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Abstract Recently discovered Mn-based kagome materials, such as RMn6Sn6 (R = rare-earth element), exhibit the coexistence of topological electronic states and long-range magnetic order, offering a platform for studying quantum phenomena. However, understanding the electronic and magnetic properties of these materials remains incomplete. Here, we investigate the electronic structure and magnetic properties of GdMn6Sn6 using x-ray magnetic circular dichroism, photoemission spectroscopy, and theoretical calculations. We observe localized electronic states from spin frustration in the Mn-based kagome lattice and induced magnetic moments in the nonmagnetic element Sn experimentally, which originate from the Sn- $$p$$ p and Mn- $$d$$ d orbital hybridization. Our calculations also reveal ferromagnetic coupling within the kagome Mn-Mn layer, driven by double exchange interaction. This work provides insights into the mechanisms of magnetic interaction and magnetic tuning in the exploration of topological quantum materials.

In order to clarify the pre-exist immunity background of different human coronaviruses (HCoV), this study investigated the positive rate of spike (S) protein antibodies of HCoV, including HCoV- severe acute respiratory syndrome (SARS) −associated coronavirus (SARS-CoV-1), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), HCoV-229E, HCoV-NL63, HCoV-HKU1 and HCoV-OC43, before and after the Coronavirus Disease 2019 (COVID-19) outbreak. We utilized pseudotyped virus-based neutralization assays (PBNA) or enzyme-linked immunosorbent assays (ELISA) to detect antibody levels against HCoV in serum samples collected in 2009–2010 and 2023. The PBNA results showed that neutralizing antibodies against SARS-CoV-1 and the MERS-CoV were negative. In the serum samples from 2009 to 2010, neutralizing antibodies against SARS-CoV-2 (D614G) were negative, whereas in the serum samples from 2023, 73 samples (73 %) showed neutralizing reactions with the SARS-CoV-2 D614G strain, 96 samples (96 %) with the BA.5 strain, and 91 samples (91 %) with the BF.7 strain. Among pre-COVID-19 samples, 33 % (33/100) showed neutralizing reactions with HCoV-229E and 63 % (63/100) with HCoV-NL63. Among post-COVID-19 samples, 50 % (50/100) showed neutralizing reactions with HCoV-229E and 49 % (49/100) with HCoV-NL63. Due to the different receptors of alpha coronavirus genus compared to other beta coronavirus genus, neutralizing antibodies against HCoV-OC43 and HCoV-HKU1 virus cannot be detected by constructing corresponding pseudotyped virus. Binding antibodies against HCoV-OC43 and HCoV-HKU1 virus were detected using ELISA. The results revealed that among pre-COVID-19 samples, 83 % (83/100) and 45 % (45/100) had binding activity with HCoV-OC43 and HCoV-HKU1, respectively. Among post-COVID-19 samples, 100 % (100/100) and 81 % (81/100) had binding activity with HCoV-OC43 and HCoV-HKU1, respectively.

Abstract Surface passivation has been developed as an effective strategy to reduce trap-state density and suppress non-radiation recombination process in perovskite solar cells. However, passivation agents usually own poor conductivity and hold negative impact on the charge carrier transport in device. Here, we report a binary and synergistical post-treatment method by blending 4-tert-butyl-benzylammonium iodide with phenylpropylammonium iodide and spin-coating on perovskite surface to form passivation layer. The binary and synergistical post-treated films show enhanced crystallinity and improved molecular packing as well as better energy band alignment, benefiting for the hole extraction and transfer. Moreover, the surface defects are further passivated compared with unary passivation. Based on the strategy, a record-certified quasi-steady power conversion efficiency of 26.0% perovskite solar cells is achieved. The devices could maintain 81% of initial efficiency after 450 h maximum power point tracking.

Abstract Background Umbilical cord blood (UCB) is a rich source of multifunctional stem cells characterized by low immunogenicity. Recent research in the fields of aging and regenerative medicine has revealed the potential of human umbilical cord blood-derived exosomes (UCB-Exos) in promoting wound healing, anti-aging, and regeneration. However, their role in neurodegenerative diseases, specifically Parkinson’s disease (PD), remains unexplored. This study investigates the potential therapeutic effects and underlying mechanisms of UCB-Exos on PD. Methods Large extracellular vesicles (LEv), Exos, and soluble fractions (SF) of human UCB plasma were extracted to investigate their effects on motor dysfunction of the MPTP-induced PD mouse model and identify the key components that improve PD symptoms. UCB-Exos were administered by the caudal vein to prevent or treat the PD mouse model. The motor function and pathological markers were detected. Differentially expressed gene and KEGG enrichment pathways were screened by transcriptome sequence. MN9D and SH-SY5Y cells were cultured and evaluated for cell viability, oxidative stress, cell cycle, and aging-related indexes by qRT-PCR, western blot, immunofluorescence, and flow cytometry. The protein expression level of the MAPK p38 and ERK1/2 signaling pathway was detected by western blot. Results We observed that LEv, Exos, and SF all exhibited potential in ameliorating motor dysfunction in MPTP-induced PD model mice, with UCB-Exos demonstrating the most significant effect. UCB-Exos showed comparable efficacy in preventing and treating motor dysfunction, cognitive decline, and substantia nigra pathological damage in PD mice. Further investigations revealed that UCB-Exos could potentially alleviate oxidative damage, aging and degeneration, and energy metabolism disorders in neurons. Transcriptome sequencing results corroborated that genes differentially expressed due to UCB-Exos were primarily enriched in the neuroactive ligand-receptor interaction, Dopaminergic synapse, and MAPK signaling pathway. We also observed that UCB-Exos significantly inhibited the hyperphosphorylation of the MAPK p38 and ERK1/2 signaling pathways both in vitro and in vivo. Conclusions Our study provides a comprehensive evaluation of UCB-Exos on the neuroprotective effects and suggests that inhibition of hyperphosphorylation of MAPK p38 and ERK 1/2 signaling pathways by regulating transcription levels of HspB1 and Ppef2 may be the key mechanism for UCB-Exos to improve PD-related pathological features. Graphical Abstract

Abstract The efficiency and stability of perovskite module devices are mainly limited by the quality of scalable perovskite films and sub-cells’ lateral contact. Here, firstly, we report constant low temperature substrate to regulate the growth of perovskite intermediate films to slow down the crystallization for obtaining high-quality homogeneous perovskite films in large scale size, which avoid the effect of the ambient temperature on the film quality. Secondly, a scribing step named P1.5 was added before the top function layers deposition, the diffusion barrier layer can be formed “naturally” at the interconnection interface without introducing any additional materials, which well alleviates the diffusion degradation process. As a result, our inverted perovskite devices exhibit a very small efficiency loss with area expansion comparable to other photovoltaic devices (for example, Cadmium Telluride), the perovskite module (aperture area 14.61 cm2) shows a certified quasi-steady-state power conversion efficiency of 22.73%, and the module maintaining over 90% of its initial efficiency after 1000 hours of continuous operation under illumination.

Abstract Background With advances in endoscopic submucosal dissection (ESD) technique, an increasing number of the Chinese population are being diagnosed with early gastric cancers (EGCs) at gastric angulus. However, the relationship between gastric angulus and EGCs remains obscure. Objectives We aimed to unveil the unreported location characteristics of gastric angulus in Chinese EGC patients and the correlation between the degree of submucosal fibrosis and ESD outcomes. Methods We retrospectively reviewed the medical records of EGC patients treated with ESD from January 2010 to March 2023. We retrospectively investigated and analyzed 740 EGC patients using multiple analyses. Results Following gastric antrum (53.1%), the gastric angulus (21.8%) emerged as the second-most prevalent site for EGCs. It had highest incidence of severe submucosal fibrosis and ulceration than the other parts. Multivariate analysis showed independent associations of submucosal fibrosis at the angulus with ulceration (OR: 3.714, 95% CI: 1.041–13.249), procedure duration (OR: 1.037, 95% CI: 1.014–1.061), and perforation complication (OR: 14.611, 95% CI: 1.626-131.277) (all P

Abstract Primary gastric adenosquamous carcinoma (PGASC) is a rare type of gastric cancer with limited research and poorly understood clinicopathological features. This study investigated the clinicopathological features and outcomes of PGASC. Patients with PGASC from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and from the published literature were enrolled in this study. Survival curves were generated using the Kaplan–Meier method, and prognostic factors were identified through Cox proportional hazards regression models. This study identified 76 eligible cases of PGASC, with 45 cases from published literature and 31 from our center. The most prevalent symptoms were abdominal pain and dysphagia, with a median age of 62 years (range: 29–84 years). The primary lesions were predominantly in the proximal stomach, with a median tumor size of 6.5 cm (range: 1.5–16.0 cm). Tumor stages II, III, and IV were detected in 12 (16.7%), 43 (59.7%), and 17 (23.6%) patients, respectively. Most tumors were poorly differentiated in both the squamous cell carcinoma (SCC) component and adenocarcinoma (AC) component. The median survival time was 17 months (range: 2–122 months). The 1, 3, and 5-year overall survival (OS) was 60.7%, 31.1%, and 24.1%, respectively. Multivariate analysis revealed that OS was independently predicted by the proportion of SCC component, differentiation of AC component, and tumor stage. PGASC is a rare disease with a poor prognosis. A high proportion of SCC components, low differentiated AC components, and advanced tumor were associated with worse survival in patients with PGASC. Adjuvant therapy did not improve survival time.

Abstract Introduction Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies. Methods A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay. Results Pharmacokinetic analysis of the drug concentration–time data showed that the mean maximum observed serum QX002N concentration (C max) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration–time curves from 0 to the time of the last quantifiable concentration (AUClast) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration–time curves from 0 to infinity (AUCinf) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%. Conclusions Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects. Trial Registration www.chinadrugtirals.org.cn , CTR20220430.

BackgroundThe pan-immune-inflammation value (PIV) is an emerging biomarker quantitatively reflecting the systemic immune-inflammatory status. The predictive value of PIV has been well-established across various clinical settings. However, its role in chronic obstructive pulmonary disease (COPD) remains unclear and necessitates further investigation.MethodsData from NHANES 1999–2018 were filtered. Logistic regression analyses were used to assess the correlation between COPD prevalence and PIV in all participants. COX regression analyses and Kaplan-Meier survival curves were used to investigate the relationship between COPD all-cause mortality and PIV in COPD patients. Restricted cubic spline (RCS) analyses and piecewise linear regression analyses were additionally employed to explore the correlation between PIV and COPD. Subgroup analyses were performed to further clarify the effects of other covariates on the associations. Sensitivity analyses were employed to assess the robustness of the results.ResultsA total of 28,485 participants aged 40 years and older were recruited for this study. After fully adjusting for covariates, higher PIV levels were independently associated with increased COPD prevalence (OR = 1.67; 95% CI: 1.39–2.01) and all-cause mortality (HR = 2.04; 95% CI: 1.41–2.95). The COPD prevalence curve exhibited an inflection point at Log10-PIV of 2.24, showing no significant correlation on the left side (OR = 0.86; 95% CI: 0.45–1.64) but a positive correlation on the right side (OR = 2.00; 95% CI: 1.57–2.55). The COPD all-cause mortality curve displayed an inflection point at Log10-PIV of 2.38, indicating a negative correlation on the left side (HR = 0.23; 95% CI: 0.12–0.44) and a positive correlation on the right side (HR = 4.12; 95% CI: 2.62–6.48). Subgroup analyses with interaction tests showed that the strength of the correlation between PIV and COPD prevalence was influenced by race, smoking status, and BMI (all p for interaction 0.05).ConclusionElevated PIV levels are associated with increased COPD prevalence. COPD patients with either elevated or reduced PIV levels experience higher all-cause mortality. Further large-scale, longitudinal studies are required to corroborate these findings.

Enhancing the endurance and efficiency of polymer electrolyte membrane fuel cells (PEMFCs) requires efficient thermal management. This comprehensive review examines the primary cooling techniques employed in PEMFC systems, concentrating on techniques for air and liquid cooling. Liquid cooling, which circulates a coolant through channels adjacent to the ability of the fuel cell stack to maintain ideal operating temperatures, is highlighted and significantly reduces temperature variations, thereby improving overall efficiency and lifespan. In contrast, air cooling, while simpler and more cost-effective, is less effective in high-power applications due to its reliance on ambient air for heat dissipation. The review also discusses advancements in thermal management strategies, including innovative designs for heat exchangers and the integration of thermal resistance networks, which enhance heat dissipation efficiency. Furthermore, the paper underscores the importance of developing durable materials to address catalyst and membrane degradation, and it explores the potential for integrating PEMFCs using renewable energy sources to encourage environmentally friendly transportation solutions. By identifying current challenges and proposing future research directions, this review aims to support the continuous creation of effective and reliable PEMFC technologies.

Abstract Background Diabetic retinopathy (DR) is a major cause of blindness and is characterized by dysfunction of the retinal microvasculature. Neutrophil stasis, resulting in retinal inflammation and the occlusion of retinal microvessels, is a key mechanism driving DR. These plugging neutrophils subsequently release neutrophil extracellular traps (NETs), which further disrupts the retinal vasculature. Nevertheless, the primary catalyst for NETs extrusion in the retinal microenvironment under diabetic conditions remains unidentified. In recent studies, cellular communication network factor 1 (CCN1) has emerged as a central molecule modulating inflammation in pathological settings. Additionally, our previous research has shed light on the pathogenic role of CCN1 in maintaining endothelial integrity. However, the precise role of CCN1 in microvascular occlusion and its potential interaction with neutrophils in diabetic retinopathy have not yet been investigated. Methods We first examined the circulating level of CCN1 and NETs in our study cohort and analyzed related clinical parameters. To further evaluate the effects of CCN1 in vivo, we used recombinant CCN1 protein and CCN1 overexpression for gain-of-function, and CCN1 knockdown for loss-of-function by intravitreal injection in diabetic mice. The underlying mechanisms were further validated on human and mouse primary neutrophils and dHL60 cells. Results We detected increases in CCN1 and neutrophil elastase in the plasma of DR patients and the retinas of diabetic mice. CCN1 gain-of-function in the retina resulted in neutrophil stasis, NETs extrusion, capillary degeneration, and retinal leakage. Pre-treatment with DNase I to reduce NETs effectively eliminated CCN1-induced retinal leakage. Notably, both CCN1 knockdown and DNase I treatment rescued the retinal leakage in the context of diabetes. In vitro, CCN1 promoted adherence, migration, and NETs extrusion of neutrophils. Conclusion In this study, we uncover that CCN1 contributed to retinal inflammation, vessel occlusion and leakage by recruiting neutrophils and triggering NETs extrusion under diabetic conditions. Notably, manipulating CCN1 was able to hold therapeutic promise for the treatment of diabetic retinopathy.

Abstract The semiconductor price index serves as a vital metric for assessing technological developments and related market trends. Establishing a more accurate forecasting model for the semiconductor price index is of significant importance for analyzing the industry’s trends and market directions. In this paper, a novel framework for semiconductor price index forecasting is proposed. In addition to traditional financial data, the study introduces search engine data (Google Trends) representing investor attention, and introduces text information extracted from online news headlines reflecting major market events and government policies as independent variables. Used to predict the dependent variable: The PHLX Semiconductor Sector (SOX). First, the XGBoost model is employed to compute the importance scores of each feature. Then, a feature weight coefficient indicator is constructed based on these importance scores to calculate the weight coefficient indicator values for each feature. These indicator values are then used to weight the kernel function of Support Vector Regression (SVR), resulting in weighted Support Vector Regression (WSVR). Finally, WSVR is utilized as the base learner for Adaptive Boosting (AdaBoost), yielding the XGBoost–WSVR–AdaBoost model based on feature weighting. The proposed model outperforms AdaBoost, RNN, ERT, LSTM, and other models in terms of Mean Absolute Percentage Error (MAPE) and goodness-of-fit ( $${R}^{2}$$ R 2 ). It also exhibits superior predictive performance compared to models in ablation experiments, and the introduction of text data or Google trends further improves the prediction performance of the model. In conclusion, the improved AdaBoost feature-weighted combination model proposed in this study offers a more accurate prediction for semiconductor price index.

Abstract Introduction This study aimed to assess the efficacy and safety of adalimumab in pediatric patients with chronic non-infectious posterior uveitis and panuveitis (not associated with juvenile idiopathic arthritis). Methods The medical records of children (

Abstract Background To investigate the role of C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) as early predictors of infectious complications after laparoscopic gastric cancer surgery. Methods Patients who underwent laparoscopic gastric cancer surgery between January 2020 and June 2022 were retrospectively enrolled. IL-6, PCT, and CRP levels were assessed before surgery and on postoperative days (PODs) 3 and 5. Differences in serum IL-6, PCT, and CRP levels between the infected and non-infected groups were compared. The diagnostic accuracy was determined using the area under the receiver operating characteristic curve (AUC). Results A total of 206 patients were enrolled, and 21 patients (10.19%) developed postoperative infections. Serum IL-6, PCT, and CRP levels in the infected group were significantly higher than those in the non-infected group on PODs 3 and 5. IL-6 with an optimal cutoff value of 84.00 pg/mL (AUC 0.84), PCT with an optimal cutoff value of 1.39 ng/mL (AUC 0.80), CRP with an optimal cutoff value of 150.00 mg/L (AUC 0.76) on POD 3 had superior diagnostic accuracy in predicting postoperative infections. Multivariate analysis identified PCT and IL-6 levels on POD 3 as independent risk factors, the AUC of the combination of IL-6 and PCT was 0.89. The Delong test showed no difference between the AUC of IL-6 alone and IL-6 combined with PCT prediction (P = 0.07, Z = 1.81). Conclusions IL-6 level on POD 3 is an excellent predictor of infectious complications following laparoscopic gastric cancer surgery. Patients with IL-6 levels lower than 84.00 pg/mL on POD 3 can ensure safe early discharge with a low probability of infection.

Abstract Quantum confinement is a restriction on the motion of electrons in a material to specific region, resulting in discrete energy levels rather than continuous energy bands. In certain materials, quantum confinement could dramatically reshape the electronic structure and properties of the surface with respect to the bulk. Here, in the recently discovered kagome superconductors CsV3Sb5, we unveil the dominant role of quantum confinement in determining their surface electronic structure. Combining angle-resolved photoemission spectroscopy (ARPES) measurement and density-functional theory simulation, we report the observations of two-dimensional quantum well states due to the confinement of bulk electron pocket and Dirac cone to the nearly isolated surface layer. The theoretical calculations on the slab model also suggest that the ARPES observed spectra are almost entirely contributed by the top two layers. Our results not only explain the disagreement of band structures between the recent experiments and calculations, but also suggest an equally important role played by quantum confinement, together with strong correlation and band topology, in shaping the electronic properties of this material.

An oxidising and substituting one-pot reaction strategy has been developed to synthesise dihydromyricetin derivatives with the aim of enhancing the inhibitory activity of dihydromyricetin against SARS-CoV-2. Different ω-methoxy-ω-oxeylkyl was introduced in C7-OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CLpro with IC50 values ranging from 0.72 to 2.36 μM. In the Vero E6-cell, compound 3 has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC50 of 15.84 μM, and so do compound 10 in the therapeutic model, with an EC50 of 11.52 μM. The results suggest that the introduction of long chain ω-oxeylkyl at C7-OH facilitate the inhibition of viral replication in the therapeutic model, which is consistent with the binding energies predicted from molecular docking conclusions. It implies that dihydromyricetin derivatives have the potential to become effective inhibitors of SARS-CoV-2 Omicron and other viruses.

The incidence of tuberculosis (TB) has declined more slowly in rural than urban areas in China, and data on the patterns of transmission and the high-risk populations in rural areas remains scarce. We conducted a population-based study of culture-positive pulmonary TB patients diagnosed in rural Linzhou City, Henan Province from July 2018 to February 2023. Genomic clusters were defined based on whole-genome sequencing and risk factors for clustering were identified by logistic regression. Transmission events were inferred with phybreak and transmission links were sought through epidemiological investigation of clustered patients. Logistic regression was used to explore the relationship between genomic differences of patient isolates and geographical distances of patient residences. Spatial hotspots were defined using kernel density estimation. Of 455 culture-positive patients, 430 were included in the final analysis. Overall, 192 (44.7%,192/430) patients were grouped into 49 clusters. Clusters containing ≥5 patients accounted for 18.4% (9/49) of the clusters and clustering was highest in student patients. No super-spreaders were detected. Confirmed epidemiologic links were identified for only 18.2% of clustered patients. The clustering risk decreased rapidly with increasing distances between patient residences, but 77.6% of clustered patient pairs lived ≥5.0 km apart. Both the Central Subdistrict and Rencun Township were identified as hotspots for TB transmission. Recent transmission appears to be an important driver of the TB burden in Linzhou. The formulation of effective strategies to reduce TB incidence in rural areas will require further studies to identify high-risk populations and venues where local inhabitants congregate and transmit the infection.

ABSTRACTFluoroquinolones (FQ) are essential for the treatment of multidrug-resistant tuberculosis (MDR-TB). The FQ resistance (FQ-R) rate in MDR-TB in China and its risk factors remain poorly understood. We conducted a retrospective, population-based genomic epidemiology study of MDR-TB patients in Shanghai, China, from 2009 to 2018. A genomic cluster was defined as strains with genetic distances ≤ 12 single nucleotide polymorphisms. The transmitted FQ-R was defined as the same FQ resistance-conferring mutations shared by ≥ 2 strains in a genomic cluster. We used multivariable logistic regression analysis to identify the risk factors for drug resistance. Among the total 850 MDR-TB patients included in the study, 72.8% (619/850) were male, the median age was 39 (interquartile range 28, 55) years, 52.7% (448/850) were migrants, and 34.5% (293/850) were previously treated patients. Most of the MDR-TB strains belong to the Beijing lineage (91.7%, 779/850). Overall, the genotypic resistance rate of FQ was 34.7% (295/850), and 47.1% (139/295) FQ-R patients were in genomic clusters, of which 98 (33.2%, 98/295) were presumed as transmitted FQ-R. Patients with treatment-naïve (aOR = 1.84; 95% CI: 1.09, 3.16), diagnosed in a district-level hospital (aOR = 2.69; 95% CI: 1.56, 4.75), and streptomycin resistance (aOR = 3.69; 95% CI: 1.65, 9.42) were significantly associated with the transmission of FQ-R. In summary, the prevalence of FQ-R among MDR-TB patients was high in Shanghai, and at least one-third were transmitted. Enforced interventions including surveillance of FQ drug susceptibility testing and screening among MDR-TB before initiation of treatment were urgently needed.

ABSTRACTInternal migrants are a challenge for TB control in large Chinese cities and understanding this epidemiology is crucial for designing effective control and prevention strategies. We conducted a prospective genomic epidemiological study of culture-positive TB patients diagnosed between June 1, 2018 and May 31, 2021 in the Longhua District of Shenzhen. Treatment status was obtained from local and national TB registries and all isolates were sequenced. Genomic clusters were defined as strains differing by ≤12 SNPs. Risk factors for clustering were identified with multivariable analysis and then Bayesian models and TransPhylo were used to infer the timing of transmission within clusters. Of the 2277 culture-positive patients, 70.1% (1596/2277) were migrants: 72.1% (1043/1446) of the migrants patients developed TB within two years of arriving in Longhua; 38.8% within 6 months of arriving; and 12.3% (104/843) had TB symptoms when they arrived. Only 15.4% of Longhua strains were in genomic clusters. More than one third (33.6%) of patients were not treated in Shenzhen but were involved in nearly one third of the recent transmission events. Clustering was associated with migrants not treated in Shenzhen, males, and teachers/trainers. TB in Longhua is prinicipally due to reactivation of infections in migrants, but a proportion may have had clinical or incipient TB upon arrival in the district. Patients diagnosed but not treated in Longhua were involved in recent local TB transmission. Controlling TB in Shenzhen will require strategies to comprehensively diagnose and treat active TB in the internal migrant population.

BackgroundImmune checkpoint blockade (ICB)-based immunotherapy has inspired new hope for advanced biliary tract cancer (BTC) treatment; however, there are no prior studies that primarily focus on different anatomical types of unresectable BTCs reacting differently to ICB.MethodsWe retrospectively collected data on advanced BTC patients who received anti-programmed cell death protein 1 (anti-PD1) therapy from two affiliated hospitals of Sun Yat-Sen university. The effects of anti-PD1 were compared for different anatomical sites. The GSE32225 and GSE132305 datasets were used to further analyze differences in the immune microenvironments between intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC).ResultsA total of 198 advanced BTC patients were enrolled in this study, comprising 142 patients with ICC and 56 with other cancer types (“Others” group), including ECC and gallbladder cancer. In the anti-PD1 treated patients, the ICC group (n = 90) achieved longer median progression-free survival (mPFS) (9.5 vs. 6.2 months, p = 0.02) and median overall survival (mOS) (15.1 vs. 10.7 months, p = 0.02) than the Others group (n = 26). However, chemotherapy did not show different effects between the two groups (mOS: 10.6 vs. 12.1 months, p = 0.20; mPFS: 4.9 vs. 5.7 months, p = 0.83). For the first-line anti-PD1 therapy, the ICC group (n = 70) achieved higher mOS (16.0 vs. 11.8 months, p = 0.04) than the Others group (n = 19). Moreover, most chemokines, chemokine receptors, major histocompatibility complex molecules, immunostimulators, and immunoinhibitors were stronger in ICC than ECC; furthermore, CD8+ T cells and M1 macrophages were higher in ICC than ECC for most algorithms. The immune differential genes were mainly enriched in antigen processing and presentation as well as the cytokine receptors.ConclusionsThis study shows that the efficacy of anti-PD1 therapy was higher in ICC than in other types of BTCs. Differences in the immune-related molecules and cells between ICC and ECC indicate that ICC could benefit more from immunotherapy.

Concrete is a widely used material for buildings, and its production reached approximately 10 billion m3 in 2022. Half of concrete-related buildings suffer seasonal freeze-thaw action, which causes frequent engineering damage, short service life and enormous economic loss. To improve the freeze-thaw resistance and durability of concretes, we used expanded graphite (EGC14) to encapsulate n-tetradecane (C14) and thus prepared a composite phase change material (EGC14). Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) tests indicate that the EGC14 is chemically stable and has excellent phase change capability. Then, five mass ratios of the EGC14 to concrete aggregates were designed to produce phase change concretes (PCCs), named as PCC-EGC14s (0%, 1%, 2%, 3%, and 4%). The PCC-EGC14s′ freeze-thaw resistance performances were systematically tested at different freeze-thaw cycles (FTCs). The test data demonstrate that the EGC14 could effectively keep the transition and capillary pores in the PCC-EGC14s from expanding into easily FTC-damaged macropores. Moreover, the more EGC14 the PCC-EGC14s contain, the less mass loss, and the larger dynamic moduli of elasticity (MOEd) and compressive strengths the PCC-EGC14s have. According to the strength requirement of C20 concretes, the PCC-EGC14 (3%) has the optimal freeze-thaw durability. Therefore, it is suggested for actual engineering applications. Of course, the mix design principle and experimental data of the new PCC-EGC14s in this work are helpful to comprehend the freeze-thaw process and mechanism of concretes and could also provide a critical reference for practical production.

BackgroundNumerous studies have shown that low levels of vitamin D are linked to a higher risk of inflammatory diseases and their progression. However, how vitamin D levels affect mortality in chronic obstructive pulmonary disease (COPD) patients is still unclear. Thus, this study aimed to explore the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and the risk of death from all causes in U.S. adults with COPD.MethodsThis study analyzed 1,876 adults with COPD from the National Health and Nutrition Examination Survey (2005–2018). Mortality data up to December 31, 2019, were obtained from the National Death Index (NDI) records. Participants were categorized into three groups according to their 25(OH)D levels: Q1 (

In order to play the important role of safety culture in accident prevention, we use the method of safety culture improvement based on accident causation “2-4” model (24Model) to study the status quo of safety culture construction in a coal enterprise and put forward improvement measures. Firstly, the applicability of the safety culture level improvement method in our country under the vision of 24Model is clarified. Then, starting with the current situation of safety culture level and safety concepts, we carry out practical research. Finally, the improvement measures are put forward. The results show that the safety culture level of the enterprise is generally better than that of the domestic or the same industry with poor safety performance, and worse than that of the enterprise with good safety performance; the enterprise’s safety concepts involves 13 aspects of 32 elements; the first-line workers, monitors, professionals and management of the enterprise have a poor understanding of some elements, and only elements 3, 4, 6, 13 and 16 of these poorly understood elements are reflected in the enterprise’s safety concepts; fourteen improved safety concepts are proposed to improve the enterprise’s safety culture level.

Abstract During the process of close-distance seam group mining, the coal pillar in the upper coal seam is a stress-concentrated area, which leads to a loss of stability of the roadway during mining of the lower coal seam. This lack of stability introduces great safety hazards to coal mines. To solve the problem of stress concentration of coal pillars, the method of gob-side entry retaining by roof cutting is proposed to remove the coal pillar. In this study, FLAC3D was used to analyze the depth and angle of pre-split blasting. LS-DYNA was used to analyze the spacing of the blasthole. Using the methods of theoretical analysis and numerical simulation, we determined that the optimal depth of the pre-split blasting was 6 m, the optimal angle for pre-split blasting was 15°, and the optimal spacing of the blasthole was 500 mm. A field test was carried out in the 1010201 ventilation roadway of the Yuwang Coal Mine, China. The on-site peeping results showed that when the spacing of the blasthole is 500 mm, connecting cracks can form under the action of blasting stress. After the working surface is mined, the roof strata could collapse and fill the gob over time when the depth and angle of the pre-split blasting are 6 m and 15°, respectively.

Electric vehicle (EV) charging spots require frequent inspections to identify potential safety hazards, and charging piles in charging spots exhibit a significant failure rate, necessitating maintenance. The efficiency and quality of inspection-maintenance are crucial components in the operation and management of charging spots, directly affecting the operation cost, service level, and user experience. The inspection-maintenance of EV charging spots requires two different types of personnel, and the impact on customer satisfaction cannot be ignored. In addition, the large-scale charging spots have further increased the difficulty of routing. A novel routing optimization problem for large-scale inspection-maintenance of EV charging spots is proposed in this paper, considering multiple types of personnel and composite customer satisfaction. While inspections can be carried out by general personnel, maintenance requires professional engineers. Composite customer satisfaction is with respect to the waiting time for maintenance of faulty charging spots and the duration of absence of professional engineers in the working station. A bi-objective routing optimization model is proposed, minimizing the cost of arranging personnel and traveling between charging spots, and the loss of composite customer satisfaction simultaneously. Due to the large scale of the problem caused by the enormous number of charging spots, an effective multi-stage solution approach is proposed. Finally, numerical experiments, managerial insights, and a case study are provided. The purpose of this research is to help the operators to decide the routes for inspection-maintenance of EV charging spots and offer valuable guidance in balancing operational efficiency with customer satisfaction.

This paper considers an agent identity privacy problem in Markov decision process. There are two types of agents with different instantaneous control reward functions, e.g., two types of energy consumption activities in smart grid. An eavesdropper is assumed to intercept the observations of agent and make a statistic inference on the agent identity, which is privacy-sensitive and can be utilized by the eavesdropper to further make corresponding malicious attacks. With regard to the agent identity privacy problem, a privacy-preserving Markov decision process is formulated and a novel adversarial reinforcement learning algorithm is further proposed by exploiting the ideas of deep reinforcement learning and variational method to design the agent policies with the aim to optimally tradeoff improving cumulative control reward and preventing agent identity privacy leakage. Experiments in a modified OpenAI Gym environment show different training process patterns and justify the effectiveness of the proposed algorithm.

Abstract Background Aging is a holistic change that has a major impact on the immune system, and immunosenescence contributes to the overall progression of aging. The bone marrow is the most important hematopoietic immune organ, while the spleen, as the most important extramedullary hematopoietic immune organ, maintains homeostasis of the human hematopoietic immune system (HIS) in cooperation with the bone marrow. However, the overall changes in the HIS during aging have not been described. Here, we describe a hematopoietic immune map of the spleen and bone marrow of young and old mice using single-cell sequencing and flow cytometry techniques. Results We observed extensive, complex changes in the HIS during aging. Compared with young mice, the immune cells of aged mice showed a marked tendency toward myeloid differentiation, with the neutrophil population accounting for a significant proportion of this response. In this change, hypoxia-inducible factor 1-alpha (Hif1α) was significantly overexpressed, and this enhanced the immune efficacy and inflammatory response of neutrophils. Our research revealed that during the aging process, hematopoietic stem cells undergo significant changes in function and composition, and their polymorphism and differentiation abilities are downregulated. Moreover, we found that the highly responsive CD62L + HSCs were obviously downregulated in aging, suggesting that they may play an important role in the aging process. Conclusions Overall, aging extensively alters the cellular composition and function of the HIS. These findings could potentially give high-dimensional insights and enable more accurate functional and developmental analyses as well as immune monitoring in HIS aging.

The effective disposal of healthcare waste is a highly concerned issue. Healthcare waste collection poses transport risks and temporary storing risks, and the deliberation undertaken by decision-makers concerning waste collection entails potential scenario wherein some hospitals have not yet submitted their service requests and may submit their requests during the healthcare waste collection procedure. A routing optimisation problem for healthcare waste collection with temporary storing risks and sequential uncertain service requests is introduced. A two-stage decision-making is proposed and mathematical models corresponding to each stage are developed. Different solution algorithms are developed for different stages or different scales of instances, including the improved $\varepsilon $ -constraint method and Non-dominated Sorting Genetic Algorithm-II for the solution procedure in Stage 1, and the Compare-choose-move algorithm for the solution procedure in Stage 2. Finally, the models and algorithms are tested by numerical instances and several suggestions for healthcare waste collection have been proposed based on sensitivity analysis.

BackgroundSarcopenia frequently occurs as a comorbidity in individuals with COPD. However, research on the impact of Appendicular Skeletal Muscle Mass (ASM) on survival in COPD patients is scarce. Moreover, there is a lack of research on the association between dietary pro-inflammatory capacity and sarcopenia in COPD.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) covering the years 1999 to 2006 and 2011 to 2018. We aimed to investigate the relationship between the Dietary Inflammatory Index (DII) and sarcopenia prevalence among adults diagnosed with COPD in the United States. Furthermore, we sought to explore the relationship between sarcopenia, ASMI, and all-cause mortality. The study included a total of 1,429 eligible adult participants, divided into four groups based on quartiles of DII, with adjustments for sample weights. Methodologically, we used multivariable logistic regression analyses and to examine the association between DII and sarcopenia. Additionally, we used restricted cubic spline (RCS) tests to evaluate potential non-linear relationships. To assess the effect of sarcopenia on overall all-cause mortality, we used Kaplan–Meier models and Cox proportional hazards models. Moreover, we used RCS analyses to investigate potential non-linear relationships between ASMI and all-cause mortality. Subgroup analyses were conducted to confirm the reliability of our study findings.ResultsIn our COPD participant cohort, individuals with higher DII scores were more likely to be female, unmarried, have lower educational attainment, and show lower ASMI. Using multivariable logistic regression models, we found a positive association between the highest quartile of DII levels and sarcopenia incidence [Odds Ratio (OR) 2.37; 95% Confidence Interval (CI) 1.26–4.48; p = 0.01]. However, analysis of RCS curves did not show a non-linear relationship between DII and sarcopenia. Throughout the entire follow-up period, a total of 367 deaths occurred among all COPD patients. Kaplan–Meier survival curves showed a significantly higher all-cause mortality rate among individuals with concurrent sarcopenia (p

ABSTRACTThere has been a suggestion of a potential protective effect of Helicobacter pylori (H. pylori) in the development of ulcerative colitis (UC). Virulence factor is an important factor in H. pylori, but little is known about the clinical characteristics of ulcerative colitis. In this retrospective study, a total of 322 patients with UC were analyzed. They were divided into three groups based on H. pylori antibody typing classification: type I H. pylori infection group, type II H. pylori infection group, and H. pylori-negative group. The study aimed to analyze the clinical characteristics of different types of H. pylori infection groups. The proportions of disease course, nationality, clinical type, and disease severity among UC patients in different types of H. pylori infection groups exhibited statistically significant differences (P < 0.05). However, no significant differences were observed in terms of sex, age, smoking status, alcohol consumption, body mass index (BMI), or lesion range (P > 0.05). Among the extraintestinal manifestations, the incidence of joint lesions in the type I H. pylori infection group was significantly lower compared with H. pylori-negative group (P < 0.05). The levels of red blood cell, hemoglobin, packed cell volume, albumin, A/G, and alanine aminotransferase were significantly higher in the type I H. pylori infection group compared with both the type II H. pylori infection group and H. pylori-negative group in the hematology index. Conversely, the levels of D-Dimer, C-reactive protein, and erythrocyte sedimentation rate were significantly lower in the type II H. pylori infection group (P < 0.05). In patients with UC, infections with the highly virulent type I H. pylori exhibit a negative correlation with both the severity of the disease and extraintestinal manifestations. While infections with the less virulent type II H. pylori are negatively correlated only with the disease severity. Therefore, the virulence factors of H. pylori play an important role in the regulation of UC.IMPORTANCEThe number of patients with ulcerative colitis (UC) has increased dramatically worldwide, posing a global public health challenge, There has been a suggestion of a potential protective effect of Helicobacter pylori in the development of UC. Virulence factor is an important factor in H. pylori, but high-quality clinical evidence is lacking. This study comprehensively analyzed the clinical characteristics of UC patients with different types of H. pylori infection. Infections with the highly virulent type I H. pylori are found to be negatively correlated with the severity of the disease as well as extraintestinal manifestations, whereas infections with the less virulent type II H. pylori demonstrate a negative correlation solely with disease severity. These results suggest that the virulence factors of H. pylori play a pivotal role in UC. Consequently, virulence factors should be taken into consideration when targeting H. pylori eradication in clinical practice, particularly in UC patients. It is crucial to evaluate the individual benefits to optimize personalized eradication therapies.

Abstract Background Laparoscopic gastrectomy (LG) is increasingly applied in locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy (NC). However, there is no study to comprehensively evaluate the clinicopathological, prognostic, and laboratory data such as nutrition, immune, inflammation-associated indexes, and tumor markers between LG and open gastrectomy (OG) for LAGC following NC. Methods The clinicopathological, prognostic, and laboratory data of LAGC patients with clinical stage of cT2-4aN1-3M0 who underwent gastrectomy after NC were retrospectively collected. The effects of LG and OG were compared after propensity score matching (PSM). Results This study enrolled 148 cases, of which 110 cases were included after PSM. The LG group had a shorter length of incision (P

Abstract Aim Atrial fibrillation (AF) is a progressive disease from paroxysmal to persistent, and persistent AF (PerAF) had worse prognosis. AF has potential link with inflammation, but it is not clear whether PerAF or paroxysmal AF (ParAF) is more closely related to inflammation. On the basis of inhibiting myocardial physiological uptake, 18F-fluorodeoxyglucosepositron emission tomography/computed tomography (18F-FDG PET/CT) is an established imaging modality to detect cardiac inflammation. We aimed to decipher the association between AF and atrial inflammatory activity by 18F-FDG PET/CT. Methods Thirty-five PerAF patients were compared to age and sex matched ParAF group with baseline 18F-FDG PET/CT scans prior to radiofrequency catheter ablation (RFCA) in the prospective case-control study. High-fat and low-carbohydrate diet and prolonged fast (HFLC+Fast) was applied to all AF patients before PET/CT. Then 22 AF patients with positive right atrial (RA) wall FDG uptake (HFLC+Fast) were randomly selected and underwent HFLC+Fast+heparin the next day. The CHA2DS2-VASc score was calculated to evaluate the risk of stroke. Clinical data, ECG, echocardiography, and atrial 18F-FDG uptake were compared. Results PerAF patients had significantly higher probability of RA wall positive FDG uptake and higher SUVmax than ParAF group [91.4% VS. 28.6%, P

Abstract Colorectal cancer (CRC) is one of the most common malignant cancers worldwide and seriously threatens human health. The clustered regulatory interspaced short palindromic repeat/CRISPR-associate nuclease 9 (CRISPR/Cas9) system is an adaptive immune system of bacteria or archaea. Since its introduction, research into various aspects of treatment approaches for CRC has been accelerated, including investigation of the oncogenes, tumor suppressor genes (TSGs), drug resistance genes, target genes, mouse model construction, and especially in genome-wide library screening. Furthermore, the CRISPR/Cas9 system can be utilized for gene therapy for CRC, specifically involving in the molecular targeted drug delivery or targeted knockout in vivo. In this review, we elucidate the mechanism of the CRISPR/Cas9 system and its comprehensive applications in CRC. Additionally, we discussed the issue of off-target effects associated with CRISPR/Cas9, which serves to restrict its practical application. Future research on CRC should in-depth and systematically utilize the CRISPR/Cas9 system thereby achieving clinical practice.

Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction. Herein, we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin (IND) and antioxidant superoxide dismutase (SOD) by assembling the biopharmaceutical SOD onto the “vector” of rod-like pure IND crystals, followed by coating with anti-ICAM-1 antibody (Ab) for targeting endothelial cells. The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39% IND and 2.3% SOD. Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide (LPS)-induced inflammatory murine model. Particularly, the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect. In vitro, the preparation shows the synergistic anti-inflammatory and antioxidant effects in LPS-activated endothelial cells. In vivo, the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers, such as TNF-α, IL-6, COX-2, and reactive oxygen species (ROS), in the lungs. In conclusion, the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation. The study offers a promising approach to combat pulmonary endothelium-associated diseases.

Accurate and effective oxaliplatin (OXP) concentration detection is essential for maximizing therapeutic advantages and reducing negative effects of this anti-cancer therapy. Using a nanocomposite-based sensor, we present in this paper a novel method for electrochemical OXP detection. It is made of graphitic carbon nitride (g-C3N4) and titanium dioxide (TiO2) nanoparticles embedded on a glassy carbon electrode (GCE) using the hydrothermal method. The X-ray diffractometer (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) structural investigations revealed that the g-C3N4-TiO2 nanocomposite material is composed of anatase TiO2 and g-C3N4 phases. Using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) analyses, electrochemical tests demonstrated that g-C3N4-TiO2/GCE was a sensitive and selective OXP sensor. According to the results, the sensor has a linear range of 10 to 2030 μM, a sensitivity value of 0.04811μA/μM, and a detection limit of 0.010 μM. The recommended sensor's effectiveness in detecting OXP in prepared real samples from blood serum and urine samples of volunteers demonstrated significant recovery values (yielding recovery values exceeding 94.00%) and satisfactory precision (with a relative standard deviation of less than 4.23%), demonstrating that the g-C3N4-TiO2/GCE sensor was dependable and accurate for measuring OXP levels in serum and urine samples.

Abstract Background The inflammasome plays an important role in rheumatoid arthritis (RA), which has rarely been systematically reported. The aim of this study was to understand whether the levels of inflammasomes were related to the severity of RA disease, which might provide a stronger theoretical basis for RA treatment. Methods The mRNA expression levels of some inflammasomes and associated molecules, including IL-1beta and IL-18, in peripheral blood mononuclear cells (PBMCs) from 30 RA patients (n = 30) and 16 healthy control (HC) individuals were determined by quantitative real-time polymerase chain reaction (qRT‒PCR), and the levels of plasma IL-1beta and IL-18 were also measured by enzyme-linked immunosorbent assay (ELISA). Moreover, the clinical characteristics and laboratory results of the patients were collected and analyzed in this study. Results The relative mRNA expression levels of NLRP3, NLRC4, AIM2, caspase-1, and IL-1beta were significantly higher and those of NLRP1, NLRP2 and NLRC5 were notably lower in the HC group than in the RA group. Moreover, the plasma IL-1beta and IL-18 levels were markedly increased in the RA group. Additionally, the mRNA level of AIM2 was negatively correlated with disease activity score 28 (DAS28) by stepwise linear regression analysis. erythrocyte sedimentation rate (ESR) was positively correlated with DAS28 by multiple linear regression analysis in the RA group. Conclusions These findings imply the critical role of NLRP3, NLRC4, AIM2, caspase-1 and plasma IL-1beta and IL-18 in the pathogenesis of RA patients, which provides potential targets for the treatment of RA.

Abstract Real-time quantitative polymerase chain reaction (RT-qPCR) is the most common method to determine mRNA expression, and Minimum Information for Publication of RT-qPCR Experiments (MIQE) proposes that a panel of reference genes for RT-qPCR is conducive to obtaining accurate results. This study aimed to screen and verify the optimal panel of reference genes in colorectal cancer (CRC) and normal colonic cell lines. In the study, eight candidate reference genes (GAPDH, ACTB, 18S, PPIA, B2M, SDHA, GUSB, and YWHAZ) were selected for RT-qPCR to detect their expression in NCM460, HT29, HCT116, SW480, SW620, DLD-1, LOVO and RKO cell lines. The stability of reference genes and the optimal panel were evaluated by geNorm, NormFinder, and BestKeeper software. As results, the expression levels of candidate reference genes differed in the colonic epithelial cell lines, and the number of optimal panel of reference genes is two. B2M and YWHAZ were the two most stable reference genes for NCM460, HCT116, SW620, LOVO, and RKO cell lines, while only one of B2M and YWHAZ was most stable in HT29 and SW480 cells. In DLD-1 cells, the stability of B2M and YWHAZ ranked 3rd and 6th, PPIA and GUSB were the most stable two. Furthermore, the YWHZA + B2M performed smaller intragroup differences than other panel or single reference gene. In conclusion, this study indicates the optimal panel of reference genes is YWHZA + B2M for the NCM460, HCT116, SW620, LOVO, RKO, SW480, and HT29 cell lines, but it is PPIA + GUSB in DLD-1 cell lines.

Abstract Background This multi-center study aimed to identify factors affecting fever and delayed defervescence in bacterial meningitis (BM) patients under 3 years of age because of the variability of fever in this patient population. Methods Only BM patients under 3 years treated at 49 centers in China from November 2018 to end-April 2021 were included in the study. Univariate and multivariate logistic regression analyses were performed to determine factors associated with afebrile presentation and fever of delayed defervescence. Results A total of 863 BM patients under 3 years were included in the study. Coagulase negative staphylococcus was associated with afebrile presentation (OR = 1.176), while septicaemia and ear-nose-throat infections were associated with fever (P

The rapidly developing additive Manufacturing (AM) technology could overcome the critical dimension limit of metallic glasses (MGs). This permits to obtain MG components with complex geometry and large dimensions. However, the residual defects, such as pores and cracks in AMed MGs, significantly deteriorate their performance. Thus, it is essential to suppress and eliminate the pores and cracks that remain after additive manufacturing.This paper critically reviews the pores and cracks in the laser powder bed fusion (LPBF) fabricated MGs, including recent achievements and challenges in depressing their initiation, alleviating their propagation, and eliminating their collapse. The recent advances in LPBFed MGs and the suppression strategies of pores and cracks, such as parameters optimization, scanning strategy alteration, second phase's introduction, substrate and MG system selection as well as components performance improvement with designed porosity, are reviewed and commented, especially for several specific MG systems. The pores and cracks initiation and alleviation mechanisms are further analyzed. Also, the unsolved issues, challenges, and future research directions are evaluated. Finally, concluding remarks and an outlook concerning the pores and cracks issues in LPBFed MGs are further provided.

The advancement of more precise remote sensing inversion technology for dust aerosols has long been a hot topic in the field of the atmospheric environment. In 2023, China experienced 18 dust-related weather events, predominantly in spring. These high-intensity and frequent dust events have attracted considerable attention. However, gridded observation data of dust intensity levels are not collected in current dust monitoring and forecasting operations. Based on the Himawari 9 geostationary satellite data, this study establishes a new method to identify spring dust events. This method integrates the brightness temperature difference method and the multiple infrared dust index, taking into account the response discrepancies of the multiple infrared dust index under various underlying surfaces. Furthermore, by obtaining dynamic background brightness temperature values eight times a day, threshold statistics are applied to analyze the correlation between the infrared difference dust index and ground-observed dust level, so as to establish a satellite-based near-surface dust intensity level identification algorithm. This algorithm aims to improve dust detection accuracy, and to provide more effective gridded observation support for dust forecasting and monitoring operations. The test results indicate that the algorithm can effectively identify the presence or absence of dust, with a misjudgment rate of less than 3%. With regard to dust intensity, the identification of blowing sand and floating dust aligns relatively well with ground-based observations, but notable uncertainties exist in determining a dust intensity of sand-storm level or above. Among these uncertainties, the differences between ground-based observations and satellite identification caused by non-grounded dust in the upper air, and the selection of dust identification thresholds, are two important error sources in the dust identification results of this study.

Privacy by design (PbD) has attracted considerable attention from researchers and information security experts due to its enormous potential for protecting private information and improving the privacy and security quality of information technology products. The adoption of PbD among information engineers is currently limited owing to its innovativeness and the distinctive traits of the information technology industry. Utilising the Technology Acceptance Model as a framework, this study innovatively explores the pivotal factors and mechanisms that influence information engineers’ decision-making in the adoption of PbD from the viewpoint of the perceived work risk. In this empirical research, professional information engineers were invited to complete a questionnaire survey. After analysing the data using partial least squares structural equation modelling, the results reveal that information engineers’ perceived work risk in PbD (PWRP) negatively affects their perceptions of the usefulness and ease of use of PbD. This negative perception subsequently reduces their intention to implement PbD (INTP) and adversely impacts their attitudes towards implementing PbD (ATTP). Furthermore, the study findings reveal that a positive ATTP among engineers boosts their INTP and positively influences their behaviours regarding information security. This study provides an in-depth examination of these findings and lays a solid theoretical groundwork for the further promotion and implementation of PbD in information technology enterprises. Moreover, the findings offer invaluable support for management decisions in both information technology companies and information security regulatory authorities, significantly contributing to the expansion and deepening of research in the field of PbD.

Lead (Pb) is a major source of heavy metal contamination, and poses a threat to biodiversity and human health. Elevated levels of Pb can hinder insect growth and development, leading to apoptosis via mechanisms like oxidative damage. The midgut of silkworms is the main organ exposed to heavy metals. As an economically important lepidopteran model insect in China, heavy metal-induced stress on silkworms causes considerable losses in sericulture, thereby causing substantial economic damage. This study aimed to investigate Pb-induced detoxification-related genes in the midgut of silkworms using high-throughput sequencing methods to achieve a deeper comprehension of the genes’ reactions to lead exposure. This study identified 11,567 unigenes and 14,978 transcripts. A total of 1265 differentially expressed genes (DEGs) were screened, comprising 907 upregulated and 358 downregulated genes. Subsequently, Gene Ontology (GO) classification analysis revealed that the 1265 DEGs were distributed across biological processes, cellular components, and molecular functions. This suggests that the silkworm midgut may affect various organelle functions and biological processes, providing crucial clues for further exploration of DEG function. Additionally, the expression levels of 12 selected detoxification-related DEGs were validated using qRT-PCR, which confirmed the reliability of the RNA-seq results. This study not only provides new insights into the detoxification defense mechanisms of silkworms after Pb exposure, but also establishes a valuable foundation for further investigation into the molecular detoxification mechanisms in silkworms.

The fuel leakage of fuel vehicles will exacerbate the occurrence of distresses on asphalt pavements, including peeling, chipping and potholes, especially under the synergistic effect of traffic load and environment. In this research, Sasobit, which is commonly used as a warm agent in asphalt, is selected as the anti-fuel erosion agent and incorporated into SBS-modified asphalt and its mixtures. Diesel and gasoline are selected as the fuel erosion media. Sasobit/SBS-modified asphalt binder and its mixtures are investigated for fuel erosion. The rheological properties of bitumen and the mechanical properties of asphalt mixtures are assessed. The experimental findings show that the dissolution velocity of SBS-modified asphalt with 3% Sasobit is 0.2%/min for diesel erosion, while it is 1.7%/min for gasoline erosion, lower than the control sample without Sasobit. Meanwhile, the rutting factor of Sasobit/SBS-modified asphalt decreases less than that of the control sample without Sasobit. Furthermore, the mass loss ratio after the Cantabro test of Sasobit/SBS-modified asphalt mixtures is 1.2% for diesel erosion, while it is 6.8% for gasoline erosion, lower than that of the control sample without Sasobit. The results of the mechanical properties for asphalt mixtures demonstrate that Sasobit can enhance the anti-fuel erosion performance. Moreover, the research results of the Sasobit modification mechanism show that Sasobit can form a microcrystalline structure in SBS-modified asphalt, which subsequently improves the anti-fuel of asphalt and its mixtures. This research provides a reference for anti-fuel erosion assessment methods and solutions to improve the anti-fuel erosion of asphalt pavement.

Self-assembled DNA nanospheres, as versatile and ideal vehicles, have offered new opportunities to create intelligent delivery systems for precise bioimaging and cancer therapy, due to their good biostability and cell permeability, large loading capacity, and programmable self–assembly behaviors. DNA nanospheres can be synthesized by the self–assembly of Y–shaped DNA monomers, ultra–long single-stranded DNA (ssDNA), and even metal–DNA coordination. Interestingly, they are size–controllable by varying some parameters including concentration, reaction time, and mixing ratio. This review summarizes the design of DNA nanospheres and their extensive biomedical applications. First, the characteristics of DNA are briefly introduced, and different DNA nanostructures are mentioned. Then, the design of DNA nanospheres is emphasized and classified into three main categories, including Y–shaped DNA unit self-assembly by Watson–Crick base pairing, liquid crystallization and the dense packaging of ultra–long DNA strands generated via rolling circle amplification (RCA), and metal–DNA coordination–driven hybrids. Meanwhile, the advantages and disadvantages of different self–assembled DNA nanospheres are discussed, respectively. Next, the biomedical applications of DNA nanospheres are mainly focused on. Especially, DNA nanospheres serve as promising nanocarriers to deliver functional nucleic acids and drugs for biosensing, bioimaging, and therapeutics. Finally, the current challenges and perspectives for self-assembled DNA nanospheres in the future are provided.

Abstract Background Improving the potency of immune response is paramount among issues concerning immunotherapy of muscle‐invasive bladder cancer (MIBC). Methods On the basis of immune subtypes, we investigated possible molecular mechanisms involved in tumor immune escape in MIBC. According to the 312 immune‐related genes, three MIBC immune subtypes were clustered. Results Cluster 2 subtype is characterized by FGFR3 mutations and has a better clinical prognosis. However, the expression levels of MHC‐I and immune checkpoints genes were the lowest, indicating that this subtype is subject to immune escape and has a low response rate to immunotherapy. Bioinformatics analysis and immunofluorescence staining of clinical samples revealed that the FGFR3 is involved in the immune escape in MIBC. Besides, after FGFR3 knockout with siRNA in RT112 and UMUC14 cells, the TLR3/NF‐kB pathway was significantly activated and was accompanied by upregulation of MHC‐I and PD‐L1 gene expression. Furthermore, the use of TLR3 agonists poly(I:C) can further improve the effect. Conclusion Together, our results suggest that FGFR3 might involve in immunosuppression by inhibition of NF‐kB pathway in BC. Considering that TLR3 agonists are currently approved for clinical treatment as immunoadjuvants, our study might provide more insights for improving the efficacy of immunotherapy in MIBC.

The malicious attacks of Byzantine nodes in federated learning was studied over the non-independent and identically distributed dataset , and a privacy protection robust gradient aggregation algorithm was proposed.A reference gradient was designed to identify “poor quality” shared gradients in model training, and the influence of heterogeneity data on Byzantine node recognition was reduced by reputation evaluation.Meanwhile, the combination of homomorphic encryption and random noise obfuscation technology was introduced to protect user privacy in the process of model training and Byzantine node recognition.Finally, through the evaluation over the real-world datasets, the simulation results show that the proposed algorithm can accurately and efficiently identify Byzantine attack nodes while protecting user privacy and has good convergence and robustness.

Abstract Background Prostate cancer (PC) is the most common cancer in older men in Europe and the United States and has the second highest death rate among male cancers. The transcription of heat shock proteins by Heat shock factor 1 (HSF1) is known to regulate cell growth and stress. Nevertheless, the impact of HSF1 on ferroptosis in PC through heat shock protein 10 (HSPE1) remains unexplored. Methods This study employed a range of analytical techniques, including proteomics sequencing, LC–MS/MS, CHIP-qPCR, Western blotting, immunohisto -chemistry, JC-1, CKK-8, MDA, and ROS assays. Bioinformatics analysis was performed using the UALCAN,GEPIA, PCaDB and Metascape platforms. Results Compared with levels observed in tumor-adjacent tissue, the levels of proteins associated with fatty acids, amino acids and the oxidative phosphorylation metabolic pathway were significantly upregulated in high-risk PC tissue (Gleason score ≥ 8). HSF1 mRNA and protein levels in high-risk PC tissues were significantly higher than those observed in medium-risk PC (Gleason score = 7) and low-risk PC (Gleason score ≤ 6) tissues. ssGSEA showed that HSF1 was involved in the proliferation and anti-apoptotic processes of PC. Further bioinformatics analysis showed that HSF1 potentially affects the mitochondrial oxidative phosphorylation (OXPHOS) system by targeting HSPE1. In addition, HSF1 alleviates ROS and MDA levels to enhance the resistance of prostate cancer cells to ferroptosis by regulating HSPE1 in vitro, and HSF1 knockout promotes the susceptibility of PC to RSL3 treatment by increasing ferroptosis in vivo. Conclusion Collectively, our findings suggest that HSF1 exerts a significant influence on PC. HSF1 may represent a promising biomarker for identifying high-risk PC, and the elimination of HSF1 could potentially enhance the therapeutic effectiveness of RSL3.

Abstract Background Autoimmune uveitis (AU) is the most common ophthalmic autoimmune disease (AD) and is characterized by a complex etiology, high morbidity, and high rate of blindness. AU remission has been observed in pregnant female patients. However, the effects of progesterone (PRG), a critical hormone for reproduction, on the treatment of AU and the regulatory mechanisms remain unclear. Methods To this end, we established experimental autoimmune uveitis (EAU) animal models and constructed a high-dimensional immune atlas of EAU-model mice undergoing PRG treatment to explore the underlying therapeutic mechanisms of PRG using single-cell RNA sequencing. Results We found that PRG ameliorated retinal lesions and inflammatory infiltration in EAU-model mice. Further single-cell analysis indicated that PRG reversed the EAU-induced expression of inflammatory genes (AP-1 family, S100a family, and Cxcr4) and pathological processes related to inflammatory cell migration, activation, and differentiation. Notably, PRG was found to regulate the Th17/Treg imbalance by increasing the reduced regulatory functional mediators of Tregs and diminishing the overactivation of pathological Th17 cells. Moreover, the Id2/Pim1 axis, IL-23/Th17/GM-CSF signaling, and enhanced Th17 pathogenicity during EAU were reversed by PRG treatment, resulting in the alleviation of EAU inflammation and treatment of AD. Conclusions Our study provides a comprehensive single-cell map of the immunomodulatory effects of PRG therapy on EAU and elaborates on the possible therapeutic mechanisms, providing novel insights into its application for treating autoimmune diseases.

Abstract Background Both inflammatory bowel disease (IBD) and hepato‐pancreato‐biliary cancers (HPBC) have been established to cause a huge socioeconomic burden. Epidemiological studies have revealed a close association between IBD and HPBC. Methods Herein, we utilized inverse‐variance weighting to conduct a two‐sample Mendelian randomization analysis. We sought to investigate the link between various subtypes of IBD and HPBC. To ensure the accuracy and consistency of our findings, we conducted heterogeneity tests, gene pleiotropy tests, and sensitivity analyses. Results Compared to the general population, IBD patients in Europe exhibited a 1.22‐fold increased incidence of pancreatic cancer (PC) with a 95% confidence interval (CI) of 1.0022–1.4888 (p = 0.0475). We also found a 1.14‐fold increased incidence of PC in Crohn's disease (CD) patients with (95% CI: 1.0017–1.3073, p = 0.0472). In the East Asian population, the incidence of hepatocellular carcinoma (HCC) was 1.28‐fold higher (95% CI = 1.0709–1.5244, p = 0.0065) in IBD patients than in the general population. Additionally, ulcerative colitis (UC) patients displayed 1.12‐fold (95% CI: 1.1466–1.3334, p

Abstract Background The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and subsequent Coronavirus Disease 2019 (COVID-19) pandemic has resulted in a significant global public health burden, leading to an urgent need for effective therapeutic strategies. Monoclonal antibodies (mAbs) are a potentially effective therapeutic option. We identified a potent antibody JMB2002 against the SARS-CoV-2 receptor binding domain. JMB2002 has demonstrated therapeutic efficacy in a SARS-CoV-2 infected rhesus macaque model. Methods We conducted a randomized, double-blind, phase 1 trial to evaluate the JMB2002’s safety, tolerability, pharmacokinetics, and immunogenicity in healthy Chinese adults. Participants were randomly assigned to one of four cohorts with sequential dose, administrated intravenously with JMB2002 or placebo, and followed up for 85 ± 5 days. Results 40 participants were recruited and completed in the study. Eight (25.0%) participants experienced 13 treatment emergent adverse events (TEAEs) that were drug-related. No serious adverse events (SAEs), dose limiting events (DLTs), or adverse events of special interest (AESIs), such as infusion related/allergic reactions, were observed, and no drop out due to adverse events (AEs) occurred. There was no significant safety difference observed between JMB2002 and the placebo, suggesting it was well tolerated. The AUC0−∞, AUC0 − t of JMB2002 infusion increased dose-dependently from 5 mg/kg to 50 mg/kg while there is also a linear trend between doses and Cmax. Conclusion Therefore, JMB2002 was well tolerated after administration of a single dose in the range of 5 mg/kg to 50 mg/kg in healthy Chinese adults. Trial registration ChiCTR2100042150 at https://www.chictr.org.cn/searchproj.aspx (14/01/2021).