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Abstract This study profiled global single cell-spatial-bulk transcriptome landscapes of hepatocellular carcinoma (HCC) ecosystem from six HCC cases and a non-carcinoma liver control donor. We discovered that intratumoral heterogeneity mainly derived from HCC cells diversity and pervaded the genome-transcriptome-proteome-metabolome network. HCC cells are the core driving force of taming tumor-associated macrophages (TAMs) with pro-tumorigenic phenotypes for favor its dominant growth. Remarkably, M1-types TAMs had been characterized by disturbance of metabolism, poor antigen-presentation and immune-killing abilities. Besides, we found simultaneous cirrhotic and HCC lesions in an individual patient shared common origin and displayed parallel clone evolution via driving disparate immune reprograms for better environmental adaptation. Moreover, endothelial cells exhibited phenotypically conserved but executed differential functions in a space-dependent manner. Further, the spatiotemporal traits of rapid recurrence niche genes were identified and validated by immunohistochemistry. Our data unravels the great significance of HCC cells in shaping vibrant tumor ecosystems corresponding to clinical scenarios.

Abstract Background This systematic review and meta-analysis aimed to evaluate the impact of perioperative immunonutrition on postoperative outcomes in patients undergoing pancreaticoduodenectomy (PD). Methods Conducted a comprehensive search in PubMed, Embase, Cochrane Library, Medline, and Web of Science databases to identify all randomized controlled trials (RCTs) on the topic of immunonutrition and PD. Subsequently screened literature, extracted data, and assessed the risk of bias in the included studies, and finally conducted a meta-analysis using RevMan 5.3 software. Results The analysis included a total of 10 RCTs with 574 patients, among whom 288 were in the immunonutrition group and 283 in the control group. The meta-analysis revealed a significantly lower incidence of postoperative infection-related complications (OR = 0.45; 95% CI: 0.27–0.74; P = 0.002) and severe postoperative complications (OR = 0.61; 95% CI: 0.38–0.98; P = 0.04) in the immunonutrition group compared to the control group. Additionally, patients in the immunonutrition group had a significantly shorter length of hospital stay (MD= -1.87; 95%CI -3.29 - -0.44; P = 0.01). However, the analysis revealed no statistically significant difference in the overall complication rate between the two groups (P = 0.67). Furthermore, the incidence of specific complications and perioperative mortality rates also did not demonstrate any statistically significant differences (all P > 0.05). Conclusions Perioperative immunonutrition in PD patients can reduce postoperative infection-related complications, but more high-quality RCTs are needed for further validation.

Abstract Background Recurrent gliomas rapidly progress and have high mortality and poor prognosis in the central nervous system. Therefore, further investigation of prognostic and therapeutic markers is needed. Methods The mRNA expression, clinical data, and coagulation-related genes (CRGs) associated with recurrent glioma were obtained and calculated from the Chinese Glioma Genome Atlas and Kyoto Encyclopedia of Genes and Genomes databases. The significant CRGs were calculated by Weighted gene co-expression network analysis and PPI network. A prediction model was constructed using the least absolute shrinkage and selection operator regression analysis. Recurrent gliomas were stratified into high and low-risk groups based on the median risk score (RS). The Kaplan–Meier curve was used to analyze the difference in overall survival (OS) between these groups, while the receiver operating characteristic (ROC) curve was used to evaluate the accuracy of the gene model at 1-, 3-, and 5-years. Clinical factors, including age, gender, MGMT methylation status, radiotherapy, chemotherapy, and RS, were included in the univariate and multivariate regression analysis. A prognostic nomogram and calibration curve were established based on these factors. Results Overall, seven CRGs associated with the prognosis were identified, including BTK, ITGB1, GNAI3, CFH, LYN, CFI, and F3. OS and survival rates were lower in the high-risk group compared with the low-risk group. The ROC curve demonstrated the area under the curve values >0.65 at 1-, 3-, and 5-years, confirming the reliability of the prognostic model. The univariate regression analysis indicated that tumor grade (grades 2, 3, and 4), histopathology (GBM or not), chemotherapy, IDH mutation, and 1p19q co-deletion status were independent prognostic indicators. Univariate and multivariate regression analyses indicated that RS was an independent prognostic factor for patients with recurrent glioma. Immune analysis revealed low infiltration of resting dendritic cells and high expression of programmed death receptor 1 in the high-risk group. Conclusion This study comprehensively investigated the correlation between CRGs and recurrent glioma prognosis, offering crucial insights for further research into glioma recurrence mechanisms and treatment strategies.

Abstract Hepatocellular carcinoma (HCC) remains one of the most prevalent malignant tumors globally, characterized by high incidence and mortality rates. Despite ongoing research, the underlying molecular mechanisms of HCC development are not yet fully understood. Utilizing bioinformatic analysis, real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blot assays, we identified that the expression of specificity protein 1 (Sp1) was significantly elevated in HCC cells compared to normal cells. Knockdown of the Sp1 gene led to a marked reduction in the viability and clonogenic potential of HCC cells. Further investigation revealed that the succinylation level of Sp1 was also increased in HCC cells. The upregulation of Sp1 expression was attributed to its succinylation, mediated by KAT2A, with lysine (K)562 identified as the succinylation site. Additionally, KAT2A and Sp1 were found to influence the upregulation of mTOR phosphorylation. Collectively, these findings suggest that KAT2A-promoted succinylation of Sp1 enhances the proliferative capacity of HCC cells by activating the mTOR pathway, providing a theoretical foundation for potential therapeutic strategies against HCC.

Abstract Crystalline silica (CS) particle exposure leads to silicosis which is characterized as progressive fibrosis. Fibroblasts are vital effector cells in fibrogenesis. Emerging studies have identified immune sentinel roles for fibroblasts in chronic disease, while their immune-modulatory roles in silicosis remain unclear. Herein, we show that group 2 innate lymphoid cell (ILC2) conversion to ILC1s is closely involved in silicosis progression, which is mediated by activated fibroblasts via interleukin (IL)−18. Mechanistically, Notch3 signaling in mechanics-activated fibroblasts modulates IL-18 production via caspase 1 activity. The mouse-specific Notch3 knockout in fibroblasts retards pulmonary fibrosis progression that is linked to attenuated ILC conversion. Our results indicate that activated fibroblasts in silicotic lungs are regulators of ILC2–ILC1 conversion, associated with silicosis progression via the Notch3–IL-18 signaling axis. This finding broadens our understanding of immune-modulatory mechanisms in silicosis, and indicates potential therapeutic targets for lung fibrotic diseases.

Abstract Background This study investigated the factors influencing the prognosis of children with steroid-resistant nephrotic syndrome (SRNS) in patients from the Guangxi region. Methods We retrospectively analyzed clinical and pathological data of 279 patients with SRNS from six tertiary hospitals in Guangxi. Clinical data were compared between initial (I-SRNS) and secondary (S-SRNS) steroid resistance subgroups and Cox regression analysis was used to determine risk factors for chronic kidney disease (CKD) and CKD stage 5 (CKD5) in patients with SRNS. Results The median age of onset was 54 months. Thirty-three patients had extra-kidney manifestations. Fifty-two, 24, 57, 33, and 41 patients had hypertension, acute kidney injury, vitamin D deficiency, high intraocular pressure, and dwarfism, respectively. One hundred eighty-two and 92 patients had I-SRNS and S-SRNS, respectively. There were significant differences in sex, ethnicity, family history, incidence of hematuria, clinical classification, efficacy of immune agents, and prognosis between groups (P

Abstract In a retrospective analysis of clinical data from 587 DLBCL (diffuse large B-cell lymphoma) patients in China, 13.8% of cases were associated with HBV (hepatitis B virus) infection, leading to distinct clinical features and poorer prognosis. Moreover, HBV infection has a more pronounced impact on the survival of the GCB (germinal center B-cell-like) type DLBCL patients compared to the ABC (activated B-cell-like) type. In this study, we found that the expression of LncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was downregulated in the HBV-infected GCB-type DLBCL patients, and the HBV core protein (HBX) directly inhibited the MALAT1 expression in DLBCL cells. Notably, the overexpression of HBX could attenuate the Erastin-induced ferroptosis in the GCB-type DLBCLs, while MALAT1 re-expression restored sensitivity in the HBX-overexpressing DLBCLs in vitro and in vivo. Mechanistically, MALAT1 competitively hindered SFPQ (splicing factor proline and glutamine-rich) from effectively splicing the pre-mRNA of SLC7A11 (solute carrier family 7 member 11), due to a shared TTGGTCT motif, which impeded the SLC7A11 pre-mRNA maturation and hence diminished its negative regulation on ferroptosis. Together, our study identified HBX’s role in inhibiting MALAT1 expression, promoting SFPQ-mediated splicing of SLC7A11 pre-mRNA, and reducing the GCB-type DLBCL sensitivity to Erastin-induced ferroptosis. Combined with the recent studies that ferroptosis may be involved in the occurrence and development of DLBCL, these findings explain our clinical data analysis that DLBCL patients with low expression of MALAT1 have poorer prognosis and shorter overall survival, and provide a valuable therapeutic target for the HBV-infected GCB-type DLBCL patients.

Abstract Background Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem). Method Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence. Results In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p

Biomass, as a renewable energy source, features wide availability, multiple functions, and carbon neutralization. The high-value resource utilization of biomass is conducive to reducing reliance on high-carbon fossil energy, ensuring national energy security, and curbing environmental pollution, aligning with the needs of China's "dual carbon" national strategy. Pyrolysis, as the foundation of biomass thermochemical conversion, is one of the best technologies to achieve a high-value utilization of biomass energy. However, it has some core issues such as low bio-oil yield and poor quality. To overcome these problems, a cryogenic technology was innovatively applied to the field of biomass pyrolysis, and a new biomass oil production method of "cryogenic + fast pyrolysis" was proposed to increase the yield and quality of pyrolytic bio-oil. Taking two types of crop straw as experimental research objects, the rapid freezing pretreatment method with liquid nitrogen was adopted to study the evolution mechanism of the product distribution and composition of biomass pyrolysis under cryogenic pretreatment. The experiments show that compared with conventional pyrolysis, the increase in the bio-oil yield after cryogenic pretreatment of biomass pyrolysis can reach 14.16% to 23.73%, and the cryogenic pretreatment temperature has a positive correlation with the bio-oil yield, and the maximum bio-oil yield (22.3% to 26.3%) is reached at −90 ℃, exceeding the bio-oil yield of the aluminum method by 8.50% to 22.71%. The cryogenic pretreatment has a significant transformation effect on the composition of the bio-oil, and the content of benzene series (BTEX) and phenolic substances in the bio-oil composition increases significantly, with the maximum increase of 43.61% and 12.45%, respectively. The cryogenic pretreatment of liquid nitrogen inhibited the release of CO2 and CO in biomass pyrolysis gas, and the proportion of components decreased by 7.2%−29.7%. In addition, the inhibition of the release of CO2 and CO in the biomass pyrolysis gas and the increase of CH4 and H2 by cryogenic pretreatment increase by 0.2% to 14.7%. Moreover, the increase in C content and the decrease in O content in the solid product under cryogenic pretreatment are conducive to improving the combustibility of biochar and reducing its risk of spontaneous combustion.

Herba Siegesbeckiae (HS) has been traditionally used for managing cardio- and cerebro-vascular diseases. Our previous study demonstrated that HS ameliorates myocardial ischemia/reperfusion (I/R) injury. Also, the differentially expressed proteins between HS and I/R groups were shown to be displayed as UCHL5 and were mainly enriched in the NLRP3 inflammasome pathway. However, further elucidation is required concerning the effective subfractions, constituents, and HS influence on the UCHL5/NLRP3 pathway. A co-immunoprecipitation assay and UCHL5 overexpression in cardiomyocyte explores were used to determine the interaction between UCHL5 and NLRP3 during myocardial I/R. The water extracts of HS were subjected to column chromatography using a macroporous adsorption resin. Four HS subfractions (HS-A [H 2 O elution], HS-B [20% ethanol elution], HS-C [50% ethanol elution], and HS-D [95% ethanol elution]) were obtained in this study. HS-C exhibited the most significant protective effect against myocardial I/R and improved I/R injury in vivo . HS-C markedly restrained the expression of UCHL5 and NLRP3 and resisted the role of UCHL5/NLRP3 in the pathogenesis of I/R. Eleven main constituents of HS-C were identified, among which kirenol best displayed anti-I/R injury activity and binding energy. Kirenol accounted for 62.4% of HS-C. Thus, HS-C effectively protected against myocardial I/R injury, which was attributed to mitigation of the UCHL5/NLRP3 pathway and kirenol was identified as the core active constituent.

Abstract Background The self-locking cage (ROI-C, LDR, Troyes, France) has been clinically applied in the treatment of cervical degenerative disc disease (CDDD). However, only a few long-term clinical and radiographic studies have been conducted on the treatment of spinal cord injury without fracture or dislocation (SCIWFD) so far. A comparison between ACDF with either ROI-C or CCP was performed to determine the better treatment for SCIWFD. Methods A total of 83 patients who underwent ACDF using either ROI-C or CCP were reviewed for radiological and clinical outcomes. The cohort comprised 60 males and 23 females, aged between 32 and 88 years old, with an average age of 58.23 years. All patients exhibited symptoms of nerve injury, including limb numbness, muscle weakness, hypoesthesia or urinary dysfunction. The preoperative ASIA classification of spinal nerve function: 7 cases of grade A, 23 cases of grade B, 34 cases of grade C and 19 cases of grade D were included in the study. Results A total of 48 patients underwent ACDF with ROI-C, while 35 patients received a conventional cage-plate. They were studied with a follow-up of 28.63 ± 17.41 months and 29.48 ± 15.43 months respectively. No significant difference was found in blood loss, JOA and ASIA between the two groups. No significant difference was found in cervical lordosis (CL) (P > 0.05). However, statistical difference was found in disc height of fused segment and T1 slope between the two groups (P 0.05). There was significant difference in the incidence of dysphagia. Both of two groups achieved bony fusion at final follow-up. Conclusion Our study demonstrated that ROI-C has the same efficacy as CCP in improving the cervical stability in treatment of SCIWFD. The migration of cage didn’t occur in ROI-C group at final follow-up, showing steadily fixed in cervical column. Moreover, the ROI-C does have the advantages of good therapeutic effect, mis-invasive, shorter operation time and fewer complications.

Abstract We investigate the propagation characteristics of transverse electric (TE) and transverse magnetic (TM) modes in a semiconductor quantum plasma-filled coaxial waveguide with a Piet Hein cross-section. The unique geometry of the Piet Hein cross-section offers intriguing possibilities for tailoring modal properties and exploiting novel nonlinear phenomena. Using analytical and numerical methods, we unveil the non-monochromatic behaviour of TE and TM modes, characterized by distinct peaks and troughs in their field components. The $$E_{z}$$ E z component of the TM mode exhibits a suppressed field within the central core and higher concentration in the cladding region, potentially minimizing energy loss within the waveguide. The $$E_{\rho }$$ E ρ component exhibits pronounced oscillations near the waveguide boundaries, suggesting constructive and destructive interference patterns. The $$E_{\xi }$$ E ξ component displays a non-monotonic behaviour with multiple pits and bumps, highlighting the interplay between the TE mode, the Piet Hein geometry, and the semiconductor quantum plasma properties. The $$B_{\rho }$$ B ρ component of the TM mode exhibits a non-monochromatic behaviour with multiple maxima and minima, attributed to the complex interactions between propagating waves with different phase shifts. The $$B_{\xi }$$ B ξ component exhibits a non-uniform distribution with distinct pits and bumps, with a resurgence towards the waveguide edges potentially due to higher-order mode contributions and local field enhancement effects. Our findings pave the way for the development of novel photonic devices with enhanced functionalities based on Piet Hein semiconductor quantum plasma waveguides.

Abstract Background and aim Woodsmoke from household fireplaces contributes significantly to outdoor air pollution in the Netherlands. The current understanding of the respiratory health effects of exposure to smoke from residential wood burning is limited. This study investigated the association between short-term changes in outdoor woodsmoke exposure and lung function, respiratory symptoms, and medication use in adults in the Netherlands. Methods This study was co-created with citizen scientists and other relevant stakeholders. A panel study was conducted with repeated observations in 46 adults between February and May 2021 in four Dutch towns. Participants recorded their symptoms and medication use in daily diaries, and conducted morning and evening home spirometry measurements. Woodsmoke exposure was characterized by measuring levoglucosan (most specific marker for woodsmoke exposure), black/brown carbon, fine and ultrafine particulate matter at central monitoring sites. Individual woodsmoke perception (smell) was recorded in daily diaries. Linear and logistic regression models were used to investigate the association between respiratory health and woodsmoke exposure. Models were adjusted for time-varying confounders and accounted for repeated observations within participants. Results Consistent positive associations were found between levoglucosan and shortness of breath (SOB) during rest and extra respiratory medication use. Odds ratios for current day exposure to levoglucosan were 1.12 (95% CI: 0.97, 1.30) for SOB during rest and 1.19 (95% CI: 1.07, 1.33) for extra medication use, expressed per interquartile range of levoglucosan concentrations (69.16 ng/m3). Positive non-significant associations were found between levoglucosan and nasal symptoms, cough and waking up with SOB. No consistent association was found between levoglucosan and lung function. Associations found between woodsmoke markers, SOB during rest and extra medication use remained after the inclusion of PM2.5 and UFP in two-pollutant models. Conclusions Adults experienced more SOB during rest, nasal symptoms and used more medication to treat respiratory symptoms on days with higher levels of outdoor woodsmoke concentrations.

Abstract This study investigates global extreme precipitation events (EPEs) during warm seasons, with a particular focus on EPEs preceded by extreme heat stress (EPE-Hs) and a comparative analysis with those not (EPE-NHs). Using reanalysis product and Earth System Model data, the spatiotemporal characteristics and temperature sensitivities of EPEs are analyzed. Results show that EPE-Hs, while less frequent, have longer duration and greater magnitude compared to EPE-NHs, particularly in high latitude regions. In the future, a significant increase is projected in the characteristics of EPE-Hs, in contrast to the stable duration and magnitude of EPE-NHs. EPE-Hs demonstrate substantially higher temperature sensitivity than EPE-NHs, especially in low latitudes. The precipitation-temperature scaling relationships diverge markedly between EPE-Hs and EPE-NHs, with notable regional variations. These insights are pivotal for crafting region-specific early warning and adaptation strategies to mitigate the risks associated with extreme precipitation under the backdrop of global warming.

Abstract Exposure to adverse life events is linked to somatic disorders. The study aims to evaluate the association between adverse events at varying life stages and the risk of chronic kidney disease (CKD), a condition affecting about 10% population worldwide. This prospective cohort study included 140,997 participants from the UK Biobank. Using survey items related to childhood maltreatment, adulthood adversity and catastrophic trauma, we performed latent class analysis to summarize five distinct patterns of exposure to adverse life events, namely “low-level exposure”, “childhood exposure”, “adulthood exposure”, “sexual abuse” and “child-to-adulthood exposure”. We used Cox proportional hazard regression to evaluate the association of patterns of exposure to adverse life events with CKD, regression-based mediation analysis to decompose the total effect, and gene-environment-wide interaction study (GEWIS) to identify interactions between genetic loci and adverse life events. During a median follow-up of 5.98 years, 2734 cases of incident CKD were identified. Compared with the “low-level exposure” pattern, “child-to-adulthood exposure” was associated with increased risk of CKD (hazard ratio 1.37, 95% CI 1.14 to 1.65). BMI, smoking and hypertension mediated 11.45%, 9.79%, and 4.50% of this total effect, respectively. Other patterns did not show significant results. GEWIS and subsequent analyses indicated that the magnitude of the association between adverse life events and CKD differed according to genetic polymorphisms, and identified potential underlying pathways (e.g., interleukin 1 receptor activity). These findings underscore the importance of incorporating an individual’s psychological encounters and genetic profiles into the precision prevention of CKD.

Abstract Various digital therapeutic products have been validated and approved since 2017. They have demonstrated efficacy and safety as a new therapeutic modality in various disorders or conditions. Hypertension is a common but serious condition that can be prevented or controlled with lifestyle changes and medicines. Although a digital therapeutic in hypertension is validated and approved in Japan, whether digital therapeutics (DTx) can significantly improve sustainable lifestyle changes is still a controversial topic. Most studies did not discuss the long‐term gain challenges. In this review, the authors discuss the definition of DTx, and analyze the motivation, engagement and adherence challenges of DTx in hypertension. Some ongoing artificial intelligence (AI)‐enabled or cognitive behavioral therapy (CBT)‐based digital interventions and behavioral strategies for implementing sustainable lifestyle changes are identified and analyzed. With AI‐enabled interventions and behavioral strategies, DTx might be one of the effective approaches to make sustainable lifestyle changes.

Background: Colon cancer is a malignant tumor with high malignancy and a low survival rate whose heterogeneity limits systemic immunotherapy. Transforming growth factor-β (TGF-β) signaling pathway-related genes are associated with multiple tumors, but their role in prognosis prediction and tumor microenvironment (TME) regulation in colon cancer is poorly understood. Using bioinformatics, this study aimed to construct a risk prediction signature for colon cancer, which may provide a means for developing new effective treatment strategies. Methods: Using consensus clustering, patients in The Cancer Genome Atlas (TCGA) with colon adenocarcinoma were classified into several subtypes based on the expression of TGF-β signaling pathway-related genes, and differences in survival, molecular, and immunological TME characteristics and drug sensitivity were examined in each subtype. Ten genes that make up a TGF-β-related predictive signature were found by least absolute shrinkage and selector operation (LASSO) regression using colon cancer data from the TCGA database and confirmed using a Gene Expression Omnibus (GEO) dataset. A nomogram incorporating risk scores and clinicopathologic factors was developed to stratify the prognosis of patients with colon cancer for accurate clinical diagnosis and therapy. Results: Two TGF-β subtypes were identified, with the TGF-β-high subtype being associated with a poorer prognosis and superior sensitivity to immunotherapy. Mutation analyses showed a high incidence of gene mutations in the TGF-β-high subtype. After completing signature construction, patients with colon cancer were categorized into high- and low-risk subgroups based on the median risk score of the TGF-β-related predictive signature. The risk score exhibited superior predictive performance relative to age, gender, and stage, as evidenced by its AUC of 0.686. Patients in the high-risk subgroup had higher levels of immunosuppressive cell infiltration and immune checkpoints in the TME, suggesting that these patients had better responses to immunotherapy. Conclusions: Patients with colon cancer were divided into two subtypes with different survival and immune characteristics using consensus clustering analysis based on TGF-β signaling pathway-related genes. The constructed risk prediction signature may show promise as a biomarker for evaluating the prognosis of colon cancer, with potential utility for screening individuals for immunotherapy.

Abstract Background Previous studies have established a positive link between nurse managers’ caring leadership and nurses’ work engagement, but the processes and conditions through which this leadership style influences positive work behaviors remain largely unexplored. To address this gap and contribute to the existing body of knowledge, we developed a chain-mediated effects model to elucidate the impact of caring leadership on nurses’ work engagement and the underlying mechanisms. In this model, we identified professional mission and affective organizational commitment as the mediating variables, offering a novel perspective on the relationship between caring leadership and work engagement. Methods A robust multi-center and large-sample cross-sectional survey was conducted, involving 2502 first-line nurses from six general tertiary hospitals across the eastern, central, and western regions of China. The data collection instruments included a comprehensive questionnaire covering demographic information, the caring leadership scale, the Chinese calling scale, the affective organizational commitment scale, and the Utrecht work engagement scale. Data were meticulously screened and analyzed, employing descriptive analysis to summarize the demographic information, correlation analysis to test the relationship among the variables, stepwise regression analysis to explore the mediating role of calling and affective organization commitment, and the bootstrap method to test the chain mediating effect. This rigorous methodology not only ensures the reliability and validity of research findings but also instills confidence in the robustness of this research. Results The results indicated a positive relationship among caring leadership, calling, affective organizational commitment, and nurses’ work engagement (p

The small modular PWR (SMPWR) usually adopts integral design. Under severe accident, the system responses are different from those large PWRs. It is necessary to study the severe accident behavior of the SMPWR. A MELCOR model is developed for SMPWR and its steady-state results are in good agreement with the design values. Severe accidents induced by secondary pipeline break accidents are simulated, and no pressure relief measures are taken to keep the primary loop under high pressure. The mitigation effects of passive containment air cooling system (PAS) and passive cavity injection system (PCIS) are evaluated under different cases. The results show that under high pressure conditions, PCIS can effectively cool the lower head. The earlier the PCIS operates, the more significant the mitigation effect can be. In addition, PAS can effectively reduce the peak pressure and temperature in the containment. This study can provide a reference for the formulation of severe accident management guidelines on SMPWRs.

Irregular bone defects, characterized by unpredictable size, shape, and depth, pose a major challenge to clinical treatment. Although various bone grafts are available, none can fully meet the repair needs of the defective area. Here, this study fabricates a dough-type hydrogel (DR-Net), in which the first dynamic network is generated by coordination between thiol groups and silver ions, thereby possessing kneadability to adapt to various irregular bone defects. The second rigid covalent network is formed through photocrosslinking, maintaining the osteogenic space under external forces and achieving a better match with the bone regeneration process. In vitro, an irregular alveolar bone defect is established in the fresh porcine mandible, and the dough-type hydrogel exhibits outstanding shape adaptability, perfectly matching the morphology of the bone defect. After photocuring, the storage modulus of the hydrogel increases 8.6 times, from 3.7 kPa (before irradiation) to 32 kPa (after irradiation). Furthermore, this hydrogel enables effective loading of P24 peptide, which potently accelerates bone repair in Sprague–Dawley (SD) rats with critical calvarial defects. Overall, the dough-type hydrogel with kneadability, space-maintaining capability, and osteogenic activity exhibits exceptional potential for clinical translation in treating irregular bone defects.

Abstract Dendritic cells (DCs) comprise diverse cell populations that play critical roles in antigen presentation and triggering immune responses in the body. However, several factors impair the immune function of DCs and may promote immune evasion in cancer. Understanding the mechanism of DC dysfunction and the diverse functions of heterogeneous DCs in the tumor microenvironment (TME) is critical for designing effective strategies for cancer immunotherapy. Clinical applications targeting DCs summarized in this report aim to improve immune infiltration and enhance the biological function of DCs to modulate the TME to prevent cancer cells from evading the immune system. Herein, factors in the TME that induce DC dysfunction, such as cytokines, hypoxic environment, tumor exosomes and metabolites, and co‐inhibitory molecules, have been described. Furthermore, several key signaling pathways involved in DC dysfunction and signal‐relevant drugs evaluated in clinical trials were identified. Finally, this review provides an overview of current clinical immunotherapies targeting DCs, especially therapies with proven clinical outcomes, and explores future developments in DC immunotherapies.

Adolescence is a crucial period for establishing lifelong healthy behaviors, and unhealthy habits developed during adolescence can increase the risk of chronic diseases in adulthood. However, few is on the relationships between health promotion behaviors and multidimensional health in Chinese middle-school students, focusing on identifying gender-specific differences. This study employed a non-experimental, correlational design using online surveys to collect data from 179 middle-school students and 103 teachers. Data analysis was conducted using SPSS v20, including ordinal logistic regression analysis, Chi-square tests and t-tests. The results indicate that approximately 43.7% of middle-school teachers perceive that rural students as having effective health promotion behaviors. Female students demonstrated higher levels of health promotion behaviors than males, with significant gender differences observed in health responsibility behavior (p = 0.011) and interpersonal relationships (p = 0.025). However, no gender differences were found in the multidimensional health of rural middle-school students. Both male and female students showed concerning levels of physical health, with only 38.2% of males and 37.78% of females rated as good or excellent. Notably, life appreciation behavior was identified as the only significant predictor of multidimensional health among these students, indicating that higher scores in this domain correlate with better health. Health educators and policymakers are advised to account for gender differences in the development and delivery of health promotion initiatives aimed at adolescents, with a particular emphasis on fostering life appreciation. Interventions focused on these aspects may offer substantial potential in diminishing health risks in adulthood and enhancing overall lifelong well-being.

Abstract Background Human amniotic membrane (AM) transplantation has been applied to treat ocular surface diseases, including corneal trauma. The focus of much deliberation is to balance the mechanical strength of the amniotic membrane, its resistance to biodegradation, and its therapeutic efficacy. It is commonly observed that the crosslinked human decellularized amniotic membranes lose the functional human amniotic epithelial cells (hAECs), which play a key role in curing the injured tissues. Methods and results In this study, we crosslinked human decellularized amniotic membranes (dAM) with genipin and re-planted the hAECs onto the genipin crosslinked AM. The properties of the AM were evaluated based on optical clarity, biodegradation, cytotoxicity, and ultrastructure. The crosslinked AM maintained its transparency. The color of crosslinked AM deepened with increasing concentrations of genipin. And the extracts from low concentrations of genipin crosslinked AM had no toxic effect on human corneal epithelial cells (HCECs), while high concentrations of genipin exhibited cytotoxicity. The microscopic observation and H&E staining revealed that 2 mg/mL genipin-crosslinked dAM (2 mg/mL cl-dAM) was more favorable for the attachment, migration, and proliferation of hAECs. Moreover, the results of the CCK-8 assay and the transwell assay further indicated that the living hAECs’ tissue-engineered amniotic membranes could facilitate the proliferation and migration of human corneal stromal cells (HCSCs) in vitro. Conclusions In conclusion, the cl-dAM with living hAECs demonstrates superior biostability and holds significant promise as a material for ocular surface tissue repair in clinical applications.

Abstract Objective To investigate the status quo of nursing practices, job burnout and social support among private hospitals in Dazhou, Sichuan Province, and perform correlational analysis. Methods A cross-sectional study was conducted. A total of 244 nurses were surveyed via convenience sampling from 7 private hospitals, which were randomly selected from Dazhou city. A self-designed demographic sociology questionnaire was applied, and the Chinese versions of the Maslach Burnout Scale and the Social Support scale administered from September to November 2022. Results The investigated nurses were relatively young (26.84 ± 4.90 years), had a short duration of service, a low academic background, a low professional title and a low income; however, they were highly satisfied with their working environment and had a low level of burnout, and their level of personal achievement was low. Overtime work, education level and number of children had significant impacts on the level of nurse burnout. The level of social support was high, and various dimensions were negatively correlated with the emotional exhaustion and depersonalization dimensions of burnout (r=-0.438, P

In the complex confined space of underground coal mine, some environmental factors such as uneven illumination of artificial light source, heavy concentration of dust and fog in the working face, and complex electromagnetic interference can seriously affect the high-definition imaging of underground surveillance video. Aiming at the problems of low resolution and blurring of mine images affected by complex environment, and the problems that the current image super-resolution reconstruction methods mostly improve the reconstruction effect at the expense of compromising network depth and width, which will increase the complexity of the algorithm greatly, as well as the memory usage of the network model, making it difficult to apply to actual edge mobile devices. In this study, a lightweight super-resolution reconstruction method of mine images based on blueprint separation convolution is proposed. Firstly, the high-efficiency blueprint separation convolution is used to replace the standard convolution in the residual block, and a lightweight residual attention module is designed by introducing coordinate attention mechanism and adding skip connections to improve the residual block, so that the model can achieve a better feature extraction ability while keeping low parameters and computation. Secondly, an enhanced hierarchical feature fusion module is designed to integrate local features first and then global features of different hierarchical features in the network, which can further promote the information flow in the network and enhance the feature utilization rate of the model. Finally, the pixel attention mechanism is added at the end of the network to enhance the attention of the network to the information features, which can improve the feature expression ability of the model and provide more detailed features for the image reconstruction module. Experimental results show that the image quality reconstructed by the lightweight super-resolution reconstruction network based on blueprint separation convolution is not only superior to other comparison algorithms in terms of objective indexes and visual perception, but also achieves a better trade-off between model performance and complexity. When the scaling factor is 4, in comparison to the lightweight algorithm AWSRN-M with the same number of parameters, the average PSNR and SSIM on the coal mine test set are increased by 0.177 2 dB and 0.010 7 respectively, and the floating-point computation is reduced by 66.9%. The results demonstrate that the proposed method can effectively extract the detailed feature information with different levels, achieve the deep fusion of shallow and deep features, and more efficiently reconstruct high-resolution images with clear texture details.

Abstract In the Internet era, the communication environment of university students’ ideological and mental health education (IMHE) has become more complex. Few studies have focused on the communication effect of Internet contact on the IMHE of university students. This study adopts a questionnaire survey method to explore Internet contact and IMHE of 2294 university students. The study found that Internet was the most important information source for university students. Nearly half of the university students spent 2–5 hours online per day for entertainment or fragmented learning. Educational films, communication and discussion, and classroom teaching were the three most popular forms of IMHE for university students, while comments on current events, psychological counseling, and national policies and regulations were the three favorite contents. Internet contact during (ICD) had significant impacts on the cognitive and behavioral communication effect of IMHE among Chinese university students. The emotional dimension had the best communication effect, followed by behavior and will, and finally the cognitive dimension. After conducting IMHE, university students had stronger emotional management abilities and were more optimistic. This finding suggested that when developing and implementing IMHE intervention for university students in schools, special attention should be paid to the impact of ICD differences on the communication effect of IMHE, especially cognitive communication needed improvement.

Abstract Extreme events with increasing frequency and intensity are significantly affecting the permafrost environment. Analysis using the ERA5-Land reanalysis data revealed that the permafrost region of the central Qinghai-Tibet Plateau (QTP) experienced the summer heat wave in 2022. Four active layer sites experienced maximum active layer thicknesses (ALT) in 2022 (mean: 207.7 cm), which was 20% higher than the mean ALT during 2000–2021 (mean: 175.9 cm). The mean annual ground temperature (MAGT) observed in 2022 was also the highest, exceeding the average of the previous years by 10%. The contribution fraction of heat wave to the seasonal thaw depth of active layer was quantified using Stefan model with ranging from 6.6% to 13.6%, and the maximum contribution fraction occurs in 2022. These findings are helpful to better understand the impact processes of extreme events on the active layer and permafrost.

Abstract Sex characteristics exhibit significant disparities in various human diseases, including prevalent cardiovascular diseases, cancers, metabolic disorders, autoimmune diseases, and neurodegenerative diseases. Risk profiles and pathological manifestations of these diseases exhibit notable variations between sexes. The underlying reasons for these sex disparities encompass multifactorial elements, such as physiology, genetics, and environment. Recent studies have shown that human body systems demonstrate sex-specific gene expression during critical developmental stages and gene editing processes. These genes, differentially expressed based on different sex, may be regulated by androgen or estrogen-responsive elements, thereby influencing the incidence and presentation of cardiovascular, oncological, metabolic, immune, and neurological diseases across sexes. However, despite the existence of sex differences in patients with human diseases, treatment guidelines predominantly rely on male data due to the underrepresentation of women in clinical trials. At present, there exists a substantial knowledge gap concerning sex-specific mechanisms and clinical treatments for diverse diseases. Therefore, this review aims to elucidate the advances of sex differences on human diseases by examining epidemiological factors, pathogenesis, and innovative progress of clinical treatments in accordance with the distinctive risk characteristics of each disease and provide a new theoretical and practical basis for further optimizing individualized treatment and improving patient prognosis.

Abstract Introduction Medical financial hardship in the United States is a growing public health concern. This study aims to assess the south vs. non-south disparities in medical financial hardship among US adults of different generations – Boomers (born between 1946 and 1964), Generation X (born between 1965 and 1980), and the Millennials (born between 1981 and 1996) across periods pre- and post- Affordable Care Act (ACA). Methods This observational study utilizes data from multiple waves of the National Health Interview Survey (NHIS) split into three periods: pre–ACA (2011–2013), ii) post ACA (2015–2018), and iii) COVID-19 pandemic (2021–2022). Multivariable logistic regressions were fitted, separately for each generation in each period, to compare the extent of medical financial hardship among those from South to rest of the US, and Karlson-Holm-Breen (KHB) decomposition was applied to analyze whether there was a mediating impact of health insurance coverage. Results Adults living in the South were more likely to experience medical financial hardship in all three periods. Residing in the South was associated with 1.7 to 2.6% points (pp) higher probability of medical financial hardship among boomers, 1.8 to 4.0 pp among generation Xers, and 1.7 to 2.8 pp among millennials. The relationship was robust after accounting for chronic comorbidities, sociodemographic and socioeconomic attributes and was partially mediated through differences in health insurance coverage. Conclusions The problem of medical financial hardship has been deeply rooted in the South across generations, which was partly attributable to the regional differences in health insurance coverage.

Abstract Patients on B cell immunosuppressive treatments have been shown to have persistent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, a woman treated with ibrutinib for chronic lymphocytic leukemia experienced more than 40 days of coronavirus disease 2019 (COVID-19) infection. Unexpectedly, her peripheral blood experiments showed a normal SARS-CoV-2-specific antibody level and a relatively elevated percentage of CD19 + B cells, while an obvious decrease in the percentages of NK cells, CD4 + T cells and CD8 + T cells. Further SARS-CoV-2-specific T cell analysis in this patient indicated a significant decrease in the percentage of SARS-CoV-2-specific IFN-γ, TNF-α or IL-2 producing CD4 + T or CD8 + T cells. Most notably, ten days after the cease of ibrutinib, the PCR for SARS-CoV-2 turned negative and the reduced proportions of peripheral CD4 + T cells and CD8 + T cells recovered. Our research predicted that the depleted B-cell function therapies may play considerable role in the development of long COVID-19 and the abnormal T-cell subset distribution might be the underlying mechanism.

Abstract This study utilizes household-level micro survey data from China to investigate the impact of homeownership on the economic status of households and the underlying mechanisms. The findings reveal that homeownership does not enhance the economic status of households. This outcome may be attributed to the inherent immobility of housing as a physical asset and the substantial financial pressure imposed by housing loans, leading to a “housing mortgage slave effect” and reduced job mobility among homeowners. These conclusions remain robust after accounting for endogeneity issues and preforming a series of robustness checks. Moreover, the study finds that homeownership is significantly and negatively associated with changes in the economic status of households without intergenerational financial support, whereas it has no significant effect on those without such support. This suggests that financial supports can alleviate the burden of mortgage debt, therefore mitigating the adverse relationship between homeownership and changes in household economic status.

Urban form contributes to crime prevention. However, most studies not only simplify the relationship between urban form and crime, they also fail to reflect the geographic structure of urban areas. This study first measured a comprehensive multidimensional urban form indicator for 1486 counties in the United States, which was used to characterize the size and geospatial structure of urban areas. Specifically, it described urban form as consisting of three components: 1) size and population distribution; 2) built environment; and 3) landscape environment. Then, generalized additive mixed models were then used to explore linear or nonlinear associations between urban form indicators and different crime types (violent and property crime). This study's main findings were that 1) the relationship between urban form and crime is not only linear but may also be nonlinear; 2) urban size, fragmentation, connectivity, forest mixing, and shrub mixing are associated with all crime types; 3) population distribution and agricultural mixing are associated with violent crime; and 4) urban patch complexity and water mixing are associated with property crime. Overall, the results of this study can provide guidance for long-term planning of urban geographic structures, contributing to the safe and sustainable development of urban areas.

Skin Exposure of skin to ionizing radiation can induce acute or chronic biological effects, resulting in radiation-induced skin injury (RSI). Premature cellular senescence, caused by oxidative stress and/or DNA damage from chemical or physical agents, leads to the decrease of cellular proliferation and physiological function. Persistent DNA damage and accumulation of senescent cells are associated with the progression of radiation-induced injury. Atopic dermatitis and RSI have similar inflammatory symptoms. The treatment of tacrolimus (TAC) in atopic dermatitis may be associated with premature cellular senescence. TAC can prevent the onset of cellular senescence by inactivating the p38 mitogen-activated protein kinase (p38 ​MAPK). The activation of p38 ​MAPK can induce the senescence-associated secretory phenotype (SASP) by enhancing the transcriptional activity of nuclear factor kappa-B (NF-κB), which ultimately leads to premature cellular senescence. FK506 binding protein 51 (FKBP51) exhibits resistance to ionizing radiation, but the mechanism of TAC regulation of ionizing radiation-induced premature senescence still needs further study. This review discusses the mechanism of cellular senescence in RSI and the role of TAC in both dermatitis and RSI.

Introducing additional oxidizers in aluminized explosives is an effective way to improve energy performance by enhancing the secondary combustion reaction. In this work, perfluorocarbon as oxidizer has been introduced into TATB/Al based energetic materials to improve combustion reaction and energy output performance. The uniform TATB/Al/perfluorocarbon composites are prepared through acoustic resonance mixed technology, and the energy and pressure output performance are fully studied in air blast and underwater explosion. A significantly exothermic peak derived from the reaction between fluorine and Al is observed between 540 ℃ and 580 ℃ for TATB/Al/perfluorocarbon. The heat of explosion of TATB/Al/perfluorocarbon is increased first and then decreased with F/Al ratio from 0 to 0.608. The highest heat of explosion is 6021 J/g for TATB/Al/perfluorocarbon with F/Al ratio of 0.274. Furthermore, the enhanced working capacity, the significantly enlarged fireball and relatively high overpressure are obtained for TATB/Al/perfluorocarbon. More importantly, the shock impulse and first bubble oscillation time of TATB/Al/perfluorocarbon have been increased by 23.2% and 21.18% during underwater explosion, respectively. The results further illustrate that adding perfluorocarbon is a feasible approach to enhance energy output due to combustion reaction between fluorine and Al, which can be applied in explosives and propellants.

Context Almonertinib is primarily metabolized by CYP3A4, so it could interact with a variety of drugs metabolized by CYP3A4, leading to the changes of systemic exposure.Objective For the purpose of this experiment, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay with accuracy and simplicity was optimized and fully validated for the simultaneous quantitative determination of almonertinib and its metabolite HAS-719, and drug-drug interactions (DDI) between almonertinib and nicardipine in vivo and in vitro was researched.Materials and methods Detection of analytes was achieved by UPLC-MS/MS coupled with multiple reaction monitoring (MRM) in the positive ion mode with ion transitions of m/z 526.01 → 72.04 for almonertinib, m/z 512.18 → 455.08 for HAS-719 and m/z 447.16 → 128.11 for IS, respectively.Results There was favourable linearity in the 0.5–200 ng/mL calibration range for almonertinib and 0.5–100 ng/mL for HAS-719. The lower limit of quantification (LLOQ) for both analytes was 0.5 ng/mL. The precision, accuracy, stability, matrix effect and extraction recovery required for methodological validation were consistent with the requirements of FDA guideline. Then, the UPLC-MS/MS assay was employed successfully on the interactions of almonertinib and nicardipine in vivo and in vitro. The half-maximal inhibitory concentration (IC50) was 1.19 μM in rat liver microsomes (RLM), where nicardipine inhibited the metabolism of almonertinib with a mixed inhibitory mechanism. In pharmacokinetic experiments of rats, it was observed that nicardipine could significantly alter the pharmacokinetic profiles of almonertinib, including AUC(0-∞), AUC(0-t) and Cmax, but had no effect on the metabolism of HAS-719.Conclusion According to the findings, it was indicated that nicardipine could inhibit the metabolism of almonertinib in vitro and in vivo.

Context The global prevalence of type 2 diabetes mellitus (T2DM) has increased significantly in recent decades. Despite numerous studies and systematic reviews, there is a gap in comprehensive and up-to-date evaluations in this rapidly evolving field.Objective This review provides a comprehensive and current overview of the efficacy of Traditional Chinese Medicine (TCM) in treating T2DM.Methods A systematic review was conducted using PubMed, Web of Science, Wanfang Data, CNKI, and Medline databases, with a search timeframe extending up to November 2023. The search strategy involved a combination of subject terms and free words in English, including ‘Diabetes,’ ‘Traditional Chinese Medicine,’ ‘TCM,’ ‘Hypoglycemic Effect,’ ‘Clinical Trial,’ and ‘Randomized Controlled Trial.’ The studies were rigorously screened by two investigators, with a third investigator reviewing and approving the final selection based on inclusion and exclusion criteria.Results A total of 108 relevant papers were systematically reviewed. The findings suggest that TCMs not only demonstrate clinical efficacy comparable to existing Western medications in managing hypoglycemia but also offer fewer adverse effects and a multitarget therapeutic approach. Five main biological mechanisms through which TCM treats diabetes were identified: improving glucose transport and utilization, improving glycogen metabolism, promoting GLP-1 release, protecting pancreatic islets from damage, and improving intestinal flora.Conclusions TCM has demonstrated significant protective effects against diabetes and presents a viable option for the prevention and treatment of T2DM. These findings support the further exploration and integration of TCM into broader diabetes management strategies.

Microscale energetic materials have garnered considerable attention because they can be integrated in microelectromechanical systems for several potential applications. Hexanitrostilbene (HNS) has been widely utilized in ignition and initiation devices owing to its excellent thermal and shock stability and high sensitivity to short pulse shock waves. To meet the energy release requirements of micro-detonation devices, HNS sticks were prepared using direct ink writing and their reaction and flame propagation properties were studied. HNS particles sized 17.5 µm to 5 µm and ∼500 nm was prepared. Then, the viscosity of HNS-based inks prepared via acoustic resonance technology decreased when the particle size decreased or when the HNS content reduced from 97 wt.%, 95 wt.%, and 92 wt.%, to 90 wt.%. Additionally, the HNS-based inks with different binders exhibited different viscosity. The effect of the inner diameter of needle (0.4 mm, 0.6 mm, and 0.9 mm), printing rate (13 mm/s, 15 mm/s, 17 mm/s, 19 mm/s), and pressure (0.05 MPa, 0.1 MPa, 0.15 MPa, 0.2 MPa) on the width of HNS sticks was also elucidated. HNS-based sticks with a diameter of 0.9 mm underwent self-sustaining combustion reactions, and the burning rate increased from 5.1 mm/s to 6.8 mm/s as the particle size decreased from 17.5 µm to 500 nm. Overall, this work provides an effective approach to prepare microscale HNS for integration into micro-energetic devices.

Context Diabetic retinopathy (DR) is one of the leading causes of vision impairment and blindness among diabetic patients globally. Despite advancements in conventional treatments, the quest for more holistic approaches and fewer side effects persists. Traditional Chinese medicine (TCM) has been used for centuries in managing various diseases, including diabetes and its complications.Objective This review evaluated the efficacy and underlying mechanisms of TCM in the management of DR, providing information on its potential integration with conventional treatment methods.Methods A comprehensive literature review was conducted using PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) with the search terms ‘traditional Chinese medicine’, ‘diabetic retinopathy’, ‘clinical efficacies’ and their combinations. Studies published before 2023 without language restriction were included, focusing on clinical trials and observational studies that assessed the effectiveness of TCM in DR treatment.Results The review synthesized evidence of empirical traditional Chinese formulas, traditional Chinese patent medicines, and isolated phytochemicals on DR treatment. The key mechanisms identified included the reduction of oxidative stress, inflammation, and neovascularization, as well as the improvement in neurovascular functionality and integrity of the retinal blood barrier.Conclusions TCM shows promising potential to manage DR. More large-scale, randomized controlled trials are recommended to validate these findings and facilitate the integration of TCM into mainstream DR treatment protocols.

Abstract Background Triangular fibrocartilage complex (TFCC) injuries, especially Palmer type IB, pose surgical management challenges due to associated distal radial ulnar joint (DRUJ) instability. Traditional surgeries entail risks of complications. Arthroscopic repair presents advantages but lacks consensus on optimal techniques. To evaluate arthroscopic dual-bone tunnel repair in patients with Palmer type IB TFCC injuries of the wrist. Methods In this retrospective case series, grip strength ratio, joint range of motion, pain visual analogue scale (VAS), modified Mayo wrist score, and Disabilities of the Arm, Shoulder, and Hand (DASH) scores were assessed before and 12 months after surgery. Results The cohort consisted of 45 patients. At 12 months, the grip strength ratio improved from 0.71 ± 0.08 to 0.93 ± 0.05 (P

Abstract Acute lung injury (ALI) is a severe clinical respiratory condition characterized by high rates of mortality and morbidity, for which effective treatments are currently lacking. In this study, lipopolysaccharide (LPS) was used to induce ALI mice, demonstrating the efficacy of tetramethylpyrazine (TMP) in ameliorating ALI. Subsequent we perfored high-throughput sequencing analysis and used Targetscan 8.0 and miRWalk 3.0 databases to predict the interaction between microRNAs and destrin (DSTN), ultimately identifying miR-369-3p as the focus of the investigation. The adenovirus carrying miR-369-3p was administered one week prior to LPS-induced in order to assess its potential efficacy in ameliorating ALI in mice. The findings indicated that the overexpression of miR-369-3p resulted in enhanced lung function, reduced pulmonary edema, inflammation, and permeability in LPS-induced ALI mice, while the suppression of miR-369-3p exacerbated the damage in these mice. Furthermore, the beneficial effects of TMP on LPS-induced ALI were negated by the downregulation of miR-369-3p. The results of our study demonstrate that TMP mitigates LPS-induced ALI through upregulation of miR-369-3p. Consequently, the findings of this study advocate for the clinical utilization of TMP in ALI treatment, with miR-369-3p emerging as a promising target for future ALI interventions.

Abstract Bioanalysis at a single-cell level has yielded unparalleled insight into the heterogeneity of complex biological samples. Combined with Lab-on-a-Chip concepts, various simultaneous and high-frequency techniques and microfluidic platforms have led to the development of high-throughput platforms for single-cell analysis. Dielectrophoresis (DEP), an electrical approach based on the dielectric property of target cells, makes it possible to efficiently manipulate individual cells without labeling. This review focusses on the engineering designs of recent advanced microfluidic designs that utilize DEP techniques for multiple single-cell analyses. On-chip DEP is primarily effectuated by the induced dipole of dielectric particles, (i.e., cells) in a non-uniform electric field. In addition to simply capturing and releasing particles, DEP can also aid in more complex manipulations, such as rotation and moving along arbitrary predefined routes for numerous applications. Correspondingly, DEP electrodes can be designed with different patterns to achieve different geometric boundaries of the electric fields. Since many single-cell analyses require isolation and compartmentalization of individual cells, specific microstructures can also be incorporated into DEP devices. This article discusses common electrical and physical designs of single-cell DEP microfluidic devices as well as different categories of electrodes and microstructures. In addition, an up-to-date summary of achievements and challenges in current designs, together with prospects for future design direction, is provided.

Abstract Background Localized scleroderma (LoS) is an autoimmune disorder that primarily affects the skin, and is often treated with autologous fat grafting (AFG). Nevertheless, the retention rate of AFG in patients with LoS is typically low. We hypothesize that the low retention rate may be partially attributed to the inherent abnormalities of adipose-derived stem cells (ASCs) from nonlesional sites of patients with LoS. Methods We performed a comparative analysis of the single-cell transcriptome of the SVF from nonlesional sites of patients with LoS and healthy donors, including cellular compositional analysis, differential expression analysis, and high-dimensional weighted gene coexpression network analysis. Experimental validation with fluorescence-activated cell sorting and bleomycin-induced skin fibrosis mice models were conducted. Results We found a significant reduction in the relative proportion of CD55high interstitial progenitors in ASCs under the condition of LoS. Differential expression analysis revealed inherent abnormalities of ASCs from patients with LoS, including enhanced fibrogenesis, reduced anti-inflammatory properties, and increased oxidative stress. Compared with CD55low ASCs, CD55high ASCs expressed significantly higher levels of secreted protein genes that had functions related to anti-inflammation and tissue regeneration (such as CD55, MFAP5, and METRNL). Meanwhile, CD55high ASCs expressed significantly lower levels of secreted protein genes that promote inflammation, such as chemokine and complement protein genes. Furthermore, we provided in vivo experimental evidence that CD55high ASCs had superior treatment efficacy compared with CD55low ASCs in bleomycin-induced skin fibrosis mice models. Conclusions We found that the low retention rate of AFG may be partially ascribed to the reduced pool of interstitial progenitor cells (CD55high) present within the ASC population in patients with LoS. We demonstrated the potential for improving the efficacy of AFG in the treatment of LoS by restoring the pool of interstitial progenitors within ASCs. Our study has significant implications for the field of translational regenerative medicine.

Abstract Background Glucagon-like peptide-1 receptor (GLP1R) agonists have been shown to reduce major cardiovascular events in diabetic patients, but their role in heart failure (HF) remains controversial. Recent evidence implies their potential benefits on cardiometabolism such as lipid metabolism, which may contribute to lowering the risk of HF. Consequently, we designed a Mendelian randomization (MR) study to investigate the causal relationships of circulating lipids mediating GLP1R agonists in HF. Methods The available cis-eQTLs for GLP1R target gene were selected as instrumental variables (IVs) of GLP1R agonism. Positive control analyses of type 2 diabetes mellitus (T2DM) and body mass index (BMI) were conducted to validate the enrolled IVs. Two-sample MR was performed to evaluate the associations between GLP1R agonism and HF as well as left ventricular ejection fraction (LVEF). Summary data for HF and LVEF were obtained from two genome-wide association studies (GWASs), which included 977,323 and 40,000 individuals of European ancestry, respectively. The primary method employed was the random-effects inverse variance weighted, with several other methods used for sensitivity analyses, including MR-Egger, MR PRESSO, and weighted median. Additionally, multivariable MR and mediation MR were applied to identify potentially causal lipid as mediator. Results A total of 18 independent IVs were included. The positive control analyses showed that GLP1R agonism significantly reduced the risk of T2DM (OR = 0.79, 95% CI = 0.75–0.85, p

Abstract Objective This study aimed to assess the efficacy and safety of bilateral superselective adrenal arterial embolization (SAAE) in patients with bilateral idiopathic hyperaldosteronism (IHA), a subtype of PA. Methods Ninety-eight patients with bilateral IHA underwent bilateral SAAE between August 2022 and August 2023. Sixty-eight patients were followed up for up to 12 months. The study outcomes were evaluated using the criteria provided by the Primary Aldosteronism Surgical Outcome (PASO) guidelines. Results The mean reductions in systolic and diastolic blood pressure were 27.4 ± 21.3 mmHg and 23.1 ± 17.4 mmHg, respectively (p

Abstract Acinetobacter baumannii is a gram-negative bacillus prevalent in nature, capable of thriving under various environmental conditions. As an opportunistic pathogen, it frequently causes nosocomial infections such as urinary tract infections, bacteremia, and pneumonia, contributing to increased morbidity and mortality in clinical settings. Consequently, developing novel vaccines against Acinetobacter baumannii is of utmost importance. In our study, we identified 10 highly conserved antigenic proteins from the NCBI and UniProt databases for epitope mapping. We subsequently screened and selected 8 CTL, HTL, and LBL epitopes, integrating them into three distinct vaccines constructed with adjuvants. Following comprehensive evaluations of immunological and physicochemical parameters, we conducted molecular docking and molecular dynamics simulations to assess the efficacy and stability of these vaccines. Our findings indicate that all three multi-epitope mRNA vaccines designed against Acinetobacter baumannii are promising; however, further animal studies are required to confirm their reliability and effectiveness.

Abstract Cultural heritage is an important contributor to sustainable urban development, and its conservation is considered a global task. Previous research has primarily focused on the conservation of heritage buildings within architectural contexts and world heritage sites within geographical contexts. However, there is a notable gap in conservation of green cultural heritage (GCH) within a landscape-based framework. This study used the extended theory of planned behavior to explore the factors and pathways that influence the public's behavioral intentions toward GCH conservation. Based on 1075 questionnaires collected in Tokyo, Japan, the hypotheses of the newly constructed theoretical model were tested using partial least squares structural equation modeling. The results show that perceived behavioral control has the greatest positive influence on citizens' GCH conservation intentions and behaviors, while social norms do not influence people's behavioral intention to conserve. In the extended factors, the environmental awareness which including heritage awareness and cultural attachment, significantly influences public attitudes towards conservation. Additionally, environmental perception, including perceived usefulness and perceived quality, significantly affects the public's conservation intentions and behaviors, respectively. Our findings have implications for local governments and policymakers to enhance public participation in GCH, as well as some several new theoretical interests for further studies.

Abstract Obesity is a global issue that warrants the identification of more effective therapeutic targets and a better understanding of the pivotal molecular pathogenesis. Annexin A1 (ANXA1) is known to inhibit phospholipase A2, exhibiting anti-inflammatory activity. However, the specific effects of ANXA1 in obesity and the underlying mechanisms of action remain unclear. Our study reveals that ANXA1 levels are elevated in the adipose tissue of individuals with obesity. Whole-body or adipocyte-specific ANXA1 deletion aggravates obesity and metabolic disorders. ANXA1 levels are higher in stromal vascular fractions (SVFs) than in mature adipocytes. Further investigation into the role of ANXA1 in SVFs reveals that ANXA1 overexpression induces lower numbers of mature adipocytes, while ANXA1-knockout SVFs exhibit the opposite effect. This suggests that ANXA1 plays an important role in adipogenesis. Mechanistically, ANXA1 competes with MYC binding protein 2 (MYCBP2) for interaction with PDZ and LIM domain 7 (PDLIM7). This exposes the MYCBP2-binding site, allowing it to bind more readily to the SMAD family member 4 (SMAD4) and promoting its ubiquitination and degradation. SMAD4 degradation downregulates peroxisome proliferator-activated receptor gamma (PPARγ) transcription and reduces adipogenesis. Treatment with Ac2-26, an active peptide derived from ANXA1, inhibits both adipogenesis and obesity through the mechanism. In conclusion, the molecular mechanism of ANXA1 inhibiting adipogenesis was first uncovered in our study, which is a potential target for obesity prevention and treatment.

Abstract Background Zhiguo ethnic groups, commonly known as “the directly-entering-socialism ethnic groups”, represent Chinese ethnic minorities who have undergone a unique social development trajectory by transforming directly from primitive societies to the socialist stage. In recent decades, significant lifestyle transformations have occurred among Zhiguo ethnic groups. Understanding their health lifestyles can play a strategic role in China’s pursuit of universal health coverage. This study aims to examine patterns of health-related lifestyle among Zhiguo ethnic groups and explore whether sociodemographic features and specific indicators related to health status are associated with particular classes. Methods A cross-sectional study was conducted in Yunnan Province, China, from July to December 2022. Stratified random sampling method was employed to recruit residents belonging to six Zhiguo ethnic groups aged between 15 and 64. Latent class analysis was performed to identify clusters of health-related behaviors within each ethnic group. Logistic regression was utilized to determine the predictors of health lifestyles. Results A total of 1,588 individuals from the Zhiguo ethnic groups participated in this study. Three latent classes representing prevalent health lifestyles among the Zhiguo ethnic groups were identified: “unhealthy lifestyle” (31.80%), “mixed lifestyle” (57.37%), and “healthy lifestyle” (10.83%). In the overall population, individuals belonging to the “healthy lifestyle” group exhibited a higher likelihood of being non-farmers (OR: 2.300, 95% CI: 1.347–3.927), women (OR: 21.459, 95% CI: 13.678–33.667), married individuals (OR: 1.897, 95% CI: 1.146–3.138), and those residing within a walking distance of less than 15 min from the nearest health facility (OR: 2.133, 95% CI: 1.415–3.215). Conversely, individuals in the age cohorts of 30–39 years (OR: 0.277, 95% CI: 0.137–0.558) and 40–49 years (OR: 0.471, 95% CI: 0.232–0.958) showed a decreased likelihood of adopting a healthy lifestyle. Conclusions A considerable proportion of the Zhiguo ethnic groups have not adopted healthy lifestyles. Targeted interventions aimed at improving health outcomes within these communities should prioritize addressing the clustering of unfavorable health behaviors, with particular emphasis on single male farmers aged 30–49, and expanding healthcare coverage for individuals residing more than 15 min away from accessible facilities.

Abstract Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo‐HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS‐IB‐1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow‐up was 507 days for survivors. The 2‐year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT‐CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05‐60.03, p = 0.045; HR = 3.64, 95%CI 1.40‐9.44, p = 0.008; respectively), while post‐transplantation cyclophosphamide based graft‐versus‐host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11‐0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.