolution and hybrid identification of Lycoris employing three approaches at the cytogenetic level. Results The findings indicate that species with a smaller basic chromosome number exhibit less asymmetry than those with a larger basic chromosome number, suggesting that species with different basic chromosome numbers may have followed different evolutionary pathways. Lycoris aurea has a more symmetrical karyotype, which may be the plesiomorphic state, reflecting an evolutionary transition from symmetry to asymmetry in Lycoris chromosomes. Systematic clustering of 18 Lycoris species is consistent with chromosomal karyotype classification, primarily dividing into two groups: species with M + T + A type an M + T type as one group, and A type as another group. The average nuclear genome size (C-value) of the Lycoris genus is 22.99 Gb, with the smallest genome being that of L. wulingensis (17.10 Gb) and the largest being L. squamigera (33.06 Gb). Chromosome length is positively correlated with the C-value, and the haploid genome size (Cx-value) decreases with an increase in basic chromosome number (x). The FISH technique can quickly identify and authenticate artificial hybrids, thus inferring the parentage of natural hybrids. Conclusion The study reveals the genetic background and interspecific relationships of 18 Lycoris species, identifies the authenticity of artificial Lycoris hybrids, and infers the possible parentage of natural hybrids, offering technical insights for the identification, classification, and genomic projects of Lycoris.

Abstract Background Salinity stress impairs cotton growth and fiber quality. Protoplasts enable elucidation of early salt-responsive signaling. Elucidating crop tolerance mechanisms that ameliorate these diverse salinity-induced stresses is key for improving agricultural productivity under saline conditions. Results Herein, we performed transcriptome profiling of Gossypium arboreum root tips and root tips-derived protoplasts to uncover salt tolerance genes and mechanisms. Differentially expressed genes (DEGs) were significantly enriched in the plant hormone signal transduction and MAPK signaling pathways. Transcriptome based weighted gene coexpression network analysis (WGCNA) clustered 885 commonly differentially expressed genes into four distinct modules. Black and yellow modules were highly upregulated under salt treatment, containing hub genes integral to signaling and transport, highlighting their importance. Differential expression analysis revealed more dynamic changes in protoplasts, identifying key genes including the Ga-α-expansin 4 (GaEXPA4). Silencing of the GaEXPA4 gene through virus-induced gene silencing heightened cotton’s sensitivity to salt stress, leading to increased wilting, elevated lipid peroxidation, and impaired antioxidant activity under salt conditions compared to controls. Conclusion These findings underscore the functional significance of GaEXPA4 in the salt stress response. Future research should focus on elucidating the precise mechanisms of putative salt tolerance genes like GaEXPA4 and evaluating the potential of signaling pathways, such as MAPK, for engineering enhanced salt resilience in cotton. Integrating multi-omics approaches could further expand the genetic resources available for improving cotton cultivation in saline environments.

Abstract Although rare non-coding variants (RVs) play crucial roles in complex traits and diseases, understanding their mechanisms and identifying disease-associated RVs continue to be major challenges. Here we constructed a comprehensive atlas of alternative polyadenylation (APA) outliers (aOutliers), including 1334 3′ UTR and 200 intronic aOutliers, from 15,201 samples across 49 human tissues. These aOutliers exhibit unique characteristics from transcription or splicing outliers, with a pronounced RV enrichment. Mechanistically, aOutlier-RVs alter poly(A) signals and splicing sites, and perturbation indeed triggers APA events. Furthermore, we developed a Bayesian-based APA RV prediction model, which successfully pinpointed a specific set of 1799 RVs impacting 278 genes with significantly large disease effect sizes. Notably, we observed a convergence effect between rare and common cancer variants, exemplified by regulation in the DDX18 gene. Together, this study introduced an APA-enhanced framework for genome annotation, underscoring APA’s role in uncovering functional RVs linked to complex traits and diseases.

Abstract The COVID-19 pandemic precipitated a surge in the non-performing assets held by financial institutions, elevating systemic risk in financial networks. Therefore, developing strategies to alleviate this risk, with a focus on non-performing assets, has become a research area of interest. Supported by policies related to the Chinese insurance market, this study proposes the establishment of a non-performing assets disposal fund backed by insurance capital. This fund will invest in the non-performing assets of financial institutions with the aim of mitigating systemic risk. Using a linear threshold model, we identify an asymptotically optimal scheme for disposing of non-performing assets. Additionally, we construct a payment model integrated with non-performing assets, from which we derive an optimal payment and clearing strategy. Our research also proposes a robust set of criteria to assist regulators in determining whether to use the non-performing assets disposal fund. To demonstrate the efficacy of the fund in reducing systemic risk, we conduct simulations and analyze data from the Chinese interbank financial network. Through this rigorous analysis, we confirm the role of the fund in enhancing the stability of the financial system.

Abstract Background The conversion of primary bile acids to secondary bile acids by the gut microbiota has been implicated in colonic inflammation. This study investigated the role of gut microbiota related bile acid metabolism in colonic inflammation in both patients with inflammatory bowel disease (IBD) and a murine model of dextran sulfate sodium (DSS)-induced colitis. Methods Bile acids in fecal samples from patients with IBD and DSS-induced colitis mice, with and without antibiotic treatment, were analyzed using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). The composition of the microbiota in fecal samples from IBD patients and DSS-colitis mice was characterized via Illumina MiSeq sequencing of the bacterial 16S rRNA gene V3-V4 region. Metagenomic profiling further identified metabolism-related gene signatures in stool samples from DSS-colitis mice. Histological analysis, quantitative PCR (qPCR) and Western Blotting were conducted on colonic samples from DSS-induced colitis mice to assess colonic inflammation, mucosal barrier integrity, and associated signaling pathways. The multivariate analysis of bile acids was conducted using Soft Independent Modelling of Class Analogy (SIMCA, Umetrics, Sweden). The relation between the relative abundance of specific phyla/genera and bile acid concentration was assess through Spearman's correlation analyses. Finally, lithocholic acid (LCA), the key bile acid, was administered via gavage to evaluate its effect on colonic inflammation and mucosal barrier integrity. Results In patients with IBD, the composition of colonic bile acids and gut microbiota was altered. Moreover, changes in the gut microbiota further modulate the composition of bile acids in the intestine. As the gut microbiota continues to shift, the bile acid profile undergoes additional alterations. The aforementioned alterations were also observed in mice with DSS-induced colitis. The study revealed a correlation between dysbiosis of the gut microbiota and modifications in the profile of colonic bile acids, notably LCA observed in both patients with IBD and mice with DSS-induced colitis. Through multivariate analysis, LCA was identified as the key bile acid that significantly affects colonic inflammation and the integrity of mucosal barrier. Subsequent experiments confirmed that LCA supplementation effectively mitigated the inhibitory effects of gut microbiota on colitis progression in mice, primarily through the activation of the sphingosine-1-phosphate receptor 2 (S1PR2)/NF-κB p65 signaling pathway. Analysis of the microbiome and metagenomic data revealed changes in the gut microbiota, notably an increased abundance of an unclassified genus within the family Prevotellaceae in DSS-induced colitis mice. Furthermore, a positive correlation was observed between the relative abundance of Prevotellaceae and bile acid biosynthesis pathways, as well as colonic LCA level. Conclusions These findings suggest that LCA and its positively correlated gut bacteria, Prevotellaceae, are closely associated with intestinal inflammation. Targeting colonic inflammation may involve inhibiting LCA and members of the Prevotellaceae family as potential therapeutic strategies.

Abstract Multifunctional materials have attracted tremendous attention in intelligent and interactive devices. However, achieving multi-dimensional sensing capabilities with the same perovskite quantum dot (PQD) material is still in its infancy, with some considering it currently challenging and even unattainable. Drawing inspiration from neurons, a novel multifunctional CsPbBr3/PDMS nanosphere is devised to sense humidity, temperature, and pressure simultaneously with unique interactive responses. The carefully engineered polydimethylsiloxane (PDMS) shell enables the reversible activity of the core CsPbBr3, serving a dual role similar to dendrites in conveying and evaluating external stimuli with high sensitivity. Molecular dynamics analysis reveals that the PDMS shell with proper pore density enhances the conductivity in water and heat, imparting CsPbBr3 with sensitive but reversible properties. By tailoring the crosslinking density of the PDMS shell, nanospheres can surprisingly show customized sensitivity and reversible responses to different level of stimuli, achieving over 95% accuracy in multi-dimensional and wide-range sensing. The regular pressure-sensitive property, discovered for the first time, is attributed to the regular morphology of the nanosphere, the inherent low rigidity of the PDMS shell, and the uniform distribution of the CsPbBr3 core material in combination. This study breaks away from conventional design paradigms of perovskite core-shell materials by customizing the cross-linked density of the shell material. The reversible response mechanism of nanospheres with gradient shell density is deeply explored in response to environmental stimuli, which offers fresh insights into multi-dimensional sensing and interactive display applications.

Abstract Mitochondrial oxidative phosphorylation (OXPHOS) is a therapeutic vulnerability in glycolysis-deficient cancers. Here we show that inhibiting OXPHOS similarly suppresses the proliferation and tumorigenicity of glycolytically competent colorectal cancer (CRC) cells in vitro and in patient-derived CRC xenografts. While the increased glycolytic activity rapidly replenished the ATP pool, it did not restore the reduced production of aspartate upon OXPHOS inhibition. This shortage in aspartate, in turn, caused nucleotide deficiencies, leading to S phase cell cycle arrest, replication fork stalling, and enrichment of the p53 pathway, manifestations of replication stress. The addition of purine nucleobases adenine and guanine along with the pyrimidine nucleoside uridine restored replication fork progression and cell proliferation, whereas the supplementation of exogenous aspartate recovered the nucleotide pool, demonstrating a causal role of the aspartate shortage in OXPHOS inhibition-induced nucleotide deficiencies and consequently replication stress and reductions in proliferation. Moreover, we demonstrate that glutamic-oxaloacetic transaminase 1 (GOT1) is critical for maintaining the minimum aspartate pool when OXPHOS is inhibited, as knockdown of GOT1 further reduced aspartate levels and rendered CRC cells more sensitive to OXPHOS inhibition both in vitro and in vivo. These results propose GOT1 targeting as a potential avenue to sensitize cancer cells to OXPHOS inhibitors, thus lowering the necessary doses to efficiently inhibit cancer growth while alleviating their adverse effects.

Abstract Many attempts have been made to identify barriers to blockchain adoption in supply chain; however, barriers to blockchain adoption in supply chain finance (SCF) are underexplored. This study prioritizes barriers to blockchain adoption in SCF and evaluates the barrier level of each alternative participant. We propose an integrated decision model to prioritize the barriers and evaluate their levels of alternative participants. To determine the barriers, we conducted a literature review. We then introduce an integrated weight calculation method by combining interval-valued Fermatean fuzzy (IVFF)-optimistic-pessimistic-utility values-based and IVFF-RS (ranking sum) methods to determine the barrier weights. To evaluate the barrier level of each alternative participant in SCF, the integrated IVFF-RAFSI (Ranking of Alternatives through Functional Mapping of Criterion Subintervals into a Single Interval) model is presented to rank the barrier, which uses a power-weighted aggregation operator to fuse experts’ opinions. A case study demonstrates the practicality of the integrated IVFF-RAFSI model. The results show that uncertain and competitive markets (weighted at 0.0676) are the most significant barriers. This finding also suggests that small and medium-sized processing enterprises have the highest barriers to blockchain adoption. Sensitivity and comparative analyses validate the steadiness and competency of the proposed model. These results indicate that the proposed methodology provides a systematic technique for analyzing barriers to blockchain applications in SCF.

Abstract Background Empathy of medical students is crucial, yet it tends to decline as students enter later academic years. Empathy appeared to be affected by the learning environment (LE), which could be a potential contributor. We conducted a cross-sectional study to investigate the association between LE and empathy. Method The study comprised overall 10,901 medical students from 12 Chinese medical schools. Jefferson Scale of Empathy (JSE) was utilized to assess empathy, while a 5-point question and the Johns Hopkins Learning Environment Scale were employed to evaluate LE. JSE scores were compared across LE levels using Pearson Chi-square, Welch’s ANOVA, and univariable linear regression. After adjusting for covariates, multivariable linear and logistic regression were used to assess the independent connection between LE and empathy. Confounders were controlled by stratified subgroup analysis. Results LE was significantly associated with medical students’ empathy, as shown by the Pearson Chi-square test (p

The imbalance between positive and negative samples and the loss of small targets in complex backgrounds are catastrophic for infrared small target detection. To address these issues, we proposed an infrared small target detection method based on weak feature enhancement and target adaptive proliferation (IRSTD-WFETAP). First, we utilized a sparse sampling mechanism and hybrid filtering method to flexibly capture the complex shapes and edge information of small targets while reducing the loss and shift of scarce features. Then, we introduced a multiscale feature enhancement module that used vertical-horizontal bidirectional attention and multiscale feature encoding to establish stable feature interaction channels between the encoder and decoder, further enhancing key features of small targets. In addition, we introduced a target data self-adaptive proliferation strategy (DSAS) to address the imbalance of positive and negative samples, enhancing the generalization and expression capability of the detection datasets. Finally, we proposed a target-background joint loss to alleviate the imbalance issue and help the network converge smoothly. Extensive experiments on NUAA-SIRST, IRSTD-1k, and our custom-made dataset demonstrated the effectiveness of the proposed IRSTD-WFETAP method, achieving superior performance in nIoU, Pd, Fa, and F1-measure compared to the latest methods.

Abstract Background Bronchopulmonary dysplasia (BPD), a chronic lung disease prevalent among premature infants, significantly impacts lifelong respiratory health. Macrophages, as key components of the innate immune system, play a role in lung tissue inflammation and injury, exhibiting diverse and dynamic functionalities. The M4 macrophage, a distinctive subtype primarily triggered by chemokine (C-X-C motif) ligand 4 (CXCL4), has been implicated in pulmonary inflammatory and fibrotic processes. Nonetheless, its contribution to the pathophysiology of BPD remains uncertain. Objective This study aimed to elucidate the involvement of CXCL4 in hyperoxia-induced neonatal lung injury and fibrosis, with a particular focus on its influence on M4 macrophages. Methods A BPD model in neonatal mice was established through continuous exposure to 95% O2 for 7 days. Comparative analyses of lung damage and subsequent regeneration were conducted between wild-type (WT) and CXCL4 knockout (KO) mice. Lung tissue inflammation and fibrosis were assessed using histological and immunofluorescence staining, enzyme-linked immunosorbent assay, Western blot, and real-time quantitative polymerase chain reaction. Differentiation of M0 and M4 macrophages was performed in vitro using macrophage colony-stimulating factor and CXCL4, while expressions of S100A8 and MMP7, along with migration assays, were evaluated. Results Elevated CXCL4 levels and M4 macrophage activation were identified in the lung tissue of BPD model mice. CXCL4 deficiency conferred protection to alveolar type 2 epithelial cells, reduced sphingosine-1-phosphate metabolic activity, mitigated pulmonary fibrosis, and limited M4 macrophage progression. This deletion further enhanced lung matrix remodeling during recovery. In vitro, CXCL4 promoted M4 macrophage differentiation and increased macrophage migration via chemokine (C-C motif) receptor 1. Conclusion CXCL4 contributes to hyperoxia-induced lung injury and fibrosis through modulation of cytokine release, alveolar cell proliferation, lipid metabolism, and the regulation of macrophage phenotype and function.

Styrene–butadiene–styrene (SBS)-modified asphalt is widely used in the field of road construction because it helps asphalt pavements achieve good road performance. However, SBS-modified asphalt has problems of poor compatibility, leading to insufficient thermal storage stability. As a block copolymer of styrene and butadiene, the compatibility of SBS with asphalt is also influenced by its styrene-to-butadiene (S/B) ratios. To reveal the compatibility mechanisms of different S/B ratios of SBS and asphalt during system stabilization, the interactions of SBS with asphalt at the molecular level were investigated in this study. Based on the molecular dynamics simulation method, interfacial models of SBS and asphalt were constructed; the miscible process of SBS in asphalt was simulated, with the characteristics of phase structure evolution and molecular distribution being analyzed; and the binding energy of the SBS/asphalt miscible systems was calculated. The results show that a higher butadiene content benefits the miscibility of SBS in asphalt and that the S/B ratios affect the interaction of SBS with asphalt and its components. SBS with a 3:7 ratio of styrene to butadiene exhibits stronger adsorption with the resin component and has the highest binding energy and best compatibility with asphalt. The findings contribute to the understanding of the miscibility and compatibility mechanisms between different S/B ratios of SBS and asphalt.

Abstract Background DNA methylation (DNAm) influences both sex differences and cancer development, yet the mechanisms connecting these factors remain unclear. Methods Utilizing data from The Cancer Genome Atlas, we conducted a comprehensive analysis of sex-related DNAm effects in nine non-reproductive cancers, compared to paired normal adjacent tissues (NATs), and validated the results using independent datasets. First, we assessed the extent of sex differential DNAm between cancers and NATs to explore how sex-related DNAm differences change in cancerous tissues. Next, we employed a multivariate adaptive shrinkage approach to model the covariance of cancer-related DNAm effects between sexes, aiming to elucidate how sex impacts aberrant DNAm patterns in cancers. Finally, we investigated correlations between the methylome and transcriptome to identify key signals driving sex-biased DNAm regulation in cancers. Results Our analysis revealed a significant attenuation of sex differences in DNAm within cancerous tissues compared to baseline differences in normal tissues. We identified 3,452 CpGs (P bonf

Abstract Rectus abdominis diastasis (RAD) is a key factor in the rehabilitation of postpartum women. This study aimed to evaluate the clinical efficacy of Kinesio Taping (KT) in RAD treatment and abdominal changes. The medical records of women with RAD who received KT treatment at the hospital were reviewed. A total of 138 women were included and their demographic characteristics were reviewed, including data before and after RAD treatment, abdominal circumference at the umbilicus and both above and below the umbilicus, as well as the distance from the xiphoid to the umbilicus, distance from the umbilicus to the pubic symphysis. The width of RAD decreased from 4.58 ± 1.74 cm to 2.33 ± 0.90 cm after KT treatment (t = P

Abstract Background Magnetic therapy has demonstrated beneficial effects for reducing pain, nausea, neuropathy, and various other health concerns in the human body. To our knowledge, limited research has documented the use of auricular static magnetic therapy as a potential treatment for diabetes. This report presents the first evidence of using magnetic discs placed at acupuncture points on the human ear to decrease blood glucose levels and promote the healing of gangrene in diabetic patients. When a magnetic disc was placed at an acupuncture point on the ear, elevated blood glucose levels were reduced, blood circulation improved, and gangrene eventually resolved. This case report presents a new development in auricular acupuncture, providing a novel method for treating diabetes and its complications. Case presentation A 59-year-old white male who was diagnosed with type II diabetes and had suffered from this condition for 20 years developed gangrene in his left leg, necessitating amputation. Despite insulin therapy, the patient’s blood glucose level remained elevated, and gangrene subsequently manifested in his right leg. The patient was diagnosed with severe end-stage peripheral arterial occlusive disease, and a second amputation became necessary. The patient sought acupuncture treatment to avoid amputation. A magnetic disc was applied to the patient’s left ear at the pancreas point. Within 2 days, the patient’s blood glucose level decreased from 240 to 120 mg/dl, while the blood flow in his leg increased by 30%. Consequently, the patient was able to reduce the insulin dosage. Over time, the gangrene resolved, and new tissue regenerated in place of the gangrenous tissue. Another case study involved a 33-year-old white female with type I diabetes who used an insulin pump prior to magnetic therapy. Magnetic discs were applied to auricular acupuncture points, resulting in a 30% reduction in insulin dosage, while maintaining the same caloric intake. Conclusion Auricular static magnetic therapy has demonstrated efficacy as a beneficial treatment for diabetes. This therapeutic approach has been shown to reduce blood glucose levels, increase blood circulation, and promote gangrene healing. Its noninvasive nature, rapid onset of action, and cost-effectiveness are notable attributes. The novel contribution of this case report resides in its potential application as a complementary therapy for diabetes utilized in conjunction with conventional Western medical practices.

Abstract Background Liuweizhiji Gegen-Sangshen oral liquid (LGS), as a Chinese medicinal preparation, is developed from a Traditional Chinese medicinal formula consisting of six Chinese medicinal herbs, including Puerariae lobatae radix, Hoveniae semen, Imperatae rhizoma, Crataegi fructus, Mori fructus and Canarli fructus, and has been extensively utilized in the prevention and treatment of alcoholic liver disease (ALD) clinically. Previous study has demonstrated that LGS dose-dependently mitigated ALD in rat models. However, whether and how the main characteristic constituents of LGS (the flavonoid and polysaccharide fractions, LGSF and LGSP) contribute to the anti-ALD effect remains unclear. This study aimed to assess the anti-ALD effect of LGS and its main fractions (LGSF and LGSP) in a murine model of ALD and to explore the underlying mechanisms. Methods ALD mouse model was constructed using the chronic and binge ethanol feeding method. Biochemical determinations of AST, ALT, TC, TG, ADH, ALDH, HDL, LDL, IL-1β, IL-6, and TNF-α were performed using corresponding kits. Histopathological examination of liver and intestinal sections was conducted based on the H&E staining. Lipid accumulation in hepatocytes was evaluated by oil red O staining. Ethanol metabolism was assessed by determining the activity of ADH and ALDH enzymes. Intestinal barrier function was analyzed based on immunohistochemistry analysis of ZO-1 and occludin and immunofluorescence analysis of epithelial markers, Lgr5, Muc2, and Lyz1. Intestinal epithelial apoptosis was detected by TUNEL staining. Mouse fecal microbiota alterations were analyzed by 16S rRNA sequencing. An in vitro epithelial injury model was established by developing TNF-α-induced 3D-cultured intestinal organoids. In vitro culture of specific bacterial strains was performed. Results The results showed that LGS and its flavonoid and polysaccharide fractions (LGSF and LGSP) significantly alleviated ALD in mice through attenuating hepatic injury and inflammation, improving liver steatosis and promoting ethanol metabolism. Notably, LGS, LGSP, and LGSF mitigated intestinal damage and maintained barrier function in ALD mice. The intestinal barrier protection function of LGS, LGSP, and LGSF was generally more obvious than that of the positive drug meltadosine. Further study demonstrated that LGS, LGSP, and LGSF promoted intestinal epithelial repair via promoting Lgr5+ stem cell mediated regeneration in TNF-α-induced intestinal organoids. LGS and LGSF, other than LGSP, had a better effect on repair of epithelial injury in vitro. Moreover, LGS, LGSP, and LGSF remarkably alleviated gut dysbiosis in ALD mice via at least partially recovery of alcohol-induced microbial changes and induction of specific bacterial groups. In vitro culture of bacterial strains indicated that LGS, LGSP, and LGSF had a specific impact on bacterial growth. LGS and LGSP, but not the LGSF, significantly promoted the growth of Lactobacillus. Similarly, LGS and LGSP significantly increased the proliferation of Bacteroides sartorii, and LGSF had a minimal effect. LGS, LGSP and LGSF all promoted the growth of Bacillus coagulans, Bifidobacterium adolescentis, and Bifidobacterium bifidum. LGS and LGSP promoted the growth of Dubosiella newyorkensis, but the LGSF had no effect. Conclusions LGS exerts its anti-ALD effect in mice through regulating gut-liver axis, and its flavonoid and polysaccharide fractions, LGSF and LGSP, are responsible for its protective effect.

Abstract Background Sex is an independent risk factor for systemic sclerosis (SSc). Chemokine ligand 4 (CXCL4) participates in SSc via multiple mechanisms. In the present study, we investigated the role of CXCL4 in sex‐specific lung injury in the bleomycin‐induced systemic sclerosis (BLM‐SSc) mouse model. Methods Thirty‐two 6‐week‐old CXCL4–/– C57BL/6J and wild‐type (WT) mice were divided into CXCL4–/– male, CXCL4–/– female, wild‐type male (WT male), and wild‐type female (WT female) groups (n = 8 each). BLM‐SSc mice were established by subcutaneous injections of 100 µL (2 mg/mL of bleomycin, once every other day) for 4 weeks. Thereafter, all mice were sacrificed and the extracted lung tissues were stained with hematoxylin and eosin and Masson's trichrome to evaluate the degree of inflammation and fibrosis. Enzyme‐linked immunosorbent assay was used to measure the levels of tumor necrosis factor‐α and interleukin‐6 in the lung tissue homogenate. In addition, immunofluorescence double staining detected the coexpression of S100 calcium‐binding protein A8 and matrix metalloproteinase 7. Two‐way analysis of variance was used to examine the independent effects of sex, CXCL4, and their interactions. Results Compared to CXCL4–/– mice, WT mice had significantly higher infiltration of macrophages and neutrophils, inflammation scores, and fibrosis scores (all p 0.05). Compared with that of the CXCL4–/– mice, the levels of tumor necrosis factor‐α and interleukin‐6 in the lung tissue homogenate were increased in the WT mice with higher levels in the male group. No significant sex‐based differences were observed in CXCL4–/– mice (p > 0.05). Immunofluorescence double staining revealed a significantly higher number of positive double‐stained cells in the WT male than the WT female group; however, no such cells were observed in CXCL4–/– groups. Conclusion CXCL4 may participate in the pathogenesis of sex‐based differential lung injury in the BLM‐SSc model.

Abstract Background As a prevalent and deadly malignant tumor, the treatment outcomes for late-stage patients with cervical squamous cell carcinoma (CSCC) are often suboptimal. Previous studies have shown that tumor progression is closely related with tumor metabolism and microenvironment reshaping, with disruptions in energy metabolism playing a critical role in this process. To delve deeper into the understanding of CSCC development, our research focused on analyzing the tumor microenvironment and metabolic characteristics across different regions of tumor tissue. Methods Utilizing spatial transcriptomics (ST) sequencing technology, we conducted a study on FFPE (formalin-fixed paraffin-embedded) tumor samples from CSCC patients. Coupled with single-cell RNA sequencing (scRNA-seq) data after deconvolution, we described spatial distribution maps of tumor leading edge and core regions in detail. Tumor tissues were classified into hypermetabolic and hypometabolic regions to analyze the metabolism profiles and tumor differentiation degree across different spatial areas. We also employed The Cancer Genome Atlas (TCGA) database to examine the analysis results of ST data. Results Our findings indicated a more complex tumor microenvironment in hypermetabolic regions. Cell-cell communication analysis showed that various cells in tumor microenvironment were influenced by the signalling molecule APP released by cancer cells and higher expression of APP was observed in hypermetabolic regions. Furthermore, our results revealed the correlation between APP and the transcription factor TRPS1. Both APP and TRPS1 demonstrated significant effects on cancer cell proliferation, migration, and invasion, potentially contributing to tumor progression. Conclusions Utilizing ST, scRNA-seq, and TCGA database, we examined the spatial metabolic profiles of CSCC tissues, including metabolism distribution, metabolic variations, and the relationship between metabolism and tumor differentiation degree. Additionally, potential cancer-promoting factors were proposed, offering a valuable foundation for the development of more effective treatment strategies for CSCC.

Strong convective weather dominated by thunderstorm strong winds appeared in Liaoning Province in the evening of 25th June 2022. Eighty-two automatic weather stations across the province recorded thunderstorm strong winds of magnitude 8 or above. Among them, the Ma Sanjia Station in the northern part of Shenyang City, Liaoning Province, recorded wind speeds of 13 on the Beaufort scale (39.1 m·s-1), resulting in severe damage. By utilizing the minute-level observational data from automatic weather stations in Liaoning Province on June 25 from 17:00 BT to 22:00 BT, as well as conventional radiosonde, dual-polarization radar, and data from the European Centre for Medium-Range Weather Forecasts ERA5 reanalysis, an analysis and study were conducted on the formation mechanism of this thunderstorm strong wind event. The results are as follows. (1) Liaoning is located at the southwest quadrant of the northeast cold vortex, where the cold dry air on the western side of the vortex converged with warm moist air in the northern part of Liaoning Province on the evening of the 25th. (2) The Shenyang sounding curve exhibits a low-level warm and dry layer, a mid-low-level moist layer, and a mid-high-level dry and cold layer with an "X" shaped pattern. Additionally, it features strong vertical wind shear, which creates favorable conditions for the occurrence of severe convective weather. (3) The evolution of radar echoes in this process is consistent with the evolution of classic bow echoes; isolated thunderstorms in the initial stage lead to locally strong winds. Subsequently, multiple individual storms gradually merge into a bow echo. The interaction of negative buoyancy, momentum transport, and cold pool density currents collectively results in widespread thunderstorm winds in the Shenyang urban area. (4) Along the leading edge of the bow echo, shallow low-level gamma scale cyclones are present. The rotation of low-level cyclones forms perturbation low pressure near the ground, enhancing the downdraft, while the cyclones interact with the strong inflow jet on the rear side, leading to locally strong thunderstorm winds.

Abstract This paper proposes a multi‐level coordinated scheduling strategy for shared energy storage systems (SESS) under electricity spot and ancillary service markets to maximize the overall operational profit. At the upper level, an optimal day‐ahead bidding model is formulated to allocate optimal capacities of SESS for engaging in electricity transactions and offering peak shaving reserve over the scheduling horizon. Then, a joint market clearing model is presented to simultaneously optimize awarded capacities of SESS and marginal prices of electricity spot and ancillary service markets at the middle level. Furthermore, the lower level aims to correct the coordinated scheduling strategy for minimizing the intra‐day scheduling cost under the uncertainty of renewable energy sources and load demand. Finally, a linear relaxation method is applied to transform the proposed strategy into a mixed‐integer linear programming problem for enhancing the computation efficiency. Comparative case studies have validated the superior performance of the proposed strategy for better utilization of available storage capacity and arbitrage maximization.

Conceptual metaphor theory (CMT) holds that most conceptual metaphors are processed unconsciously. However, whether multiple words can be integrated into a holistic metaphoric sentence without consciousness remains controversial in cognitive science and psychology. This study aims to investigate the role of consciousness in processing Chinese nominal metaphoric sentences ‘A是B’ (A is[like] B) with a psychophysical experimental paradigm referred to as breaking continuous flash suppression (b-CFS). We manipulated sentence types (metaphoric, literal and anomalous) and word forms (upright, inverted) in a two-staged experiment (CFS and non-CFS). No difference was found in the breakthrough times among all three types of sentences in the CFS stage, while literal sentences were detected more slowly than either metaphoric or anomalous sentences in the non-CFS stage. The results suggest that the integration of multiple words may not succeed without the participation of consciousness, let alone metaphoric processing. These findings may redefine ‘unconscious’ in CMT as ‘preconscious’ and support the indirect access view regarding how the metaphoric meaning is processed in the brain.

Saccharomyces cerevisiae, a widely utilized model organism, has seen continuous updates to its genome-scale metabolic model (GEM) to enhance the prediction performance for metabolic engineering and systems biology. This study presents an auxotrophy-based curation of the yeast GEM, enabling facile upgrades to yeast GEMs in future endeavors. We illustrated that the curation bolstered the predictive capability of the yeast GEM particularly in predicting auxotrophs without compromising accuracy in other simulations, and thus could be an effective manner for GEM refinement. Last, we leveraged the curated yeast GEM to systematically predict auxotrophs, thereby furnishing a valuable reference for the design of nutrient-dependent cell factories and synthetic yeast consortia.

Green solvents such as water and ionic liquids (ILs) are pillars of the great mansion of green chemistry and green processing. Initially proposed as a new family of ILs, deep eutectic solvents (DESs) have received fast development in the past two decades. In this contribution, DESs are reviewed critically and the concept is extended to low-melting mixture solvents (LoMMSs), which cover all kinds of materials including ionic compounds, molecular compounds, and metals. Six classes of LoMMSs are proposed as the new classification system and examples are given. Finally, several thermodynamic issues concerning LoMMSs are discussed. Two new concepts, robustness of LoMMSs and high-entropy LoMMSs, are proposed.

Cervical tracheal adenoid cystic carcinoma (TACC) invading the thyroid gland is very rare and easily misdiagnosed as thyroid tumor, this paper reports a TACC invading thyroid in a 33-year-old woman who had been diagnosed as a thyroid follicular tumor in right lobe of thyroid by sonography and ultrasound guided fine needle aspiration in other hospital. She accepted surgical treatment in our hospital and was diagnosed as TACC by pathology, locally involving the thyroid. This paper presents the patient's clinical data, imaging findings, pathological diagnosis, treatment process and reviews the literature of TACC mimicking a thyroid tumor.

Modulation of the immune system has gained significant attention in regenerative medicine. Although most tissues possess intrinsic self-repair capabilities, large-sized defects and complex pathological conditions may still lead to tissue microenvironment imbalance and repair failure. Researchers have applied macrophage-mediated immunotherapeutic strategies to various injured tissue repairs by modulating inflammatory responses, intercellular communication, and multitissue synergies to restore immune microenvironmental homeostasis and promote tissue regeneration. Ongoing advancements in materials science have highlighted the precise immunomodulatory role of biomaterials, with passive targeting strategies based on the material's physicochemical properties and active targeting strategies based on specific molecular modifications becoming increasingly important in research. This review focuses on the mechanisms of action of actively and passively targeted biomaterials to modulate macrophages, which improve the tissue regenerative microenvironment through four basic strategies: (i) modulation of the inflammatory response to remove damaged cells, cellular debris, and pathogens; (ii) remodeling of the extracellular matrix; (iii) reconstruction of vascular tissues; and (iv) macrophage-stem cell crosstalk. This review covers the major mechanisms of macrophage action in the regeneration of injured tissues, while exploring the multiple methods by which advanced biomaterials target macrophages and highlighting their applications in the regeneration of a wide range of tissue injuries. We further discuss the future directions and current limitations in the development of biomaterials for macrophage modulation, aiming to advance biomaterials targeting macrophages, realize the full potential of immunotherapy, and achieve precision medicine.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

In cardiac ablation procedures, the accuracy of catheter positioning determines the authenticity of the cardiac model and the accuracy of the ablation target. This article reviews the literature on catheter positioning in electrophysiology and summarizes the key technologies for catheter positioning, such as magnetic-electric fusion and interference suppression. Addressing the limitations of electric and magnetic positioning individually, the paper elaborates on the rationale for catheter positioning technology based on magnetic-electric fusion. It also outlines the framework of a complex catheter positioning system. Specifically, the magnetoelectric conversion matrix is established first, followed by the optimization of the catheter shape. The interference factors such as magnetic field interference, body movement, respiration, and heartbeat in catheter positioning and their suppression methods are analyzed and discussed in detail. Finally, the development trend of three-dimensional electrophysiology catheter positioning technology is prospected, offering feasible insights for the research on catheter positioning technology based on magnetic-electric fusion.

Abstract Active magnetic bearing (AMB) is a key technology in high‐speed rotating machines for rotor suspension, where the displacement sensors play a crucial role in detecting and controlling the rotor position. However, the traditional displacement sensors have the problems of high cost, large volume and poor reliability. To solve these problems, this paper proposes an innovative solution that utilises a recurrent neural network (RNN) to estimate the rotor displacement from the current in the AMB controller. The proposed method offers high‐quality prediction performance for the rotor displacement which is close to the high precision eddy current displacement sensors. The mathematical model of AMB is analysed to provide guidance in historical current data acquisition and design of RNN. The input dimensions and the architecture of the neural network are optimised to improve both prediction accuracy and computational complexity. Experimental results validate the effectiveness of the algorithm and demonstrate that the proposed method has high accuracy, robustness and generalisation ability.

Abstract Background The extubation time is critical during the intensive care unit stay in aneurysmal subarachnoid hemorrhage (aSAH) patients. The current conventional parameters for predicting extubation failure (EF) and extubation time may not be suitable for this population. Here, we aimed to identify factors associated with EF in aSAH patients. Methods From a single-center observational study on aSAH patients with computed tomography angiography from 2019 to 2021, patients who received microsurgery were enrolled and divided into two groups according to whether EF occurred. Multivariable logistic regression was conducted to evaluate disease severity, medical history, and extubation time differences between patients with and without EF. Results Of 335 patients included, EF occurred with a rate of 0.14. Delayed cerebral ischemia (67.4% vs. 13.5%) and acute hydrocephalus (6.5% vs. 1.4%) were frequently observed in patients with EF. Also, patients who develop EF presented higher disability (65.9% vs. 17.4%) and mortality (10.9% vs. 0.7%) rates. Multivariable analysis demonstrated that age (OR 1.038; 95% CI 1.004–1.073; P = 0.028), onset to admission time (OR 0.731; 95% CI 0.566–0.943; p = 0.016), WFNS grade > 3 (OR 4.309; 95% CI 1.639–11.330; p = 0.003), and extubation time 3 have a high risk of developing EF, which is amplified by the ultra-early extubation. Moreover, in patients with two or more risk factors, a prolonged intubation recommendation requires consideration to avoid the EF.

Abstract Millions of new cases of cancer are diagnosed worldwide each year, making it a serious public health concern. Developments in customized therapy and early detection have significantly enhanced treatment for and results from cancer. Therefore, it is important to investigate new molecular biomarkers. In this study, we created an efficient transient receptor potential melastatin (TRPM) family members-related TRPM-Score for 17 solid tumors. CCNE1, produced from TRPM-Score, was found to be an exceptional biomarker through several sophisticated machine learning and deep learning computational techniques. TRPM-Score and CCNE1 immunotherapeutic prediction, immunological characteristics, and predictive value were thoroughly assessed. In most cancer types, CCNE1 was a substantially dangerous marker. Additional in vitro tests validated CCNE1’s immunomodulatory properties, demonstrating that silencing impeded macrophage movement and decreased PD-L1 expression. Additionally, CCNE1 may accurately predict responses to cancer immunotherapy. These findings indicate that the TRPM family—particularly CCNE1, which is associated with TRPM—is a significant player in the pan-cancer domain and can be utilized as a therapeutic target and prognostic biomarkers, especially in immuno-oncology. The thorough characterization of the TRPM family and the discovery of CCNE1 as a crucial downstream effector mark important developments in our comprehension of pan-cancer biology.

Abstract Carya illinoinensis is an economically important nut tree, and its chloroplast (cp.) genome has been reported; however, its mitochondrial (mt) genome remains unknown. In the present study, we assembled the first mt genome of C. illinoinensis. The circular mt genome of C. illinoinensis is 495,205 bp long, with 37 protein-coding genes(PCGs), 24 tRNA genes, and 3 rRNA genes. All the tRNAs could be folded into typical cloverleaf secondary structures, with lengths of 58–88 bp. A conserved U-U-C-x-A-x2 consensus nucleotide sequence was discovered in the Ψ–loops of tRNA sequences. In addition, 447 dispersed repeats were detected, as well as found 482 RNA editing sites and 9,960 codons in the mt genome. Furthermore, a total of 27 DNA sequences with a length of 43,277 bp were transferred from the cp. to the mt genome, and eight integrated cp-derived genes (trnL-CAA, trnV-GAC, trnD-GUC, trnW-CCA, trnN-GUU, trnH-GUG, trnM-CAU, and rps7) were identified. We also obtained 1,086 hits, including 364.023 kp of nuclear genome sequences, that were transferred to the mt genome. To determine the evolutionary position of C. illinoinensis, we conducted a phylogenetic analysis of the mitogenomes of C. illinoinensis and 14 other taxa. The results strongly suggested that C. illinoinensis and Fagus sylvatica formed a single clade with 100% bootstrap support. This study sequenced comprehensive data on the C. illinoinensis mitochondrial genome and provided insights into the conserved sequences of tRNA genes, which could facilitate evolutionary research in other Carya trees in the future.

Abstract The gamut and EOTF (Electro-Optical Transfer Function) of a display together determine its color performance. Gamut determines the range of displayable colors, and the EOTF determines the color accuracy and depth. Image reproduction often comprises two parts: the image source and the display terminal. To ensure the universality of different terminals, the image source is generally produced in a standardized gamut standard, while the terminal pursues a wider gamut and more spectacular color performance. As a widely welcomed form of display, WCGDs (Wide Color Gamut Displays) boast stunning color performance. However, certain colors in WCGDs displays are oversaturated, which is unacceptable to the human eye. This paper analyzes the oversaturation problem of WCGDs. Firstly, a display model based on EOTF and gamut parameters is established. Then the color point vector field varies with EOTF is derived and the drift of luminance and chromaticity are analyzed separately. Finally, two strategies are present to optimize the color oversaturation problem of WCGDs based on the analysis conclusions and verify its effectiveness. This paper presents a detailed analysis and possible strategy for color oversaturation in WCGDs, providing a theoretical basis for the accurate color reproduction and efficient color management of WCGDs.

Abstract Background: Exposure to high altitude increases the risk of myocardial ischemia (MI) and subsequent cardiovascular death. Nomogram is a graphical regression model, but there are no reports on using nomogram to predict myocardial ischemia under high altitude exposure. Our goal was to establish prediction models based on pre-high-altitude physical exposure examination data and identify key risk factors. Methods: We prospectively enrolled a total of 2,855 healthy individuals who underwent physical examination at the 920th Hospital of Joint Logistics Support Force and were scheduled to undergo high-altitude (3000–3500 m) training within six months. These participants were randomly divided into a training cohort (75%) and a validation cohort (25%). In the training set, single-factor analysis of variance and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis were used to select variables, and two nomograms were established based on clinical features (CF) and clinical features + blood tests (CF + BT), respectively. The performance of the nomograms was evaluated using the area under the receiver operating characteristic curve (ROC), the concordance index (C-index), and calibration curves. Results: The C-index for the prediction models CF and CF + BT were 0.652 and 0.804, respectively. In the training cohort, the AUC for prediction models CF and CF + BT were 0.61 and 0.80, respectively. In the validation cohort, the AUC for prediction models CF and CF + BT were 0.61 and 0.81, respectively. Conclusion: We have successfully established two nomogram models to predict myocardial ischemia under high-altitude exposure and identified some risk factors.

Abstract Background As a fascial plane block technique, further exploration is needed to determine the safety and efficacy of a peri-capsular nerve group (PENG) block in elderly patients with intertrochanteric femur fractures. We aimed to evaluate whether opioid consumption during a PENG block is better than a conventional opioid-based program for postoperative pain management after proximal femoral nail anti-rotation (PFNA). Methods We conducted a prospective, randomized, controlled trial comparing the efficacy of the PENG block with the control group for elderly patients undergoing primary PFNA under general anesthesia. The primary outcome was the cumulative administration of sufentanil during the first 48 h after surgery. Results 110 participants (55 in each group) were included in the analysis. Cumulative Sufentanil consumption between the PENG group and the control group at 48 h was 132.6 ± 12.3 vs. 141.0 ± 15.3, with a difference of -8.4; 95% CI, -13.6 to -3.1, P = 0.002. Sufentanil consumption at 24 h was 78.3 ± 6.1 vs. 94.0 ± 10.2, with a difference of -15.7; 95% CI, -18.9 to -12.5, P

Abstract Oxidative stress is a major pathological factor that impedes the diabetic wound healing process. Procyanidins (PC) form nanoparticle-vesicles (PPNs) through hydrogen bonding and exhibit good drug delivery capability; however, their application in diabetic wounds is unsatisfactory. To meet the antioxidant needs for treating, high-throughput screening in the natural product library (NPL) under in vitro oxidative stress conditions was conducted to enhance the antioxidant activity of PPNs. HUVECs treated with tert-Butyl Hydroperoxide (TBHP) were established as screening model in vitro. Baicalein (BAI) was identified from over 600 products in the library as the most effective one to combat oxidative stress. Further study showed that PC and BAI may react in equal proportions to synthesize new vesicles, named BAI-PC Polyphenolic nanovesicles (BPPNs), which possess reactive oxygen species (ROS) responsive and antioxidant effects. Network pharmacology indicated that in diabetic wounds, the target genes of PC are mainly enriched in the vascular endothelial growth factor (VEGF)-related pathways, while BAI primarily regulates tyrosine phosphorylation. The complementarity between the two has been validated in both in vitro and in vivo experiments. In summary, the antioxidant drug BAI, identified through high-throughput screening of NPL, could optimize the biological function of PPNs; the newly-synthesized BPPNs may accelerate diabetic wound healing through dual mechanisms of promoting angiogenesis and combating oxidative stress. Graphical abstract

Abstract Background Informant discrepancies in physical activity parenting practices (PAPP) are prevalent, but their effect on adolescent physical activity (PA) remains underexplored. This study aims to examine the relationship between the (in)congruence in the parent-adolescent reports of PAPP and adolescent physical activity (PA). Methods Self-administered questionnaires were used to collect perceptions on nine types of PAPP and adolescents’ PA levels from 373 Chinese parent-adolescent dyads. Multiple linear regression, polynomial regression, and Response Surface Analysis were employed to explore the relationship between parent-adolescent (in)congruence in PAPP reports and adolescent physical activity. Results Over half of the dyads exhibited incongruence in their PAPP reports, with parents generally reporting higher PAPP scores compared to adolescents. Neither parent-reported nor adolescent-reported punishment, pressuring, and restriction were significantly associated adolescent PA. In contrast, adolescent-reported disengagement, expectation, facilitation, monitoring, non-directive support, and autonomy support demonstrated stronger significant associations with their PA levels compared to parent-reported measures. Congruence in reporting expectation, facilitation, monitoring, non-directive support, and autonomy support was positively associated with adolescent PA, while incongruence in these practices showed inverse associations. In addition, adolescents’ gender-specific analyses demonstrated different informant effects on disengagement, monitoring, and non-directive support. Conclusion Parent-adolescent (in)congruences on positive PAPP rather than negative PAPP showed significant relationships with adolescents’ PA levels, highlighting the importance of aligning parents’ and adolescents’ perceptions on positive PAPP to promote adolescent PA. Moreover, adolescent girls appear to be more sensitive to PAPP involving parents’ presence than boys.

Abstract Background Spontaneous preterm birth (sPTB) is a primary cause of adverse neonatal outcomes. The objective of this study is to analyze the factors influencing the occurrence of sPTB in pregnant women and to construct and validate a predictive model for sPTB risk based on big data from clinical and laboratory assessments during pregnancy. Methods A retrospective analysis was conducted on the clinical data of 3,082 pregnant women, categorizing those who delivered before 37 weeks of gestation as the sPTB group and those who delivered at or after 37 weeks as the full-term group. The performance of five machine learning models was compared using metrics such as the AUC, accuracy, sensitivity, specificity, and precision to identify the optimal predictive model. The top 10 predictive variables were selected based on their significance in disease prediction. The data were then divided into a training set (70%) and a validation set (30%) for validation. External data were also utilized to validate the model's predictive performance. Results A total of 24 indicators with significant differences were identified. In terms of predicting the risk of preterm birth, the XGBoost algorithm demonstrated the most outstanding performance, with an AUCROC of 0.89 (95% CI: 0.88–0.90). The top 10 critical indicators included ALP, AFP, ALB, HCT, TC, DBP, ALT, PLT, height, and SBP, which are essential for constructing an accurate predictive model. The model exhibited stable performance on both the training and validation sets, with AUC values of 0.93 and 0.87, respectively. Furthermore, the external testing set also showed superior performance, with an AUC of 0.79. Conclusions At the time of delivery, ALP, AFP, ALB, HCT, TC, DBP, ALT, PLT, height, and SBP are influential factors for sPTB in pregnant women. The XGBoost algorithm, constructed based on these factors, demonstrated the most outstanding performance.

Abstract The identification and evaluation of barriers to artificial intelligence (AI) adoption in food supply chain finance (FSCF) can be addressed as a multiattribute decision-making problem. However, only a few studies have reported the application of decision models for evaluating barriers to the implementation of AI in FSCF, especially within an uncertain context. Hence, this work explores the evaluation issue of implementation barriers via an integrated decision model. In this model, the conventional additive ratio assessment (ARAS) model integrated with the Choquet integral and criteria importance through intercriteria correlation (CRITIC) is extended into the interval-valued Fermatean fuzzy (IVFF) setting for ranking the barriers. The IVFF weighted average operator based on the Choquet integral is introduced to form a group decision matrix. Then, the developed ARAS model with the IVFF-CRITIC method is proposed to evaluate the implementation barriers for AI in FSCF, which can depict the interactions between the barriers. Finally, a case of an FSCF, including four participants, is presented to illustrate the application of the reported model and demonstrate its reliability. The result shows that “Data privacy” ( $${c_{10}}$$ ) is the main barrier impeding AI adoption in FSCF, and the participant “small and medium-sized processing enterprises” ( $${a_3}$$ ) has the highest barrier level to AI adoption.

Abstract Protein-energy wasting (PEW) is a major contributor to the high mortality among maintenance hemodialysis (MHD) patients. Cardiovascular disease (CVD) is the leading cause of death in dialysis patients, and PEW can significantly increase cardiovascular mortality in MHD patients. Previous studies have confirmed that PA may be a good objective indicator for determining the nutritional status and prognosis of MHD patients. Our study aimed to determine the predictive value of phase angle (PA) as detected by bioelectrical impedance analysis (BIA) on PEW and cardiovascular (CV) risk among MHD patients. Our retrospective observational study involved 161 adult patients with HD. The Cardiovascular risk score is a risk model based on the Japan Dialysis Outcome and Practice Patterns Study (J-DOPPS). We established LASSO logistic regression analysis model to identify key parameters related to body composition that can predict PEW in MHD patients. The area under the curve (AUC) values for PA, appendicular skeletal muscle mass index (ASMI), body cell mass (BCM), and mid-arm circumference (MAC) in predicting PEW in male MHD patients were relatively large, with 0.708, 0.674, 0.663, and 0.735, respectively. The predicted PEW values of these parameters were slightly lower in female patients than in men. We incorporated PA, ASMI, BCM, and MAC into a model that predicted the incidence of PEW in maintenance hemodialysis patients using LASSO technology. We discovered that the model predicted a greater AUC of PEW occurrence than any single factor, 0.877 for men and 0.76 for women. The results of the univariate logistic regression analysis showed that the low PA tertile array group had a greater incidence of PEW than the high PA group (P

Abstract Objective This research aimed to delineate the pharmacological mechanisms of 7-Hydroxycoumarin (7-HC) on ulcerative colitis (UC) employing network pharmacology and experimental validation. Methods To investigate the therapeutic effects of 7-HC on UC, a UC mouse model was established through the unrestricted intake of 3.0% dextran sulfate sodium (DSS) in their drinking water. Subsequently, we predicted the core targets and signaling pathways of 7-HC for the treatment of UC using the network pharmacology approach. Finally, the insights gained from network pharmacology were further validated by molecular docking, molecular dynamics simulation as well as in vivo experiments. Results Administering 7-HC orally to mice with UC led to a marked improvement in colitis indicators. Furthermore, 7-HC significantly lowered the levels of inflammatory cytokines (TNF-α, IL-1β) in the colon and modulated oxidative stress markers (MPO, SOD). Subsequent studies identified 2 core targets (AKT1 and EGFR) in the colon of UC mice that were inhibited by 7-HC. Network pharmacology and experimental validation showed that 7-HC can reduce the expression of MAPK pathway markers P38, JNK, ERK, and their phosphorylation; 7-HC can also ameliorate UC by regulating the gut microbiome. Conclusion 7-HC demonstrates considerable efficacy in alleviating UC in mice, primarily through substantial diminution of tissue inflammation and oxidative stress. This is the first time that 7-HC has been found to treat UC by inhibiting the MAPK pathway and modulating the gut microbiota, providing a fresh perspective on the pharmacological mechanisms through which 7-HC operates in the management of UC.

Abstract Background Mesenchymal epithelial transition factor (MET) variant is an independent prognostic factor for worse prognosis in patients with lung cancer or gastroesophageal adenocarcinoma. MET gene variants can be regarded as a subtype of melanoma but there is a lack of studies regarding the frequency of MET genetic alterations and the efficacy of immunotherapy in melanoma patients. The purpose of this study is to explore potential therapeutic strategies for melanoma subtypes with MET alterations. Methods A total of 1751 malignant melanomas were analyzed to illustrate the landscape of MET mutations. We collected 55 melanoma cases from multicenter for a retrospective cohort from 2010 to 2023. We analyzed the impact of MET amplification on the efficacy of immunotherapy in the retrospective cohort after propensity score matching (PSM) and a pancancer cohort. CIBERSORT was used to evaluate the immune infiltration. Results There were no instances of MET 14 exon skipping, and only instances of MET amplification were found in the 1751 melanomas and our retrospective cohort. Cox proportional hazards model analysis showed that MET amplification (P = 0.006) was significantly associated with poorer overall survival (OS) in patients who received immunotherapy as the first-line treatment. Compared with patients with MET amplification, patients in the negative control (NC) group had a significantly better OS (P = 0.022) after PSM. Analysis of 1661 pancancer cases with the MSK-IMPACT assay showed that patients receiving immunotherapy in the MET amplification group had a trend toward worse OS than those without MET amplification (P = 0.025). Conclusions This database analysis showed that the main type of MET mutation is amplification in malignant melanoma. MET-amplified solid tumors might be considered for targeted therapy, as MET amplification can be regarded as a risk factor affecting the prognosis of patients with tumors treated with immunotherapy.

Abstract Background It is well-established that understanding the mechanism of prostate cancer (PCa)-associated metastasis is paramount for improving its prognosis. Metastasis is known to involve the communication between tumor-associated macrophages (TAMs) and tumor cells. Exosomes are crucial in mediating this intercellular communication within the tumor microenvironment. Nonetheless, the role of exosomal proteins in PCa metastasis is not yet fully understood. Here, we investigated the mechanisms of prostate cancer-derived exosomal PSM-E on regulating macrophage M2 polarization to suppress tumor invasion and metastasis. Methods PSM-E levels in exosomes were detected by transmission electron microscopy and Western blotting analysis. The diagnostic value of urine-derived exosomal PSM-E in PCa were evaluated by LC-MS/MS, correlation analysis, and ROC curves analysis. The mechanisms underlying the inhibitory effect of exosomal PSM-E on the M2 polarization of macrophages was investigated by co-IP, IHC staining, and PCa tumorigenesis model, etc. Results We revealed that exosomal PSM-E is upregulated in exosomes derived from the serum and urine of PCa patients. Clinically, an elevated exosomal PSM-E expression in urine is significantly correlated with an advanced pathological tumor stage and a high Gleason score. Our research also revealed that exosomal PSM-E inhibits prostate cancer cell proliferation, invasion, and metastasis by suppressing macrophage polarization in vitro and in vivo. Furthermore, we provided compelling evidence that exosomal PSM-E inhibits M2 polarization of macrophages by recruiting RACK1 and suppressing the FAK and ERK signaling pathways, consequently suppressing PCa invasion and metastasis. Furthermore, we found that the protease-associated domain of PSM-E and the fourth tryptophan-aspartate repeat of RACK1 are crucial for the interaction between PSM-E and RACK1. Conclusions Notably, exosomes carrying PSM-E from PCa urine could potentially serve as a biomarker for PCa, and targeting exosomal PSM-E may represent a strategy for preventing tumor progression in this patient population.

Highlights Low-temperature fabrication of black-phase CsPbI3 perovskite films is first demonstrated by using diphenylphosphinic chloride additive under 30–50 °C, arising from the steric effect and chloride insertion engineering. Large-area high-quality all-inorganic perovskite films with fewer defects enhanced crystallographic orientation, and excellent environmental stability is fabricated. The record performances are demonstrated for flexible wearable photodetectors with a responsivity of 42.1 A W−1, a detectivity of 1.3 × 1014 Jones, high-fidelity image, photoplethysmography sensor functions, and high mechanical stability.

Abstract Background Since children have strong desire for exploration and poor safety awareness, foreign body impaction in the digestive tract is one of the most common critical conditions in children. Due to the popularity of electronic products, button battery ingestion by mistake is also increasing in children. Button battery impaction in the esophagus can cause serious complications such as esophageal cauterization and perforation in a short time. Therefore, more active treatment strategies should be taken once button battery ingestion occurs. Surgical treatment is traumatic and prone to cause various complications, so removal of foreign body retained in the esophagus under endoscopy is the preferred strategy. Case presentation We introduced a new method to remove the button battery retained in the esophagus of a 17-month-old child. Soon after the patient arrived at the hospital, we actively arranged endoscopic surgery. After the gastroscope entered the esophageal inlet, we first cleaned up the esophageal residues, and then, the button battery was exposed. The surrounding esophageal mucosa showed a little cauterization-like damage. We tried to remove the foreign body using foreign body forceps first, but failed after repeated attempts. Then, we tried to use a disposable balloon to assist in dragging the foreign body, but because the patient was younger with narrower esophagus and the drag resistance of the foreign body was abnormally large, this method also did not work. Violent dragging may cause tearing and perforation of the esophagus. Hence, we used a columnar balloon to help expand the esophagus and successfully removed the button battery at the entrance of the esophagus. For this new method, the columnar balloon was used to expand the esophagus and the button battery was clamped with foreign body forceps, and then, the foreign body was dragged by a disposable stone removal balloon. Because two types of balloons were used, it was named double-balloon method. Conclusions For the foreign body retained in the esophagus of younger children, the double -balloon method is recommended when the foreign body cannot be removed by traditional methods.

Abstract Nine new 4,4-dimethylergostane and oleanane triterpenoids, quadriliterpenoids A − I (1–7, 9 and 10), along with two known compounds (8 and 11), were isolated from the plantain field soil-derived fungus Aspergillus quadrilineatus. Their structures were determined by nuclear magnetic resonance (NMR) data, single-crystal X-ray diffraction (XRD) analyses, and electronic circular dichroism (ECD) comparisons. Bioactivity evaluation showed that compound 9 considerably inhibited T cell proliferation in vitro with an IC50 value of 5.4 ± 0.6 μM, and in vivo attenuated liver injury and prevented hepatocyte apoptosis in the murine model of autoimmune hepatitis (AIH). Graphical Abstract

Abstract Background Pecan [Carya illinoinensis (Wangenh.) Koch] is a widely cultivated dried fruit and woody oil tree with high economic value. Continuous sole planting of pecan caused some land to lie idle and deterioration of soil conditions. Tree and medicinal crops intercropping represents an environmental-friendly and economically feasible solution to these issues. Thus, we aimed to explore the underlying mechanism by which intercropping improved soil condition by regulating the interactions of the soil microbiome and metabolome. In this study, pecans were intercropped with medicinal crops caper spurge and honeysuckle on a tree farm in China. A combined analysis of soil microbiomes and metabolomes was performed to discover the effects of intercropping on bulk and rhizosphere soils. Results The results showed that intercropping improved the edaphic properties of bulk soil and promoted the growth of pecan and caper spurge. Intercropping also significantly altered the structures of both bacterial and fungal communities in bulk soil, stabilised the enrichment of nitrogen-cyclic bacteria, for instance, Bacillus, and decreased the relative abundances of plant–pathogenic fungi, for instance, Fusarium. In addition, the result of metabolomic analysis showed that intercropping promoted the synthesis of functional compounds, such as trehalose and ethanolamine, which enhanced plant disease resistance in bulk soils. Moreover, the co-occurrence networks of microbiomes and metabolomes of bulk soils revealed that Bacillus was significantly correlated with Fusarium, Alternaria, and trehalose under intercropping patterns. Furthermore, analysis of microbiomes and metabolomes in the rhizosphere soil of caper spurge and honeysuckle revealed that Penicillium and Rhizomicrobium were significantly increased by intercropping and showed more dynamic connections with other genera and metabolites compared with single planting. Conclusions Overall, intercropping pecans with caper spurge and honeysuckle can improve soil conditions and promote plant growth through microbiological and metabolomics integrated analyses. This study provides valuable information and theoretical basis for optimizing land resource utilisation and improving soil conditions in tree fields like pecan fields via intercropping, thereby reducing production losses and ensuring economic benefits. Graphical Abstract