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Abstract Vetiveria zizanioides, renowned for its robust stability and exceptional capacity to sequester heavy metals, has garnered widespread application in tailings ecological restoration efforts. Arbuscular mycorrhizal fungi (AMF), which are capable of forming symbiotic relationships with more than 80% of terrestrial plant roots, play a pivotal role in enhancing plant nutrient uptake and bolstering resilience. In this study, we conducted a comprehensive investigation into the physiological and biochemical responses of Vetiveria zizanioides subjected to varying levels of copper stress (with copper concentrations ranging from 0 mg/kg to 400 mg/kg), with or without AMF inoculation. Additionally, we performed nontargeted metabonomic analyses to gain deeper insights into the metabolic changes that occur in vetiver grass under AMF inoculation and copper stress. Our findings revealed that Vetiveria zizanioides inoculated with AMF consistently demonstrated superior growth performance across all copper stress levels compared with noninoculated counterparts. Using nontargeted metabonomic analyses, inoculation with AMF affects the metabolism of phenylalanine and related pathways in vetiver as well as contributing to the promotion of the formation of phytochelatins (PCs) from glutamate, thereby alleviating copper stress. The results highlight the potential of AMF-inoculated Vetiveria zizanioides as a promising bioremediation tool capable of effectively mitigating the adverse effects of heavy metal pollution.

Low tumor immunogenicity, immunosuppressive tumor microenvironment, and bacterial infections have emerged as significant challenges in postsurgical immunotherapy and skin regeneration for preventing melanoma recurrence. Herein, an immunotherapeutic hydrogel booster (GelMA-CJCNPs) was developed to prevent postoperative tumor recurrence and promote wound healing by incorporating ternary carrier-free nanoparticles (CJCNPs) containing chlorine e6 (Ce6), a BRD4 inhibitor (JQ1), and a glutaminase inhibitor (C968) into methacrylic anhydride-modified gelatin (GelMA) dressings. GelMA-CJCNPs reduced glutathione production by inhibiting glutamine metabolism, thereby preventing the destruction of reactive oxygen species generated by photodynamic therapy, which could amplify oxidative stress to induce severe cell death and enhance immunogenic cell death. In addition, GelMA-CJCNPs reduced M2-type tumor-associated macrophage polarization by blocking glutamine metabolism to reverse the immunosuppressive tumor microenvironment, recruiting more tumor-infiltrating T lymphocytes. GelMA-CJCNPs also downregulated IFN-γ-induced expression of programmed cell death ligand 1 to mitigate acquired immune resistance. Benefiting from the amplified systemic antitumor immunity, GelMA-CJCNPs markedly inhibited the growth of both primary and distant tumors. Moreover, GelMA-CJCNPs demonstrated satisfactory photodynamic antibacterial effects against Staphylococcus aureus infections, thereby promoting postsurgical wound healing. Hence, this immunotherapeutic hydrogel booster, as a facile and effective postoperative adjuvant, possesses a promising potential for inhibiting tumor recurrence and accelerating skin regeneration.

Oral cancer, a common malignancy of the head and neck, is a major public health concern due to its high incidence and low five-year survival rate. Treatment and prognosis are influenced by several factors, with timely medical consultation being of paramount importance. Studies have shown that delays of more than three months between the onset of symptoms and seeking medical attention significantly increase the risk of oral cancer progression to advanced stages. This paper provides a comprehensive review of the current literature on delayed medical consultation in oral cancer patients, both nationally and internationally. It analyzes various factors that may influence patient behavior, including oral cancer awareness and knowledge, psychosocial variables, health literacy, socioeconomic status, and oral examination habits. It also examines the role of screening programs in increasing early detection rates. This review provides valuable insights for understanding and addressing the issue of delayed medical consultation among oral cancer patients in China, and provides a basis for developing effective prevention and control strategies.

Abstract Background Clinically relevant postoperative pancreatic fistula (CR-POPF) is a common postoperative complication after pancreaticoduodenectomy (PD) and is associated with severe complications. Drainage is an effective method to treat POPF and prevent POPF-related complications. However, controversy still exists about whether different drainage methods reduce the incidence or the severity of POPF after PD. Methods A closed suction drainage was placed posterior to pancreaticojejunostomy in PD except for other routine drainage placements. A retrospective study was conducted to calculate the incidence and severity of CR-POPF and POPF-related complications and to evaluate the efficacy of this drainage method. Results 295 patients who underwent PD were enrolled in this study, 130 patients in the trial group and 165 patients in the control group. The two groups were comparable in both preoperative and intraoperative characteristics. The overall incidence of CR-POPF was similar between the two groups. The trial group had a significantly decreased incidence of grade C POPF (0% vs. 3.6%, p

Abstract Background Cervical ripening is a multifactorial outcome, and the association between cervical ripening and vaginal microbiota remains unexplored in term primiparous women. A new sequencing technology, microbiome 2bRAD sequencing (2bRAD-M) that provides a higher level of species discrimination compared to amplicon sequencing. We applied 2bRAD-M to analyze the vaginal microbiota in a population with variations in cervical ripeness and to explore potential microbiota factors influencing cervical ripening. Methods A total of 30 full-term primigravid women participated in this study, with 15 belonging to the low scoring group of cervical ripeness and 15 to the high scoring group. Clinical information was collected from the participants, and the vaginal microbiota and community structure of both groups were analyzed using 2bRAD-M sequencing. Microbiota diversity and differential analyses were conducted to explore potential factors influencing cervical ripening. Results A total of 605 species were detected. There was no difference in vaginal microbiota diversity between the two groups, and the vaginal microbial composition was structurally similar. In the two groups, Lactobacillus crispatus and Lactobacillus iners were identified as the two pivotal species through random forest analysis. Concurrent, extensive and close connections between species within the two groups were observed in the correlation analysis, influencing the aforementioned two species. Pairwise comparisons showed that Sphingomonas (P = 0.0017) and three others were abundant in high scoring group, while Alloprevotella (P = 0.0014), Tannerella (P = 0.0033), Bacteroides (P = 0.0132), Malassezia (P = 0.0296), Catonella (P = 0.0353) and Pseudomonas (P = 0.0353) and so on showed higher abundance in low scoring group. Linear discriminant analysis effect size identified 29 discriminative feature taxa. Conclusion For the first time, vaginal microbiota was sequenced using 2bRAD-M. With a relatively simple structure, a more stable vaginal microbiota is associated with higher cervical ripeness, and certain microorganisms, such as Sphingomonas, may play a beneficial role in cervical ripening.

Abstract Chimeric antigen receptor (CAR) T-cell therapy represents a highly efficacious treatment modality demonstrated to enhance outcomes in patients afflicted with malignancies, particularly those enduring relapsed or refractory hematological malignancies. However, the escalating adoption of CAR T-cell therapy has unveiled several life-threatening toxicities, notably cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, and hematological toxicities (HTs), thereby hindering the broad implementation of CAR T-cell therapy. HTs encompass a spectrum of adverse effects, including cytopenias, hemophagocytic lymphohistiocytosis (HLH), coagulopathies, and B-cell aplasia. While our comprehension of the underlying mechanisms governing CRS and ICANS is advancing, the intricate pathophysiology of HTs remains inadequately elucidated. Such knowledge gaps may precipitate suboptimal therapeutic decisions, potentially culminating in substantial medical resource depletion and detriment to patients’ quality of life. In this comprehensive review, based on recent updated findings, we delineate various mechanisms contributing to HTs subsequent to CAR T-cell therapy, explicate manifestations of HTs, and proffer strategic interventions to mitigate this relevant clinical challenge.

Abstract Pancreatic neuroendocrine neoplasms (Pan-NEN) represent a group of highly heterogeneous cancers, characterized by complex and diverse biological behavior. The objective of this study was to systematically investigate the immunological features of the tumor microenvironment (TME) in Pan-NEN, aiming to identify prognostic biomarkers and explore the therapeutic potential of immunotherapy for Pan-NEN. Tumor and adjacent normal tissues were collected from 56 patients with Pan-NEN. Immunohistochemical analysis was conducted on tumor tissues using a panel of monoclonal antibodies targeting key immune markers. The expression levels of these markers were quantitatively assessed and correlated with clinicopathological features and overall survival. Low expression of CD3, CD8, CD4, CD68, CD163, Foxp3, CD56, CD69, GZMB, HLA-1, HLA-II, PD-1, and PD-L1 were observed in the majority of Pan-NEN patient samples. PD-1 expression was positively correlated with CD4 and Foxp3 expression, while PD-L1 expression was positively correlated with CD68, CD163, and Foxp3 expression; HLA-II expression was positively correlated with GZMB expression. Infiltration of lymphocytes (CD3 + or CD8+) and macrophages (CD68 + or CD163+) and expression of PD-1/PD-L1 were more pronounced in poorly differentiated neuroendocrine carcinoma (Pan-NEC) compared to well-differentiated neuroendocrine tumors (Pan-NET), while CD68 and PD-L1 correlated with advanced disease stage. Conversely, HLA-I antigen expression was commonly downregulated in Pan-NEC. Univariate Cox proportional hazard analysis demonstrated that tumor grade, stage; CD4+, CD68+, and CD163 + cell count; and expression of PD-1 and PD-L1 were significantly associated with poor survival outcomes, while the positive expression of HLA-I was correlated with a more favorable survival prognosis. Furthermore, multivariate Cox proportional hazard analyses revealed that tumor grade, stage, and PD-1 expression are independent prognostic factors. The immunological landscape of Pan-NEN offers potential prognostic value and therapeutic targets. The findings suggest that immunotherapy, particularly targeting the PD-1/PD-L1 pathway, may serve as a promising strategy for the treatment of Pan-NEN, especially for Pan-NEC patients.

Sterile and infection-associated inflammatory diseases are becoming increasingly prevalent worldwide. Conventional drug therapies often entail significant drawbacks, such as the risk of drug overdose, the development of drug resistance in pathogens, and systemic adverse reactions, all of which can undermine the effectiveness of treatments for these conditions. Nanomaterials (NMs) have emerged as a promising tool in the treatment of inflammatory diseases due to their precise targeting capabilities, tunable characteristics, and responsiveness to external stimuli. Ultrasound (US), a non-invasive and effective treatment method, has been explored in combination with NMs to achieve enhanced therapeutic outcomes. This review provides a comprehensive overview of the recent advances in the use of US-mediated NMs for treating inflammatory diseases. A comprehensive introduction to the application and classification of US was first presented, emphasizing the advantages of US-mediated NMs and the mechanisms through which US and NMs interact to enhance anti-inflammatory therapy. Subsequently, specific applications of US-mediated NMs in sterile and infection-associated inflammation were summarized. Finally, the challenges and prospects of US-mediated NMs in clinical translation were discussed, along with an outline of future research directions. This review aims to provide insights to guide the development and improvement of US-mediated NMs for more effective therapeutic interventions in inflammatory diseases.

BackgroundIt remains unclear how pre-pregnancy body mass index (BMI) affects preeclampsia in the Chinese population, primarily due to insufficient large-scale research on this topic.ObjectiveThe study aimed to determine the relationship between pre-pregnancy BMI and (severe) preeclampsia in the Chinese population, providing a detailed description of the findings.MethodsThe retrospective study included a total of 75,773 pregnant women registered between 2016 and 2020. These participants were categorized into four groups based on their pre-pregnancy BMI: underweight (BMI

Psoriasis is a chronic inflammatory skin condition characterized by erythematous plaques with white scales. Its pathogenesis is closely linked to oxidative stress and an imbalance in Th1/Th2 immune responses. Current treatments for psoriasis, such as topical agents, systemic therapies and phototherapy, frequently fail to achieve complete remission in clinical settings. Monomethyl fumarate (MMF), which has been approved by the US Food and Drug Administration in 2020 for multiple sclerosis, has demonstrated efficacy in psoriasis management. Additionally, our previous studies have identified aluminum ions as beneficial in psoriasis treatment. This present study investigates the combined therapeutic effects of MMF and aluminum ions and observed that the combination treatment achieves superior efficacy compared to either treatment alone in a psoriasis mouse model through the modulation of the Nrf2/NF-κB signaling pathway, as demonstrated in cellular models. The combination first activates Nrf2 nuclear translocation and induces antioxidant gene expression, followed by the inhibition of NF-κB nuclear translocation and phosphorylation, which reduces Th1 cytokine production and cellular chemotaxis. Concurrently, the treatment elevates Th2 cytokine secretion, thereby increasing the anti-inflammatory response in HaCaT cells. Overall, these findings support the MMF and aluminum ions combination (MMFAL) as a potential therapeutic strategy for psoriasis, effectively diminishing inflammation and oxidative stress.

The vaginal microbiota is proposed to be associated with reproductive health. Exposure to metals during pregnancy is a risk factor for premature rupture of membranes (PROM). PROM can lead to serious maternal complications, thus, identifying the cause and therapeutic targets for it is crucial. However, the role of vaginal microbiota in the association between metals exposure and the risk of PROM are not clear. Based on a prospective birth cohort study including 668 pregnant women, maternal blood levels of 15 metals in the first trimester (n=668) and microbiota of vaginal secretions in the third trimester (n=244) were assessed. The metals that significantly associated with the risk of PROM were screened out via four statistical models, the top three were barium (Ba), chromium (Cr) and thallium (Tl) according to their weight indices. The results from the BKMR model showed a positive association of the mixture (Ba, Cr and Tl) with the risk of PROM. PROM and non-PROM were characterised by different beta diversities, moreover, the relative abundances of Bifidobacterium, Corynebacterium and Collinsella were statistically and negatively related to the risk of PROM [the adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were 0.06 (0.00, 0.82), 0.32 (0.14, 0.74) and 0.50 (0.30, 0.84), respectively]. On the other hand, women with different levels of Ba exposure were also characterised by different beta diversities (p value = 0.047); and blood Ba levels were also negatively associated with the relative abundances of Collinsella; additionally, Cr levels were positively associated with alpha diversity indices [Shannon index: β (95 % CI) = 0.25 (0.01, 0.50); Simpson index: β (95 % CI) = 0.08 (0.00, 0.17), respectively]. The results from mediation analysis showed the proportion of the relationship between Ba exposure and PROM risk mediated by the relative abundance of Collinsella was 26.4 %. Further verification analysis exploring the potential cause of the above phenomenon indicated that the neutrophil count, one of blood inflammation indicators for PROM, was higher in women with the absence of Collinsella (p value = 0.039), moreover, the cumulative hazard of PROM for women with the presence of Collinsella was also significantly lower than that of those without Collinsella (p value = 0.007). Collectively, the changes in the diversity and composition of the bacterial community, especially the reduction in Collinsella abundance caused by metal exposure, may be related to the occurrence of PROM, which provides a new microbiota-based perspective for intervention in metal exposure-related PROM. Confirming these relationships and determining the possible processes at play will require more investigation.

BackgroundNonalcoholic fatty liver disease (NAFLD) has emerged as a significant global health concern, with advanced fibrosis increasing mortality risks. Despite the abundance of dietary guidelines for managing NAFLD, the precise impact of diet quality on mortality among individuals with advanced fibrosis remains elusive. This study aims to explore the influence of five dietary quality indexes on mortality among NAFLD patients and advanced fibrosis patients.MethodsThis study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2018 to assess dietary quality based on the Alternate Mediterranean Diet (aMED), Healthy Eating Index-2020 (HEI-2020), Dietary Approach to Stop Hypertension (DASH), Alternate Healthy Eating Index (AHEI), and Dietary Inflammatory Index (DII). Weighted Cox proportional hazard regression models along with restricted cubic splines and subgroup analyses were employed in this study.ResultsThe analysis encompassed 3,634 NAFLD patients. After a median follow-up of 89 months, it was found that higher scores on the aMED (HR 0.814, 95% CI 0.681–0.972), HEI-2020 (HR 0.984, 95% CI 0.972–0.997), DASH (HR 0.930, 95% CI 0.883–0.979), and AHEI (HR 0.980, 95% CI 0.966–0.995) were associated with lower mortality risks, while DII scores (HR 1.280, 95% CI 1.098–1.493) indicated an increased risk of mortality. Additionally, a nonlinear relationship was identified solely between AHEI scores and all-cause mortality in NAFLD patients. Notably, among patients with advanced fibrosis, HEI-2020 as a categorical variable (T3: HR 0.519, 95% CI 0.280–0.964), DASH as a continuous variable (continuous: HR 0.921, 95% CI 0.849–0.999), AHEI (continuous: HR 0.971, 95% CI 0.945–0.997; T2: HR 0.545, 95% CI 0.310–0.960; T3: HR 0.444, 95% CI 0.245–0.804), and DII (continuous: HR 1.311, 95% CI 1.121–1.534; T3: HR 2.772, 95% CI 1.477–5.202) exhibited significant associations with all-cause mortality. Subgroup analyses revealed an interaction between AHEI scores and sex among NAFLD patients, where higher AHEI scores correlated with lower all-cause mortality in females, but no such association was observed in males. For other dietary quality, subgroup analyses indicated that their relationships with mortality were robust.ConclusionOur study suggests that a high-quality diet could potentially mitigate mortality risk in both NAFLD and advanced fibrosis patients.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) stands as a cornerstone in the treatment of hematological malignancies, recognized for its remarkable efficacy. However, the persistent challenge of graft-versus-host disease (GVHD) continues to represent a significant barrier, often being the leading cause of nonrelapse mortality after allo-HSCT. To address this limitation, hematopoietic stem cell microtransplantation (MST) has emerged as a novel therapeutic strategy that synergistically combines chemotherapy, allo-HSCT, and cellular immunotherapy. This innovative approach is designed to retain the patient’s immune function, promote the establishment of microchimerism, and achieve a potent graft-versus-tumor (GVT) response, all while significantly minimizing the risk of GVHD. MST has primarily been applied in the treatment of hematological malignancies, where it has demonstrated promising outcomes, including marked improvements in complete remission rates, overall survival rates, and progression-free survival rates. Moreover, MST facilitates hematopoietic recovery, decreases the likelihood of infections, and reduces the incidence of GVHD, thus contributing to an improved quality of life for patients. A deeper and more comprehensive understanding of MST’s mechanisms could enhance its clinical utility and integration into standard treatment protocols. This review aims to explore the underlying mechanisms, current clinical applications, and challenges of MST, shedding light on its potential role in advancing the management of hematological malignancies.

Abstract Background Insulin resistance (IR) is prevalent in individuals undergoing peritoneal dialysis (PD) and is related to increased susceptibility to coronary artery disease and initial peritonitis. In recent investigations, correlations have been found between indices of IR and the incidence of all-cause mortality in various populations. However, such correlations have not been detected among individuals undergoing PD. Hence, the present study’s aim was to explore the connections between IR indices and the incidence of all-cause mortality in PD patients. Methods Peritoneal dialysis patients (n = 1736) were recruited from multiple PD centres between January 2010 and December 2021. Cox proportional hazards and restricted cubic spline regression models were used to evaluate the connections between the triglyceride–glucose (TyG) index, triglyceride–glucose/body mass index (TyG–BMI), and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and the occurrence of all-cause mortality. All three IR indices were integrated into the same model to assess the predictive stability. Furthermore, a forest plot was employed to display the findings of the subgroup analysis of PD patients. Results Overall, 378 mortality events were recorded during a median follow-up time of 2098 days. Among PD patients, a higher TyG index, TyG–BMI, and TG/HDL-C ratio were identified as independent risk factors for all-cause mortality according to Cox proportional hazards analyses (hazard ratio (HR) 1.588, 95% confidence interval (CI) 1.261–2.000; HR 1.428, 95% CI 1.067–1.910; HR 1.431, 95% CI 1.105–1.853, respectively). In a model integrating the three IR indices, the TyG index showed the highest predictive stability. According to the forest plot for the TyG index, no significant interactions were observed among the subgroups. Conclusion Significant associations were found between the TyG index, TyG–BMI, and TG/HDL-C ratio and the incidence of all-cause mortality among PD patients. The TyG index may be the most stable of the three surrogate IR markers. Finally, a correlation was identified between IR and the risk of all-cause mortality in patients undergoing PD.

Abstract Background Postoperative complications of pancreaticoduodenectomy (PD) are still a thorny problem. This study aims to verify the preventative impact of T-tube on them. Methods The electronic medical records and follow-up data of patients who received pancreaticoduodenectomy in our center from July 2016 to June 2020 were reviewed. According to whether T tube was placed during the operation, the patients were divided into T-tube group and not-T-tube group. Propensity score matching analysis was performed to minimize selection bias. Results A total of 330 patients underwent PD (Not-T-tube group =226, T-tube group=104). Propensity score matching resulted in 222 patients for further analysis (Not-T-tube group =134, T-tube group=88). Patients' demographics were comparable in the matched cohorts. Significantly higher incidences of clinically relevant postoperative pancreatic fistula (CR-POPF) ((14 (10.45%) VS 20 (22.73%)), P=0.013) were observed in the T-tube group. The total incidence of biliary anastomotic stricture (BAS) was 3.15%. The incidence was slightly lower in the T-tube group, but there was no statistically significant differentiation (6 (4.48%) VS 1 (1.14%), P=0.317). Conclusions It is not feasible to prevent postoperative complications with the application of a T-tube in PD.

In response to the issue that traditional lung nodule detection models cannot dynamically optimize and update with the increase of new data, a new lung nodule detection model—task incremental meta-learning model (TIMLM) is proposed. This model comprises of two loops: the inner loop imposes incremental learning regularization update constraints, while the outer loop employs a meta-update strategy to sample old and new knowledge and learn a set of generalized parameters that adapt to old and new data. Under the condition that the main structure of the model is not changed as much as possible, it preserves the old knowledge that was learned previously. Experimental verification on the publicly available lung dataset showed that, compared with traditional deep network models and mainstream incremental models, TIMLM has greatly improved in terms of accuracy, sensitivity, and other indicators, demonstrating good continuous learning and anti-forgetting capabilities.

Abstract Heart-on-a-chip (HoC) has emerged as a highly efficient, cost-effective device for the development of engineered cardiac tissue, facilitating high-throughput testing in drug development and clinical treatment. HoC is primarily used to create a biomimetic microphysiological environment conducive to fostering the maturation of cardiac tissue and to gather information regarding the real-time condition of cardiac tissue. The development of architectural design and advanced manufacturing for these “3S” components, scaffolds, stimulation, and sensors is essential for improving the maturity of cardiac tissue cultivated on-chip, as well as the precision and accuracy of tissue states. In this review, the typical structures and manufacturing technologies of the “3S” components are summarized. The design and manufacturing suggestions for each component are proposed. Furthermore, key challenges and future perspectives of HoC platforms with integrated “3S” components are discussed. Architecture design concepts of scaffolds, stimulation and sensors in chips.

Self-direction skill (SDS) is an essential 21st-century skill that can help learners be independent and organized in their quest for knowledge acquisition. While some studies considered learners from higher education levels as the target audience, providing opportunities to start the SDS practice by K12 learners is still rare. Further, practicing such skills requires a concrete context and scaffolding during the skill acquisition. This article introduces the Goal Oriented Active Learner (GOAL) system that facilitates SDS acquisition in learners utilizing daily activities as context. The GOAL architecture integrates learning logs from online environments and physical activity logs from wearable trackers to provide a data-rich environment for the learners to acquire and practice their SDS. The GOAL users follow DAPER, a five-phase process model, to utilize the affordances in the system while practicing SDS. We implemented the GOAL system at a K12 public institution in Japan in 2019. Learners used the online environments for extensive reading and smartwatches for tracking walking and sleeping activities. This study analyzes detailed interaction patterns in GOAL while learners planned and monitored their self-directed actions. The results illustrate the strategies for DAPER behaviors that emerge in different activity contexts. We discuss the potentials and challenges of this technology ecosystem that connects learners’ learning logs and physical activity logs, specifically in the K12 context in Japan and, more generally, from the learning analytics research perspective to provide a context to practice SDS.

Skin trauma is a matter of great concern for public health, emphasizing the importance of reconstructing the microenvironment at the trauma site to facilitate tissue regeneration. Therefore, the investigation of innovative wound dressings has significant research and clinical implications. In this study, we prepared a thermosensitive hydrogel based on a hydrophilic-hydrophobic-hydrophilic triblock polycarbonate polymer (PTP), and created a composite hydrogel, PTPH-AZP, by incorporating amorphous zinc phosphate (AZP) nanoclusters. We evaluated the effects of PTPH-AZP on human umbilical vein endothelial cells (HUVECs) and the ability to promote skin wound healing. According to the results, PTPH-AZP was found to promote the proliferation, migration, and tube formation of HUVECs through the sustained release of Zn2+ at appropriate concentrations. In vivo experiments demonstrated that in the early-mid stages of wound healing, PTPH-AZP promotes increases in Platelet Endothelial Cell Adhesion Molecule-1 (CD31) and α-Smooth Muscle Actin (α-SMA) content within the wound area, facilitating accelerated re-epithelialization and enhanced collagen deposition. In later healing stages, epidermal thickness in the PTPH-AZP treated group was significantly improved, aligning with surrounding intact skin with no instances of attenuated or hypertrophic scarring observed. The findings from the in vivo study suggested that PTPH-AZP may have a positive impact on vascularization and wound healing. In conclusion, this study presents a promising strategy for skin wound healing, highlighting the potential of PTPH-AZP as an effective therapeutic approach.

ObjectiveTo analyze the effect of implementing continuity of care for postoperative patients with cervical cancer, to improve the continuity of care model in China, and to provide comprehensive, continuous, and personalized care services for patients.MethodsPubMed, Web of Science, Science Direct, China Knowledge Network, Wanfang database, China Biomedical sources Service System, Wipro, Cochrane Library, Embase, and other databases were searched for relevant sources on the effect of continuity of care on postoperative cervical cancer patients. The Cochrane Handbook of Systematic Evaluation and Revman 5.3 software was used to evaluate the quality of the retrieved sources and perform meta-analysis.ResultsCompared with the control group, extended care could improve patients’ quality of life [SMD=1.35,95%CI(1.05,1.64), P

Purpose Gastrointestinal bleeding is an important gastrointestinal complication among peritoneal dialysis patients and correlated with a higher risk of mortality. Increased uric acid levels are a significant complication for peritoneal dialysis patients and have been associated with an increased risk of hemorrhagic stroke. The objective of the present study was to investigate the relationship between serum uric acid levels and gastrointestinal bleeding in peritoneal dialysis patients.Methods A total of 2498 peritoneal dialysis patients were recruited. Based on the optimal uric acid cutoff value, two groups of patients were divided. We constructed a propensity-score-matched population of 1762 patients by matching sex, age, and body mass index. Survival outcomes between the two groups were compared using adjusted Kaplan–Meier curves. We constructed the restricted cubic splines regression to assess the correlation between levels of uric acid and gastrointestinal bleeding. A multivariate Cox proportional hazards regression was performed to test whether higher levels of uric acid are an independent risk factor for gastrointestinal bleeding. We performed a forest plot to show interaction effects in different subgroups.Results According to restricted cubic splines regression, uric acid levels were positively correlated with the risk of gastrointestinal bleeding events. After adjusted different confounding factors, patients with high levels of uric acid were prone to experience gastrointestinal bleeding (HR 1.868, 95%CI 1.001–3.486). In subgroups, the interaction between higher levels of uric acid and utilizing proton pump inhibitors was significant (P for interaction = 0.034). Further research found that taking proton pump inhibitors could decrease the risk of gastrointestinal bleeding in peritoneal dialysis patients accompanied high levels of uric acid.Conclusion The baseline high levels of uric acid are an independent risk factor for gastrointestinal bleeding in patients undergoing peritoneal dialysis.

Nephrolithiasis is one of the most common diseases in urology, characterized by notable incidence and recurrence rates, leading to significant morbidity and financial burden. Despite its prevalence, the precise mechanisms underlying stone formation remain incompletely understood, thus hindering significant advancements in kidney stone management over the past three decades. Investigating the pivotal biological molecules that govern stone formation has consistently been a challenging and high-priority task. A significant portion of mammalian genomes are transcribed into noncoding RNAs (ncRNAs), which have the ability to modulate gene expression and disease progression. They are thus emerging as a novel target class for diagnostics and pharmaceutical exploration. In recent years, the role of ncRNAs in stone formation has attracted burgeoning attention. They have been found to influence stone formation by regulating ion transportation, oxidative stress injury, inflammation, osteoblastic transformation, autophagy, and pyroptosis. These findings contributes new perspectives on the pathogenesis of nephrolithiasis. To enhance our understanding of the diagnostic and therapeutic potential of nephrolithiasis-associated ncRNAs, we summarized the expression profiles, biological functions, and clinical significance of these ncRNAs in the current review.

IntroductionImmune checkpoint inhibitors (ICIs) have transformed advanced gastric cancer treatment, yet patient responses vary, highlighting the need for effective biomarkers. Common markers, such as programmed cell death ligand-1 (PD-L1), microsatellite instability/mismatch repair (MSI/MMR), tumor mutational burden, tumor-infiltrating lymphocytes, and Epstein–Barr virus, face sampling challenges and high costs. This study seeks practical, minimally invasive biomarkers to enhance patient selection and improve outcomes.MethodsThis multicenter retrospective study analyzed 617 patients with advanced gastric or gastroesophageal junction cancer treated with programmed cell death protein-1 (PD-1)/PD-L1 inhibitors from January 2019 to March 2023. Clinical data and peripheral blood marker data were collected before and after treatment. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included the objective response rate (ORR) and disease control rate (DCR). Least absolute shrinkage and selection operator (LASSO)-Cox and LASSO logistic regression analyses identified independent factors for OS, PFS, and ORR. Predictive nomograms were validated using receiver operating characteristic (ROC) curves, areas under the curve (AUCs), C-indices, and calibration curves, with clinical utility assessed via decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).ResultsOS-related factors included treatment line, T stage, ascites, pretreatment indirect bilirubin (pre-IBIL), posttreatment CA125, CA199, CA724, and the PLR. PFS-related factors included treatment lines, T stage, metastatic sites, pre-IBIL, posttreatment globulin (GLOB), CA125, and CA199 changes. ORR-related factors included treatment line, T stage, N stage, liver metastasis, pretreatment red cell distribution width-to-platelet ratio (RPR), CA125, and CA724 changes. The nomograms showed strong predictive performance and clinical utility.ConclusionsEarly treatment, lower T stage, the absence of ascites, and lower pre-IBIL, post-CA125, CA199, CA724, and PLR correlate with better OS. Factors for improved PFS include early treatment, lower T stage, fewer metastatic sites, and lower pre-IBIL, post-GLOB, and post-CA125 levels. Nomogram models can help identify patients who may benefit from immunotherapy, providing valuable clinical guidance.

Abstract Breast cancer patients may initially benefit from cytotoxic chemotherapy but experience treatment resistance and relapse. Chemoresistant breast cancer stem cells (BCSCs) play a pivotal role in cancer recurrence and metastasis, however, identification and eradication of BCSC population in patients are challenging. Here, an mRNA‐based BCSC signature is developed using machine learning strategy to evaluate cancer stemness in primary breast cancer patient samples. Using the BCSC signature, a critical role of polyamine anabolism in the regulation of chemotherapy‐induced BCSC enrichment, is elucidated. Mechanistically, two key polyamine anabolic enzymes, ODC1 and SRM, are directly activated by transcription factor HIF‐1 in response to chemotherapy. Genetic inhibition of HIF‐1‐controlled polyamine anabolism blocks chemotherapy‐induced BCSC enrichment in vitro and in xenograft mice. A novel specific HIF‐1 inhibitor britannin is identified through a natural compound library screening, and demonstrate that coadministration of britannin efficiently inhibits chemotherapy‐induced HIF‐1 transcriptional activity, ODC1 and SRM expression, polyamine levels, and BCSC enrichment in vitro and in xenograft and autochthonous mouse models. The findings demonstrate the key role of polyamine anabolism in BCSC regulation and provide a new strategy for breast cancer treatment.

Chinese urban development has entered the stage of stock planning, and as an important part of urban public space, the construction of street space has a direct impact on urban development. High-quality street space contributes to sustainable urban development.High-quality street spaces are highly important for constructing vibrant and sustainable cities. Taking Jiaozuo city, a medium-sized city, as an example, this article establishes an evaluation index system for commercial street space quality from the aspects of external characterization and objective material space and uses the Pearson correlation coefficient to explore the influencing factors of urban commercial street space quality. This study finds that (1) crowd activities on commercial streets have different temporal and spatial patterns on weekdays and days off; (2) the external characterization of urban street space quality has a significant positive correlation with objective material spatial elements such as the density of public transportation stops, functional density, functional mixing, interface continuity, and spatial green visibility rate; (3) the enhancement of street accessibility and fine-tuning of functions are key to improving the spatial quality of commercial streets.This study provides theoretical basis and ideas for improving the spatial quality of commercial streets in medium-sized cities in China and promoting sustainable urban development.

Abstract Background The primary duodenal gastrointestinal stromal tumor (GIST) is a rare type of gastrointestinal tract tumor. Limited resection (LR) has been increasingly performed for duodenal GIST. However, only a few studies reported minimally invasive limited resection (MI-LR) for primary duodenal GIST. Methods The clinical data of 33 patients with primary duodenal GIST from December 2014 to February 2024 were retrospectively analyzed including 23 who received MI-LR and 10 who received laparoscopic or robotic pancreaticoduodenectomy (LPD/RPD). Results A total of 33 patients with primary duodenal GIST were enrolled and retrospectively reviewed. Patients received MI-LR exhibited less OT (280 vs. 388.5min, P=0.004), EBL (100 vs. 450ml, P

Abstract Plant species like the Venus flytrap possess unique abilities to intelligently respond to various external stimuli, ensuring successful prey capture. Their nerve-devoided structure provides valuable insights for exploring natural intelligence and constructing intelligent systems solely from materials, but limited knowledge is currently available and the engineering realization of such concept remains a significant challenge. Drawing upon the flytrap’s action potential resulting from ion diffusion, we propose a signal accumulation/attenuation model and a corresponding liquid metal-based logic module, which operates on the basis of the shape change of liquid metal within a sodium hydroxide buffer solution. The module itself exhibits memory and counting properties without involving any other electronic components, intelligently responding to various stimulus sequences, and reproducing the flytrap’s most logical function. We also demonstrate and forecast its potential as a moving window integration-based high-pass filter, artificial synapse in neural networks, and other related applications. This research provides a fresh perspective on comprehending the intelligence inherent in nature and its realization through physical structures, which is expected to inspire logic device development in a broad engineering field.

Traffic-related air pollutants (TRAPs) pose significant health risks in megacities, yet fixed monitoring sites often fail to capture their complexity. To characterize the TRAP concentrations which fixed sites cannot address, we employed a mobile platform to effectively capture real-time hyperlocal-scale TRAP variations in Chengdu, China. A 17-day sampling campaign was conducted covering the National Holiday of China and collected ~1.2 × 105 1 Hz paired data. We measured particle number concentration (PNC), black carbon (BC), and nitrogen oxides (NOx) across urban and rural freeway environments to assess the impact of reduced heavy-duty diesel vehicles (HDDVs) during the holiday (i.e., holiday effect). No clear impact of wind direction on TRAP concentrations was found in this study. However, substantial differences (two times) were observed when comparing non-holiday to holiday campaigns. Spearman correlations (0.21–0.56) between TRAPs persistently exceeded Pearson correlations (0.14–0.41), indicating non-linear relationships and suggesting the necessity for data transformations (e.g., logarithms) in TRAP analysis. The comparison of the background subtracted TRAPs concentrations between non-holiday and holidays, revealing approximately a 50% reduction in TRAPs across microenvironments. Among the TRAPs, NOx emerged as a reliable indicator of HDDV emissions. The study provides insights into vehicle fleet composition impacts, paving the way for enhanced exposure assessment strategies.

Microspheres with well-defined hollow structures have been attracting interest due to their unique morphology and fascinating properties. Herein, a strategy for morphology and size control of hollow polymer@silica microspheres is proposed. Multilayer core–shell polymer microspheres, containing substantial carboxyl groups inside, evolve into microspheres with a 304 nm hollow structure after alkali treatment, which are used to construct hollow polymer@silica microspheres by coating the inorganic layer using the layer-by-layer (LBL) and sol–gel methods, respectively. The inorganic shell thickness of hollow polymer@silica microspheres can be adjusted from 15 nm to 33 nm by the self-assembled layers in the LBL method and from 15 nm to 63 nm by the dosage of precursor in the sol–gel method. Compared to the LBL method, the hollow polymer@silica microspheres prepared via the sol–gel method have a uniform and dense inorganic shell, thus ensuring the complete spherical morphology of the microspheres after calcination, even if the inorganic shell thickness is only 15 nm. Moreover, the hollow polymer@silica microspheres prepared via the sol–gel method exhibit improved compression resistance and good opacity, remaining intact at 16,000 psi and providing the corresponding coating with transmittance lower than 35.1%. This work highlights the morphology regulation of microspheres prepared by different methods and provides useful insights for the design of composites microspheres with controllable structures.

Introduction Blended learning is a teaching approach that integrates online self-learning and classroom teaching. It emphasizes students’ self-directed learning, actively engaging, as well as communication and collaboration. Blended learning develops the qualities in nursing undergraduate students with problem-solving ability, clinical thinking, and communication skills as nurses have. Currently, learners’ experience has become an important factor in determining the success of blended learning. Aim To learn about the experiences and perceptions of undergraduate nursing students regarding blending learning in pediatric nursing. Methods A mixed methods design beginning with a quantitative data collection and analysis phase to inform the subsequent qualitative phase was utilized. This study was conducted among undergraduate nursing students at one university in China. In the quantitative study phase, a convenience sample of 59 students completed the online survey while the qualitative study phase included nine students recruited by purposive sampling. The qualitative data were collected using individual semistructured in-depth interviews. Audio data were transcribed and subjected to thematic analysis. The findings from those two phases were integrated into the final analysis. Results The majority (89.8%) of students reported satisfaction with blended learning. Among various teaching methods, case-based learning (CBL) was the most preferred (98.3%). Regarding the qualitative data, students reported positive experiences with blended learning including well-organized course structure, resourceful course content, and high teacher quality. They stated that blended learning improved the learning outcomes such as improving problem-solving ability and developing clinical thinking. They also provided suggestions for achieving better learning outcomes, including providing stressful learning activities, optimizing online course design, and improving the quality of group learning. Conclusions The blended learning model of pediatric nursing based on the Community of Inquiry framework provides a positive learning experience for nursing undergraduate students. However, ongoing assessment and improvement of the blended learning process are also needed.

Abstract Membranes with precise Li+/Na+ and Li+/K+ separations are imperative for lithium extraction from brine to address the lithium supply shortage. However, achieving this goal remains a daunting challenge due to the similar valence, chemical properties, and subtle atomic‐scale distinctions among these monovalent cations. Herein, inspired by the strict size‐sieving effect of biological ion channels, a membrane is presented based on nonporous crystalline materials featuring structurally rigid, dimensionally confined, and long‐range ordered ion channels that exclusively permeate naked Li+ but block Na+ and K+. This naked‐Li+‐sieving behavior not only enables unprecedented Li+/Na+ and Li+/K+ selectivities up to 2707.4 and 5109.8, respectively, even surpassing the state‐of‐the‐art membranes by at least two orders of magnitude, but also demonstrates impressive Li+/Mg2+ and Li+/Ca2+ separation capabilities. Moreover, this bioinspired membrane has to be utilized for creating a one‐step lithium extraction strategy from natural brines rich in Na+, K+, and Mg2+ without utilizing chemicals or creating solid waste, and it simultaneously produces hydrogen. This research has proposed a new type of ion‐sieving membrane and also provides an envisioning of the design paradigm and development of advanced membranes, ion separation, and lithium extraction.

Abstract Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as the microbiota–gut–brain axis (MGBA). The MGBA influences the host's nervous system development, emotional regulation, and cognitive function through neurotransmitters, immune modulation, and metabolic pathways. Factors like diet, lifestyle, genetics, and environment shape the gut microbiota composition together. Most research have explored how gut microbiota regulates host physiology and its potential in preventing and treating neurological disorders. However, the individual heterogeneity of gut microbiota, strains playing a dominant role in neurological diseases, and the interactions of these microbial metabolites with the central/peripheral nervous systems still need exploration. This review summarizes the potential role of gut microbiota in driving neurodevelopmental disorders (autism spectrum disorder and attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's and Parkinson's disease), and mood disorders (anxiety and depression) in recent years and discusses the current clinical and preclinical gut microbe‐based interventions, including dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation. It also puts forward the current insufficient research on gut microbiota in neurological disorders and provides a framework for further research on neurological disorders.

Objective: To investigate the effects of excessive light exposure during gestation on intrauterine development and early growth of neonates in rats. Methods: Pregnant rats were randomly allocated to three groups: the constant light exposure group, non-light exposure group and control group. Blood samples were collected from the tail vein to analyze melatonin and cortisol levels. Weight, daily food and water consumption were recorded. Uterine weight, placental weight and placental diameter were measured on gestational day 19. Natural birth and neonate growth were also monitored. The expression of NR1D1(nuclear receptor subfamily 1 group D member 1) in offspring’s SCN (suprachiasmatic nuclei), liver and adipose tissue was measured. Expression of NR1D1, MT1(melatonin 1 A receptor) and 11β-HSD2 (placental 11β-hydroxysteroid dehydrogenase type 2) in placenta was also measured. Finally, the expression of MT1 and 11β-HSD2 in NR1D1 siRNA transfected JEG-3 cells was evaluated. Results: There were no significant differences in maternal weight gain, pregnancy duration, uterine weight, placental body weight, placental diameter, fetal number among three groups. There were no significant differences in weights or lengths of offspring at birth. Compared to other two groups, constant light exposure group showed significantly more rapid growth of offspring in 21st day post-birth. The expression of NR1D1 in SCN, liver and adipose tissues of offspring was not significantly different among three groups. The maternal serum melatonin and cortisol levels of the constant light exposure group were lower and higher than other two groups, respectively. The expressions of NR1D1, MT1 and 11β-HSD2 were all decreased in placenta of the constant light exposure group. The expression of MT1 and 11β-HSD2 in JEG-3 cells were decreased after NR1D1 siRNA transfection. Conclusion: Excessive light exposure during pregnancy results in elevated cortisol and reduced melatonin exposure to fetuses in uterus, potentially contributing to an accelerated early growth of offspring in rats.

BackgroundCardiovascular disease (CVD) is a leading cause of global mortality, with atherosclerosis (AS) contributing to its pathological basis. Inflammation plays a critical role in the pathophysiological process of AS, and the NOD-like receptor protein 3 (NLRP3) inflammasome has been extensively studied in this context. This study aimed to analyze the research status of the NLRP3 inflammasome in cardiovascular disease and provide research directions for further exploration in this field.MethodsUsing the “Bibliometrix” and “CiteSpace” software, a total of 516 articles were retrieved from the Web of Science (WoS) database published between 2012 and 2023. The search query used the keywords “[“CVD” OR “cardiovascular disease”] AND [“NLRP3 inflammasome “OR “NLRP3”]”. Visual analysis was performed on authors, countries, institutions, journal sources, keywords, references, and future trends.ResultsA total of 516 English articles were retrieved, showing an overall upward trend in annual publication volume with slight fluctuations. China, the United States, and Europe were the countries and regions with the highest number of published articles. Among them, China had the highest article count (170), while the United States had the highest citation count (18,664), centrality score (0.43), and h-index (90), indicating its influential role in this research area. These countries also possessed elite institutions, professional researchers, and high-impact journals, making them leading contributors in this field. The main pathogenic mechanisms of the NLRP3 inflammasome in CVD were identified as “oxidative stress”, “pyroptosis”, and “inflammation”. The most frequently studied signaling pathways included “NF-κB”, “IL-1”, and “C-reactive protein”. The most studied disease types were coronary heart disease, atherosclerosis, metabolic syndrome, and myocardial infarction. Additionally, research on the correlation between cholesterol markers and inflammatory indicators associated with NLRP3 inflammasome in CVD risk assessment has gained significant momentum, with the main mechanism being NLRP3/IL-6/hs-CRP and cholesterol lipoproteins emerging as a major keyword in this context.ConclusionThis study provides valuable insights into the research hotspots and emerging trends of the NLRP3 inflammasome in cardiovascular disease. The findings offer guidance for researchers and scholars in this field and facilitate the exploration of new research directions.

AimThis study aimed to systematically dissect the role of Scinderin (SCIN) in tumorigenesis.MethodsBioinformatics techniques were employed based on cancer data from TCGA, ENCORI, HPA, GEPIA2, UALCAN, Kaplan-Meier plotter, TIMER, TISIDB, cBioPortal, HCCDB, GeneMANIA and LinkedOmics database. Experiments in vitro and in vivo were conducted to dissect the role of SCIN in liver hepatocellular carcinoma (LIHC).ResultsSignificantly differential expression of SCIN was found in nine types of cancers, including LIHC. Through pan-cancer analysis, the correlations between SCIN expression with prognosis and immune cell infiltration were proven, especially in LIHC, ovarian serous cystadenocarcinoma and lung adenocarcinoma. The highest frequency of alteration in SCIN (6.81%) was seen in patients with uterine corpus endometrial carcinoma, in which “mutation” was the predominant type, with a frequency of about 5.29%; meanwhile, S673F and S381Y were the two most frequent mutation sites. Furthermore, the abnormal expression of SCIN exhibited a strong relationship with immune cell subtypes, immune checkpoint genes, tumor mutation burden, microsatellite instability, neoantigen, molecular subtypes, mismatch repair signatures and DNA methyl-transferase in different cancer types. Through comparative analysis, we discovered that SCIN was dramatically up-regulated in LIHC, and associated with poor survival. Experiments in vitro and in vivo suggested the knockdown of SCIN could suppress tumor cell proliferation and improve the survival rate partly in animal models.ConclusionThis study reveals SCIN may be a promising biomarker for prognosis and treatment in certain cancers, especially in LIHC.

We employ the block negative dislocation model to invert the distribution of fault coupling and slip rate deficit on the different segments of the Tanlu (Tancheng-Lujiang) fault zone, according to the GPS horizontal velocity field from 1991 to 2007 (the first phase) and 2013 to 2018 (the second phase). By comparing the deformation characteristics results, we discuss the relationship between the deformation characteristics with the M earthquake in Japan. The results showed that the fault coupling rate of the northern section of Tancheng in the second phase reduced compared with that in the first phase. However, the results of the two phases showed that the northern section of Juxian still has a high coupling rate, a deep blocking depth, and a dextral compressive deficit, which is the enrapture section of the 1668 Tancheng earthquake. At the same time, the area strain results show that the strain rate of the central and eastern regions of the second phase is obviously enhanced compared with that of the first phase. The occurrence of the great earthquake in Japan has played a specific role in alleviating the strain accumulation in the middle and south sections of the Tanlu fault zone. The results of the maximum shear strain show that the shear strain in the middle section of the Tanlu fault zone in the second phase is weaker than that in the first phase, and the maximum shear strain in the southern section is stronger than that in the first phase. The fault coupling coefficient of the south Sihong to Jiashan section is high, and it is also the unruptured section of historical earthquakes. At the same time, small earthquakes in this area are not active and accumulate stress easily, so the future earthquake risk deserves attention.

Abstract Background This study aimed to investigate the potential associations between alveolar bone thickness, bucco-palatal inclination of maxillary lateral incisors, and lateral incisor root resorption in patients with unilateral maxillary impacted canines (UMICs). Methods A total of three hundred and five subjects (120 males, 185 females; mean age, 16.39 years; standard deviation, 4.04) with UMICs were included. Canine position and root resorption were assessed using CBCT. UMICs were divided into palatal, buccal and mid-alveolus groups (PICs, BICs and MAICs), with 117, 137 and 51 subjects, respectively. Alveolar bone thickness and bucco-palatal inclination of lateral incisors were measured using the Dolphin software. Results The prevalence of lateral incisor root resorption was significantly lower in the BICs (13.9%) than MAICs (29.4%) and PICs (29.1%). Alveolar bone thickness of the apical area was smaller in UMICs with lateral incisor root resorption than no resorption in both PICs (8.33 ± 1.64 vs 10.53 ± 2.55 mm) and BICs (8.94 ± 1.85 vs 10.76 ± 2.28 mm). Furthermore, lateral incisors on the impacted side were more buccally inclined in PICs with lateral incisor root resorption than no resorption, while in both BICs and MAICs, there was no statistical difference between lateral incisor root resorption than no resorption. Moreover, alveolar bone thickness of the apical area, rather than bucco-palatal inclination of lateral incisors, was significantly correlated with lateral incisor root resorption both in PICs and BICs. Conclusions Lateral incisor root resorption is less common in BICs. Thinner alveolar bone thickness at the apical area of lateral incisors can be considered as a potential risk factor for lateral incisor root resorption in UMICs.

Abstract Background Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. Methods This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. Discussion This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. Trial registration ChiCTR1800017646.

Abstract Purpose To create radiomics signatures based on habitat to assess the instant response in lung metastases of colorectal cancer (CRC) after radiofrequency ablation (RFA). Methods Between August 2016 and June 2019, we retrospectively included 515 lung metastases in 233 CRC patients who received RFA (412 in the training group and 103 in the test group). Multivariable analysis was performed to identify independent risk factors for developing the clinical model. Tumor and ablation regions of interest (ROI) were split into three spatial habitats through K-means clustering and dilated with 5 mm and 10 mm thicknesses. Radiomics signatures of intratumor, peritumor, and habitat were developed using the features extracted from intraoperative CT data. The performance of these signatures was primarily evaluated using the area under the receiver operating characteristics curve (AUC) via the DeLong test, calibration curves through the Hosmer-Lemeshow test, and decision curve analysis. Results A total of 412 out of 515 metastases (80%) achieved complete response. Four clinical variables (cancer antigen 19–9, simultaneous systemic treatment, site of lung metastases, and electrode type) were utilized to construct the clinical model. The Habitat signature was combined with the Peri-5 signature, which achieved a higher AUC than the Peri-10 signature in the test set (0.825 vs. 0.816). The Habitat+Peri-5 signature notably surpassed the clinical and intratumor radiomics signatures (AUC: 0.870 in the test set; both, p

Abstract Background The risk factors associated with niche on the cesarean scar have been reported, however, the degree of these factors associated with large niche and the accumulation effects of these risk factors on the development of large niche are unclear. Methods Large niche was evaluated by transvaginal sonography during mid-follicular phase. Logistic regression model was used to assess 32 risk factors by univariate analysis. Then, a scoring model based on the screened risk factors was generated. The performance of this model was evaluated by area under curve (AUC). Finally, the scoring model was applied in 123 women to assess the external validation. Result(s) In the training cohort study, 163 women were diagnosed with large niche. The final scoring model involves eight risk factors with the rating scores including age at delivery (30–34 years: 1 point; ≥ 35 years: 4.5 points), retroflexed uterus (8.5 points), meconium-stained amniotic fluid (4.5 points), twice CSs (4.0 points), postpartum endometritis (4.5 points), premature rupture of membranes (2.5 points), intrahepatic cholestasis of pregnancy (mild to moderate: 3 points; severe: 6.5 points), and cervical dilatation (1-3 cm: 2.0 points; 4-10 cm: 4.5 points). The accumulation effect with a cut-off value of 8.0 in the scoring was associated with the large niche after CS. Conclusion(s) This is the first scoring model to objectively quantify the risk of a large niche after CS. Optimal risk factors control by avoiding high score factors and multiple factors accumulation may eliminate the risk of large niche development.

To investigate the mechanism of rockburst prevention by spraying water onto the surrounding rocks, 15 experiments are performed considering different water absorption levels on a single face. High-speed photography and acoustic emission (AE) system are used to monitor the rockburst process. The effect of water on sandstone rockburst and the prevention mechanism of water on sandstone rockburst are analyzed from the perspective of energy and failure mode. The results show that the higher the absorption degree, the lower the intensity of the rockburst after absorbing water on single side of sandstone. This is reflected in the fact that with the increase in the water absorption level, the ejection velocity of rockburst fragments is smaller, the depth of the rockburst pit is shallower, and the AE energy is smaller. Under the water absorption level of 100%, the magnitude of rockburst intensity changes from medium to slight. The prevention mechanism of water on sandstone rockburst is that water reduces the capacity of sandstone to store strain energy and accelerates the expansion of shear cracks, which is not conducive to the occurrence of plate cracking before rockburst, and destroys the conditions for rockburst incubation.

Abstract Background The global issue of low breastfeeding rates has been widely reported. Quantitative studies have shown the positive effects of peer support on breastfeeding. However, the experiences of mothers who receive breastfeeding peer support have been found to vary. To date, no systematic qualitative summary has been conducted to document the impact of peer support, nor to provide advice for its implementation from the perspective of breastfeeding mothers. This review aims to systematically synthesize qualitative findings on mothers’ experiences of breastfeeding peer support to provide evidence for optimizing peer support services and ultimately enhancing their role in promoting breastfeeding. Methods PubMed, Embase, Cochrane Library, Ovid, Web of Science, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang Datebase, VIP Database and Chinese Biomedical Database (CBM) were searched from the inception of each database until January 2023, to collect qualitative studies and mixed methods studies that included qualitative findings on mothers’ experiences with breastfeeding peer support. The Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) was used to extract data and evaluate the quality of the included articles. The meta-integration method was used to explain and integrate the research findings. The review process was carried out by two authors independently, and the disagreements were resolved through consensus. Results A total of 15 articles were included in the study, consisting of 13 qualitative studies and 2 mixed methods studies. The analysis identified four integrated themes: (1) obtaining psycho-emotional support; (2) acquiring knowledge and skills; (3) expectations for breastfeeding peer support; and (4) feeding perceptions and behavior change. It should be noted that the articles reviewed are in English and mostly originate from developed countries or regions. Therefore, the generalizability of the integrated findings to underdeveloped regions or non-English speaking countries may be limited. Conclusion Mothers perceived that peer support had a positive impact on breastfeeding. To improve the effectiveness of peer support in promoting breastfeeding, it is important to consider the individual needs of each mother. It is recommended that peer support services should be standardized in the future, including the accreditation, training, supervision, and management of peer supporters.

Introduction: Spleen-preserving distal pancreatectomy (SPDP) can be carried out by the Kimura technique (KT) or Warshaw technique (WT). This study aimed to evaluate the long-term post-operative outcomes of the two minimally invasive SPDP methods under the 'Kimura-first' strategy with a particular focus on the haemodynamic changes in the splenogastric circulation. Patients and Methods: The electronic medical records and follow-up data of patients who underwent minimally invasive SPDP in our centre from March 2016 to July 2022 were reviewed. The haemodynamic changes in splenogastric circulation were monitored by post-operative computed tomography (CT) images, and the risks they caused were assessed by long-term follow-up. Results: A total of 112 patients (KT = 93 and WT = 19) were included in the study. The tumour size in the WT group was significantly larger than that in the KT group (P = 0.02). We also found less blood loss for patients who underwent KT (P = 0.02). The occurrence of gastric varices was significantly higher in the WT group (P = 0.022). There was no gastrointestinal bleeding in either group. There were two cases of splenic infarction in the WT group (11.1%), and the incidence was higher than that in the KT group (P = 0.026). The infarct area gradually decreased during periodic CT examinations and disappeared completely at the last review. The two groups of patients had similar results across the 15 items in three areas of the quality of life questionnaire. Conclusions: The 'Kimura-first' strategy, in which the WT is used as an alternative to the KT when the splenic vessels cannot be safely preserved, is feasible, and safe for minimally invasive SPDP.

The Arctic river basins, among the most sensitive regions to climate warming, are experiencing rapid temperature rise and permafrost thawing that profoundly affect their hydrological and hydrochemical systems. However, our understanding of chemical export from Arctic basins to oceans remains limited due to scarce data, particularly in permafrost-dominated regions. This study examines the spatiotemporal variations and seasonal dynamics of major ions (Na+, K+, Mg2+, Ca2+, Cl−, SO42−) and dissolved organic carbon (DOC) concentrations across three river basins with varying permafrost extents: the Severnaya Dvina (2006–2008, 2012–2014), the Pechora (2016–2019) and the Taz Rivers (2016–2020). All the data were sourced from published Chemical Geological researches and were taken from Mendeley and PANGAEA datasets. Our results showed that DOC concentrations ranged from 1.75 to 26.40 mg/L, with the Severnaya Dvina River exhibiting the highest levels of DOC concentrations, alongside significantly elevated ion concentrations compared to the other two basins. A positive correlation was observed between DOC concentrations and river discharge, with peaks during the spring flood and summer baseflow due to leaching processes. The Severnaya Dvina and Pechora Rivers exhibited the highest DOC values during the spring flood, reaching 26.40 mg/L and 8.07 mg/L, respectively. In contrast, the Taz River had the highest runoff during the spring flood season, but the DOC concentration reached its highest value of 11.69 mg/L in the summer. Specifically, a 1% increase in river discharge corresponded to a 1.25% rise in DOC concentrations in the Severnaya Dvina River and a 1.04% increase in the Pechora River, while there was no significant correlation between runoff and DOC concentrations in the Taz River. Major ion concentrations demonstrated a negative correlation with river discharge, remaining relatively high during winter low-flow period. A robust power-law relationship between river discharge and concentration of DOC and major ions was observed, with distinct variations across the three river basins depending on permafrost extent. The Pechora and Taz Rivers, characterized by extensive permafrost, exhibited increasing trends in river discharge and DOC concentrations, accompanied by decreasing major ion concentrations, whereas the non-permafrost-dominated Severnaya Dvina River basin showed the opposite pattern. The Taz River, with the most extensive permafrost, also displayed a delayed DOC peak and more complex seasonal ion concentration patterns. These findings highlight the importance of varying permafrost extents and their implications for water quality and environmental protection in these vulnerable regions.

Ecosystem service value (ESV) assessment is a crucial indicator of regional ecological quality and ecological management effectiveness. Ecosystem services (ES) provide the environmental foundation for human existence and social advancement. However, the future course of land use change (LUC) in urban agglomerations and its implications for human society remains uncertain, which presents a challenge to maintaining a balance between ecological service functions and regional socioeconomic growth. This paper took the Beijing-Tianjin-Hebei (BTH) urban agglomeration as an example and used the future land use simulation (FLUS) model to project the spatial distribution of land use under the natural development scenario (NDS), food security scenario (FSS), and ecological priority scenario (EPS) of BTH in 2030, 2040, and 2050. Next, the changes to ESV under various scenarios were investigated through the equivalent coefficient method. In order to make more targeted recommendations for regional development, the study also used hotspot analyses to explore the impacts of LUCs on ESV. The results showed that: (1) from 2000 to 2020, the LUC in the BTH was dramatic and mainly focused on the interconversions among the three land use categories of cropland, grassland, and built-up land. The total ESV demonstrated the tendency to decrease from CNY 386,859.89 × 106 in 2000 to CNY 371,968.78 × 106 in 2020. (2) Compared with 2020, the ESV in BTH in 2050 under the FSS loses 16,568.78 × 106 CNY, followed by the NDS (CNY 10,960.84 × 106), while the ESV under the EPS increases by CNY 9373.74 × 106. The results of the scenario simulation showed that there was significant variability in ESV under different political orientations. (3) Hotspot analysis indicated that the ESV changes were clustered in the northeastern part and the eastern coastal region of the BTH. On this basis, we identified Chengde, Beijing, Tianjin, and Zhangjiakou as the key cities to focus on and made meaningful suggestions for their future regional environmental protection and sustainable development. This research can serve as a guide in creating sustainable BTH development policies and offer fresh perspectives for investigating how land use patterns affect the ecological environment’s regional quality under various policy trajectories.

Abstract Background It has been long known that thyroid hormone regulates placental villi development, which is associated with the occurrence of miscarriage. However, whether abnormal thyroid hormone metabolism and transport in placental villi are involved in miscarriage is still to be verified. Methods Placental villi of elective terminations of pregnancies (ETPs) and miscarriage were collected. Proliferative activity and apoptosis of villi trophoblasts and angiogenesis were detected by TUNEL and immunochemistry. The expressions of thyroid hormone receptors (THRs), transthyretin (TTR), monocarboxylate transporter 8 (MCT8), organic anion transporting polypeptides 1A1 (OATP1A1), deiodinase 2 (Dio2) and Dio3 were examined by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. JEG3 cell was treated with iopanoic acid (IOP), an inhibitor of Dio2 activity, the expressions of Dio2, placenta growth factor (PLGF) and sFlt1 were detected by RT-PCR and Western blot. Results Cell proliferation was suppressed and apoptosis was increased in placental villi cytotrophoblasts of miscarriage. CD34+ vessel number and vascular endothelial growth factor (VEGF) protein abundance were decreased in miscarriage. In miscarriage group, the gene expression of Dio2, Dio3, TTR and THRα, but not THRβ, MCT8 and OATP1A1, were downregulated. The protein abundances of TTR and THRα were downregulated in miscarriage group, but not THRβ. The protein abundance of Dio2 in miscarriage villi was decreased compared with that in ETP. In JEG3 cells, the gene expression of PLGF was decreased and the expression of sFlt1 was increased in IOP treatment; The protein abundance of Dio2 was downregulated but the gene expression of Dio2 was unaffected in IOP treatment. Conclusion Thyroid hormone transport and metabolism in miscarriage were disturbed and may impaired angiogenesis of placental villi, which was associated with the occurrence of miscarriage.

Abstract Exosomes are lipid bilayer vesicles with a diameter of 40–100 nm secreted by almost all cells. They have been found play crucial regulatory roles in various diseases. With the development of exosomes engineering technology, exosome-based drug delivery has also rapidly evolved. Bladder cancer is a worldwide disease with high morbidity and recurrence but lack of funding, so it is also called Cinderella. Some explorations have demonstrated that exosomes are important in the development, prognosis, diagnosis and drug delivery of bladder cancer. With the rapid development of Mass spectrometry and next-generation sequencing, increasing numbers of differentially expressed molecules derived from exosomes have been found in bladder cancer. Exosomes and their contents are largely involved in bladder cancer progression, engineering of these exosomes with the targeted genes improves their potential for drug delivery of bladder cancer. Furthermore, exosomes and their contents are relate to many characteristics of bladder cancer. Herein, we briefly search 59 researches to explore the cargoes encapsuled in exosomes of bladder cancer patients. We also summarize the biogenesis, function, expression profiles, engineering approaches and biological mechanisms of exosomes and their contents for the diagnosis, prognosis and drug delivery for bladder cancer. We aim to make it clear whether exosomes are the glass slippers of Cinderella. Graphical Abstract

Guzheng tune progression involves intricately harmonizing melodic motif transitions. Effectively navigating this vast creative possibility space to expose musically consistent elaborations presents challenges. We develop a specialized large long short-term memory (LSTM) model for generating musically consistent Guzheng tune transitions. First, we propose novel firefly algorithm (FA) enhancements, e.g., adaptive diversity preservation and adaptive swim parameters, to boost exploration effectiveness for navigating the vast creative combinatorics when generating Guzheng tune transitions. Then, we develop a specialized stacked LSTM architecture incorporating residual connections and conditioned embedding vectors that can leverage long-range temporal dependencies in Guzheng music patterns, including unsupervised learning of concise Guzheng-specific melody embedding vectors via a variational autoencoder, encapsulating unique harmonic signatures from performance descriptors to provide style guidance. Finally, we use LSTM networks to develop adversarial generative large models that enable realistic synthesis and evaluation of Guzheng tunes switching. We gather an extensive 10+ hour corpus of solo Guzheng recordings spanning 230 musical pieces, 130 distinguished performing artists, and 600+ audio tracks. Simultaneously, we conduct thorough Guzheng data analysis. Comparative assessments against strong baselines over systematic musical metrics and professional listeners validate significant generation fidelity improvements. Our model achieves a 63 % reduction in reconstruction error compared to the standard FA optimization after 1000 iterations. It also outperforms baselines in capturing characteristic motifs, maintaining modality coherence with under 2 % dissonant pitch errors, and retaining desired rhythmic cadences. User studies further confirm the superior naturalness, novelty, and stylistic faithfulness of the generated tune transitions, with ratings close to real data.

Gestational cadmium exposure increases the risk of preeclampsia. Placenta mitophagy was activated in preeclampsia. The aim of present study was to explore the mechanism of cadmium-induced mitophagy activation and its association with preeclampsia. Mitophagy markers expression levels were detected by quantitative real-time PCR, Western blot, immunofluorescence and immunochemistry in preeclampsia placenta. JEG3 cells were treated with CdCl2, iopanoic acid (IOP), 3-methyladenine and PGC1α SiRNA to verify mechanism of cadmium-induced mitophagy. Mitophagy marker LC3BII/I and P62 expression were increased and mitochondrial membrane receptor protein TOM20 and FUNDC1 expression were decreased in preeclampsia placenta as compared with that in normotension control. Mitophagy marker LC3BII/I and P62 expression were increased and TOM20 and FUNDC1 expression was decreased in CdCl2-treated JEG3 cells. Meanwhile, mitochondrial biogenesis regulator, PGC1α expression was decreased in preeclampsia and CdCl2-treated JEG3 cells. The expressions of LC3B and P62 were increased and the expressions of TOM20, FUNDC1 and PGC1α were decreased in IOP-treated cell. PGC1α SiRNA transfection led to increased expression of LC3BII/I and P62 and decreased expression of TOM20 and FUNDC1. The expression of sFlt1 was increased in preeclampsia placenta, CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. 3-methyladenine treatment protected the increased expression of sFlt1 in CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. Meanwhile, co-treatment of cadmium and IOP or PGC1αSiRNA led to a reduce expressions of OPA1, MFN1, MFN2 and FUNDC1 as compared to cadmium-treated, IOP-treated and PGC1α SiRNA-treated cells. These results elucidated that maternal cadmium exposure activated placenta mitophagy through downregulation of thyroid hormone receptor signal mediated decreased expression of PGC1α and was associated with the occurrence of preeclampsia.