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This study aimed to study the effects of three current popular high-temperature treatments (electric roasting, air frying and superheated steam) on the physicochemical properties and taste quality of grass carp meat. Physicochemical properties were analyzed by measuring pH, water holding capacity, color value, thiobarbituric acid reactive substance and protein carbonyl content of fish meat. Taste quality was characterized by measuring the free amino acids content and flavor nucleotides content of fish meat. The results showed that compared with the raw grass carp meat in the control group, the indexes of physicochemical properties of grass carp meat processed by different high-temperature treatments were significantly increased in different degrees (P

In the event of severe accidents in pressurized water reactor (PWR) nuclear power plants, the potential leakage of radioactive aerosols through containment cracks poses a considerable radioactive hazard to the public. Understanding aerosol transport and retention in cracks helps reduce the conservatism and uncertainty of radioactive hazard assessment. Concrete cracks are recognized as a pivotal pathway for the leakage of radioactive aerosols, and several researchers have undertaken experimental investigations concerning the aerosol transport and retention in concrete cracks. However, the majority of these studies have rather low gas flow Reynolds numbers. In this work, an experimental setup is built to study aerosol transport and retention in concrete cracks under high Reynolds number flow. The TiO2 aerosol with a mass median diameter of 1 μm and two concrete crack specimens are used in experiments. The results of gas flow experiments indicate that the Reynolds number is capable of reaching 10547. Combining the flow experimental data and Suzuki's formula, the equivalent heights of these two crack specimens are approximated as 303.67 μm and 231.48 μm. The experimental results indicate a notably high retention rate of aerosols, exceeding 0.8. Furthermore, under high Reynolds number flow, the retention rate varies over a relatively narrow range, with the larger the equivalent height of the crack resulting in a lower retention rate. The experimental results match well with the mechanistic analysis based on inertial deposition theory, demonstrating the rationality of the inertial deposition theory.

Abstract Objective This study aims to assess the performance of various scoring systems in predicting the 28-day mortality of patients with aortic aneurysms (AA) admitted to the intensive care unit (ICU). Methods We utilized data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) to perform a comparative analysis of various predictive systems, including the Glasgow Aneurysm Score (GAS), Simplified Acute Physiology Score (SAPS) III, SAPS II, Logical Organ Dysfunction System (LODS), Sequential Organ Failure Assessment (SOFA), Systemic Inflammatory Response Syndrome (SIRS), and The Oxford Acute Illness Severity Score (OASIS). The discrimination abilities of these systems were compared using the area under the receiver operating characteristic curve (AUROC). Additionally, a 4-knotted restricted cubic spline regression was employed to evaluate the association between the different scoring systems and the risk of 28-day mortality. Finally, we conducted a subgroup analysis focusing on patients with abdominal aortic aneurysms (AAA). Results This study enrolled 586 patients with AA (68.39% male). Among them, 26 patients (4.4%) died within 28 days. Comparative analysis revealed higher SAPS II, SAPS III, SOFA, LODS, OASIS, and SIRS scores in the deceased group, while no statistically significant difference was observed in GAS scores between the survivor and deceased groups (P = 0.148). The SAPS III system exhibited superior predictive value for the 28-day mortality rate (AUROC 0.805) compared to the LODS system (AUROC 0.771), SOFA (AUROC 0.757), SAPS II (AUROC 0.759), OASIS (AUROC 0.742), SIRS (AUROC 0.638), and GAS (AUROC 0.586) systems. The results of the univariate and multivariate logistic analyses showed that SAPS III was statistically significant for both 28-day and 1-year mortality. Subgroup analyses yielded results consistent with the overall findings. No nonlinear relationship was identified between these scoring systems and 28-day all-cause mortality (P for nonlinear > 0.05). Conclusion The SAPS III system demonstrated superior discriminatory ability for both 28-day and 1-year mortality compared to the GAS, SAPS II SIRS, SOFA, and OASIS systems among patients with AA.

Abstract Normal veins could develop to varicose vein (VV) by some risk factors, and might further progress to shallow vein thrombosis (SVT). However, the molecular mechanism of key genes associated with the progression and regression of VV are still not thorough enough. In this study, the healthy control (HC), VV, and SVT vascular samples were collected for transcriptome sequencing. The differentially expressed genes (DEGs) were screened by “DESeq2”, including DEGs1 (HC vs. VV), DEGs2 (HC vs. SVT) and DEGs3 (VV vs. SVT). And their functional enrichment analyses were conducted by “ClusterProfiler”. The receiver operating characteristic (ROC) curve was used to obtain the key genes (KGs) of the pathogenesis of VV and SVT. The qRT-PCR assay was performed to validate the expressions of KGs. Immune cell infiltration analyses were conducted based on ssGSEA method. The competitive endogenous RNAs (ceRNAs) regulatory network was constructed. The target drugs of KGs were predicted using DrugBank database. The biofunctions of DACT3 were further investigated through a series of experiments in vitro. All of these DEGs were associated with inflammation and immunity related functions. Immune cell infiltration was significantly different between VV and SVT. Six key genes including PLP2, DACT3, LRRC25, PILRA, MSX1 and APOD that were associated with the progression and regression of VV were screened. The expression of LRRC25 and PILRA was significantly negatively associated with central memory T cell, and significantly positively associated with B cell. Besides, XIST was the critical regulator of multiple KGs. Cimetidine was potential drug for VV and SVT therapy. Overexpression of DACT3 significantly inhibited the proliferation and migration of vascular smooth muscle cells (VSMCs), and affected their cell cycle and phenotypic transition. This study identified six key genes associated with the progression and regression of VV. Among them, DACT3 was proved to hinder VV progression. These findings may help to deepen understanding its underlying mechanisms.

Abstract Introduction This study analyzed and discussed the characteristics of peripheral blood lymphocytes (PBLs) in patients with endometrial carcinoma (EC) to explore the PBLs’ clinical application value. Methods This single-center case‒control study analyzed the clinical data of patients with EC and uterine fibroids who underwent surgery at the First Affiliated Hospital of Chongqing Medical University between October 2018 and October 2023 retrospectively. The Center for Clinical Molecular Medical Detection of our hospital performed PBLs detection using flow cytometry, and recorded the detection results in the electronic medical records system. Between-group and subgroup comparisons of PBLs in patients with EC were analyzed using t-test or Mann–Whitney U test. The effect of surgery on PBLs in patients with EC was assessed using a paired t-test or the Wilcoxon signed rank test. Results The immune function of patients with EC was significantly lower than that of healthy people (P < 0.05) and those with benign uterine diseases (P < 0.05) and was related to body mass index (BMI), hypertension, diabetes, and blood lipids (P < 0.05). In patients with EC, the PBLs counts decreased significantly after surgery (P < 0.05) and more kinds of lymphocytes were affected in the laparoscopic surgery group than in the open surgery group. Conclusions With the decrease of PBLs counts, the immune status of patients with EC is impaired. Metabolic syndrome (Mets), including obesity, hypertension, diabetes, and high blood lipids, also affects the immune function of patients with EC. And for EC patients, the effect of laparoscopic surgery is greater than that of open surgery. PBLs has the potential to be one of indicator during the diagnosis and treatment of EC. Trial registration This study was retrospectively registered by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (approval number K2023-578).

Abstract In large-scale software development, the increasing complexity of software products poses a daunting challenge to maintaining software quality. Given this challenge, software fault prediction (SFP) is a critical endeavor for effective budgeting and refinement of the testing process. Quantitative insights into software quality gained through measurements are crucial in enabling accurate SFP. With the proliferation of software in various fields, ensuring software reliability throughout the software life cycle has become paramount. Anticipating software bugs, which have the potential to reduce software maintenance costs dramatically, is a key approach to improving software reliability. In this regard, using nature-inspired metaheuristic algorithms is promising because of their ability to predict future conditions and identify software anomalies. This study examines the potential of various meta-heuristic algorithms, particularly particle swarm optimization, genetic, ant colony optimization, cuckoo search, lion optimization, firefly, moth-flame, whale optimization, and artificial bee colony algorithms, in addressing the SFP challenge. The study outlines the challenging problems, compares approaches based on fundamental variables, and offers suggestions for future studies, providing a comprehensive and systematic analysis of these algorithms in the context of SFP.

Abstract Background Clinical trials have shown that immunotherapy based on Vγ9Vδ2 T cells (Vδ2 T cells) is safe and well-tolerated for various cancers including cervical cancer (CC), but its overall treatment efficacy remains limited. Therefore, exploring the mechanisms underlying the suboptimal efficacy of Vδ2 T cell-based cancer immunotherapy is crucial for enabling its successful clinical translation. Methods Tumor samples from CC patients and CC cell line-derived xenograft (CDX) mice were analyzed using flow cytometry to examine the exhausted phenotype of tumor-infiltrating Vδ2 T cells. The interrelationship between BTN3A1 expression and Vδ2 T cells in CC, along with their correlation with patient prognosis, was analyzed using data from The Cancer Genome Atlas (TCGA) database. CC cell lines with BTN3A1 knockout (KO) and overexpression (OE) were constructed through lentivirus transduction, which were then co-cultured with expanded Vδ2 T cells, followed by detecting the function of Vδ2 T cells using flow cytometry. The pathways and transcription factors (TFs) related to BTN3A1-induced Vδ2 T cells exhaustion and the factors affecting BTN3A1 expression were identified by RNA-seq analysis, which was confirmed by flow cytometry, Western Blot, and gene manipulation. Results Tumor-infiltrating Vδ2 T cells exhibited an exhausted phenotype in both CC patients and CDX mice. BTN3A1 expressed in CC is highly enhancing exhaustion markers, while reducing the secretion of effector molecules in Vδ2 T cells. Blocking TCR or knocking down nuclear receptor subfamily 4 group A (NR4A) 2/3 can reverse BTN3A1-induced exhaustion in Vδ2 T cells. On the other hand, IFN-γ secreted by Vδ2 T cells promoted the expression of BTN3A1 and PD-L1. Conclusions Through binding γδ TCRs, BTN3A1 expressed on tumor cells, which is induced by IFN-γ, can promote Vδ2 T cells to upregulate the expression of TFs NR4A2/3, thereby affecting their activation and expression of exhaustion-related molecules in the tumor microenvironment (TME). Therefore, targeting BTN3A1 might overcome the immunosuppressive effect of the TME on Vδ2 T cells in CC.

Abstract Expressive suppression is an abnormal emotion regulation strategy, and its relationship with rumination traits is unclear. In this study with 395 participants in China (33.9% female, Mean age = 21.22, SD = 2.11), we estimated the association between expressive suppression and rumination traits, using the Rumination Response Scale (RRS) and the Emotion Regulation Questionnaire (ERQ) respectively. Considering there may be complex correlations between different behavioral symptoms of expressive suppression (“Keeping emotions to myself”, “Inhibiting positive emotion responses”, “Controlling emotions by not expressing them”, “Inhibiting negative emotion responses”) and different subtypes of rumination traits, this study employed a symptom-based network analysis method to uncover the differential association between rumination traits and expressive suppression, and the key symptoms linking the two. The study found the S3 node (Controlling emotions by not expressing them) had significant positive correlations with symptom rumination, brooding, and reflective pondering. Among the network, the S3 node acts as a bridge between two variables. This suggests that interventions targeting the S3 symptom may improve rumination traits. The present study was a cross-sectional study with limitations in revealing the causal relationships between expression suppression and rumination traits. Future studies could employ longitudinal tracing methods to explore the relationship between them.

The potential effects of combining biochar with hyperaccumulator plants on heavy metal stabilization and uptake in Cd and Pb-contaminated soils have received limited attention. This study used biochar (BC) at levels ranging from 0 to 40 t ha-1 as soil amendments in Cd and Pb contaminated rice paddy soil. Biochar significantly decreased soil bioavailable Cd and Pb concentrations 6.7 to 16.6% and 10.6 to 39.7%, respectively, compared to the control. The shoot and root Cd concentrations in Arabidopsis helleri increased significantly by 33.5% and 133.1%, respectively, in the C3 treatment compared to the control. Similarly, shoot Pb concentrations showed a 57.5% increase compared to the control, but no significant changes were observed in root Pb concentrations. The Arabidopsis helleri bioconcentration factor (BCF) saw an increase of up to 40.5% for Cd and 57.8% for Pb with the C3 treatment. Conversely, the Cd translocation factor (TF) decreased 42.8 to 49.1%, while the Pb TF increased 32.8 to 96.6% with biochar application. The majority of Arabidopsis helleri-biochar Cd and Pb was found in the B3 fraction (organic fraction), constituting over 50%, and even over 80% for Cd. The Arabidopsis helleri-biochar primarily contained organic char binding Cd and exhibited slow-release characteristics.

The propagation of rumors indisputably inflicts profound negative impacts on society and individuals. This article introduces a new unaware ignorants-aware ignorants-spreaders-recovereds $ (2ISR) $ rumor spreading model that combines individual vigilance self-awareness with nonlinear spreading rate. Initially, the positivity of the system solutions and the existence of its positive invariant set are rigorously proved, and the rumor propagation threshold is solved using the next-generation matrix method. Next, a comprehensive analysis is conducted on the existence of equilibrium points of the system and the occurrence of backward bifurcation. Afterward, the stability of the system is validated at both the rumor-free equilibrium and the rumor equilibrium, employing the Jacobian matrix approach as well as the Lyapunov stability theory. To enhance the efficacy of rumor propagation management, a targeted optimal control strategy is formulated, drawing upon the Pontryagin's Maximum principle as a guiding framework. Finally, through sensitivity analyses, numerical simulations, and tests of real cases, we verify the reliability of the theoretical results and further consolidate the solid foundation of the above theoretical arguments.

Abstract At present, the diagnosis of lower respiratory tract infections (LRTIs) is difficult, and there is an urgent need for better diagnostic methods. This study enrolled 136 patients from 2020 to 2021 and collected bronchoalveolar lavage fluid (BALF) specimens. We used metatranscriptome to analyze the lower respiratory tract microbiome (LRTM) and host immune response. The diversity of the LRTM in LRTIs significantly decreased, manifested by a decrease in the abundance of normal microbiota and an increase in the abundance of opportunistic pathogens. The upregulated differentially expressed genes (DEGs) in the LRTIs group were mainly enriched in infection immune response-related pathways. Klebsiella pneumoniae had the most significant increase in abundance in LRTIs, which was strongly correlated with host infection or inflammation genes TNFRSF1B, CSF3R, and IL6R. We combined LRTM and host transcriptome data to construct a machine-learning model with 12 screened features to discriminate LRTIs and non-LRTIs. The results showed that the model trained by Random Forest in the validate set had the best performance (ROC AUC: 0.937, 95% CI: 0.832–1). The independent external dataset showed an accuracy of 76.5% for this model. This study suggests that the model integrating LRTM and host transcriptome data can be an effective tool for LRTIs diagnosis.

Abstract Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer’s disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored. Here we conduct the largest genome-wide association study (GWAS) of PSP which includes 2779 cases (2595 neuropathologically-confirmed) and 5584 controls and identify six independent PSP susceptibility loci with genome-wide significant (P

Abstract Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation. The hypothesis of our study posits that instead of directly applying high doses of radiation, which is risky, a strategy could be developed to harness the immune-stimulating benefits of high-dose irradiation indirectly. This involves using nanoparticles to enhance antigen presentation and immune responses in a safer manner. Angiopep-2 (A2) was proved a satisfactory BBB and brain targeting and Dbait is a small molecule that hijack DNA double strand break damage (DSB) repair proteins to make cancer cells more sensitive to radiation. In view of that, the following two nanoparticles were designed to combine immunity of GBM, radiation resistance and BBB innovatively. One is cationic liposome nanoparticle interacting with Dbait (A2-CL/Dbait NPs) for radiosensitization effect; the other is PLGA-PEG-Mal nanoparticle conjugated with OX40 antibody (A2-PLGA-PEG-Mal/anti-OX40 NPs) for tumor-derived protein antigens capture and optimistic immunoregulatory effect of anti-OX40 (which is known to enhance the activation and proliferation T cells). Both types of nanoparticles showed favorable targeting and low toxicity in experimental models. Specifically, the combination of A2-CL/Dbait NPs and A2-PLGA-PEG-Mal/anti-OX40 NPs led to a significant extension in the survival time and a significant tumor shrinkage of mice with GBM. The study demonstrates that combining these innovative nanoparticles with conventional radiotherapy can effectively address key challenges in GBM treatment. It represents a significant step toward more effective and safer therapeutic options for GBM patients.

Abstract Background Advances in minimally invasive surgery and the development of Enhanced Recovery After Surgery (ERAS) have favored the spread of day-surgery programs. Even though Vaginal natural orifice transvaginal endoscopic surgery (vNOTES) is accepted as an innovative treatment for benign ovarian cysts that is rapidly gaining recognition worldwide, the safety and feasibility of same-day surgery (SDS) have yet to be established. Objective This study aimed to evaluate the safety and feasibility of day surgery compared to inpatient surgery of patients undergoing vNOTES for benign ovarian cysts by determining perioperative outcomes. Materials and methods The study consisted of 213 patients who underwent vNOTES for ovarian cystectomy at a single institution from January 2020 to November 2022. Based on the hospital stay, patients were classified into the same-day surgery group (SDSG) and the inpatient surgery group (ISG); after data processing and screening considering the balance of the two groups, SDSG has 83 samples(n = 83), and ISG has 113 samples(n = 113). The patient’s demographic characteristics and follow-up data were collected during the perioperative period by doctors and nurses for medical tracking and analysis purposes and 1-month postoperatively by doctors in charge of their operation. Independent sample t-tests were performed to verify if there was any major difference between these two groups for continuous data like age, BMI, and cyst diameter, and Pearson’s chi-squared tests were used to test whether there was a major difference between these two groups for categorical data like cyst count, abdominal surgery history and whether their cyst is bilateral ovarian cysts or not. The association between exhaust time and postoperative characteristics and the association between levels of pain and postoperative characteristics were further analyzed to unveil the confounding factors contributing to the same-day discharge method’s quick recovery nature. Results Upon performing propensity score matching, 196 patients were finally enrolled in this study for the matched comparison, including 83(42.3%) patients in the SDSG and 113(57.7%) patients in the ISG. There was no statistical difference between the two groups in terms of duration of operation (85.0 ± 41.5 min vs. 80.5 ± 33.5 min), estimated blood loss (27.7 ± 28.0 ml vs. 36.3 ± 33.2 ml), preoperative hemoglobin levels (128.8 ± 13.2 g/L vs. 128.6 ± 14.0 g/L), postoperative hemoglobin difference at 24 h (16.5 ± 15.4 g/L vs. 19.3 ± 9.1 g/L), pelvic adhesions (42 (50.6%) vs. 47 (41.6%)), and postoperative complications (7(8.4%) vs. 4(3.5%)). The SDSG group showed less time of feeding/off-bed/exhaust/urination after surgery, shorter hospitalization duration, a lower postoperative 6-hour pain score, and a lower incidence of analgesic drug use. Multiple linear regression analysis showed that advancing the time of postoperative off-bed activity and feeding reduced the postoperative exhaust time by 0.34 (95% CI: 0.185–0.496, 0.34 h, p

Abstract Background The escalating global prevalence of polypharmacy presents a growing challenge to public health. In light of this issue, the primary objective of our study was to investigate the status of polypharmacy and its association with clinical outcomes in a large sample of hospitalized older patients aged 65 years and over. Methods A two-year prospective cohort study was carried out at six tertiary-level hospitals in China. Polypharmacy was defined as the prescription of 5 or more different medications daily, including over-the-counter and non-prescription medications. Baseline polypharmacy, multimorbidity, and other variables were collected when at admission, and 2-year outcomes were recorded by telephone follow-up. We used multivariate logistic regression analysis to examine the associations between polypharmacy and 2-year outcomes. Results The overall response rate was 87.2% and 8713 participants were included in the final analysis. The mean age was 72.40 years (SD = 5.72), and women accounted for 42.2%. The prevalence of polypharmacy among older Chinese inpatients is 23.6%. After adjusting for age, sex, education, marriage status, body mass index, baseline frailty, handgrip strength, cognitive impairment, and the Charlson comorbidity index, polypharmacy is significantly associated with frailty aggravation (OR 1.432, 95% CI 1.258–1.631) and mortality (OR 1.365, 95% CI 1.174–1.592), while inversely associated with readmission (OR 0.870, 95% CI 0.764–0.989). Polypharmacy was associated with a 35.6% increase in the risk of falls (1.356, 95%CI 1.064–1.716). This association weakened after adjustment for multimorbidity to 27.3% (OR 1.273, 95%CI 0.992–1.622). Conclusions Polypharmacy was prevalent among older inpatients and was a risk factor for 2-year frailty aggravation and mortality. These results highlight the importance of optimizing medication use in older adults to minimize the risks associated with polypharmacy. Further research and implementing strategies are warranted to enhance the quality of care and safety for older individuals exposed to polypharmacy. Trial registration Chinese Clinical Trial Registry, ChiCTR1800017682, registered 09/08/2018.

Abstract IgA antibodies play an important role in mucosal immunity. However, there is still no effective way to consistently boost mucosal IgA responses, and the factors influencing these responses are not fully understood. We observed that colonization with the murine intestinal symbiotic protozoan Tritrichomonas musculis (T.mu) boosted antigen-specific mucosal IgA responses in wild-type C57BL/6 mice. This enhancement was attributed to the accumulation of free arachidonic acid (ARA) in the intestinal lumen, which served as a signal to stimulate the production of antigen-specific mucosal IgA. When ARA was prevented from undergoing its downstream metabolic transformation using the 5-lipoxygenase inhibitor zileuton or by blocking its downstream biological signaling through genetic deletion of the Leukotriene B4 receptor 1 (Blt1), the T.mu-mediated enhancement of antigen-specific mucosal IgA production was suppressed. Moreover, both T.mu transfer and dietary supplementation of ARA augmented the efficacy of an oral vaccine against Salmonella infection, with this effect being dependent on Blt1. Our findings elucidate a tripartite circuit linking nutrients from the diet or intestinal microbiota, host lipid metabolism, and the mucosal humoral immune response.

Abstract Objective This study aimed to evaluate the impact of adding 4 mg estradiol valerate to progesterone for luteal support on pregnancy rates in IVF cycles following a long protocol with reduced luteal serum estradiol levels post-hCG triggering. Design, setting, and participants The prospective randomized controlled trial was conducted at a public tertiary hospital reproductive center with 241 patients who experienced a significant decrease in serum estrogen levels post-oocyte retrieval. Interventions Participants received either a daily 4 mg dose of estradiol valerate in addition to standard progesterone or standard progesterone alone for luteal support. Results The ongoing pregnancy rate did not show a significant difference between the E2 group and the control group (56.6% vs. 52.2%, with an absolute rate difference (RD) of 4.4%, 95% CI -0.087 to 0.179, P = 0.262). Similarly, the live birth rate, implantation rate, clinical pregnancy rate, early abortion rate, and severe OHSS rate were comparable between the two groups. Notably, the E2 group had no biochemical miscarriages, contrasting significantly with the control group (0.0% vs. 10.7%, RD -10.7%, 95% CI -0.178 to -0.041, P = 0.000). In the blastocyst stage category, the clinical pregnancy rate was notably higher in the E2 group compared to the control group (75.6% vs. 60.8%, RD 14.9%, 95% CI 0.012 to 0.294, P = 0.016). Conclusion Adding 4 mg estradiol valerate to progesterone for luteal support does not affect the ongoing pregnancy rate in embryo transfer cycles using a long protocol with a significant decrease in serum estradiol levels after hCG triggering. However, it may reduce biochemical miscarriages and positively impact clinical pregnancy rates in blastocyst embryo transfer cycles. Trial registration ChiCTR1800020342.

Copper-based nanomaterials demonstrate promising potential in cancer therapy. Cu+ efficiently triggers a Fenton-like reaction and further consumes the high level of glutathione, initiating chemical dynamic therapy (CDT) and ferroptosis. Cuproptosis, a newly identified cell death modality that represents a great prospect in cancer therapy, is activated. However, active homeostatic systems rigorously keep copper levels within cells exceptionally low, which hinders the application of cooper nanomaterials-based therapy. Herein, a novel strategy of CRISPR-Cas9 RNP nanocarrier to deliver cuprous ions and suppress the expression of copper transporter protein ATP7A for maintaining a high level of copper in cytoplasmic fluid is developed. The Cu2O and organosilica shell would degrade under the high level of glutathione and weak acidic environment, further releasing RNP and Cu+. The liberated Cu+ triggered a Fenton-like reaction for CDT and partially transformed to Cu2+, consuming intracellular GSH and initiating cuproptosis and ferroptosis efficiently. Meanwhile, the release of RNP effectively reduced the expression of copper transporter ATP7A, subsequently increasing the accumulation of cooper and enhancing the efficacy of CDT, cuproptosis, and ferroptosis. Such tumor microenvironment responsive multimodal nanoplatform opens an ingenious avenue for colorectal cancer therapy based on gene editing enhanced synergistic cuproptosis/CDT/ferroptosis.

Abstract With the proceeding of global warming and water eutrophication, the phenomenon of green tide has garnered significant societal interest. Consequently, researchers had increasingly focused on the potential applications of green algae biomass, particularly its polysaccharides. The polysaccharide serves as the primary active constituent of green algae and has demonstrated numerous advantageous biological activities, including antioxidant, antiviral, anticoagulant, hypolipidemic and immuno-modulatory activities. The favorable bioavailability and solubility of green algae oligosaccharides are attributed to their low molecular weight. So there has been a growing interest in researching green algae polysaccharides and oligosaccharides for the utilization of marine biological resources. This review summarized the extraction, purification, chemical structure, composition, biological activity, and potential applications prospect of polysaccharides and oligosaccharides derived from green algae. The review could be helpful for expanding the applications of polysaccharides and oligosaccharides of green algae. Graphical Abstract

Abstract The association between obstructive sleep apnea (OSA) and proteinuria is undetermined, with few studies on hypertension, a high-risk group for renal impairment. Therefore, we aimed to explore whether OSA is an independent risk factor for proteinuria in patients with hypertension. We investigated the cross-sectional association between OSA and proteinuria. Participants were divided into groups by apnea hypopnea index (AHI) category. Multivariable Logistic regression analysis was used to evaluate the association between OSA severity, objectively measured sleep dimensions, and proteinuria which is mainly defined by 24-h urine protein quantification > 300 mg/24 h. Sensitivity analyses were performed by excluding those with comorbidities (primary aldosteronism and homocysteine ≥ 15 μmol/L). Of the 2106 participants, the mean age was 47.57 ± 10.50 years, 67.2% were men, and 75.9% were OSA patients. In total participants, compared with those without OSA, patients with mild OSA, moderate OSA, and severe OSA showed 1.09 (95% CI 0.80–1.40), 1.24 (95% CI 0.89–1.74) and 1.47 (95% CI 1.04–2.08) fold risk for proteinuria with a trend test P trend

Abstract Tumor cells possess complex immune evasion mechanisms to evade immune system attacks, primarily through metabolic reprogramming, which significantly alters the tumor microenvironment (TME) to modulate immune cell functions. When a tumor is sufficiently immunogenic, it can activate cytotoxic T-cells to target and destroy it. However, tumors adapt by manipulating their metabolic pathways, particularly glucose, amino acid, and lipid metabolism, to create an immunosuppressive TME that promotes immune escape. These metabolic alterations impact the function and differentiation of non-tumor cells within the TME, such as inhibiting effector T-cell activity while expanding regulatory T-cells and myeloid-derived suppressor cells. Additionally, these changes lead to an imbalance in cytokine and chemokine secretion, further enhancing the immunosuppressive landscape. Emerging research is increasingly focusing on the regulatory roles of non-tumor cells within the TME, evaluating how their reprogrammed glucose, amino acid, and lipid metabolism influence their functional changes and ultimately aid in tumor immune evasion. Despite our incomplete understanding of the intricate metabolic interactions between tumor and non-tumor cells, the connection between these elements presents significant challenges for cancer immunotherapy. This review highlights the impact of altered glucose, amino acid, and lipid metabolism in the TME on the metabolism and function of non-tumor cells, providing new insights that could facilitate the development of novel cancer immunotherapies.

Adhesive bonding is widely used in aeronautical carbon fiber-reinforced polymer (CFRP)/titanium (Ti) alloy hybrid structures to satisfy the demands of high-strength and lightweight. The physicochemical properties of adherend surfaces significantly impact the bonding performance. In this study, laser-induced surface reconstruction (LISR) was designed for the reliable joining of Ti alloy and CFRP. A three-level-three-factor central composite design (CCD) approach-based response surface methodology (RSM) analysis was applied to statistically specify parameter optimization of the laser energy output. Surface morphology and wettability of CFRP ablated were studied. Chemical compositions were determined by X-ray photoelectron spectroscopy (XPS). Tensile-shear tests were performed, and fractured surfaces were analyzed. The tensile shear strength with LISR process has been improved by 19.1%, in comparison with that of mechanical grinding treatment. The cross-like texture based on designed geometric configuration was fabricated without damaging the underlying fibers, thus increasing the surface roughness and contact area at interface. The wettability transition mechanism was investigated, demonstrating that the hydrophilicity of reconstructed surfaces primarily attributes to the more polar groups (C–O, CO, etc.) on CF surfaces. This study provides a reliable surface treatment method for fabricating high-performance composite structures by adhesive bonding.

To investigate the effect of baking on the flavor of albino green tea, Baiye 1 green tea samples with different treatment (0, 40, 80, and 120 min at 60 ℃) were conducted in the study. The dynamic changes of metabolites were detected and analyzed by UHPLC-Q-Exactive/MS and GC-MS. The result showed that green tea sample treated by 40 min at 60 ℃ exhibited a better quality than other green tea samples. The thickness of green tea infusions and the aroma intensity went a downtrend with the increase of baking time, while the intensity of astringency increased. The content of total free amino acids and caffeine increased remarkable with time up (P1, P

Objectives: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) poses a significant threat to public health. This study reports an infection related to hv-CRKp in a premature infant and reveals its colistin resistance and evolutionary mechanisms within the host. Methods: Three KPC-producing CRKp strains were isolated from a patient with sepsis and CRKp osteoarthritis who had been receiving colistin antimicrobial therapy. The minimum inhibitory concentrations (MICs) of ceftazidime, ceftazidime-avibactam (CAZ-AVI), meropenem, imipenem, tigecycline, amikacin, minocycline, sulfamethoxazole/trimethoprim, ciprofloxacin, levofloxacin, aztreonam, cefepime, cefoperazone/sulbactam, piperacillin/tazobactam, and colistin were determined using the microbroth dilution method. The whole-genome sequencing analysis was conducted to determine the sequence types (STs), virulence genes, and antibiotic resistance genes of the three CRKp strains. Results: Whole-genome sequencing revealed that all three CRKp strains belonged to the ST11 clone and carried a plasmid encoding blaKPC-2. The three strains all possessed the iucABCDiutA virulence cluster, peg-344 gene, and rmpA/rmpA2 genes, defining them as hv-CRKp. Further experiments and whole-genome analysis revealed that a strain of K. pneuomniae had developed resistance to colistin. The mechanism found to be responsible for colistin resistance was a deletion mutation of approximately 9000 bp including the mgrB gene. Conclusion: This study characterizes colistin resistance of the ST11 clone hv-CRKp during colistin treatment and its rapid evolution within the host.

Non-alcoholic fatty liver disease (NAFLD), a type of liver disease for which no treatment is currently approved, remains a major concern worldwide. It is manifested as simple hepatocyte steatosis and can develop into inflammation, fibrosis, cirrhosis and liver cancer in severe cases. However, due to the lack of appropriate in vitro drug testing platforms, an in-depth understanding of the therapeutic activity of ginsenoside Rb1 in NAFLD remains challenging. Here, we proposed a NAFLD model on a liver organoids (LOs)-on-a-chip platform to evaluate the therapeutic effect of ginsenoside Rb1 in a dynamic, multi-condition and high-throughput manner. This platform allowed us to reshape certain features such as multicellular types and liver-specific functions of the physiology of the human-relative liver. Free fatty acids (FFAs)-induced LOs displayed typical pathological characteristics of NAFLD progression, including steatosis, oxidative stress, lipid peroxidation, inflammation and fibrosis. With ginsenoside Rb1 intervention, these pathological features can be significantly improved, which may provide new insights into the potential mechanisms of NAFLD progression and treatment and suggest the clinical implications for humans. The proposed system enables the formation, differentiation, and function of LOs to serve as a scalable, high-throughput and sensitive drug testing model, to potentially expedite the NAFLD drug discovery.

Abstract Background In recent years, significant morbidity and mortality in patients with severe inflammatory bowel disease (IBD) and cytomegalovirus (CMV) have drawn considerable attention to the status of CMV infection in the intestinal mucosa of IBD patients and its role in disease progression. However, there is currently no high-throughput sequencing data for ulcerative colitis patients with CMV infection (CMV + UC), and the immune microenvironment in CMV + UC patients have yet to be explored. Method The xCell algorithm was used for evaluate the immune microenvironment of CMV + UC patients. Then, WGCNA analysis was explored to obtain the co-expression modules between abnormal immune cells and gene level or protein level. Next, three machine learning approach include Random Forest, SVM-rfe, and Lasso were used to filter candidate biomarkers. Finally, Best Subset Selection algorithms was performed to construct the diagnostic model. Results In this study, we performed transcriptomic and proteomic sequencing on CMV + UC patients to establish a comprehensive immune microenvironment profile and found 11 specific abnormal immune cells in CMV + UC group. After using multi-omics integration algorithms, we identified seven co-expression gene modules and five co-expression protein modules. Subsequently, we utilized various machine learning algorithms to identify key biomarkers with diagnostic efficacy and constructed an early diagnostic model. We identified a total of eight biomarkers (PPP1R12B, CIRBP, CSNK2A2, DNAJB11, PIK3R4, RRBP1, STX5, TMEM214) that play crucial roles in the immune microenvironment of CMV + UC and exhibit superior diagnostic performance for CMV + UC. Conclusion This 8 biomarkers model offers a new paradigm for the diagnosis and treatment of IBD patients post-CMV infection. Further research into this model will be significant for understanding the changes in the host immune microenvironment following CMV infection.

Abstract Background Sunitinib, a multi-targeted tyrosine kinase inhibitor, is used as a second-line therapy for gastrointestinal stromal tumors (GIST) resistant to imatinib. However, its impact on the vascular endothelial growth factor (VEGF) pathway can lead to significant toxicities, including hypertension and thrombotic microangiopathy (TMA). Case presentation This case report describes a unique instance of a patient with metastatic GIST who developed endocapillary proliferative glomerulonephritis (EPGN) with IgA2 deposits and TMA following sunitinib treatment. The patient presented with severe hypertension, nephrotic syndrome, and acute kidney injury. Renal biopsy confirmed the diagnosis, revealing IgA2 deposits, which are not commonly associated with TMA. Discontinuation of sunitinib led to a rapid improvement in renal function and proteinuria. The potential mechanisms underlying sunitinib-induced glomerular injury may involve the blockade of VEGFR-1, affecting immune cell recruitment and function, and the disruption of the nitric oxide and endothelin systems, leading to endothelial damage and immune dysregulation. Management of these toxicities requires a personalized approach, with options ranging from symptomatic relief to drug discontinuation. The use of endothelin receptor antagonists and other therapeutic alternatives for GIST management is discussed. Conclusions This case highlights the complex interplay between the therapeutic effects of sunitinib and its potential renal and cardiovascular toxicities, emphasizing the need for close monitoring and effective management strategies to optimize patient outcomes.

Abstract Background To explore the surgical outcome of enlarged posterior column osteotomy (EPCO) plus intervertebral cage strutting (ICS) for patients with lumbosacral nerve bowstring disease (BSD). Methods The clinical data of 27 patients with BSD that surgically treated with EPCO plus ICS from January 2018 to March 2021 were retrospectively reviewed. Patient demographics including age, gender, body mass index (BMI), duration, length of hospital stay, SF-36 were recorded. Surgical data including operation time, blood loss, surgical level, and complications were recorded. Inter-pedicle distance and regional lumbar lordosis was measured at lateral X-ray at both pre- and postoperative. Results All patients underwent the operation successfully. EPCO plus ICS was performed at L4-L5 in 9 patients, at L5-S1 in 7 patients, at L4-S1 in 6 patients, at L3-L5 in 5 patients. The mean operation time was 96.3 ± 18.0 min, mean blood loss was 350.0 ± 97.9 mL. Relaxation of thecal sac was noticed after pedicle screw-rod compression bilaterally. The mean decrease of inter-pedicle distance was 0.57 ± 0.18 cm, the mean increase of regional lumbar lordosis was 17.6 ± 6.7 degrees. Relaxation of cauda equina within the thecal sac was noticed at intra-operative after pedicle screw-rod compression bilaterally in all the patients. Most patients achieved neurological function improvement at two-year follow up. Conclusions EPCO plus ICS procedure is an effective surgical method for lumbosacral nerve BSD through restoring the coordination between column and cord, visual relaxation of cauda equina within the thecal sac at intraoperative is the key factor in determining the relief of neurological function at postoperative.

Abstract Background Non-tuberculous mycobacteria (NTM) are present widely in the natural environment and can invade the human body through the respiratory tract, gastrointestinal tract, and skin. Immunocompromised patients are particularly prone to infection, which primarily affects multiple organs, including the lungs, lymph nodes, and skin. However, cases of NTM bloodstream infections are rare. Here, we report a rare case of Mycobacterium marseillense bloodstream infection with concurrent skin fungal infection in a patient after kidney transplantation. Related literature was reviewed to enhance the understanding of this rare condition. Case presentation A 58-year-old male with a history of long-term steroid and immunosuppressant use after kidney transplantation presented with limb swelling that worsened over the past two months. Physical examination revealed redness and swelling of the skin in all four limbs, with a non-healing wound on the lower left limb. Skin tissue analysis by metagenomic next-generation sequencing (mNGS) and fungal culture indicated infection with Trichophyton rubrum. Blood culture results suggested infection with Mycobacterium marseillense. After receiving anti-NTM treatment, the patient’s symptoms significantly improved, and he is currently undergoing treatment. Conclusion Mycobacterium marseillense is a NTM. Gram staining suffered from misdetection, and the acid-fast staining result was positive. This bacterium was identified by mass spectrometry and mNGS analyses. Antimicrobial susceptibility tests for NTM were performed using the broth microdilution method. The results of the susceptibility test showed that Mycobacterium marseillense was sensitive to clarithromycin, an intermediary between moxifloxacin and linezolid. Bacterial clearance requires a combination of drugs and an adequate course of treatment. NTM bloodstream infections are relatively rare, and early identification and proactive intervention are key to their successful management.

Abstract To assess the impact of Enhanced Recovery After Surgery (ERAS) protocol in children undergoing corrective surgery for congenital scoliosis. A retrospective analysis was conducted on children undergoing surgical correction for congenital scoliosis, with participants categorized into either the ERAS group or the control group. Comparative evaluations were made across clinical, surgical, laboratory, and quality of life parameters. Following propensity score matching, 156 patients were analyzed. Within the initial 3 days following surgery, the ERAS cohort demonstrated lower pain intensity and exhibited higher daily oral intake compared to their counterparts in the control group. A mere 14.1% of patients in the ERAS group experienced a peak body temperature exceeding 38.5°, illustrating a significantly lower incidence compared to the 33.3% recorded in the control group. The ERAS cohort displayed expedited timeframes for the onset of initial bowel function and postoperative discharge when contrasted with the control group. Levels of IL-6 assessed on the third day post-surgery were markedly reduced in the ERAS group in comparison to the control group. Noteworthy is the similarity observed in postoperative hemoglobin and albumin levels measured on the first and third postoperative days between the two groups. Assessments of quality of life using SF-36 and SRS-22r questionnaires revealed comparable scores across all domains in the ERAS group when juxtaposed with the control cohort. ERAS protocol has demonstrated a capacity to bolster early perioperative recovery, alleviate postoperative stress responses, and uphold favorable quality of life outcomes in children undergoing corrective surgery for congenital scoliosis.

Abstract Background The combination of immunotherapy and antiangiogenic therapy has shown potential in the treatment of numerous malignant tumors, but limited evidence was available for soft tissue sarcomas (STS). Therefore, the aim of the present study is to assess the efficacy and safety of immunotherapy in conjunction with antiangiogenic therapy in patients diagnosed with advanced STS (aSTS). Methods The study enrolled patients with aSTS from January 2014 to October 2022. Eligible participants had previously received anthracycline-based chemotherapy, presented with an anthracycline-resistant sarcoma subtype, or were ineligible for anthracycline treatment due to medical conditions. Following enrollment, these patients received a combination of immunotherapy and antiangiogenic therapy. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS), while the secondary endpoints included the disease control rate (DCR), overall survival (OS), and the incidence of adverse events. Results Fifty-one patients were included in this cohort study. The median duration of follow-up was 15.8 months. The ORR and DCR were 17.6%, and 76.5%, respectively. The median PFS (mPFS) was 5.8 months (95% CI: 4.8–6.8) for all patients, and the median OS had not been reached as of the date cutoff. Multivariate analysis indicated that Eastern Cooperative Oncology Group performance status of 0–1 and ≤ second-line treatment were positive predictors for both PFS and OS. Patients with alveolar soft part sarcoma or clear cell sarcoma had longer mPFS (16.2 months, 95% CI: 7.8–25.6) when compared to those with other subtypes of STS (4.4 months, 95% CI: 1.4–7.5, P

Abstract Developing light yet strong aluminum (Al)-based alloys has been attracting unremitting efforts due to the soaring demand for energy-efficient structural materials. However, this endeavor is impeded by the limited solubility of other lighter components in Al. Here, we propose to surmount this challenge by converting multiple brittle phases into a ductile solid solution in Al-based complex concentrated alloys (CCA) by applying high pressure and temperature. We successfully develop a face-centered cubic single-phase Al-based CCA, Al55Mg35Li5Zn5, with a low density of 2.40 g/cm3 and a high specific yield strength of 344×103 N·m/kg (typically ~ 200×103 N·m/kg in conventional Al-based alloys). Our analysis reveals that formation of the single-phase CCA can be attributed to the decreased difference in atomic size and electronegativity between the solute elements and Al under high pressure, as well as the synergistic high entropy effect caused by high temperature and high pressure. The increase in strength originates mainly from high solid solution and nanoscale chemical fluctuations. Our findings could offer a viable route to explore lightweight single-phase CCAs in a vast composition-temperature-pressure space with enhanced mechanical properties.

Abstract Background Offspring consistently exhibit similar imaging features as their parents in cases of degenerative lumbar scoliosis (DLS). Nevertheless, the role of genetic factors in the pathogenesis of DLS remains uncertain. Methods A prospective analysis was conducted on 35 patients with DLS and their 36 offspring. Genomic DNA was extracted from 71 blood samples for gene mutation analysis using whole exome sequencin. Various demographic and imaging parameters were compared. Results In 11 pedigrees of the 35 family members with DLS, 13 suspected pathogenic genes were identified. Among the 35 DLS patients, 11/35(31.5%) exhibited susceptibility gene mutations (mutant group), while 24/35(68.5%) had no pathogenic gene mutations (non-mutant group). AVR was more severe in mutant group than that in no-mutant group (p

Abstract Clinical metagenomics (CMg) Nanopore sequencing can facilitate infectious disease diagnosis. In China, sub-lineages ST11-KL64 and ST11-KL47 Carbapenem-resistant Klebsiella pneumoniae (CRKP) are widely prevalent. We propose PathoTracker, a specially compiled database and arranged method for strain feature identification in CMg samples and CRKP traceability. A database targeting high-prevalence horizontal gene transfer in CRKP strains and a ST11-only database for distinguishing two sub-lineages in China were created. To make the database user-friendly, facilitate immediate downstream strain feature identification from raw Nanopore metagenomic data, and avoid the need for phylogenetic analysis from scratch, we developed data analysis methods. The methods included pre-performed phylogenetic analysis, gene-isolate-cluster index and multilevel pan-genome database and reduced storage space by 10-fold and random-access memory by 52-fold compared with normal methods. PathoTracker can provide accurate and fast strain-level analysis for CMg data after 1 h Nanopore sequencing, allowing early warning of outbreaks. A user-friendly page ( http://PathoTracker.pku.edu.cn/ ) was developed to facilitate online analysis, including strain-level feature, species identifications and phylogenetic analyses. PathoTracker proposed in this study will aid in the downstream analysis of CMg.

Abstract Background Pulmonary hypertension (PH) is a long-term disease that impacts approximately 1% of the world’s population. Currently, levosimendan (Lev) is proposed for PH treatment. However, the mechanism of Lev in the treatment of PH is unknown. Methods We used hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) to establish a PH cell model. A number of cell biology methods were performed to assay alterations in cell proliferation, migration and apoptosis after Lev treatment. qRT-PCR and WB were performed to test the levels of circUSP34 and miR-1298, and BMP/Smad protein respectively. In addition, the regulatory relationship between circUSP34 or BMPR2 with miR-1298 was verified through the use of double luciferase as well as RIP assay. In addition, we explored the regulatory effect of Lev on the circUSP34/miR-1298/BMP/Smad axis using a rat PH model. Results Our results demonstrate that Lev inhibited PASMCs cell proliferation, migration and promoted apoptosis exposed to hypoxia. In hypoxia-treated PASMCs, circUSP34 expression got downregulated while miR-1298 upregulated, whereas the addition with Lev resulted in upregulation of circUSP34 expression and downregulation of miR-1298 expression, indicating that circUSP34 can target and regulate miR-1298. In addition, miR-1298 targets and regulates the expression of BMPR2. In a rat PH model induced by hypoxia combined with SU5416, Lev upregulated circUSP34 targeting miR-1298-mediated BMP/Smad axis to alleviate the PH phenotype. Conclusion We have shown that Lev can be used as a therapeutic drug for PH patients, which works through the circUSP34/miR-1298/BMP/Smad axis to alleviate PH symptoms.

Abstract Background and context of the study This research employed a person-centred approach to evaluate the effectiveness of a recruitment intervention aimed at attracting STEM undergraduate students to the teaching profession. The study aimed to identify participant profiles based on changes of interest in teaching, examine the demographic factors associated with these profiles, and explore the outcomes associated with the identified profiles. A total of 267 participants from 18 universities in England were recruited for the study. The intervention involved presenting 12 vignettes that depicted different motivations for choosing teaching as a career. Participants rated their change of interest in teaching after reading each vignette. Results The latent profile analysis revealed four distinct profiles: dissuaded participants, unpersuaded participants, moderately persuaded participants, and highly persuaded participants. The highly persuaded profile reported the highest levels of self-efficacy, interest, perceived fit, and enjoyment in teaching. Participants from higher socioeconomic backgrounds were more likely to be persuaded by the recruitment intervention, but gender, ethnicity, or program levels did not significantly affect profile membership. Conclusions The findings demonstrate the potential of recruitment interventions to influence the interest of STEM undergraduate students in teaching and underscore the importance of considering individual characteristics and motivations when attracting prospective teachers to the profession.

Abstract In the Loess Plateau, the impact of abandoned farmland on soil properties and enzyme activity, along with its temporal variations and potential driving factors, remains a mystery. This study was designed to systematically and comprehensively examine the variations in soil enzyme activities, particle size distribution, and stability of soil aggregates at different stages of ecological recovery in the Loess Plateau. Our findings reveal a nuanced temporal pattern: with the progression of cropland abandonment, there is a notable decrease in soil bulk density. Concurrently, a dynamic trend in enzyme activities is observed—initially exhibiting a decline, followed by an increase over extended periods of recovery. Notably, prolonged abandonment leads to marked enhancements in soil structure. Parameters such as the mean weight diameter (MWD) and geometric mean diameter (GMD) of soil aggregates show an overall increasing trend. In terms of the Relative Dissipation Index (RSI), our data indicate a sequence of control > 2 years of abandonment > 4 years > 6 years > 14 years. From this, it can be seen that fallowing may be an effective natural restoration strategy for improving the physical structure of soils in the Loess Plateau and restoring soil nutrients. However, positive changes may take a long time to become evident.

Abstract Existing knowledge graph-based recommendation algorithms either use Knowledge Graphs (KGs) as auxiliary information or use KG prediction tasks as regular terms to constrain recommendation with multi-task learning. However, the first method, which introduces multi-hop neighbors to enhance item representations, also weakens the relationship information within individual triples to some extent. The second method ignores neighboring information and thus fails to capture the long-range connectivity between items, which leads to a lack of utilization of the structural information in the KG. In response to the limitations of existing recommendation algorithms that do not fully leverage the relational and structural information within KGs, we propose a novel method named Knowledge-Enhanced Multi-Task Parallelized Recommendation Algorithm Incorporating Attention-Embedded Propagation (KMPR-AEP). It employs a parallel approach to simultaneously incorporate KG as auxiliary information and a regular term. We take into account the multi-hop neighbor information of users and items as well as enhance the relations among individual triples, which considers both the structural and relational information of KG. Extensive experiments conducted on three real-world datasets for CTR prediction and Top-K recommendation scenarios demonstrate the superiority of our proposed method over the state-of-the-art. On average, our KMPR-AEP shows improvements of 2.44% in AUC, 3.49% in ACC, and 2.64% in F1.

Abstract Background Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs). Method In this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed. Results Our analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer’s disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73 × 10–3) in PSP. Conclusions Through WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions.

Abstract Tumor spread through air spaces (STAS) is a distinctive metastatic pattern affecting prognosis in lung adenocarcinoma (LUAD) patients. Several challenges are associated with STAS detection, including misdetection, low interobserver agreement, and lack of quantitative analysis. In this research, a total of 489 digital whole slide images (WSIs) were collected. The deep learning-based STAS detection model, named STASNet, was constructed to calculate semi-quantitative parameters associated with STAS density and distance. STASNet demonstrated an accuracy of 0.93 for STAS detection at the tiles level and had an AUC of 0.72–0.78 for determining the STAS status at the WSI level. Among the semi-quantitative parameters, T10S, combined with the spatial location information, significantly stratified stage I LUAD patients on disease-free survival. Additionally, STASNet was deployed into a real-time pathological diagnostic environment, which boosted the STAS detection rate and led to the identification of three easily misidentified types of occult STAS.

Abstract Polyamorphic transition (PT) is a compelling and pivotal physical phenomenon in the field of glass and materials science. Understanding this transition is of scientific and technological significance, as it offers an important pathway for effectively tuning the structure and property of glasses. In contrast to the PT observed in conventional metallic glasses (MGs), which typically exhibit a pronounced first-order nature, herein we report a continuous PT (CPT) without first-order characteristics in high-entropy MGs (HEMGs) upon heating. This CPT behavior is featured by the continuous structural evolution at the atomic level and an increasing chemical concentration gradient with temperature, but no abrupt reduction in volume and energy. The continuous transformation is associated with the absence of local favorable structures and chemical heterogeneity caused by the high configurational entropy, which limits the distance and frequency of atomic diffusion. As a result of the CPT, numerous glass states can be generated, which provides an opportunity to understand the nature, atomic packing, formability, and properties of MGs. Moreover, this discovery highlights the implication of configurational entropy in exploring polyamorphic glasses with an identical composition but highly tunable structures and properties.

Urban land use information is essential for urban planning and sustainable development. However, the increasing prevalence of Mixed-Use Urban Land (MUUL) introduces uncertainty in land use mapping. Due to the compatibility of different human activities within MUUL, identifying MUUL is still a challenge for scholars. In this study, we proposed a novel framework by integrating geographic big data and machine learning to identify it. First, to be consistent with urban planning practices, we delineated mapping units from urban planning map. Second, based on the variability of the spatial pattern of POIs, two indices, the Amount of POI (AP) and the Deviation Index (DI), were developed. Finally, the random forest model was employed. The empirical study in the Jianghan District of Wuhan, China, showed that the MUUL and non-MUUL exhibited significant spatial pattern of POIs separability, the average AP and DI of the MUUL were much larger than those of the non-MUUL. Moreover, the relatively high identification accuracy (Kappa Coefficient (KC) = 0.85, Hellden’s Mean Accuracy (MA) = 0.87) further demonstrated the effectiveness of the developed indices. The proposed framework in this study can reduce the adverse impacts of MUUL on urban land identification by avoiding the MUUL from being incorrectly identified as a single function. Moreover, by extracting MUUL in advance, it can improve the research efficiency by avoiding the application of the segmentation algorithm to all mapping units as in the previous study. Overall, this study provides important references for scholars to increase the accuracy of urban land use identification and allows authorities and policymakers to monitor the dynamics of MUUL that are essential to urban vibrancy. The spatial pattern indices proposed in this study can also be applied to urban land use identification studies as important features.

Abstract According to external pressure theory and reputation theory, reputation-oriented enterprises will experience external pressure as societal attention increases, and enhanced ESG performance can mitigate information asymmetry and boost reputation, thereby signaling to customers the company’s commitment to sustainable development. Based on the data of A-share listed firms in China, this paper manually compiles the detailed information of corporate customers, and explores the relationship between firm’s ESG performance and customer stability using a two-way fixed-effects model. The results show that: (1) Firms with ESG advantages can enhance customer stability, and the higher the ESG score, the more significant the improvement in customer stability; (2) The mechanism test indicates that firms’ ESG performance improves customer stability by strengthening internal and external regulation as well as enhancing corporate reputation; (3) The heterogeneity analysis indicates that in high governance level and small-sized firms, the effect of firms’ ESG performance on customer stability is more significant, and in the ESG sub-test, environmental and social responsibility have a more significant impact on customer stability. This paper provides implications for improving firms’ social responsibility and stabilizing the supply chain.

Abstract Parents of children with retinoblastoma, the most common primary ocular malignant tumour in childhood, bear a heavy caregiving burden and are very susceptible to fatigue. However, little is known about their current status of fatigue and factors influencing fatigue; therefore,this study, based on the theory of unpleasant symptoms, and included 317 parents of children with retinoblastoma in China, whose general demographic data were collected, and on whom the fatigue severity scale (FSS), the generalized anxiety disorder (GAD-7) and 2-item patient health questionnaire (PHQ-2) were administered, from 9 March to 1 June 2020. The parents’ FSS score and fatigue incidence were 4.41 ± 1.14 and 67.19%, respectively. The fatigue level was positively correlated with anxiety, depression, education, times of hospitalisations, and treatment types (r = 0.125–0.468, P

Abstract The segment misalignment is a common defect in the segment installation of a shield tunnel construction, due to the complexity and uncertainty of its construction conditions. This raises a concerning about the safety of the segment lining for the shield tunnel. In this paper, the integrated numerical models with surrounding rock, peastone grouting and segment lining were built using three-dimensional finite element method, by introducing two kinds of misaligned defects of segments. One was the misalignment that elongated the horizontal axis of the transversal ring section of segment lining, another was the misalignment between adjacent rings of segments. To eliminate the impact of boundary on numerical results, seven rings of segments are built for the three-dimensional finite element models, and the middle ring is dealt with for the results analysis under V-class surrounding rock, including the circumferential stress of outer and inner layers of the segment, the contact stress on joint surface between segments, and the stress of locating pins between adjacent rings. Results indicate that the two kinds of misaligned defects create pronounced impact on tensile stress of segment at the bottom and the crown segments, respectively, which produces a greater tensile stress to increase cracking risk even abrupt fracture of segment. However, the misaligned defects have a slight impact on the contact stress and the locating pins stress. Therefore, attention should be paid to the cracking of bottom or crown segments in the segment lining of shield tunnel.

Asymptomatic aortoiliac occlusive disease, while less common compared to other peripheral arterial diseases, presents unique clinical challenges. Our center recently encountered a case involving a patient with chronic occlusion of the distal abdominal aorta and bilateral iliac arteries. Remarkably, this patient had developed an extensive network of collateral circulation, effectively compensating for the reduced blood supply to the pelvic and lower limb areas. This adaptive physiological response resulted in the patient exhibiting no significant clinical symptoms. To reveal the most effective diagnostic and treatment strategies for asymptomatic peripheral artery disease patients to avoid complications and other challenges, more clinical studies are needed in the future.

Abstract Previous studies revealed that MIR155HG possessed an oncogenic role in many types of tumors including lung adenocarcinoma (LUAD), along with higher expression in tumors. However, in our study, we observed a positive correlation between MIR155HG expression and overall survival across different cohorts. The transferred PBMC on the NCG mouse model abrogated the tumor intrinsic oncogenic role of MIR155HG in LUAD. Upregulation of MIR155HG positively correlated with CD8+ T cell infiltration both in vitro and in vivo, as well as LUAD tissues. Mechanistically, we revealed that MIR155HG increased the cytokine CCL5 expression at the transcriptional level, which depended on the interaction between MIR155HG and YBX1 protein, a novel transcription factor of CCL5, resulting in the more protein stability of YBX1 through dampening ubiquitination. Additionally, we also observed that MIR155 could increase PD-L1 expression to hamper the activity of recruited CD8+ T cells, which could be rescued through PD-L1 mAb addition. Finally, we uncovered that patients with high MIR155HG expression had a higher response rate to immunotherapy, and the combination of MIR155HG overexpression and PD-L1 mAb increased the efficacy of PD-L1 mAb. Together, our study provides a novel biomarker and potential combination treatment strategy for patients who received immunotherapy.