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Abstract TIMM9 has been identified as a mediator of essential functions in mitochondria, but its association with pan-cancer is poorly understood. We herein employed bioinformatics, computational chemistry techniques and experiments to investigate the role of TIMM9 in pan-cancer. Our analysis revealed that overexpression of TIMM9 was significantly associated with tumorigenesis, pathological stage progression, and metastasis. Missense mutations (particularly the S49L variant), copy number variations (CNV) and methylation alterations in TIMM9 were found to be associated with poor cancer prognosis. Moreover, TIMM9 was positively related with cell cycle progression, mitochondrial and ribosomal function, oxidative phosphorylation, TCA cycle activity, innate and adaptive immunity. Additionally, we discovered that TIMM9 could be regulated by cancer-associated signaling pathways, such as the mTOR pathway. Using molecular simulations, we identified ITFG1 as the protein that has the strongest physical association with TIMM9, which show a promising structural complement.

Abstract Background Breakthrough cancer pain (BTcP) has a negative impact on patients’ quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25μg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. Methods The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30). Results A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p

ObjectiveA local dynamic collision avoidance algorithm based on an improved fast-marching square (IFMS) method is proposed to solve the multi-vessel collision avoidance problem of unmanned sailboats in open water. MethodsConsidering the uncontrollable speed of a sailboat, its collision avoidance behavior is transformed into a heading control problem, with the direction of the total potential field gradient decreasing as the desired collision avoidance heading. When sailing without risk of collision or downwind, a temporal potential field is constructed to avoid all stationary irregular obstacles and reach the target point. When the sailboat has sailing constraints, Gaussian likelihood functions are designed for specific encounter situations to dynamically construct obstacle potential fields according to the convention on the international regulations for preventing collisions at sea (COLREGS), while the local wind potential field is introduced to consider the dead zone of a sailboat and realize the application requirements of combining dynamic collision avoidance with a zigzag sailing strategy. ResultsThe results show that the proposed algorithm can enable an unmanned sailboat to successfully achieve collision avoidance operations with other sailboats and restricted motor vessels in various encounter situations, while complying with collision avoidance rules and avoiding navigational dead zones. Compared with the original fast-marching square (FMS) algorithm, the upwind sailing time is significantly reduced and the planned collision avoidance trajectory is safer and more reasonable.ConclusionThe proposed method complies with the characteristics of sailboat motion and collision avoidance rules, has high safety and robustness in complex environments, and possesses scientific value regarding the development of autonomous obstacle avoidance technology for unmanned sailboats.

Abstract Sprint interval training (SIT) is a potent exercise strategy to enhance athletes’ anaerobic capacity in a time-efficient manner. This study aimed to investigate the impact of low-volume, court-based SIT on the anaerobic capacity and sport-specific performance in competitive tennis players. Twenty-four competitive collegiate tennis players were randomly assigned to either the SIT group (n = 12; three sessions per week of court-based repeated-sprint training) or the traditional endurance training (ET) group (n = 12; three sessions per week of 45-min continuous treadmill running, n = 12) for a 6-weeks intervention. Baseline and post-intervention assessments included the Wingate Anaerobic Test, elimination rate of blood lactate (BLAer), tennis-specific repeated sprint ability (RSA), and the Yo-Yo Intermittent Recovery Test Level 2 (YoYo-IR2). The results showed that SIT group demonstrated significant improvements in peak and average power during the Wingate test (p = 0.07; p

Abstract The free-field switching of the perpendicular magnetization by the out-of-plane polarized spin current induced spin-orbit torque makes it a promising technology for developing high-density memory and logic devices. The materials intrinsically with low symmetry are generally utilized to generate the spin current with out-of-plane spin polarization. However, the generation of the out-of-plane polarized spin current by engineering the symmetry of materials has not yet been reported. Here, we demonstrate that paramagnetic CaRuO3 films are able to generate out-of-plane polarized spin current by engineering the crystal symmetry. The non-uniform oxygen octahedral tilt/rotation along film’s normal direction induced by oxygen octahedral coupling near interface breaks the screw-axis and glide-plane symmetries, which gives rise to a significant out-of-plane polarized spin current. This spin current can drive field-free spin-orbit torque switching of perpendicular magnetization with high efficiency. Our results offer a promising strategy based on crystal symmetry design to manipulate spin current and could have potential applications in advanced spintronic devices.

Abstract Background Breastfeeding has many benefits for mothers and infants. Lactogenesis II is one of the key steps in the implementation of breastfeeding. If lactogenesis II occurs more than 72 h after delivery, it is termed delayed onset of lactation (DOL). DOL is associated with decreased milk production, shortened breastfeeding time, and pathological neonatal weight loss. A comprehensive summary of the incidence and factors influencing DOL is needed to provide a basis for improving breastfeeding practices and health outcomes. Methods Studies on the incidence and factors influencing DOL were retrieved from 13 Chinese and English databases (PubMed, Embase, Web of Science, Cochrane Library, CINAHL, etc.) from database inception to August 2023. Two researchers independently conducted the study screening, data extraction and quality evaluation. Stata 16.0 SE software was used for data analysis, and sensitivity analysis and publication bias tests were also performed. The qualitative description method was used to analyse studies that could not be combined quantitatively. Results A total of 35 studies involving 19,176 parturients, including 4,922 who had DOL, were included. The mean Newcastle‒Ottawa scale score of the included studies was ≥ 6, indicating that the quality was relatively high. Finally, the incidence of DOL was 30%, and 13 factors influencing DOL with robust results and no publication bias were obtained: prepregnancy body mass index (overweight or obesity), gestational diabetes, gestational hypertension, thyroid disease during pregnancy, serum albumin levels (

Abstract Eleocharis dulcis (Burm. f.) Trin. ex Hensch., commonly known as Chinese water chestnut, is a traditional aquatic vegetable in China, and now is widely cultivated throughout the world because of its high nutritional value and unique tastes. Here, we report the assembly of a 493.24 Mb telomere-to-telomere (T2T) genome of E. dulcis accomplished by integrating ONT ultra-long reads, PacBio long reads and Hi-C data. The reference genome was anchored onto 111 gap-free chromosomes, containing 48.31% repeat elements and 33,493 predicted protein-coding genes. Whole genome duplication (WGD) and inter-genomic synteny analyses indicated that chromosome breakage and genome duplication in E. dulcis possibly occurred multiple times during genome evolution after its divergence from a common ancestor with Rhynchospora breviuscula at ca. 35.6 Mya. A comparative time-course transcriptome analysis of corm development revealed different patterns of gene expression between cultivated and wild accessions with the highest number of differentially expressed genes (DEGs, 15,870) at the middle swelling stage and some of the DEGs were significantly enriched for starch metabolic process.

Acute pancreatitis (AP) is a potentially fatal condition with no targeted treatment options. Although inhibiting xanthine oxidase (XO) in the treatment of AP has been studied in several experimental models and clinical trials, whether XO is a target of AP and what its the main mechanism of action is remains unclear. Here, we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP. We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models. We also found that allopurinol and febuxostat, as purine-like and non-purine XO inhibitors, respectively, exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points. Moreover, we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity. Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha (HIF-1α)-regulated lactate dehydrogenase A (LDHA) and NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathways and reduced the enrichment of 13C6-glucose to 13C3-lactate. Lastly, we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels, while pancreatic XO and urate were also increased in severe AP patients. These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.

Abstract Objective To determine the prevalence of and risk factors for overweight and obese among Chinese children and adolescents. Methods This analytical cross-sectional study included 16,640 children and adolescents aged 6–18 years across four provinces of China in 2016. Physical characteristics and responses to questionnaires were analyzed. Body Mass Index (BMI) and the prevalence of overweight and obesity were calculated. Results Among children and adolescents, the overall prevalence of overweight and obesity in 2016 in four regions of China was 27.2% and 29.6%, respectively. Among different stages and sexes, the highest prevalence of obesity (15.8%) was observed in adolescent boys. From childhood to adolescence, the obesity rate among boys increased by 0.7% (from 15.1% to 15.8%), while the obesity rate among girls decreased by 0.9% (from 10.8% to 9.9%). Children and adolescents who were overweight or obese had significantly higher systolic blood pressures, larger waist circumferences and larger hip sizes than those with a normal BMI. Logistic regression analyses identified thirteen factors associated with overweight or obesity in children and adolescents. Conclusions Our results indicate that the prevalence of overweight and obesity is high among children and adolescents, especially among male adolescents in four regions of China. A suitable intervention program should not only help parents understand the serious risk of childhood obesity but also, more importantly, help to encourage a healthy lifestyle among children and adolescents.

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. Methods We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. Results A functional assay identified that transforming growth factor-β1 (TGF-β1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. Conclusions These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.

Abstract Fractional quantum Hall (FQH) states are exotic quantum many-body phases whose elementary charged excitations are anyons obeying fractional braiding statistics. While most FQH states are believed to have Abelian anyons, the Moore–Read type states with even denominators – appearing at half filling of a Landau level (LL) – are predicted to possess non-Abelian excitations with appealing potential in topological quantum computation. These states, however, depend sensitively on the orbital contents of the single-particle LL wavefunctions and the LL mixing. Here we report magnetotransport measurements on Bernal-stacked trilayer graphene, whose multiband structure facilitates interlaced LL mixing, which can be controlled by external magnetic and displacement fields. We observe robust FQH states including even-denominator ones at filling factors ν = − 9/2, − 3/2, 3/2 and 9/2. In addition, we fine-tune the LL mixing and crossings to drive quantum phase transitions of these half-filling states and neighbouring odd-denominator ones, exhibiting related emerging and waning behaviour.

Abstract Background The modifiable mechanisms underlying the association between socioeconomic status (SES) and preterm birth remain unclear. This study aimed to investigate the relationship between preterm birth and maternal SES or gestational weight gain (GWG), as well as the role of GWG in mediating SES disparities in preterm birth. Methods Data was from a hospital-based sub-study of physical growth and development survey for Chinese newborns with various gestational ages. Singleton newborns aged from 24 to 42weeks’ gestation and their mothers were included. Using information from maternal questionnaire, a composite SES was constructed with parental education and family annual income. GWG as mediator was calculated by deducting pre-pregnancy weight from maternal weight at delivery. Logistic regression model was adopted to investigate the association of preterm birth with SES or GWG. Causal mediation analysis was performed to measure mediating effect of GWG on the pathway from SES to preterm birth. Results After controlling for potential confounders, risk of preterm birth was reduced by 12.4% (OR = 0.876, 95%CI:0.855–0.879) for per one-kilogram increase of GWG, and risk of preterm birth was reduced by 24% (OR = 0.760, 95%CI: 0.717–0.806) for per one-unit increase of SES score. Mediation analysis supported a significant association between higher SES and decreased risk of preterm partly through higher GWG, in which estimated proportion mediated by GWG was 13.04% (95%CI: 11.89–16.25). GWG also played a significant role as a mediator when socioeconomic status was indicated by maternal education, paternal education or family income. GWG mediated approximately 11.03% (95% CI: 8.56–18.25) of the total effect of SES on very preterm birth, which was greater than that for moderate preterm birth (6.72%, 95%CI: 2.72–31.52) and late preterm birth (9.04%, 95%CI: 5.24–24.04). A series of sensitive analysis confirmed the robustness of association of interest. Conclusion Increased GWG and higher socioeconomic status are strongly associated with a lower risk of preterm birth. GWG mediates socioeconomic disparities in preterm birth, most notably in very preterm birth. Understanding this mechanism will aid in the development of interventions and policy for maternal and child health care.

Abstract Objective To reveal the contributing effects of MTDH gene SNPs in the risk of invasive ductal breast cancer (IDC). Patients and methods A case–control study was conducted, recruiting a total of 300 cases of IDC and 565 cancer-free controls from East China. Genotyping of three single-nucleotide polymorphisms (SNPs) in the MTDH gene was performed. Genomic DNA was extracted from peripheral blood samples of patients. The three SNPs (rs1311 T > C, rs16896059 G > A, rs2449512 A > G) in the MTDH gene were selected for detection using a TaqMan real-time polymerase chain reaction assay. The association between MTDH and the risk of IDC was analyzed employing an epidemiology case–control study and a multinomial logistic regression model. Results Among the three evaluated SNPs, rs1311 T > C, rs16896059 G > A, and rs2449512 A > G demonstrated a significant association with an increased risk of IDC. Furthermore, stratified analysis revealed that individuals carrying the rs1311 CC genotype, rs16896059 GA/AA genotypes, and rs2449512 GG genotype were more susceptible to developing IDC in subgroups of patients younger than 53 years, without family history of IDC, pre-menopause status, clinical stage 2, high grade, with no distant metastasis or invasion, Her2-positive type, ER positive, PR positive, and Ki67 cells less than 10%. However, carriers of the rs16896059 GA/AA genotypes and rs2449512 GG genotype had an elevate the risk of IDC in patients with tumor size larger than 2 cm, post-menopause status, clinical stage 3, with invasion, lymph node infiltration, ER negative, PR negative, Her2 negative, and Ki67 cells exceeding 10%. Compared to the reference haplotype TGA, haplotypes TAA, TAG, and TGG were significantly associated with an increased IDC risk. Conclusion In this study, we demonstrated a significant association between MTDH gene polymorphisms and an increased risk of IDC. Moreover, our findings suggested that MTDH gene polymorphisms could serve as a potential biomarker for IDC subtyping and therapeutic selection.

Purpose: To determine whether the overexpression of the Argonaute RNA-induced silencing complex catalytic component 2 (Ago2) improves erectile function in mice after cavernous nerve injury (CNI). Materials and Methods: Lentiviruses containing Ago2 open reading frame (ORF) mouse clone (Ago2 O/E) were used to overexpress Ago2, and lentiviruses ORF negative control particles (NC) were used as a negative control. Three days before preparing the CNI model, we injected lentiviruses into the penises of 8-week-old male C57BL/6 mice. Animals were then divided into four groups: the sham operation control group and the CNI+phosphate-buffered saline, CNI+NC, and CNI+Ago2 O/E groups. One week later, erectile function was assessed by electrically stimulating cavernous nerves bilaterally and obtaining intracavernous pressure parameters. Penile tissue was also collected for molecular mechanism studies. Results: Ago2 overexpression improved erectile function in mice after CNI-induced erectile dysfunction (ED). Immunofluorescence staining and Western blot analysis showed that under Ago2 overexpressing conditions, the contents of endothelial cells, pericytes, and neuronal cells increased in the penile tissues of CNI mice, and this was attributed to reduced apoptosis and ROS production. In addition, we also found that Ago2 overexpression could restore penile mitochondrial function, thereby improving erectile function in CNI-induced ED mice. Conclusions: Our findings demonstrate that Ago2 overexpression can reduce penile cell apoptosis, restore penile mitochondrial function, and improve erectile function in CNI-induced ED mice.

Abstract Purpose Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials. Methods Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined “EBV response” as 3 consecutive timepoints of load below 50% of baseline, and “EBV progression” as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples. Results We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p

AIM: To examine the regulatory role of microRNA-204 (miR-204) on silent information regulator 1 (SIRT1) and vascular endothelial growth factor (VEGF) under high-glucose-induced metabolic memory in human retinal pigment epithelial (hRPE) cells. METHODS: Cells were cultured with either normal (5 mmol/L) or high D-glucose (25 mmol/L) concentrations for 8d to establish control and high-glucose groups, respectively. To induce metabolic memory, cells were cultured with 25 mmol/L D-glucose for 4d followed by culture with 5 mmol/L D-glucose for 4d. In addition, exposed in 25 mmol/L D-glucose for 4d and then transfected with 100 nmol/L miR-204 control, miR-204 inhibitor or miR-204 mimic in 5 mmol/L D-glucose for 4d. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect miR-204 mRNA levels. SIRT1 and VEGF protein levels were assessed by immunohistochemical and Western blot. Flow cytometry was used to investigate apoptosis rate. RESULTS: It was found that high glucose promoted miR-204 and VEGF expression, and inhibited SIRT1 activity, even after the return to normal glucose culture conditions. Upregulation of miR-204 promoted apoptosis inhibiting SIRT1 and increasing VEGF expression. However, downregulation of miR-204 produced the opposite effects. CONCLUSION: The study identifies that miR-204 is the upstream target of SIRT1and VEGF, and that miR-204 can protect hRPE cells from the damage caused by metabolic memory through increasing SIRT1 and inhibiting VEGF expression.

RNA plays an extensive role in a multi-dimensional regulatory system, and its biomedical relationships are scattered across numerous biological studies. However, text mining works dedicated to the extraction of RNA biomedical relations remain limited. In this study, we established a comprehensive and reliable corpus of RNA biomedical relations, recruiting over 30,000 sentences manually curated from more than 15,000 biomedical literature. We also updated RIscoper 2.0, a BERT-based deep learning tool to extract RNA biomedical relation sentences from literature. Benefiting from approximately 100,000 annotated named entities, we integrated the text classification and named entity recognition tasks in this tool. Additionally, RIscoper 2.0 outperformed the original tool in both tasks and can discover new RNA biomedical relations. Additionally, we provided a user-friendly online search tool that enables rapid scanning of RNA biomedical relationships using local and online resources. Both the online tools and data resources of RIscoper 2.0 are available at http://www.rnainter.org/riscoper.

Ultraviolet (UV) radiation causes skin damage including oxidative stress, inflammation, and photoaging. Extremophile fermentation products have been found to effectively protect the skin from UV-induced damage. This study aimed to investigate the impact of acid-induced stress on the content of bioactive compounds, as well as the anti-inflammatory and anti-photoaging properties of sorghum fermentation by the extremophilic Monascus pilosus. The study compared acid-stress fermentation (ASF) of sorghum with conventional fermentation (CF) and examined differences in total phenolic content, antioxidant activity, and short-chain fatty acid levels. Using gas chromatography–mass spectrometry assay, the ASF sample had lower total phenolic content compared to CF, but significantly higher levels of short-chain fatty acids. Butyric acid was the predominant metabolite in the ASF sample, followed by propionic acid. The ASF sample exhibited superior protection for UV-irradiated human keratinocytes by inhibiting apoptosis, reducing ROS, and downregulating inflammatory mediators. It also decreased metalloproteinases expression levels, increased collagen and elastin production, and mitigated UV-induced photoaging. The effects of ASF samples were evaluated in volunteers, and the results confirmed the ASF sample's effectiveness in ameliorating UV-induced skin symptoms, including pigmentation, redness, and wrinkles. These findings conclude that acid-stress enhances the anti-inflammatory and anti-photoaging capabilities of Monascus pilosus fermented sorghum.

Abstract Excitons, pairs of electrons and holes, undergo a Bose-Einstein condensation at low temperatures. An important platform to study excitons is double-layer two-dimensional electron gases, with two parallel planes of electrons and holes separated by a thin insulating layer. Lowering this separation (d) strengthens the exciton binding energy, however, leads to the undesired interlayer tunneling, resulting in annihilation of excitons. Here, we report the observation of a sequences of robust exciton condensates (ECs) in double bilayer graphene twisted to ~ 10° with no insulating mid-layer. The large momentum mismatch between two graphene layers suppresses interlayer tunneling, reaching a d ~ 0.334 nm. Measuring the bulk and edge transport, we find incompressible states corresponding to ECs when both layers are in half-filled N = 0, 1 Landau levels (LLs). Theoretical calculations suggest that the low-energy charged excitation of ECs can be meron-antimeron or particle-hole pair, which relies on both LL index and carrier type. Our results establish a novel platform with extreme coupling strength for studying quantum bosonic phase.

Abstract Purpose The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its correlation with 2-deoxy-2[18F]fluoro-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters. Methods The TIMER database, GEPIA database, TCGA, and GEO database were used to analyze the expression profile of BATF in human cancers. The reverse transcription‑quantitative PCR and western blot analyses were used to evaluate the mRNA level and protein expression in different CRC cell lines. The expression of BATF in SW620 and HCT116 cells was silenced and cell counting kit-8 assays and clonogenic assay were utilized to evaluate the role of BATF in CRC proliferation. The expression of tumor BATF and glucose transporter 1 (GLUT-1) were examined using immunohistochemical tools in 37 CRC patients undergoing preoperative 18F-FDG PET/CT imaging. The correlation between the PET/CT parameters and immunohistochemical result was evaluated. Results In database, BATF was highly expressed in pan-cancer analyses, including CRC, and was associated with poor prognosis in CRC. In vitro, the results showed that knocking down of BATF expression could inhibit the proliferation of SW620 and HCT116 cells. In CRC patients, BATF expression was upregulated in tumor tissues compared with matched para-tumoral tissues, and was related with gender and Ki-67 levels. BATF expression was positively related to GLUT-1 expression and PET/CT parameters, including tumor size, maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis. The multiple logistic analyses showed that SUVmax was an independent predictor of BATF expression. With 15.96 g/cm3 as the cutoff, sensitivity was 85.71%, specificity 82.61%, and area-under-the-curve 0.854. Conclusion BATF may be an oncogene associated with 18F-FDG PET/CT parameters in CRC. SUVmax may be an independent predictor of BATF expression.

Abstract Background Ischemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear. Methods PC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting. Results In vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32–40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA. Conclusions ICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke. Graphical Abstract

Summary: Objectives: The exostosins (EXT), which are responsible for heparan sulfate backbone synthesis and play a vital role in tissue homeostasis, have been reported to be correlated with prognosis of various cancers. However, the expression, prognostic value, and immune infiltration of EXT1 and EXT2 in head and neck squamous cell carcinoma (HNSC) remain uncertain. Methods: GEPIA, UALCAN, and Xiantao bioinformatics tools were used to explore the EXT1 and EXT2 expression level in HNSC. GEPIA and Sangerbox were utilised to obtain the prognostic value of EXT1 and EXT2 in HNSC. Genetic alterations, immune cell infiltration, and single-cell analysis were conducted in cBioPortal, TIMER, and TISCH2. In addition, the expressions of EXT1 and EXT2 were validated by real-time polymerase chain reaction (PCR) in HNSC samples. Results: EXT1 and EXT2 were highly expressed in HNSC, especially in malignant cells. Only EXT2 was significantly negatively correlated to the prognosis of patients with HNSC. EXT1 and EXT2 were found to be associated with focal adhesin and cell adhesin molecule binding. EXT1 expression levels were considerably connected with CD8+ T cell infiltrating levels, whilst EXT2 expression levels were considerably negatively connected with infiltrating levels of CD4+ T cells, macrophages, neutrophils, and dendritic cells in HNSC. The gene mutation rates of EXT1 and EXT2 in HNSC were 7% and 2.8%, respectively. Moreover, EXT2 was validated to be highly expressed in HNSC samples by real-time PCR. Conclusion: EXT2 was highly expressed and presented negative correlation with the prognosis and immune infiltration of HNSC, which might be a potential biomarker for HNSC.

Abstract Poor implantation positioning of hip prostheses is considered the primary factor affecting postoperative joint wear. Cup anteversion in direct anterior approach (DAA) total hip arthroplasty (THA) is often excessive. Intraoperative fluoroscopy (IF) are effective for improving implant placement accuracy. This study aimed to analyze IF’s reliability and accuracy in assessing intraoperative anteversion. Sixty-two consecutive hips underwent primary THA utilizing DAA alongside IF for cup placement. Intraoperative anteversion was measured using IF images, while postoperative CT and standard anteroposterior (AP) radiographs were used to calculate true anteversion component angles. Differences and correlations between intraoperative and true anteversions were analyzed, and intraclass correlation coefficients (ICC) determined the inter- and intra-observer reliabilities. Excellent intra- and inter-observer reliabilities were observed for all radiographic and CT methods (ICC > 0.9). Strong correlations (PCC > 0.6) existed between anteversion measured on IF image and postoperative CT and AP pelvic measurements. Intraoperative anteversion measured on IF images (16.8 ± 3.2°) was smaller than anteversion measured postoperatively on AP X-rays (21.3 ± 4.7°, P

Abstract Background The left-behind children (LBC), children and adolescents aged 0–18 whose parents have migrated for economic purposes for extended periods exceeding three months, present a unique social concern. These children remain in their place of household registration, often under the guardianship of relatives, while receiving compulsory education. LBC with growing Internet addiction (IA) have made it urgent to take a close look at the mechanisms and effective interventions for them. Anxiety has been proven to be correlated with IA in adolescents; however, the mechanisms of addiction in this population are less well-fully grasped. Based on the current theories and empirical results, the study examined whether and how social support (SS) and family types moderated the associations between anxiety and IA among left-behind secondary students. Methods Stratified cluster sampling survey. A questionnaire was administered to 5290 secondary school children (2553 classified as left-behind) to explore the relationships between anxiety, IA, left-behind types, family types, and social support. This cross-sectional study employed a stratified cluster sampling survey of students in the ethnic areas of southeast Chongqing. The study sought to appraise the relationships between anxiety and IA in different types of left-behind children and to assess the potential moderating effect of SS on the relationship among the population and its family types differences. Results The relationship between anxiety and IA was moderated significantly by social support and family types. Notably, the impact of social support on the moderating effect between IA and anxiety varied among students from both family types. For students from families where both parents had migrated, social support weakened the association between IA and anxiety. Conversely, for students from single-parent families where the parent had migrated, social support seemed to strengthen the relationships between these two issues. Conclusions The moderating effects of SS on the relationship between anxiety and IA differs based on family type among various groups of left-behind secondary students. Gaining insights into the IA mechanisms can guide the development of targeted intervention strategies aimed at minimizing IA among diverse groups of left-behind students.

Abstract Background Immunotherapy has brought about a paradigm shift in the treatment of cancer. However, the majority of patients exhibit resistance or become refractory to immunotherapy, and the underlying mechanisms remain to be explored. Methods Sing-cell RNA sequencing (scRNA‑seq) datasets derived from 1 pretreatment and 1 posttreatment achieving pathological complete response (pCR) patient with lung adenocarcinoma (LUAD) who received neoadjuvant immunotherapy were collected, and pySCENIC was used to find the gene regulatory network (GRN) between cell types and immune checkpoint inhibitor (ICI) response. A regulon predicting ICI response was identified and validated using large‑scale pan-cancer data, including a colorectal cancer scRNA‑seq dataset, a breast cancer scRNA‑seq dataset, The Cancer Genome Atlas (TCGA) pan-cancer cohort, and 5 ICI transcriptomic cohorts. Symphony reference mapping was performed to construct the myeloid cell map. Results Thirteen major cluster cell types were identified by comparing pretreatment and posttreatment patients, and the fraction of myeloid cells was higher in the posttreatment group (19.0% vs. 11.8%). A PPARG regulon (containing 23 target genes) was associated with ICI response, and its function was validated by a colorectal cancer scRNA‑seq dataset, a breast cancer scRNA‑seq dataset, TCGA pan-cancer cohort, and 5 ICI transcriptomic cohorts. Additionally, a myeloid cell map was developed, and cluster I, II, and III myeloid cells with high expression of PPARG were identified. Moreover, we constructed a website called PPARG ( https://pparg.online/PPARG/ or http://43.134.20.130:3838/PPARG/ ), which provides a powerful discovery tool and resource value for researchers. Conclusions The PPARG regulon is a predictor of ICI response. The myeloid cell map enables the identification of PPARG subclusters in public scRNA-seq datasets and provides a powerful discovery tool and resource value.

Abstract Background Thoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are mainly caused by variants in the MYH11 gene, which encodes the heavy chain of myosin 11. The aim of this study was to evaluate the genotype–phenotype correlation of MYH11 from a distinctive perspective based on a pair of monozygotic twins. Methods The detailed phenotypic characteristics of the monozygotic twins from the early fetal stage to the infancy stage were traced and compared with each other and with those of previously documented cases. Whole-exome and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of the genotype–phenotype correlation of MYH11. Results The monozygotic twins were premature and presented with PDA, pulmonary hypoplasia, and pulmonary hypertension. The proband developed heart and brain abnormalities during the fetal stage and died at 18 days after birth, whereas his sibling was discharged after being cured and developed normally post follow-up. A novel variant c.766 A > G p. (Ile256Val) in MYH11 (NM_002474.2) was identified in the monozygotic twins and classified as a likely pathogenic variant according to the American College of Medical Genetics/Association for Molecular Pathology guidelines. Reviewing the reported cases (n = 102) showed that the penetrance of MYH11 was 82.35%, and the most common feature was TAAD (41.18%), followed by PDA (22.55%), compound TAAD and PDA (9.80%), and other vascular abnormalities (8.82%). The constituent ratios of null variants among the cases with TAAD (8.60%), PDA (43.8%), or compound TAAD and PDA (28.6%) were significantly different (P = 0.01). Further pairwise comparison of the ratios among these groups showed that there were significant differences between the TAAD and PDA groups (P = 0.006). Conclusion This study expands the mutational spectrum of MYH11 and provides new insights into the genotype–phenotype correlation of MYH11 based on the monozygotic twins with variable clinical features and outcomes, indicating that cryptic modifiers and complex mechanisms beside the genetic variants may be involved in the condition.

In the built environment (BE) of tourism-service-oriented villages, understanding visitor flow volumes and behaviours is crucial for guiding space revitalization and tourism management. This research uncovers quantitative relationships between visitor flow volume, spatial visual exposure, and visitors’ behaviour at 12 sites in the Tabian Rural Section of Qingshan Village, a typical tourism service-oriented village in Hangzhou. The methodologies employed in this study are based on two space syntax algorithms: 3-D isovist analysis and agent-based models (ABMs). Visual Exposure Rates (VERs) in 3-D isovists along visitors’ routes were calculated using parametric programming, and visitor flow simulation was conducted using two ABMs. Real-world visitor volumes (RWFVs) and visitors’ behaviors were also recorded during an in-situ survey. A comprehensive correlation analysis revealed multiple associations. The results demonstrated that combined simulations from ABM I, and VERs explained 50.5% of the overall variability in RWFVs. Notably, VERs were found to be associated with visitors’ behaviours of photography and seating, while the outputs from ABM I showed a moderate correlation with RWFVs. This study innovatively combines space syntax models for extended application in the research of rural BEs, providing guidance for optimizing strategies to improve spatial configuration in homogeneous villages.

Abstract Background Circular RNAs (circRNAs) are a novel kind of non-coding RNAs proved to play crucial roles in the development of multiple diabetic complications. However, their expression and function in diabetes mellitus (DM)-impaired salivary glands are unknown. Results By using microarray technology, 663 upregulated and 999 downregulated circRNAs companied with 813 upregulated and 525 downregulated mRNAs were identified in the parotid glands (PGs) of type2 DM mice under a 2-fold change and P

Abstract Introduction Lung cancer is a prevalent malignancy globally, and immunotherapy has revolutionized its treatment. However, resistance to immunotherapy remains a challenge. Abnormal cholinesterase (ChE) activity and choline metabolism are associated with tumor oncogenesis, progression, and poor prognosis in multiple cancers. Yet, the precise mechanism underlying the relationship between ChE, choline metabolism and tumor immune microenvironment in lung cancer, and the response and resistance of immunotherapy still unclear. Methods Firstly, 277 advanced non-small cell lung cancer (NSCLC) patients receiving first-line immunotherapy in Sun Yat-sen University Cancer Center were enrolled in the study. Pretreatment and the alteration of ChE after 2 courses of immunotherapy and survival outcomes were collected. Kaplan–Meier survival and cox regression analysis were performed, and nomogram was conducted to identify the prognostic and predicted values. Secondly, choline metabolism-related genes were screened using Cox regression, and a prognostic model was constructed. Functional enrichment analysis and immune microenvironment analysis were also conducted. Lastly, to gain further insights into potential mechanisms, single-cell analysis was performed. Results Firstly, baseline high level ChE and the elevation of ChE after immunotherapy were significantly associated with better survival outcomes for advanced NSCLC. Constructed nomogram based on the significant variables from the multivariate Cox analysis performed well in discrimination and calibration. Secondly, 4 choline metabolism-related genes (MTHFD1, PDGFB, PIK3R3, CHKB) were screened and developed a risk signature that was found to be related to a poorer prognosis. Further analysis revealed that the choline metabolism-related genes signature was associated with immunosuppressive tumor microenvironment, immune escape and metabolic reprogramming. scRNA-seq showed that MTHFD1 was specifically distributed in tumor-associated macrophages (TAMs), mediating the differentiation and immunosuppressive functions of macrophages, which may potentially impact endothelial cell proliferation and tumor angiogenesis. Conclusion Our study highlights the discovery of ChE as a prognostic marker in advanced NSCLC, suggesting its potential for identifying patients who may benefit from immunotherapy. Additionally, we developed a prognostic signature based on choline metabolism-related genes, revealing the correlation with the immunosuppressive microenvironment and uncovering the role of MTHFD1 in macrophage differentiation and endothelial cell proliferation, providing insights into the intricate workings of choline metabolism in NSCLC pathogenesis.

The rapid growth of the Chinese economy has fueled the expansion of power grids. Power transformers are key equipment in power grid projects, and their price changes have a significant impact on cost control. However, the prices of power transformer materials manifest as nonsmooth and nonlinear sequences. Hence, estimating the acquisition costs of power grid projects is difficult, hindering the normal operation of power engineering construction. To more accurately predict the price of power transformer materials, this study proposes a method based on complementary ensemble empirical mode decomposition (CEEMD) and gated recurrent unit (GRU) network. First, the CEEMD decomposed the price series into multiple intrinsic mode functions (IMFs). Multiple IMFs were clustered to obtain several aggregated sequences based on the sample entropy of each IMF. Then, an empirical wavelet transform (EWT) was applied to the aggregation sequence with a large sample entropy, and the multiple subsequences obtained from the decomposition were predicted by the GRU model. The GRU model was used to directly predict the aggregation sequences with a small sample entropy. In this study, we used authentic historical pricing data for power transformer materials to validate the proposed approach. The empirical findings demonstrated the efficacy of our method across both datasets, with mean absolute percentage errors (MAPEs) of less than 1% and 3%. This approach holds a significant reference value for future research in the field of power transformer material price prediction.

Abstract Rainwater is the main water source in arid and semiarid areas of the Loess Plateau, where rainfall is generally insufficient, ineffective and underutilized during the growing season. Thus, improving rainwater utilization efficiency is essential for sustainable agricultural development. A new system composed of rainwater harvesting, an infiltrator bucket with multiple holes and mulching (RHM), was designed to maintain soil moisture at a proper level in rain-fed orchards in arid and semiarid areas of the Loess Region of China. However, there is a lack of clarity on the effectiveness of RHM. In this study, changes in the soil environment and the growth and physiology of apricot trees were monitored via two treatments: (1) Rain-harvesting irrigation system (RHM) treatment and (2) traditional orchard treatment (CK) as a baseline. The results showed that (1) RHM could effectively improve soil water storage at depths of 0–45 cm and at a horizontal distance of 40 cm from the trunk. For the 1.4 mm light rain event, the soil water content increased by 6.3–12%, and for the two moderate rains, the soil water content increased by 12–25%. The change in the soil relative water content predicted by the LSTM model is consistent with the overall trend of the measured value and gradually decreases, and the prediction accuracy is high, with an error of 0.65. (2) The average soil temperatures at 5 cm, 20 cm and 40 cm under RHM were 17.0% (2.4 °C), 13.6% (1.9 °C) and 7.5% (1 °C) greater than those under CK, respectively. (3) Compared with the control treatment, RHM improved the growth and WUEL of apricot trees. The results highlighted the efficiency of the RHM system in enhancing the soil environment and regulating the growth and physiology of apricot trees, which has greater popularization value in arid and semiarid areas.

Abstract In the realm of ferroelectric memories, HfO2-based ferroelectrics stand out because of their exceptional CMOS compatibility and scalability. Nevertheless, their switchable polarization and switching speed are not on par with those of perovskite ferroelectrics. It is widely acknowledged that defects play a crucial role in stabilizing the metastable polar phase of HfO2. Simultaneously, defects also pin the domain walls and impede the switching process, ultimately rendering the sluggish switching of HfO2. Herein, we present an effective strategy involving acceptor-donor co-doping to effectively tackle this dilemma. Remarkably enhanced ferroelectricity and the fastest switching process ever reported among HfO2 polar devices are observed in La3+-Ta5+ co-doped HfO2 ultrathin films. Moreover, robust macro-electrical characteristics of co-doped films persist even at a thickness as low as 3 nm, expanding potential applications of HfO2 in ultrathin devices. Our systematic investigations further demonstrate that synergistic effects of uniform microstructure and smaller switching barrier introduced by co-doping ensure the enhanced ferroelectricity and shortened switching time. The co-doping strategy offers an effective avenue to control the defect state and improve the ferroelectric properties of HfO2 films.

Abstract Background Frequent repairs of pediatric flexible bronchoscopes can lead to a huge financial burden for the hospital. This study aimed to investigate the common causes of the failures in pediatric flexible bronchoscopes and propose the measures to prevent the failures. Methods This was a retrospective study. We collected repair information of the pediatric flexible bronchoscopes reprocessed in the Department of Sterile Processing at a hospital between September 1, 2018 and September 1, 2022 in order to investigate the causes and possible factors associated with the failures in pediatric flexible bronchoscopes. Results The Department of Sterile Processing staff reprocessed the pediatric flexible bronchoscopes 4280 times. A total of 29 failures were identified. The failure rate was 0.678%. The average repair cost was USD7246.60. The common failures in the pediatric flexible bronchoscopes included dim video image, black dots, improper video image display or no image during angulation adjustment, and pressure marks in the insertion tube. The failure rates in flexible electronic bronchoscopes and small-diameter flexible bronchoscopes were 65.5% and 93.1%, respectively. The failure rate in the pediatric flexible bronchoscopes reprocessed by the staff members with less work experience was 75.9%. Conclusion The failure rate in the pediatric flexible bronchoscopes was not high but the repair costs were extremely high. The types and size of the flexible bronchoscopes and work experience of the staff members responsible for bronchoscope reprocessing were the possible factors associated with the failure rate in the pediatric flexible bronchoscopes. It is advisable to further optimize the central workflow and management mode for reprocessing the pediatric flexible bronchoscopes, thereby extending their useful life and reducing costs.

Abstract Aims Red blood cell distribution width‐to‐albumin ratio (RAR), an innovate biomarker of inflammation, can independently predict adverse cardiovascular outcomes. However, the association between RAR and prognosis in patients with non‐ischaemic heart failure (NIHF) remains unclear. Methods and results A total of 2077 NIHF patients admitted to the Heart Failure Care Unit, Fuwai Hospital, were consecutively enrolled from December 2006 to October 2017 in this retrospective study. The primary endpoint was a composite outcome of all‐cause mortality and heart transplantation. The correlation between RAR and the composite outcome was assessed by the Kaplan–Meier survival analysis and the Cox regression analysis. Incremental predictive values and the clinical performance of RAR for all‐cause mortality or heart transplantation were also assessed based on a 12‐variable traditional risk model. The median follow‐up time in this study was 1433 (1341, 1525) days. As the gender no longer satisfied the Cox proportional risk assumption after 1150 days, we set 1095 days as the follow‐up time for analysis. A total of 500 patients reached the composite outcome. Multivariable Cox regression showed that per log2 increase of RAR was significantly associated with a 132.9% [hazard ratio 2.329, 95% confidence interval (CI) 1.677–3.237, P

BackgroundAreca nut (AN) is a traditional Chinese herbal medicine used for centuries to treat gastrointestinal (GI) disorders. Charred AN (CAN) is a processed product of AN with similar therapeutic effects. This study aimed to investigate the therapeutic mechanisms of AN and CAN for constipation via metabolomics and gut microbiota analysis.MethodsIn this study, the rats were randomly divided into 5 groups (n = 6): control, constipation model, positive drug, AN treatment, and CAN treatment groups. Constipation was induced by intragastric administration of loperamide hydrochloride, followed by 14-day treatment with mosapride, AN, or CAN. The efficacy difference between AN and CAN was assessed by evaluating the weight gain, fecal water content, GI transit rate, colonic histopathology, serum levels of GI hormones, gut microbiota, and fecal metabolites.ResultsThe results demonstrated that both AN and CAN could alleviate loperamide-induced constipation. Furthermore, they significantly elevated the serum levels of motilin, vasoactive intestinal peptide, substance P, and acetylcholine. 16S rRNA analysis revealed that AN regulated the relative abundance of Bacillus, UCG-005, norank_f_Muribaculaceae, Candidatus_Saccharimonas, and Ruminococcus, whereas CAN modulate the relative abundance of Lactobacillus, Bacillus, norank_f_Muribaculaceae, Ruminococcus, unclassified_f_Oscillospiraceae, and unclassified_f_Prevotellaceae. Moreover, the metabolic profile of AN- and CAN-treated rats was also different, where AN treatment involved pathways of citrate cycle (TCA) and tyrosine, alanine, aspartate, and glutamate metabolisms. Whereas CAN treatment involved pathways of steroid and primary bile acid biosynthesis, as well as pyrimidine and purine metabolisms. Spearman correlation analysis indicated a close relationship between gut microbiota and fecal metabolites.ConclusionIn summary, this study revealed that AN may protect GI mucosa, enhance GI motility, and alleviate constipation symptoms by regulating the relative abundance of specific gut microbiota (Bacillus, UCG-005, norank_f_Muribaculaceae, Candidatus_Saccharimonas, Ruminococcus) as well as citrate cycle or tyrosine, alanine, aspartate, and glutamate metabolic pathways. Furthermore, CAN was observed to promote gastric emptying and intestinal propulsion, thereby alleviating constipation, by modulating the relative abundance of specific gut microbiota (Lactobacillus, Bacillus, norank_f_Muribaculaceae, Ruminococcus, unclassified_f_Oscillospiraceae, unclassified_f_Prevotellaceae) as well as steroid and primary bile acid biosynthesis, as well as pyrimidine and purine metabolic pathways.

Snow depth (SD) is essential for studying climate change and hydrological cycle on the Tibetan Plateau (TP). Despite the effectiveness of passive microwave remote sensing for large-scale SD measurement, its low spatial resolution and scanning gaps limit its application, particularly in the TP region where the terrain is complex and snow distribution exhibits obvious heterogeneity. This study developed Advanced Microwave Scanning Radiometer 2 (AMSR2) SD downscaling models for the TP using ensemble learning methods and AMSR2 brightness temperature data from October 1, 2012, to April 30, 2021. We employed five ensemble methods—AdaBoost, GBDT, XGBoost, LightGBM, and Random Forest—with LightGBM achieving the highest accuracy (RMSE=2.66 cm). Recursive feature elimination (RFE) was applied to the LightGBM model, optimizing factor selection and maintaining high accuracy. The models excelled in estimating shallow snow areas (SD

Background: A two-way relationship exists between type 2 diabetes (T2DM) and human nonalcoholic steatohepatitis (NASH). Several diabetic NASH models have the disadvantages of long cycles or inconsistent with the actual incidence of human disease, which would be costly and time-consuming to investigate disease pathogenesis and develop drugs. Therefore, there is an urgent need to establish a diabetic NASH mouse model. Methods: The combination between Fructose-palmitate-cholesterol diet (FPC) and Streptozotocin (STZ) (FPC+STZ) was used to construct diabetic NASH mouse model. The in vivo effects of silencing acid-sensitive Ion Channel 1a (ASIC1a) were examined with an adeno-associated virus 9 (AAV9) carrying ASIC1a short hairpin RNA (shRNA) in FPC+STZ model. Results: The mice fed with FPC for 12 weeks had insulin resistance, hyperinsulinemia, lipid accumulation, and increased hepatic levels of inflammatory factors. However, it still did not develop remarkable liver fibrosis. Most interestingly, noticeable fibrotic scars were observed in the liver of mice from FPC+STZ group. Furthermore, insulin therapy significantly ameliorated FPC+STZ-induced NASH-related liver fibrosis, indicating that hyperglycemia is of great significance in NASH development and progression. Importantly, ASIC1a was found to be involved in the pathogenesis of diabetic NASH as demonstrated that silencing ASIC1a in HSCs significantly ameliorated FPC+STZ-induced NASH fibrosis. Mechanistically, ASIC1a interacted with Poly Adp-adenosine ribose polymerase (PARP1) to promote HSC activation by inducing autophagy. Conclusion: A FPC diet combined with an injection of STZ induces a diabetic NASH mouse model in a shorter period. Targeting ASIC1a may provide a novel therapeutic target for the treatment of diabetic NASH.

The aim of this study was to review all systematic reviews and meta-analyses of alcohol consumption among Asian Americans in the U.S. An in-depth literature search was conducted using the following electronic databases: MEDLINE, Academic Search Premier, Education Resource Information Center (ERIC), PsycARTICLES, and CINAHL Plus with Full Text. The keywords used for the search were: Alcohol Consumption, Asian Americans, Social Determinants, and Cultural Differences. The results suggested the determinants of alcohol consumption in American society include gender, race and ethnicity, marital status, membership in social groups, genetic factors, sexual orientation, poverty, place of residence and education. Alcohol consumption among Asian Americans is also dependent on their societal perceptions towards alcohol consumption. Other factors determining the consumption of alcohol include affiliation to different social groups, social-cultural affiliations, acculturation and acculturation stress, and cultural observances.

The pursuit of enhanced scientific, refined, and precise ozone and air quality control continues to pose significant challenges. Using data visualization techniques and random forest (RF) algorithms, the temporal distribution of atmospheric pollutants and the interrelationship between O3 concentration and its influential factors were investigated with one-year monitoring data in Deqing county in 2021. The local atmospheric conditions predominantly belonged to NOx-sensitive and transition zone. Extremely high O3 concentration were primarily observed when temperatures (T) exceeded 30 °C, with relative humidity (RH) ranging between 30 and 60 %. NO2, RH and T were identified as the top 3 important factors, and O3 concentration have stronger linearly relationship to RH and T, while stronger nonlinearly relationship to NO2. By employing an optimized RF model, controlling consistent mild and high reaction atmospheric conditions, the O3 concentration response to the change of individual influencing factors was acquired. The O3 concentration increased and then decreased in response to the increasing NO2 concentration, displaying a characteristic inflection point at 10 μg m−3. More reactive radicals produced at higher VOCs concentration and continuing NOx cycle at lower NO2 concentration, resulting in the acceleration in the direction of producing more O3. Therefore, the significant different O3 response to variation of VOCs and NOx concentration between mild and high reaction atmospheric conditions, as well as the existing of oxidant elevation should be considered in local air quality control. This study demonstrates the efficacy of ML methods in simulating nonlinear response of O3, supports the understanding of local O3 formation and quick guidance for precise local O3 pollution control and the related strategies.

Summary: Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II–III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3–67.6) and 41 of 70 (58.6%, 95% CI 46.2–70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1–2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

Liver disease affects millions of people in the world, and China has the highest prevalence of liver disease in the world. Small ubiquitin-related modifier (SUMO) modification is a highly conserved post-translational modification of proteins. They are widely expressed in a variety of tissues, including the heart, liver, kidney and lung. SUMOylation of protein plays a key role in the occurrence and development of liver disease. Therefore, this study reviewed the effects of SUMO protein on non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis (HF), hepatocellular carcinoma (HCC), and other liver diseases to provide novel strategies for targeted treatment of liver disease.

Abstract Lithium metal batteries with inorganic solid‐state electrolytes have emerged as strong and attractive candidates for electrochemical energy storage devices because of their high‐energy content and safety. Nonetheless, inherent challenges of deleterious lithium dendrite growth and poor interfacial stability hinder their commercial application. Herein, we report a liquid metal‐coated lithium metal (LM@Li) anode strategy to improve the contact between lithium metal and a Li6PS5Cl inorganic electrolyte. The LM@Li symmetric cell shows over 1000 h of stable lithium plating/stripping cycles at 2 mA cm−2 and a significantly higher critical current density of 9.8 mA cm−2 at 25°C. In addition, a full battery assembled with a high‐capacity composite LiNbO3@LiNi0.7Co0.2Mn0.1O2 (LNO@NCM721) cathode shows stable cycling performance. Experimental and computational results have demonstrated that dendrite growth tolerance and physical contact in solid‐state batteries can be reinforced by using LM interlayers for interfacial modification.

ObjectivesEndoscopic full-thickness resection (EFTR) has proven effective and economical for patients with gastric submucosal tumors (SMTs). However, the poor operative field of view, the risk of massive hemorrhage, and the difficulties in defect closure have limited its widespread application. Herein, we described a modified EFTR technique developed to simplify the dissection and defect closure procedures using common and economical endoscopic accessories.MethodsForty-two patients who underwent the modified EFTR for gastric SMTs in the Shenzhen Guangming District People’s Hospital were enrolled in the case series. Following a cross incision to expose the intraluminal surface the tumors were captured by suction through a transparent cap and the roots were ligated using a loop. The tumors and part of the suction tissue were removed along the ligated root. A tension-relieving closure was performed by clipping the raised plica in four quadrants outside the ligated root. Patient demographics, tumor characteristics, and therapeutic outcomes were evaluated retrospectively.ResultsAll tumors had an R0 resection. The median procedure time was 51.8 min (IQR 34.25 min). No severe perioperative adverse events occurred. No residual lesion or recurrence was reported during the follow-up period of 9.84 months (IQR 5.0 months).ConclusionThe safety and practicability of Modified-EFTR could allow for wide clinical application in patients with micro-gastric SMTs.

Summary: The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Summary: Time-restricted eating (TRE) is a promising obesity management strategy, but weight-loss efficacy varies among participants, and the underlying mechanism is unclear. The study aimed to investigate the role of gut microbiota in weight-loss response during long-term TRE intervention. We analyzed data from 51 obese adults in a 12-month TRE program, categorizing them into distinct weight loss groups (DG) and moderate weight loss groups (MG) based on their TRE responses. Shotgun metagenomic sequencing analysis revealed a significant increase in species closely associated with weight loss effectiveness and metabolic parameter changes in the DG group. Pathways related to fatty acid biosynthesis, glycogen biosynthesis, and nucleotide metabolism were reduced in the DG group and enhanced in the MG group. Next, we identified nine specific species at baseline that contributed better responses to TRE intervention and significant weight loss. Collectively, gut microbiota contributes to responsiveness heterogeneity in TRE and can predict weight-loss effectiveness.

Summary: Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10−6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

GDF15 is a stress response cytokine and a distant member of the transforming growth factor beta (TGFβ) superfamily, its levels increase in response to cell stress and certain diseases in the serum. To exert its effects, GDF15 binds to glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL), which was firstly identified in 2017 and highly expressed in the brain stem. Many studies have demonstrated that elevated serum GDF15 is associated with anorexia and weight loss. Herein, we focus on the biology of GDF15, specifically how this circulating protein regulates appetite and metabolism in influencing energy homeostasis through its actions on hindbrain neurons to shed light on its impact on diseases such as obesity and anorexia/cachexia syndromes. It works as an endocrine factor and transmits metabolic signals leading to weight reduction effects by directly reducing appetite and indirectly affecting food intake through complex mechanisms, which could be a promising target for the treatment of energy-intake disorders.

Solute carrier family 27 member 2 (SLC27A2) is involved in fatty acid metabolism in tumors and represents a prospective target for cancer therapy. However, the role and mechanism of action of SLC27A2 in acute lymphoblastic leukemia (ALL) remain unclear. In this study, we aimed to explore the intrinsic associations between SLC27A2 and ALL and evaluate the prognostic significance, biological functions, and correlation with immune infiltration. We used the transcriptome and clinical data from the TARGET dataset. Differentially expressed genes (DEGs) in the SLC27A2 low- and high-expression groups were analyzed for prognostic implications and functional enrichment. Furthermore, we analyzed the relationship between SLC27A2 gene expression and immune cell infiltration using the ESTIMATE method, which was evaluated using the TIGER platform. Finally, we knocked down SLC27A2 in the Jurkat ALL cell line and conducted cell proliferation, western blotting, flow cytometry, and CCK-8 assays to elucidate the biological function of SLC27A2 in ALL. Patients with ALL who have higher expression levels of SLC27A2 have poorer overall survival and event-free survival. According to gene set enrichment analysis, the DEGs were primarily enriched with immune system processes and the PI3K-Akt signaling pathway. There was an inverse relationship between SLC27A2 expression and immune cell invasion, suggesting involvement of the former in tumor immune evasion. In vitro experiments showed that knockdown of SLC27A2 inhibited cell proliferation and protein expression and altered the Akt pathway, with a reduced proportion of B cells. In conclusion, SLC27A2 plays a vital role in the development of ALL.