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Abstract Background: There may be potential associations between various pathogens, antibody immune responses, and breast cancer (BC), but the specific mechanisms and causal relationships remain unclear. Methods: First, multiple Mendelian randomization (MR) methods were used for univariable MR analysis to explore potential causal relationships between 34 antibody immune responses (related to 12 pathogens), 46 antibody immune responses (related to 13 pathogens), antibody responses post-COVID-19 vaccination, 731 immune cell types, and various BC subtypes (including overall BC, ER-positive, ER-negative, Luminal A, Luminal B, Luminal B HER2-negative, HER2-positive, and triple-negative BC). The primary results were then subjected to reverse MR analysis, heterogeneity testing using Cochran’s Q, and horizontal pleiotropy testing. Robust findings were further used to design mediation pathways involving antibody immune responses, immune cells, and BC. After adjusting the effect estimates using multivariable MR (MVMR), a two-step mediation analysis was conducted to explore mediation pathways and mediation proportions. Finally, linkage disequilibrium score regression (LDSC) was applied to analyze the genetic correlation between phenotypes along mediation pathways, and cross-phenotype association analysis (CPASSOC) was performed to identify pleiotropic SNPs among three phenotypes along these pathways. Bayesian colocalization tests were conducted on pleiotropic SNPs using the multiple-trait-coloc (moloc). Results: We identified potential causal relationships between 15 antibody immune responses to 8 pathogens (Hepatitis B virus, Herpes Simplex Virus 2, Human Herpesvirus 6, Polyomavirus 2, BK polyomavirus, Cytomegalovirus, Helicobacter pylori, Chlamydia trachomatis), 250 immune cell phenotypes, and various BC subtypes. MVMR-adjusted mediation analysis revealed four potential mediation pathways. LDSC results showed no significant genetic correlation between phenotypes pairwise. CPASSOC analysis identified two potential mediation pathways with common pleiotropic SNPs (rs12121677, rs281378, rs2894250). However, none of these SNPs passed the Bayesian colocalization test by moloc. These results excluded horizontal pleiotropy, stabilizing MR analysis results. Conclusion: This study utilized MR methods to analyze potential causal relationships between various antibody immune responses, immune cell types, and BC subtypes, identifying four potential regulatory mediation pathways. The findings of this study offer potential targets and research directions for virus-related and immunotherapy-related studies, providing a certain level of theoretical support. However, limitations such as GWAS sample size constraints and unclear specific pathophysiological mechanisms need further improvement and validation in future studies.

Abstract The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CLpro), and papain-like protease (PLpro) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CLpro inhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CLpro from SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms. Through the application of a structure-based drug design (SBDD) approach, we discover a series of novel potent non-covalent PLpro inhibitors with remarkable in vitro potency and in vivo PK properties. The co-crystal structures of PLpro with lead compounds reveal that the residues D164 and Q269 around the S2 site are critical for improving the inhibitor’s potency. The lead compound GZNL-P36 not only inhibits SARS-CoV-2 and its variants at the cellular level with EC50 ranging from 58.2 nM to 306.2 nM, but also inhibits HCoV-NL63 and HCoV-229E with EC50 of 81.6 nM and 2.66 μM, respectively. Oral administration of the GZNL-P36 results in significantly improved survival and notable reductions in lung viral loads and lesions in SARS-CoV-2 infection mouse model, consistent with RNA-seq data analysis. Our results indicate that PLpro inhibitors represent a promising SARS-CoV-2 therapy.

Abstract Pancreatic ductal adenocarcinoma (PDAC), characterized by a dense extracellular matrix (ECM), presents significant therapeutic challenges due to its poor prognosis and high resistance to chemotherapy. Current chemodrugs and diagnostic agents largely fail to cross the barrier posed by the ECM, which severely limits the PDAC theranostics. This study introduces a novel theranostic strategy using thioether-hybridized hollow mesoporous organosilica nanoparticles (dsMNs) for the co-delivery of copper (Cu) and disulfiram (DSF), aiming to induce cuproptosis in PDAC cells. Our approach leverages the ECM-degrading enzyme collagenase, integrated with dsMNs, to enhance drug penetration by reducing matrix stiffness. Furthermore, the innovative use of a pancreatic cancer cell membrane coating on the nanoparticles enhances tumor targeting and stability (dsMCu-D@M-Co). The multifunctional platform not only facilitates deep drug penetration and triggers cuproptosis effectively but also utilizes the inherent properties of Cu to serve as a T1-weighted magnetic resonance imaging (MRI) contrast agent. In vitro and in vivo assessments demonstrate significant tumor size reduction in PDAC-bearing mice, highlighting the dual functionality of our platform in improving therapeutic efficacy and diagnostic precision. This integrated strategy represents a significant advancement in the management of PDAC, offering a promising new direction for overcoming one of the most lethal cancers. Graphical Abstract

Abstract Background Dental implants are becoming a popular treatment of choice. Immediate implant placement with immediate loaded full-arch fixed dental prostheses (IPILFFDP) presents an attractive solution for edentulous and partially edentulous patients because of its high success rate, reduction in overall treatment time, and improved esthetics. However, whether it can minimize the risk of temporomandibular disorder (TMD) has not been previously studied. Objective To quantitatively evaluate the temporomandibular joint (TMJ) morphology changes before and after IPILFFDP, using cone beam computed tomography (CBCT). Methods Twelve participants without TMJ symptoms undergoing IPILFFDP were included in the study. Preoperative and 1-year postoperative assessment of CBCT scans were performed on 18 items related to TMJ and vertical dimensions. Mimics software was used for data analysis. T-test, Pearson, and Spearman correlation analyses were performed. Results There were no significant differences in bilateral joints between pre and post IPILFFDP. Compared with pre-treatment CBCT, post-treatment CBCT showed a significant increase in posterior joint space. There was an approximately 2 mm increase in the vertical dimension after IPILFFDP, which is correlated with an increase in the medial joint space. Conclusions For patients without TMJ-related signs and symptoms, the IPILFFDP could keep the neuromuscular memory of patient’s facial muscles and occlusion, and use adapted centric posture as a guide, which led to more precise restoration of the original jaw position and may shed light in future related clinical studies.

Abstract Background Previous studies have yielded inconsistent findings regarding the association between age at menopause and bone health, with limited exploration of potential mediating factors, particularly in the less-developed muti-ethnic regions of China. Our objective was to analyze the association between age at menopause and bone health among postmenopausal women in southwest China, while also examining the mediating effect of body mass index (BMI) and the moderating effect of years since menopause on this association. Methods and results The analysis included a total of 15,352 naturally postmenopausal women obtained from the baseline data of the China Multi-Ethnic Cohort (CMEC) Study. Multiple linear regression was used for multivariate analysis. Mediation analysis was conducted to examine the mediating role of BMI in the association between age at menopause and bone health. A significant positive association was observed between age at menopause and bone health index (Quantitative ultrasound index, QUI). Specifically, with each year’s delay in age at menopause, there was an increase of 0.260 (95% confidence interval (CI): 0.152–0.368) in QUI. Notably, women with later menopause (menopausal age ≥ 53 years) exhibited a higher QUI (β: 2.684, 95%CI: 1.503–3.865). Additionally, BMI partially mediated the relationship between age at menopause and QUI, accounting for 9.0% of the total effect, with an indirect effect coefficient β(95%CI) was 0.023(0.014, 0.032). Besides, it is worth mentioning that years since menopause moderated the association between age at menopause and bone health as well as the mediating effect of BMI. Conclusion Naturally postmenopausal women with a later age at menopause demonstrate enhanced bone health. Maintaining a moderately high BMI, without progressing to overweight or obesity, may provide health benefits for postmenopausal women, especially for those with a longer duration since menopause.

Abstract Hydrogel-based tissue expansion combined with mass spectrometry (MS) offers an emerging spatial proteomics approach. Here, we present a filter-aided expansion proteomics (FAXP) strategy for spatial proteomics analysis of archived formalin-fixed paraffin-embedded (FFPE) specimens. Compared to our previous ProteomEx method, FAXP employed a customized tip device to enhance both the stability and throughput of sample preparation, thus guaranteeing the reproducibility and robustness of the workflow. FAXP achieved a 14.5-fold increase in volumetric resolution. It generated over 8 times higher peptide yield and a 255% rise in protein identifications while reducing sample preparation time by 50%. We also demonstrated the applicability of FAXP using human colorectal FFPE tissue samples. Furthermore, for the first time, we achieved bona fide single-subcellular proteomics under image guidance by integrating FAXP with laser capture microdissection.

Abstract Sepsis-associated encephalopathy (SAE) is a frequent and severe complication in septic patients, characterized by diffuse brain dysfunction resulting from systemic inflammation. Accurate prediction of long-term mortality in these patients is critical for improving clinical outcomes and guiding treatment strategies. We conducted a retrospective cohort study using the MIMIC IV database to identify adult patients diagnosed with SAE. Patients were randomly divided into a training set (70%) and a validation set (30%). Least absolute shrinkage and selection operator regression and multivariate logistic regression were employed to identify significant predictors of 1-year mortality, which were then used to develop a prognostic nomogram. The model’s discrimination, calibration, and clinical utility were assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis, respectively. A total of 3,882 SAE patients were included in the analysis. The nomogram demonstrated strong predictive performance with AUCs of 0.881 (95% CI: 0.865, 0.896) in the training set and 0.859 (95% CI: 0.830, 0.888) in the validation set. Calibration plots indicated good agreement between predicted and observed 1-year mortality rates. The decision curve analysis showed that the nomogram provided greater net benefit across a range of threshold probabilities compared to traditional scoring systems such as Glasgow Coma Scale and Sequential Organ Failure Assessment. Our study presents a robust and clinically applicable nomogram for predicting 1-year mortality in SAE patients. This tool offers superior predictive performance compared to existing severity scoring systems and has significant potential to enhance clinical decision-making and patient management in critical care settings.

Abstract Background Glehnia littoralis F. Schmidt ex Miq., an endangered plant species with significant medicinal, edible, and ecological value, is now a central concern for conservation and sustainable utilization. Investigating the physiological and ecological mechanisms leading to its endangerment and elucidating its genetic background constitutes the foundation for conducting in-depth research on G. littoralis. Results Our observations have revealed a significant degree of floral sterility in wild populations of G. littoralis. The inflorescences of G. littoralis are classified into three types: completely fertile, completely sterile, and partially fertile compound umbels. Moreover, the flowers of G. littoralis can be categorized into fertile and sterile types. Sterile flowers exhibited abnormalities in the stigma, ovary, and ovules. This study is the first to discover that the presence or absence of a giant cell at the funiculus during the initiation of ovule primordium determines whether the flower can develop normally, providing cytological evidence for female sterility in G. littoralis. Conversely, both fertile and sterile flowers produced normally developed pollen. Field observations have suggested that robust plants bear more fertile umbels, while weaker ones have fewer or even no fertile umbels, indicating a close relationship between flower fertility and plant nutritional status. Our model correctly predicted that the eastern coastal regions of China, as well as prospective areas in Neimenggu and Sichuan, are suitable environments for its cultivation. Additionally, Using flow cytometry and genome survey, we estimated the genome size of G. littoralis to be 3.06 Gb and the heterozygosity to be 4.58%. Conclusion The observations and findings presented in this study were expected to provide valuable insights for further conserving its genetic resources and sustainable utilization of G. littoralis.

Abstract Intracranial aneurysm is the primary cause of nontraumatic subarachnoid hemorrhage. To assess aneurysm metabolism, we present a method of intra-operatively collecting blood samples from the aneurysm neck, as well as the proximal and distal responsible vessels, using microcatheters. Through these paired comparisons, we can eliminate the interpatient variation usually observed in plasma samples taken from the peripheral vein. We utilized 39 plasma samples from 13 intracranial patients to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry. Our findings revealed that l-tyrosine is upregulated at relatively high levels at the aneurysm neck than the proximal and distal aneurysm, whereas phenylpyruvic acid, l-cystine, and l-ornithine are downregulated. Based on this, there was also a significant decrease in arginine within small aneurysm of the internal carotid artery. The 6-month follow-up indicated that patients who experienced good recovery had lower levels of biliverdin, bilirubin, and metabolites of coenzyme Q within the aneurysm. In conclusion, our investigation provides a comprehensive overview of plasma metabolites in patients with intracranial aneurysms, shedding light on potential pathogenetic mechanisms in unruptured intracranial aneurysms. Moreover, the study proposes innovative ideas for establishing postoperative follow-up timelines for flow diverter devices.

Abstract Background To compare the difference of postoperative anastomotic leakage (AL) rate between neoadjuvant chemoradiotherapy (NCRT) with pembrolizumab and NCRT group, and investigate the risk factors of developing AL for locally advanced esophageal squamous cell cancer (ESCC). Materials and methods The GF was contoured on the pretreatment planning computed tomography and dosimetric parameters were retrospectively calculated. Univariate and multivariate logistic regression analysis was performed to determine the independent risk predictors for the entire cohort. A nomogram risk prediction model for postoperative AL was established. Results A total of 160 ESCC patients were included for analysis. Of them, 112 were treated with NCRT with pembrolizumab and 44 patients with NCRT. Seventeen (10.6%) patients experienced postoperative AL with a rate of 10.7% (12/112) in NCRT with pembrolizumab and 11.4% (5/44) in NCRT group. For the entire cohort, mean, D50, Dmax, V5, V10 and V20 GF dose were statistically higher in those with AL (all p

Abstract Not all patients with glioblastoma multiforme (GBM) eligible for systemic chemotherapy after upfront surgery and radiotherapy finally receive it. The information on patients with GBM was retrieved from the surveillance, epidemiology, and end results database. Patients who underwent upfront surgery or biopsy and external beam radiotherapy between 2010 and 2019 were eligible for systemic chemotherapy. The available patient and tumor characteristics were assessed using multivariable logistic regression and chi-squared test. Out of the 16,682 patients eligible, 92.1% underwent systemic chemotherapy. The characteristics linked to the lowest systemic chemotherapy utilization included tumors of the brain stem/cerebellum (P = 0.01), former years of diagnosis (P = 0.001), ≥ 80 years of age (P

Abstract Electrocatalytic CO2 reduction to multi-carbon products is a promising approach for achieving carbon-neutral economies. However, the energy efficiency of these processes remains low, particularly at high current densities. Herein, we demonstrate that the low energy efficiencies are, in part, sometimes significantly, attributed to the high concentration overpotential resulting from the instability (i.e., flooding) of catalyst-layer during electrolysis. To tackle this challenge, we develop copper/gallium bimetallic catalysts with reduced activation energies for the formation of multi-carbon products. Consequently, the reduced activation overpotential allows us to achieve practical-relevant current densities for CO2 reduction at low cathodic potentials, ensuring good stability of the catalyst-layer and thereby minimizing the undesired concentration overpotential. The optimized bimetallic catalyst achieves over 50% cathodic energy efficiency for multi-carbon production at a high current density of over $$1.0 \, {{\rm{A}}} \, {{\rm{cm}}}^{-2}$$ 1.0 A cm − 2 . Furthermore, we achieve current densities exceeding $$2.0 \, {{\rm{A}}} \, {{\rm{cm}}}^{-2}$$ 2.0 A cm − 2 in a zero-gap membrane-electrode-assembly reactor, with a full-cell energy efficiency surpassing 30%.

Abstract Grouting technology is the primary method for repairing cracks in earthen sites. However, there has been a long-standing lack of effective methods for evaluating grouting effectiveness. This paper proposes a field evaluation method based on P-wave velocity. This method explicitly discusses two scenarios where the P-wave velocity of the grout is either higher or lower than that of the soil, using the depth ℎ of the “hypothetical crack” as the evaluation indicator. The experimental results indicate that specimens with 20% and 40% defects show increases in ℎ values of 0.0113 m and 0.0166 m, respectively. Laboratory tests have demonstrated that this method can accurately evaluate grouting effectiveness and is not affected by the P-wave velocity of the soil. The application of this evaluation method to three typical earthen sites resulted in more reliable and easily quantifiable evaluation outcomes. By considering the width of grout, the method provides a more intuitive comparison of reparation effectiveness. The study demonstrates the feasibility of the proposed method, thereby facilitating effective crack reparation in earthen sites.

Abstract Extensive efforts have been dedicated to exploring the impact of tumor heterogeneity on cancer treatment at both histological and genetic levels. To accurately measure intra-tumoral heterogeneity, a non-invasive imaging technique, known as habitat imaging, was developed. The technique quantifies intra-tumoral heterogeneity by dividing complex tumors into distinct sub- regions, called habitats. This article reviews the following aspects of habitat imaging in cancer treatment, with a focus on radiotherapy: (1) Habitat imaging biomarkers for assessing tumor physiology; (2) Methods for habitat generation; (3) Efforts to combine radiomics, another imaging quantification method, with habitat imaging; (4) Technical challenges and potential solutions related to habitat imaging; (5) Pathological validation of habitat imaging and how it can be utilized to evaluate cancer treatment by predicting treatment response including survival rate, recurrence, and pathological response as well as ongoing open clinical trials.

Abstract Preharvest sprouting (PHS) is a serious problem in rice production as it leads to reductions in grain yield and quality. However, the underlying mechanism of PHS in rice remains unclear. In this study, we identified and characterized a preharvest sprouting and seedling lethal (phssl) mutant. The heterozygous phssl/+ mutant exhibited normal plant development, but severe PHS in paddy fields. However, the homozygous phssl mutant was seedling lethal. Gene cloning and genetic analysis revealed that a point mutation in OsABA3 was responsible for the mutant phenotypes. OsABA3 encodes a molybdenum cofactor (Moco) sulfurase. The activities of the sulfureted Moco-dependent enzymes such as aldehyde oxidase (AO) and xanthine dehydrogenase (XDH) were barely detectable in the phssl mutant. As the final step of abscisic acid (ABA) de novo biosynthesis is catalyzed by AO, it indicated that ABA biosynthesis was interrupted in the phssl mutant. Exogenous application of ABA almost recovered seed dormancy of the phssl mutant. The knock-out (ko) mutants of OsABA3 generated by CRISPR-Cas9 assay, were also seedling lethal, and the heterozygous mutants were similar to the phssl/+ mutant showing reduced seed dormancy and severe PHS in paddy fields. In contrast, the OsABA3 overexpressing (OE) plants displayed a significant increase in seed dormancy and enhanced plant resistance to PHS. The AO and XDH activities were abolished in the ko mutants, whereas they were increased in the OE plants. Notably, the Moco-dependent enzymes including nitrate reductase (NR) and sulfite oxidase (SO) showed reduced activities in the OE plants. Moreover, the OE plants exhibited enhanced resistances to osmotic stress and bacterial blight, and flowered earlier without any reduction in grain yield. Taken together, this study uncovered the crucial functions of OsABA3 in Moco sulfuration, plant development, and stress resistance, and suggested that OsABA3 is a promising target gene for rice breeding.

Abstract Respiratory syncytial virus (RSV) hijacks cholesterol or autophagy pathways to facilitate optimal replication. However, our understanding of the associated molecular mechanisms remains limited. Here, we show that RSV infection blocks cholesterol transport from lysosomes to the endoplasmic reticulum by downregulating the activity of lysosomal acid lipase, activates the SREBP2–LDLR axis, and promotes uptake and accumulation of exogenous cholesterol in lysosomes. High cholesterol levels impair the VAP-A-binding activity of ORP1L and promote the recruitment of dynein–dynactin, PLEKHM1, or HOPS VPS39 to Rab7–RILP, thereby facilitating minus-end transport of autophagosomes and autolysosome formation. Acidification inhibition and dysfunction of cholesterol-rich lysosomes impair autophagy flux by inhibiting autolysosome degradation, which promotes the accumulation of RSV fusion protein. RSV-F storage is nearly abolished after cholesterol depletion or knockdown of LDLR. Most importantly, the knockout of LDLR effectively inhibits RSV infection in vivo. These findings elucidate the molecular mechanism of how RSV co-regulates lysosomal cholesterol reprogramming and autophagy and reveal LDLR as a novel target for anti-RSV drug development.

Abstract Background Protein phosphatase class 2 C (PP2C) is the largest protein phosphatase family in plants. Members of the PP2C gene family are involved in a variety of physiological pathways in plants, including the abscisic acid signalling pathway, the regulation of plant growth and development, etc., and are capable of responding to a wide range of biotic and abiotic stresses, and play an important role in plant growth, development, and response to stress. Apocynum is a perennial persistent herb, divided into Apocynum venetum and Apocynum hendersonii. It mainly grows in saline soil, deserts and other harsh environments, and is widely used in saline soil improvement, ecological restoration, textiles and medicine. A. hendersonii was found to be more tolerant to adverse conditions. The main purpose of this study was to investigate the PP2C gene family and its expression pattern under salt stress and to identify important candidate genes related to salt tolerance. Results In this study, 68 AvPP2C genes and 68 AhPP2C genes were identified from the genomes of A. venetum and A. hendersonii, respectively. They were classified into 13 subgroups based on their phylogenetic relationships and were further analyzed for their subcellular locations, gene structures, conserved structural domains, and cis-acting elements. The results of qRT-PCR analyses of seven AvPP2C genes and seven AhPP2C genes proved that they differed significantly in gene expression under salt stress. It has been observed that the PP2C genes in A. venetum and A. hendersonii exhibit different expression patterns. Specifically, AvPP2C2, 6, 24, 27, 41 and AhPP2C2, 6, 24, 27, 42 have shown significant differences in expression under salt stress. This indicates that these genes may play a crucial role in the salt tolerance mechanism of A. venetum and A. hendersonii. Conclusions In this study, we conducted a genome-wide analysis of the AvPP2C and AhPP2C gene families in Apocynum, which provided a reference for further understanding the functional characteristics of these genes.

Abstract Controlling the concentrations of H2O and CO2 at the reaction interface is crucial for achieving efficient electrochemical CO2 reduction. However, precise control of these variables during catalysis remains challenging, and the underlying mechanisms are not fully understood. Herein, guided by a multi-physics model, we demonstrate that tuning the local H2O/CO2 concentrations is achievable by thin polymer coatings on the catalyst surface. Beyond the often-explored hydrophobicity, polymer properties of gas permeability and water-uptake ability are even more critical for this purpose. With these insights, we achieve CO2 reduction on copper with Faradaic efficiency exceeding 87% towards multi-carbon products at a high current density of −2 A cm−2. Encouraging cathodic energy efficiency (>50%) is also observed at this high current density due to the substantially reduced cathodic potential. Additionally, we demonstrate stable CO2 reduction for over 150 h at practically relevant current densities owning to the robust reaction interface. Moreover, this strategy has been extended to membrane electrode assemblies and other catalysts for CO2 reduction. Our findings underscore the significance of fine-tuning the local H2O/CO2 balance for future CO2 reduction applications.

Abstract Comprehending the catalyst structural evolution during the electrocatalytic process is crucial for establishing robust structure/performance correlations for future catalysts design. Herein, we interrogate the structural evolution of a promising Cu-Ag oxide catalyst precursor during electrochemical carbon monoxide reduction. By using extensive in situ and ex situ characterization techniques, we reveal that the homogenous oxide precursors undergo a transformation to a bimetallic composite consisting of small Ag nanoparticles enveloped by thin layers of amorphous Cu. We believe that the amorphous Cu layer with undercoordinated nature is responsible for the enhanced catalytic performance of the current catalyst composite. By tuning the Cu/Ag ratio in the oxide precursor, we find that increasing the Ag concentration greatly promotes liquid products formation while suppressing the byproduct hydrogen. CO2/CO co-feeding electrolysis and isotopic labelling experiments suggest that high CO concentrations in the feed favor the formation of multi-carbon products. Overall, we anticipate the insights obtained for Cu-Ag bimetallic systems for CO electroreduction in this study may guide future catalyst design with improved performance.

Articular cartilage has limited self-healing ability, resulting in injuries often evolving into osteoarthritis (OA), which poses a significant challenge in the medical field. Although some treatments exist to reduce pain and damage, there is a lack of effective means to promote cartilage regeneration. Reactive Oxygen Species (ROS) have been found to increase significantly in the OA micro-environment. They play a key role in biological systems by participating in cell signaling and maintaining cellular homeostasis. Abnormal ROS expression, caused by internal and external stimuli and tissue damage, leads to elevated levels of oxidative stress, inflammatory responses, cell damage, and impaired tissue repair. To prevent excessive ROS accumulation at injury sites, biological materials can be engineered to respond to the damaged microenvironment, release active components in an orderly manner, regulate ROS levels, reduce oxidative stress, and promote tissue regeneration. Hydrogels have garnered significant attention due to their excellent biocompatibility, tunable physicochemical properties, and drug delivery capabilities. Numerous antioxidant hydrogels have been developed and proven effective in alleviating oxidative stress. This paper discusses a comprehensive treatment strategy that combines antioxidant hydrogels with existing treatments for OA and explores the potential applications of antioxidant hydrogels in cartilage tissue engineering.

Photodynamic therapy and ferroptosis induction have risen as vanguard oncological interventions, distinguished by their precision and ability to target vulnerabilities in cancer cells. Photodynamic therapy’s non-invasive profile and selective cytotoxicity complement ferroptosis’ unique mode of action, which exploits iron-dependent lipid peroxidation, offering a pathway to overcome chemoresistance with lower systemic impact. The synergism between photodynamic therapy and ferroptosis is underscored by the depletion of glutathione and glutathione peroxidase four inhibitions by photodynamic therapy-induced reactive oxygen species, amplifying lipid peroxidation and enhancing ferroptotic cell death. This synergy presents an opportunity to refine cancer treatment by modulating redox homeostasis. Porphyrin-based nanoscale metal-organic frameworks have unique hybrid structures and exceptional properties. These frameworks can serve as a platform for integrating photodynamic therapy and ferroptosis through carefully designed structures and functions. These nanostructures can be engineered to deliver multiple therapeutic modalities simultaneously, marking a pivotal advance in multimodal cancer therapy. This review synthesizes recent progress in porphyrin-modified nanoscale metal-organic frameworks for combined photodynamic therapy and ferroptosis, delineating the mechanisms that underlie their synergistic effects in a multimodal context. It underscores the potential of porphyrin-based nanoscale metal-organic frameworks as advanced nanocarriers in oncology, propelling the field toward more efficacious and tailored cancer treatments.

IntroductionGas migration in low-permeability buffer materials is a crucial aspect of nuclear waste disposal. This study focuses on Gaomiaozi bentonite to investigate its behavior under various conditions.MethodsWe developed a coupled hydro-mechanical model that incorporates damage mechanisms in bentonite under flexible boundary conditions. Utilizing the elastic theory of porous media, gas pressure was integrated into the soil's constitutive equation. The model accounted for damage effects on the elastic modulus and permeability, with damage variables defined by the Galileo and Coulomb–Mohr criteria. We conducted numerical simulations of the seepage and stress fields using COMSOL and MATLAB. Gas breakthrough tests were also performed on bentonite samples under controlled conditions.ResultsThe permeability obtained from gas breakthrough tests and numerical simulations was within a 10% error margin. The experimentally measured gas breakthrough pressure aligned closely with the predicted values, validating the model's applicability.DiscussionAnalysis revealed that increased dry density under flexible boundaries reduced the damage area and influenced gas breakthrough pressure. Specifically, at dry densities of 1.4 g/cm³, 1.6 g/cm³, and 1.7 g/cm³, the corresponding gas breakthrough pressures were 5.0 MPa, 6.0 MPa, and 6.5 MPa, respectively. At a dry density of 1.8 g/cm³ and an injection pressure of 10.0 MPa, no continuous seepage channels formed, indicating no gas breakthrough. This phenomenon is attributed to the greater tensile and compressive strengths associated with higher dry densities, which render the material less susceptible to damage from external forces.

Background Early recognition and accurate diagnosis are particularly important in the context of gastric cancer. This study mainly aimed to investigate primary care physicians’ (PCPs’) clinical behaviour and their readiness to consider investigation or referral for symptoms possibly indicative of gastric cancer.Design Cross-sectional study.Setting A self-administered online survey was carried out in five selected cities in the Fujian province of China between February 2022 and May 2022.Participant PCPs working in the departments, such as Internal Gastroenterology and Hepatology, General Internal Medicine, Internal Medical Oncology Gastrointestinal Surgery or other clinical departments, have the chance to diagnose or treat patients with suspected gastric cancer.Main outcome measures Percentage of PCPs identifying gastric cancer patients either by undertaking an endoscopy at the primary hospital or by referring patients to an upper-level hospital.Results A total of 1210 complete responses were received. Nearly half of responding PCPs (46.4%) only had less than 5 years of clinical experience, and the majority worked in suburban or rural regions (64.4%). Direct access to blood tests for cancer diagnosis (77.9%), X-ray (77.2%), CT (55.7%), ultrasound (85.3%), upper gastrointestinal endoscopy (54.4%) and colonoscopy (51.9%) was common. Of the respondents, 85.5% reported that they could get specialist advice for a suspected cancer patient within 48 hours in terms of investigations and 84.0% in terms of referral. Patients’ waiting time to either conduct a test or have a result was mostly less than 1 week. In patients indicative of gastric cancer, a total of 1148 (94.8%) physicians were ready to investigate cancer either by sending patients to an endoscopy test (49.7%) or referring them to an upper-level hospital (45.1%).Conclusions Findings indicate that PCPs in five selected cities of Southeastern China have wide and rapid access to diagnostic tests and specialist advice. Furthermore, PCPs in this region seem to have a high level of readiness to consider investigation or referral for symptoms possibly indicative of gastric cancer.

BackgroundThe purpose of this real-world study was to investigate the risk factors for developing recurrence among patients with pathological T1-3N0 breast cancer (BC) treated with breast-conserving surgery (BCS) followed by whole breast irradiation alone (WBI) and identify those clinically high-risk BCs who could benefit from regional nodal irradiation (RNI).Materials and methodsFemale BC patients treated at Shanghai Ruijin hospital from 2009 to 2016 were retrospectively reviewed. The disease-free survival (DFS), breast cancer specific survival (BCSS) and overall survival (OS) were estimated by the Kaplan-Meier method, and survival differences were compared with the log-rank test. Univariate and multivariate analysis was performed using Cox proportional hazards regression analysis. An external validation was conducted by using SEER database.ResultsA total of 622 BC patients treated with BCS+WBI alone were included. With a median follow-up of 82 months, the 7-year OS, BCSS and DFS for the entire cohort was 97%, 99% and 91%, respectively. Multivariable Cox analysis indicated that tumor size (p=0.006), tumor location (p=0.033), lymphovascular invasion (LVI) status (p=0.0028) and Ki-67 index (p=0.051) were independent risk factors for DFS. A scoring system was developed using these four factors and the 7-year DFS and OS were 97% and 96% for patients with 0-1 risk factors, 95% and 82% for patients with ≥2 risk factors (p

Abstract The collection of multiple-channel electrophysiological signals enables a comprehensive understanding of the spatial distribution and temporal features of electrophysiological activities. This approach can help to distinguish the traits and patterns of different ailments to enhance diagnostic accuracy. Microneedle array electrodes, which can penetrate skin without pain, can lessen the impedance between the electrodes and skin; however, current microneedle methods are limited to single channels and cannot achieve multichannel collection in small areas. Here, a multichannel (32 channels) microneedle dry electrode patch device was developed via a dimensionality reduction fabrication and integration approach and supported by a self-developed circuit system to record weak electrophysiological signals, including electroencephalography (EEG), electrocardiogram (ECG), and electromyography (EMG) signals. The microneedles reduced the electrode–skin contact impedance by penetrating the nonconducting stratum corneum in a painless way. The multichannel microneedle array (MMA) enabled painless transdermal recording of multichannel electrophysiological signals from the subcutaneous space, with high temporal and spatial resolution, reaching the level of a single microneedle in terms of signal precision. The MMA demonstrated the detection of the spatial distribution of ECG, EMG and EEG signals in live rabbit models, and the microneedle electrode (MNE) achieved better signal quality in the transcutaneous detection of EEG signals than did the conventional flat dry electrode array. This work offers a promising opportunity to develop advanced tools for neural interface technology and electrophysiological recording.

This is an article in the field of environmental engineering. In this article, the composition, structural characteristics and surface properties of coal gasification crude slag (CGCS) and coal gasification fine slag (CGFS) were characterized by X-ray fluorescence analyzer, scanning electron microscopy, FTIR spectroscopy, specific surface area and pore size analysis, and the results showed that CGFS had a more developed pore size structure and larger specific surface area. The adsorption test results show that the adsorption of n-butyl sodium xanthate by the two coal gasification slags is consistent with the Langmuir adsorption isotherm model and is a spontaneous heat process, which conforms to the quasi-secondary kinetic model, and the adsorption rate constant CGFS > CGCS. Among them, the adsorption performance of CGFS to n-butyl sodium xantho can reach 181.95 mg/g due to CGCS.

Abstract Background The interaction of dysbiosis of gut microbiota (GM) with diabetic nephropathy (DN) drew our attention and a better understanding of GM on DN might provide potential therapeutic approaches. However, the exact causal effect of GM on DN remains unknown. Methods We applied two-sample Mendelian Randomization (MR) analysis, including inverse variance weighted (IVW), MR-Egger methods, etc., to screen the significant bacterial taxa based on the GWAS data. Sensitivity analysis was conducted to assess the robustness of MR results. To identify the most critical factor on DN, Mendelian randomization-Bayesian model averaging (MR-BMA) method was utilized. Then, whether the reverse causality existed was verified by reverse MR analysis. Finally, transcriptome MR analysis was performed to investigate the possible mechanism of GM on DN. Results At locus-wide significance levels, the results of IVW suggested that order Bacteroidales (odds ratio (OR) = 1.412, 95% confidence interval (CI): 1.025–1.945, P = 0.035), genus Akkermansia (OR = 1.449, 95% CI: 1.120–1.875, P = 0.005), genus Coprococcus 1 (OR = 1.328, 95% CI: 1.066–1.793, P = 0.015), genus Marvinbryantia (OR = 1.353, 95% CI: 1.037–1.777, P = 0.030) and genus Parasutterella (OR = 1.276, 95% CI: 1.022–1.593, P = 0.032) were risk factors for DN. Reversely, genus Eubacterium ventriosum (OR = 0.756, 95% CI: 0.594–0.963, P = 0.023), genus Ruminococcus gauvreauii (OR = 0.663, 95% CI: 0.506–0.870, P = 0.003) and genus Erysipelotrichaceae (UCG003) (OR = 0.801, 95% CI: 0.644–0.997, P = 0.047) were negatively associated with the risk of DN. Among these taxa, genus Ruminococcus gauvreauii played a crucial role in DN. No significant heterogeneity or pleiotropy in the MR result was found. Mapped genes (FDR

Introduction Our goal was to systematically review the current evidence comparing the relative effectiveness of two maxillary sinus floor elevation (MSFE) approaches (internal and external) without bone grafts with that of conventional/grafted MSFE in patients undergoing implantation in the posterior maxilla. Material and Methods Medical databases (PubMed/Medline, Embase, Web of Science, and Cochrane Library) were searched for randomised controlled trials published between January 1980 and May 2023. A manual search of implant-related journals was also performed. Studies published in English that reported the clinical outcomes of MSFE with or without bone material were included. The risk of bias was assessed using the Cochrane Handbook Risk Assessment Tool. Meta-analyses and trial sequence analyses were performed on the included trials. Meta-regression analysis was performed using pre-selected covariates to account for substantial heterogeneity. The certainty of evidence for clinical outcomes was assessed using GRADEpro GDT online (Guideline Development Tool). Results Seventeen studies, including 547 sinuses and 696 implants, were pooled for the meta-analysis. The meta-analysis showed no statistically significant difference between MSFE without bone grafts and conventional MSFE in terms of the implant survival rate in the short term (n = 11, I2 = 0%, risk difference (RD): 0.03, 95% confidence intervals (CI): –0.01–0.07, p = 0.17, required information size (RIS) = 307). Although conventional MSFE had a higher endo-sinus bone gain (n = 13, I2 = 89%, weighted mean difference (WMD): –1.24, 95% CI: –1.91– –0.57, p = 0.0003, RIS = 461), this was not a determining factor in implant survival. No difference in perforation (n = 13, I2 = 0%, RD = 0.03, 95% CI: –0.02–0.09, p = 0.99, RIS = 223) and marginal bone loss (n = 4, I2 = 0%, WMD = 0.05, 95% CI: –0.14–0.23, p = 0.62, no RIS) was detected between the two groups using meta-analysis. The pooled results of the implant stability quotient between the two groups were not robust on sensitivity analysis. Because of the limited studies reporting on the visual analogue scale, surgical time, treatment costs, and bone density, qualitative analysis was conducted for these outcomes. Conclusions This systematic review revealed that both non-graft and grafted MSFE had high implant survival rates. Owing to the moderate strength of the evidence and short-term follow-up, the results should be interpreted with caution.

Abstract Pancreatic cancer is one of the most malignant tumor types and is characterized by high metastasis ability and a low survival rate. As a chromatin-binding protein, HMGA2 is widely overexpressed and considered an oncogene with various undefined regulatory mechanisms. Herein, we demonstrated that HMGA2 is highly expressed in pancreatic cancer tissues, mainly distributed in epithelial cells, and represents a subtype of high epithelial–mesenchymal transition. Deletion of HMGA2 inhibits tumor malignancy through cell proliferation, metastasis, and xenograft tumor growth in vivo. Moreover, HMGA2 enhanced the cellular redox status by inhibiting reactive oxygen species and promoting glutathione production. Importantly, ferroptotic cell death was significantly ameliorated in cells overexpressing HMGA2. Conversely, HMGA2 deletion exacerbated ferroptosis. Mechanistically, HMGA2 activated GPX4 expression through transcriptional and translational regulation. HMGA2 binds and promotes cis-element modification in the promoter region of the GPX4 gene by enhancing enhancer activity through increased H3K4 methylation and H3K27 acetylation. Furthermore, HMGA2 stimulated GPX4 protein synthesis via the mTORC1-4EBP1 and -S6K signaling axes. The overexpression of HMGA2 alleviated the decrease in GPX4 protein levels resulting from the pharmacologic inhibition of mTORC1. Conversely, compared with the control, HMGA2 deletion more strongly reduced the phosphorylation of 4EBP1 and S6K. A strong positive correlation between HMGA2 and GPX4 expression was confirmed using immunohistochemical staining. We also demonstrated that HMGA2 mitigated the sensitivity of cancer cells to combination treatment with a ferroptosis inducer and mTORC1 inhibition or gemcitabine. In summary, our results revealed a regulatory mechanism by which HMGA2 coordinates GPX4 expression and underscores the potential value of targeting HMGA2 in cancer treatment.

This paper investigates the surface enhancement treatment of 12Cr17Mn6Ni5N steel weld joints using the Strengthened Grinding Process (SGP) and explores its effect on their surface characteristics and tensile performance. The study begins by examining the influence of different SGP durations on the weld joints' surface morphology, microhardness, and residual stress. Subsequently, the tensile properties of the SGP-treated samples are analyzed and the potential mechanisms by which SGP enhances the tensile performance of 12Cr17Mn6Ni5N steel weld joints are discussed. The results reveal that SGP treatment increases the maximum microhardness of 12Cr17Mn6Ni5N steel weld joints to 519.3 HV, marking a 109.9 % improvement as compared to untreated samples. Additionally, the samples’ surface residual stress was changed from residual tensile stress (46.5 MPa) to residual compressive stress (−1253.1 MPa). The SGP-treated samples exhibit a tensile strength of 671.43 MPa, marking an 8.51 % increase as compared to the untreated samples, while also achieving a simultaneous elongation of 16.42 %. The research demonstrates that SGP is an effective method for enhancing the tensile performance of specific mechanical components.

Backgroud: Autoimmune diseases (AIDs) have been associated with various cardiovascular diseases (CVDs) in observational data. However, the causality of these associations remains uncertain. Therefore, a systematic assessment of the impact of AIDS on cardiovascular risk is required. Results: We assessed the impact of 19 common AIDs on 14 CVDs using bidirectional Mendelian randomization (MR). Celiac disease (odds ratio [OR] = 2.949, 95 % confidence interval [CI]: 1.111–7.827, P = 0.030) and type 1 diabetes mellitus (T1DM) (OR = 1.044, 95 % CI: 1.021–1.068, P = 1.82e-4) were associated with an increased risk of peripheral arterial disease (PAD). Additionally, celiac disease was linked to an increased risk of arrhythmia (OR = 1.008, 95 % CI: 1.002–1.013, P = 0.004), multiple sclerosis to venous thromboembolism (OR = 1.001, 95 % CI: 1.000–1.001, P = 0.010), and psoriasis to heart failure (OR = 1.048, 95 % CI: 1.021–1.077, P = 0.001). Sensitivity analyses were conducted to enhance the robustness of these findings. Predominantly, immune response and inflammation-related pathways were enriched in the aforementioned associations. Mediation analysis identified human leukocyte antigen-DR positive myeloid dendritic cells as partially mediating the effect of T1DM on PAD, with a mediated proportion of 16.61 % (P = 0.028). Potential therapeutic agents, such as tumor necrosis factor-alpha inhibitors and interferon, may have efficacy in treating AID-related CVDs. Conclusions: This study presents genetic evidence of certain AIDs impacting specific CVDs and identifies potential mediators and drugs.

The ROCO family is a family of GTPases characterized by a central ROC-COR tandem domain. Interest in the structure and function of ROCO proteins has increased with the identification of their important roles in human disease. Nevertheless, the functions of most ROCO proteins are still unknown. In the present study, we characterized the structure, evolution, and expression of ROCOs in four species of brown algae. Brown algae have a larger number of ROCO proteins than other organisms reported to date. Phylogenetic analyses showed that ROCOs have an ancient origin, likely originated in prokaryotes. ROCOs in brown algae clustered into four groups and showed no strong relationship with red algae or green algae. Brown algal ROCOs retain the ancestral LRR-ROC-COR domain arrangement, which is found in prokaryotes, plants and some basal metazoans. Remarkably, individual LRR motifs in ROCO genes are each encoded by separate exons and exhibit intense exon shuffling and diversifying selection. Furthermore, the tandem LRR exons exhibit alternative splicing to generate multiple transcripts. Both exon shuffling and alternative splicing of LRR repeats may be important mechanisms for generating diverse ligand-binding specificities as immune receptors. Besides their potential immune role, expression analysis shows that many ROCO genes are responsive to other stress conditions, suggesting they could participate in multiple signal pathways, not limited to the immune response. Our results substantially enhance our understanding of the structure and function of this mysterious gene family.

Introduction Postoperative radiotherapy in patients with breast cancer with one to three lymph node metastases, particularly within the pT1–2N1M0 cohort with a low clinical risk of local–regional recurrence (LRR), has incited a discourse surrounding personalised treatment strategies. Multigene testing for Recurrence Index (RecurIndex) model capably differentiates patients based on their level of LRR risk. This research aims to validate whether a more aggressive treatment approach can enhance clinical outcomes in N1 patients who possess a clinically low risk of LRR, yet a high RecurIndex-determined risk of LRR. Specifically, this entails postoperative whole breast irradiation combined with regional lymph node irradiation (RNI) following breast-conserving surgery or chest wall irradiation with RNI after mastectomy.Methods and analysis The RIGAIN (RecurIndex-Guided postoperative radiotherapy with or without Avoidance of Irradiation of regional Nodes in 1–3 node-positive breast cancer) Study is a multicentre, prospective, randomised, open-label, phase III clinical trial that is being conducted in China. In this study, patients with low clinical LRR risk but high RecurIndex-LRR risk are randomly assigned in a 1:1 ratio to the experimental group or the control group. In the experimental group, RNI is performed and the control group omits RNI. Efficacy and safety analyses will be conducted, enrolling a total of 540 patients (270 per group). The primary endpoint is invasive disease-free survival, and secondary endpoints include any first recurrence, LRR-free survival, distant metastasis-free survival, recurrence-free survival, overall survival, disease-free survival, breast cancer-specific mortality and assessment of patient quality of life. The study began in April 2023 and with a follow-up period of 60 months after the last participant completes radiation therapy.Ethics and dissemination The study was approved by the Ethics Committee of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University (SYSKY-2022-097-02, V.3.1). It adheres to the Helsinki Declaration and Good Clinical Practice. Research findings will be submitted for publication in peer-reviewed journals.Trial registration number NCT04069884.

To explore the mechanism of carnosine in improving atherosclerosis, ApoE-/- mice fed a high-fat diet (HFD) were orally administered different doses of carnosine for 16 weeks. Carnosine intervention significantly reduced the arterial plaque area and expression levels of IL-6, TNF-α, and IL-1β mRNA and increased the expression levels of IL-10 mRNA. Carnosine intervention increased LC3B, Beclin-1, and Atg7 mRNA expression levels and reduced ASC, NLRP3, and Caspase-1 mRNA expression levels. Meanwhile, carnosine could increase Arg-1, CD163, and CD206 mRNA expression levels and decrease iNOS mRNA expression levels. These results suggested that carnosine might regulate macrophage polarization by inhibiting the NLRP3 inflammasome through autophagy to alleviate atherosclerosis, which revealed a novel idea for carnosine to suppress atherosclerosis and offered a scientific foundation for the production of carnosine-enriched dietary products.

Breast cancer is still suffering from its poor diagnosis and the lack of effective treatment. Despite of recent development of some novel chemicals, which are found to have inspiring therapeutic effects in vitro, their outcomes in clinic trails are disappointing, mainly due to the lack of suitable therapeutic vehicles. Thanks to their ability to encapsulate bio-molecules, extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, hold great promise in becoming a suitable candidate in the breast cancer diagnosis and therapy. Currently, EVs are increasingly evaluated as potential indicators in the diagnosis of breast cancer since they are actively involved in different stages of breast cancer development, including promoting cancer occurrence and metastasis, establishing tumor ecology, and promoting tumor growth. Moreover, they are also considered as promising new platforms in breast cancer therapy. Here, we discuss the potential therapeutic applications of EVs, including EVs as biomarkers for diagnosis and therapeutic drug delivery to tumor sites. The promising data and technologies indicate the potential applicability of EVs in clinical management of patients with breast cancer.

BackgroundCannabidiol (CBD), as an important therapeutic property of the cannabis plants, is mainly produced in the flower organs. Auxin response factors (ARFs) are play a crucial role in flower development and secondary metabolite production. However, the specific roles of ARF gene family in cannabis remain unknown.MethodsIn this study, various bioinformatics analysis of CsARF genes were conducted using online website and bioinformatics, quantitative real time PCR technology was used to investigate the expression patterns of the CsARF gene family in different tissues of different cannabis varieties, and subcellular localization analysis was performed in tobacco leaf.ResultsIn this study, 22 CsARF genes were identified and found to be unevenly distributed across 9 chromosomes of the cannabis genome. Phylogenetic analysis revealed that the ARF proteins were divided into 4 subgroups. Duplication analysis identified one pair of segmental/whole-genome duplicated CsARF, and three pairs of tandemly duplicated CsARF. Collinearity analysis revealed that two CsARF genes, CsARF4 and CsARF19, were orthologous in both rice and soybean. Furthermore, subcellular localization analysis showed that CsARF2 was localized in the nucleus. Tissue-specific expression analysis revealed that six genes were highly expressed in cannabis male flowers, and among these genes, 3 genes were further found to be highly expressed at different developmental stages of male flowers. Meanwhile, correlation analysis between the expression level of CsARF genes and CBD content in two cultivars ‘H8’ and ‘Y7’ showed that the expression level of CsARF13 was negatively correlated with CBD content, while the expression levels of six genes were positively correlated with CBD content. In addition, most of CsARF genes were responsive to IAA treatment.ConclusionOur study laid a foundation for the further studies of CsARFs function in cannabis, and provides candidate genes for breeding varieties with high CBD yield in cannabis production.

Maillard reaction products (MRPs) derived from rice protein isolate hydrolysate and D-xylose, with or without L-cysteine, were developed as a potential meat flavoring. The combined impact of temperature (80–140 °C) and cysteine on fundamental physicochemical characteristics, antioxidant activity, and flavor of MRPs were investigated through assessments of pH, color, UV–visible spectra, fluorescence spectra, free amino acids, volatile compounds, E-nose, E-tongue, and sensory evaluation. Results suggested that increasing temperature would reduce pH, deepen color, promote volatile compounds formation, and reduce the overall umami and bitterness. Cysteine addition contributed to the color inhibition, enhancement of DPPH radical-scavenging activity and reducing power, improvement in mouthfulness and continuity, reduction of bitterness, and the formation of sulfur compounds responsible for meaty flavor. Overall, MRPs prepared at 120 °C with cysteine addition could be utilized as a potential meat flavoring with the highest antioxidant activity and relatively high mouthfulness, continuity, umami, meaty aroma, and relatively low bitterness.

Proton exchange membrane fuel cells (PEMFCs) should further reduce the platinum consumption to lower their manufacturing costs and life-cycle carbon emissions. However, the performance of the catalyst layers with low-Pt loading needs to be improved. Short-side-chain (SSC) ionomers have been proven to enhance the catalytic activity of conventional catalyst layers. In this work, the SSC ionomer was applied to the electrospun catalyst layer, and achieved a remarkable improvement in the performance. With the use of commercially available catalyst, the membrane electrode assemblies (MEAs) prepared in this work exhibited a low total-Pt-consumption of 0.064 g kW−1 (stoichiometric ratios of 1.5/2.5 for H2/air, 80°C, 100 kPa) and achieved the 2025 target proposed by the US Department of Energy. Separating activation, ohmic, and concentration overpotentials, the performance enhancement of the electrospun catalyst layer mainly came from the decrease of ohmic overpotential and concentration overpotential. The electrospun ionomer membrane without catalyst was used as a research model to explore the proton transport properties inside the electrospun catalyst layer. The results showed that in the range of PEMFC operating temperature, the proton conductivity of the electrospun catalyst layer could be higher, but meanwhile the proton-conduction activation energy was also elevated. Compared with the conventional catalyst layer, the electrospun catalyst layer showed obviously better performance before and after accelerated stress test, thus verifying the practicality of the electrospun catalyst layers. This work provided a reference for the development of low platinum and high performance catalyst layers.

Abstract Purpose The purpose of this study was to develop a functional clinical nomogram for predicting 8-year overall survival (OS) of patients with prostate cancer (PCa) primary based on peripheral lymphocyte. Patients and methods Using data from a single-institutional registry of 94 patients with PCa in China, this study identified and integrated significant prognostic factors for survival to build a nomogram. The discriminative ability was measured by concordance index (C-index) and ROC curves (Receiver Operating Characteristic Curves). And the predictive accuracy was measured by the calibration curves. Decision curve analyses (DCA) was used to measure the clinical usefulness. Results A total of 94 patients were included for analysis. Five independent prognostic factors were identified by LASSO-Cox regression and incorporated into the nomogram: age, the T stage, the absolute counts of peripheral CD3(+)CD4(+) T lymphocytes, CD3(-)CD16(+)CD56(+) NK cells and CD4(+)/CD8(+) ratio. The area under the curve (AUC) values of the predictive model for 5-, 8-, and 10-year overall survival were 0.81, 0.76, and 0.73, respectively. The calibration curves for probability of 5-,8- and 10-year OS showed optimal agreement between nomogram prediction and actual observation. The stratification into different risk groups allowed significant distinction. DCA indicated the good clinical application value of the model. Conclusion We developed a novel nomogram that enables personalized prediction of OS for patients diagnosed with PCa. This finding revealed a relative in age and survival rate in PCa, and a more favorable prognosis in patients exhibiting higher levels of CD4 + T, CD4+/CD8 + ratio and CD3(-)CD16(+)CD56(+) NK cells specifically. This clinically applicable prognostic model exhibits promising predictive capabilities, offering valuable support to clinicians in informed decision-making process.

Abstract In this paper, we propose a new interference-suppression beamformer design and a Direction-of-Arrival (DoA) estimation method for Line-of-Sight (LoS) multi-user communication systems with circular Large Intelligent Surfaces (LISs). This symmetrical circular-shaped LIS allows signals defined on it to be formed by combining Fourier and Bessel series. The Fourier harmonics are orthogonal along the rotational direction and the Bessel functions constituting the Bessel series are orthogonal along the radial direction. Synthesizing basis functions from these two series results in the proposed interference-suppression beamformer, with their coefficients designed to cancel inter-user interference. Also by exploiting signal structure of a circular LIS communicating with Mobile Stations (MSs), we devise a DoA estimation method to obtain directional information of incoming signals. Under LoS channel, the DoA corresponds to elevation and Azimuth angles of MSs relative to the LIS. This method is numerically demonstrated to have promising performance with high-frequency carriers.

Abstract This study aimed to predict the outcome of patient specific quality assurance (PSQA) in IMRT for breast cancer using complexity metrics, such as MU factor, MAD, CAS, MCS. Several breast cancer plans were considered, including LBCS, RBCS, LBCM, RBCM, left breast, right breast and the whole breast for both Edge and TrueBeam LINACS. Dose verification was completed by Portal Dosimetry (PD). The receiver operating characteristic (ROC) curve was employed to determine whether the treatment plans pass or failed. The area under the curve (AUC) was used to assess the classification performance. The correlation of PSQA and complexity metrics was examined using Spearman’s rank correlation coefficient (R s ). For LINACS, the most suitable complexity metric was found to be the MU factor (Edge R s = − 0.608, p

Summary: High energy and low sensitivity have been the focus of developing new energetic materials (EMs). However, there has been a lack of a quick and accurate method for evaluating the stability of diverse EMs. Here, we develop a machine learning prediction model with high accuracy for bond dissociation energy (BDE) of EMs. A reliable and representative BDE dataset of EMs is constructed by collecting 778 experimental energetic compounds and quantum mechanics calculation. To sufficiently characterize the BDE of EMs, a hybrid feature representation is proposed by coupling the local target bond into the global structure characteristics. To alleviate the limitation of the low dataset, pairwise difference regression is utilized as a data augmentation with the advantage of reducing systematic errors and improving diversity. Benefiting from these improvements, the XGBoost model achieves the best prediction accuracy with R2 of 0.98 and MAE of 8.8 kJ mol−1, significantly outperforming competitive models.

PurposeA mouse model of irradiation (IR)-induced heart injury was established to investigate the early changes in cardiac function after radiation and the role of cardiac macrophages in this process.MethodsCardiac function was evaluated by heart-to-tibia ratio, lung-to-heart ratio and echocardiography. Immunofluorescence staining and flow cytometry analysis were used to evaluate the changes of macrophages in the heart. Immune cells from heart tissues were sorted by magnetic beads for single-cell RNA sequencing, and the subsets of macrophages were identified and analyzed. Trajectory analysis was used to explore the differentiation relationship of each macrophage subset. The differentially expressed genes (DEGs) were compared, and the related enriched pathways were identified. Single-cell regulatory network inference and clustering (SCENIC) analysis was performed to identify the potential transcription factors (TFs) which participated in this process.ResultsCardiac function temporarily decreased on Day 7 and returned to normal level on Day 35, accompanied by macrophages decreased and increased respectively. Then, we identified 7 clusters of macrophages by single-cell RNA sequencing and found two kinds of stage specific macrophages: senescence-associated macrophage (Cdkn1ahighC5ar1high) on Day 7 and interferon-associated macrophage (Ccr2highIsg15high) on Day 35. Moreover, we observed cardiac macrophages polarized over these two-time points based on M1/M2 and CCR2/major histocompatibility complex II (MHCII) expression. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses suggested that macrophages on Day 7 were characterized by an inflammatory senescent phenotype with enhanced chemotaxis and inflammatory factors, while macrophages on Day 35 showed enhanced phagocytosis with reduced inflammation, which was associated with interferon-related pathways. SCENIC analysis showed AP-1 family members were associated with IR-induced macrophages changes.ConclusionWe are the first study to characterize the diversity, features, and evolution of macrophages during the early stages in an IR-induced cardiac injury animal model.

The development of cost‐effective and stable electrocatalysts that can replace the prevailing Pt‐based and Ir‐based catalysts for water splitting remains a formidable challenge. The electrocatalytic performance of a catalyst depends on its chemical composition and environment during catalysis. Herein, a Ru–Mo composite is used as an example to highlight the significance of tailoring the chemical environments of the active‐sites. This customization enhances the cathodic and anodic reactions involved in water splitting, ultimately leading to an improved full reaction efficiency. Specifically, the chemically reduced state of Ru–Mo demonstrates promising hydrogen evolution activity and exhibits low overpotentials of 48 and 34 mV at the current density of 10 mA cm−2 in acidic and alkaline electrolytes, respectively. The chemically oxidized state of Ru–Mo, derived from the same precursor, demonstrates proficient oxygen evolution activity and exhibits low overpotentials of 260 and 270 mV at 10 mA cm−2 in acidic and alkaline electrolytes, respectively. Additionally, in both cases, the Ru–Mo composites exhibit significantly improved stability under typical water‐splitting conditions. Despite the close chemical compositions of these two catalysts, they show poor performance in the counter electrode reactions, demonstrating the importance of establishing a suitable chemical environment for efficient electrocatalysis.

Abstract Two-dimensional (2D) Cr(1+δ)Te2 materials exhibit strong magnetic ordering and high Curie temperatures, making them attractive for various applications. It is crucial to achieve controllable synthesis for their successful integration into device technologies. In this study, we present the synthesis of phase-controllable 2D Cr(1+δ)Te2 films on the Si (111) substrate via molecular beam epitaxy. The composition and phase transition of the as-grown Cr(1+δ)Te2 films are characterized by using in-situ reflection high-energy electron diffraction, scanning tunneling microscopy, ex-situ X-ray photoelectron spectroscopy, X-ray diffraction, and theoretical calculations. At low growth temperatures, by carefully adjusting the film thickness from 2 to more than 3 layers, we achieve precise control over the phase of Cr(1+δ)Te2, from CrTe2 to Cr intercalated Cr2Te3. At a relatively elevated growth temperature, it is demonstrated that the Cr(1+δ)Te2 phase is independent of the film thickness, only Cr2Te3 forms and its growth mode is thickness-dependent. These phase transitions at low growth temperatures and growth mode changes at elevated growth temperatures are attributed to interfacial effects and the phase stability of Cr(1+δ)Te2 compounds. Additionally, we utilize scanning tunneling spectroscopy and computations to gain insights into the electronic properties of Cr2Te3. The magnetic measurements reveal that the 30-nm Cr2Te3 film exhibits ferromagnetic behavior with a Curie temperature of about 180 K. Our work offers a robust method for the controllable growth of high-quality 2D Cr(1+δ)Te2 films on Si substrates, providing an ideal platform for investigating their intrinsic properties and advancing the development of 2D magnet-based spintronics devices.

This paper used ultrasonic strengthening grinding (USGP) to process 254SMo welded joints. The mechanical properties of processed and unmachined samples of welded joints, including grain size, dislocation, microhardness, residual stress, and high-temperature oxidation resistance at 900 °C, were investigated. The results indicate that the grains of the processed samples exhibit significant refinement and a high dislocation density and that the maximum microhardness and residual compressive stress are 392.5 HV0.3 and −633.44 MPa, respectively. In addition, the processed sample exhibits excellent oxidation at high temperatures. At 900 °C, the mass gain of the USGP-processed sample is reduced by 47.5 % compared to its mass gain prior to processing. These results highlight the potential of this method in improving the high-temperature resistance of various mechanical components, particularly those made from special materials.

Abstract The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock targeting ligands, such as anti-CD71 and anti-programmed cell death-ligand 1 (PD-L1) antibodies. The resulting immunogenic sEVs (imsEV) preferentially target glioblastoma cells and generate potent antitumour activities in vivo, including against tumours intrinsically resistant to immunotherapy. Together, these results provide an adaptive approach to engineering mRNA-loaded sEVs with targeting functionality and pave the way for their adoption in cancer immunotherapy applications.

Based on the JRA-55 surface sensible and latent heat flux， reanalysis circulation data provided by Japan Meteorological Agency （JMA）， monthly grid precipitation data provided by the National Meteorological Information Center （NMC） during the period of 1971 -2019.The effects of thermal anomalies over the Iran Plateau and the Qinghai-Xizang Plateau on summer precipitation over the Tarim Basin are analyzed.Results show that the sensible heat over the Iran Plateau and the latent heat over the Qinghai-Xizang Plateau play main roles in summer heating.The singular value decomposition （SVD） analysis has indicated that the surface thermal anomalies over the two plateaus are well related to summer precipitation over the Tarim Basin.Correlations suggest that thermal anomalies in the two plateaus have better relationships with summer precipitation over the Tarim Basin than one in single plateau.When the sensible heat strengthens over the Iran Plateau， and the latent heat strengthen in northern Qinghai-Xizang Plateau and weaken in southern Qinghai-Xizang Plateau， which can cause the middle to upper tropospheric cooling over central Asia.On the one hand， the subtropical westerly jet will shift south over central Asia， and there is an anomalous cyclone over central Asia and an anomalous anticyclone over Mongolian Plateau， which result in anomalous south wind prevailing over the Tarim Basin.On the other hand， the water vapor can be transport to the Tarim Basin by an anomalous anticyclone over the Arabian Sea and an anomalous cyclone over central Asia， meanwhile， the anomalous anticyclone over north China also can transport the water vapor from northwest Pacific to the Tarim Basin.Above both are contributed to more summer precipitation over the Tarim Basin.The single thermal anomalies over the Iran Plateau and the Qinghai-Xizang Plateau both can influence the summer precipitation over the Tarim Basin， but show partial difference related to the source and path of water vapor.The former only can affect water vapor transmission in the tropical Indian Ocean， but the latter can affect water vapor transmission in both the Indian Ocean and northwest Pacific.

Abstract Introduction The optimal first-line immunotherapy regimen for advanced non-squamous non-small cell lung cancer (NS-NSCLC) patients with programmed cell death ligand 1 (PD-L1) expression ≥ 50% remains unclear. Our aim is to determine the most effective treatment regimen through a network meta-analysis (NMA) comparing these treatments. Methods A systematic search was performed in PubMed, Cochrane Library, Web of Science, and Embase databases, and a Bayesian network meta-analysis was conducted. To ensure transparency, the study was registered in the International Prospective Register of Systematic Reviews (CRD42022349712). Results The analysis included 11 randomized controlled trials (RCTs) with 2037 patients and 12 immunotherapy combinations. ICI-ICI, ICI alone, and chemotherapy-ICI showed significant advantages over chemotherapy in terms of overall survival (OS) and progression-free survival (PFS). Pembrolizumab plus chemotherapy showed the best OS results compared to chemotherapy. Tislelizumab plus chemotherapy and sintilimab plus chemotherapy provided the best PFS results. Conclusions For NS-NSCLC patients with PD-L1 ≥ 50%, pembrolizumab plus chemotherapy, tislelizumab plus chemotherapy, and sintilimab plus chemotherapy are recommended as good treatment options based on the results of this Network meta-analysis (NMA).