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Abstract The purpose of this study is to identify and analyze the application barriers and internal mechanisms of BIM technology in green building projects. It is found that BIM technology can effectively integrate information and optimize management, but its application still faces economic externalities and requires government intervention to promote its development. Through the analysis of five aspects of technology, economy, management, policy and environment, we identified 16 influencing factors and focused on nine key factors, such as insufficient technology maturity and high-cost issues. Research shows that policy and management factors play a fundamental role in BIM adoption and influence economic effectiveness through complex interactions. Based on the ISM-ANP coupling model, we propose that the government should encourage technological innovation and personnel training to promote the effective application of BIM technology in green buildings. This study provides a theoretical reference for the application of BIM and green building on a global scale.

Fibrinogen–fibrin degradation products (DR-70) are derived from tumor cells or metastases. Our previous study reported the diagnostic values in dogs with tumors, but no research has yet to be conducted to establish DR-70 as a prognostic marker. Herein, we investigated changes in DR-70 concentrations and disease courses in dogs with tumors. Overall survival time (OST) analysis was performed in 195 dogs with tumors, stratified with a recommended cut-off (1.514 µg/mL). Continual DR-70 measurements were performed during the medical interventions of 27 dogs with neoplasms. Clinical conditions and medical records were retrospectively reviewed. According to a cut-off value, dogs with plasma DR-70 concentrations above 1.514 µg/mL had shorter survival rates than those with concentrations below this threshold. In cases with complete or partial remission in response to treatment, the DR-70 concentration was decreased compared with that at the first visit, whereas it was increased in patients with disease progression. Our study suggested that changes in DR-70 concentration can be used as a prognostic biomarker for canine neoplasms. Furthermore, increased plasma DR-70 levels might be associated with shorter survival, and DR-70 concentrations may reflect responses to medical intervention.

Abstract Stomach adenocarcinoma (STAD) is known for its high prevalence and poor prognosis, which underscores the need for novel therapeutic targets. Peroxidasin (PXDN), an enzyme with peroxidase activity, has been linked to cancer development in previous studies. However, its specific role in STAD is not well understood. In our study, we used public databases and clinical specimens to determine that PXDN expression is significantly elevated in STAD tissues and serves as an independent prognostic marker for patient outcomes. Our in vitro assays demonstrated that silencing PXDN significantly reduced STAD cell proliferation, invasion, and migration. Mechanistically, we found that PXDN promotes epithelial‒mesenchymal transition and angiogenesis in STAD cells and may be regulated by the PI3K/AKT pathway. Further analysis revealed that PXDN levels affect the sensitivity of STAD cells to various chemotherapeutic and small molecule drugs. Additionally, we observed a significant association between PXDN levels and the abundances of various immune cell types in patients with STAD. Our study highlighted a strong link between PXDN levels and the tumor immune microenvironment (TIM), suggesting that PXDN is a useful metric for evaluating the response to immune checkpoint inhibitors. Moreover, we found that PXDN is significantly associated with multiple immune checkpoints. In summary, our findings indicate that PXDN plays a critical role in STAD and that its level could serve as a potential prognostic biomarker. Thus, targeting PXDN may represent an effective treatment strategy for STAD.

Modifying the surface of metallic materials with graphene (Gr) holds significant potential for achieving high electrical conductivity in metal-based composites, leveraging the synergistic effect of the high carrier concentration in metals and the high carrier mobility of Gr. However, the strong van der Waals forces and large specific surface area of Gr sheets often lead to agglomeration in slurrys, adversely affecting the arrangement of Gr layers within the coating structure. In this study, we introduce reduced Gr oxide (rGO) into the Gr slurry to enhance the electrostatic stability and dispersion of Gr sheets through π-π interactions. By precisely controlling the composition of the coating, a compact, low-roughness coating was prepared on the surface of the copper (Cu) wire. The fabricated Gr/rGO/Cu composite wire exhibited a high conductivity of 104.2% IACS, with a tensile strength of 266.1 MPa and the elongation of 36.3%, respectively. This study demonstrates that the addition of rGO improves the dispersibility of Gr in the slurry, leading to a more compact and effective composite structure. The Gr/rGO/Cu composite wires exhibit superior electrical and mechanical properties, making them promising candidates for high-performance applications in electrical and electronic industries.

Abstract Photosynthesis requires chloroplasts, in which most proteins are nucleus-encoded and produced via cytoplasmic translation. The translation initiation factor eIF5B gates the transition from initiation (I) to elongation (E), and the Kozak motif is associated with translation efficiency, but their relationship is previously unknown. Here, with ribosome profiling, we determined the genome-wide I-E transition efficiencies. We discovered that the most prevalent Kozak motif is associated with high I-E transition efficiency in Arabidopsis, rice, and wheat, thus implicating the potential of the Kozak motif in facilitating the I-E transition. Indeed, the effects of Kozak motifs in promoting translation depend on HOT3/eIF5B1 in Arabidopsis. HOT3 preferentially promotes the translation of photosynthesis-associated nuclear genes in a Kozak motif-dependent manner, which explains the chloroplast defects and reduced photosynthesis activity of hot3 mutants. Our study linked the Kozak motif to eIF5B-mediated I-E transition during translation and uncovered the function of HOT3 in the cytoplasmic translational control of chloroplast biogenesis and photosynthesis.

Functional microstructured surfaces are becoming increasingly important in the fields of optics, microfluidics, and surface engineering. These parts' functional surface roughnesses and microstructure molding accuracies directly affect their final service performance characteristics. To improve the machining qualities of functional microstructured surfaces, subsequent polishing treatment is necessary. This paper discusses the different polishing methods and effects of functional microstructured surface parts. Moreover, the challenges and bottlenecks in polishing functional microstructured surfaces are analyzed and discussed by considering the microstructure feature sizes, shapes, and substrate surface shapes. Then, the advantages, disadvantages, applications, and limitations of functional microstructured surface polishing methods are elucidated. Finally, the development trends of form-preserving polishing methods for functional microstructured surfaces are noted.

Abstract Gastric cancer (GC) is a highly heterogeneous and aggressive malignant tumor that seriously affects the life safety of people all over the world. Its early manifestations are subtle. The present study aimed to investigate the clinical significance of serum lipid profiles, insulin resistance markers including the triglyceride-glucose (TyG) index and the atherosclerotic index (AI), in GC patients. A retrospective analysis encompassed 215 GC patients and 827 healthy individuals. The study results show that the total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein levels, and the TyG index of GC patients were significantly lower than those of the control group before and after propensity score matching analysis. In the GC group, the levels of CEA, CA199, CA125, and CA724 tumor markers were higher than those in the healthy control group. Patients in advanced stages exhibited lower serum levels of serum lipids and TyG index compared to those in early stages. ROC analysis revealed that the TyG index, CA125, and CA199 combination yielded the highest positive prediction rate for GC at 98.6%. TyG index is significantly associated with the risk of adverse reactions after chemotherapy (OR = 1.104, 95% CI 1.028–1.186, P

Abstract Background The inflammatory microenvironment plays an essential role in bone healing after fracture. The signaling lymphocytic activation molecule family (SLAMF) members deeply participate in inflammatory response and make a vast difference. Methods We identified SLAMF8 in GEO datasets (GSE129165 and GSE176086) and co-expression analyses were performed to define the relationships between SLAMF8 and osteogenesis relative genes (RUNX2 and COL1A1). In vitro, we established SLAMF8 knockdown and overexpression mouse bone marrow mesenchymal stem cells (mBMSCs) lines. qPCR, Western blot, ALP staining, ARS staining, Oil Red O staining and Immunofluorescence analyses were performed to investigate the effect of SLAMF8 in mBMSCs osteogenesis and adipogenesis. In vivo, mice femoral fracture model was performed to explore the function of SLAMF8. Results SLAMF8 knockdown significantly suppressed the expression of osteogenesis relative genes (RUNX2, SP7 and COL1A1), ALP activity and mineral deposition, but increased the expression of adipogenesis relative genes (PPARγ and C/EBPα). Additionally, SLAMF8 overexpression had the opposite effects. The role SLAMF8 played in mBMSCs osteogenic and adipogenic differentiation were through S100A6 and Wnt/β-Catenin signaling pathway. Moreover, SLAMF8 overexpression mBMSCs promoted the healing of femoral fracture. Conclusions SLAMF8 promotes osteogenesis and inhibits adipogenesis of mBMSCs via S100A6 and Wnt/β-Catenin signaling pathway. SLAMF8 overexpression mBMSCs effectively accelerate the healing of femoral fracture in mice.

Abstract Background Patellar tendinopathy (PT) is a common sport injury prone to recurrence. Heavy Slow Resistance Training (HSR) and High-Dose Therapeutic Ultrasound (TUS) are frequently used interventions for PT. However, the combined effectiveness of these therapies remains unclear. This study investigated the impact of combination therapy on functional outcomes in patients with PT. Methods Fifty-one college students aged 18–25, diagnosed with PT via musculoskeletal ultrasound, were randomly assigned to one of three groups (n = 17 per group): combined HSR and high-dose TUS, HSR training alone, or high-dose TUS alone. The eight-week intervention included assessments using the Victorian Institute of Sport Assessment-Patella (VISA-P), Visual Analogue Scale (VAS), Y-balance Test (YBT), Modified Thomas Test (MTT), Horizontal Jumping Distance, Maximum Isometric Muscle Strength Test, and musculoskeletal ultrasound for patellar tendon thickness and blood flow. Assessments were conducted at baseline and post-intervention, with a follow-up VISA-P assessment at week 16. This randomized, single-blind controlled trial was registered on ISRCTN11447397 ( www.ISRCTN.com ) on February 17, 2024 (retrospectively registered). Results All groups demonstrated significant improvements in VISA-P scores at the end of the intervention compared to baseline (p

Abstract Effective geographical origin discrimination of Chinese rice requires a large database of samples to ensure sufficient data for origin verification at a regional scale. In this study, environmental similarity was used to establish a spatial database of rice nutrient element, and then the validity of the database was verified using the back propagation artificial neural networks modeling (BPNN). The spatial distribution model of 14 rice nutrient element (Al, Ba, Ca, Cu, Cr, Fe, K, Mg, Mn, Mo, Na, Ni, Rb, and Zn) on regional scale was built using an environmental similarity method for the first time. Elemental concentrations of 692 samples were used to build a simulated geographical origin prediction model for northeastern (N‐E), middle to lower Yangtze River plain (Y‐R), southwestern (S‐W), and southeastern (S‐E) in China. The results indicated that the performance of the environmental similarity model for these four growing regions was S‐W > N‐E > S‐E > Y‐R based on the lowest ranking root mean square error (RMSE) for each region. For example, the RMSEs of Zn in S‐W, N‐E, S‐E, and Y‐R regions were 2.0, 2.4, 2.7, and 3.7 mg/kg, respectively. A case study on the traceability of Japonica rice was shown that Japonica rice could be discriminated with higher origin accuracy using a simulated database (91.8%) than by the actual database (87.0%) using the BPNN model. This indicates that a simulated rice element database could improve the accuracy of geographical origin discrimination for Chinese rice and potentially be applied to other large national‐scale crop datasets.

Abstract The removal and discharge of coal powders from coalbed methane wellbore is the key to maintaining continuous production. For this reason, based on the submerged jet theory, the force and migration starting conditions of coal powder particles deposited at the bottom of the coalbed methane well are analyzed by analyzing the cohesiveness of coal powders, and a model for the starting and migration of coal powders at the bottom of the well under submerged jet conditions is established; Considering the adhesion between coal dust, the adhesion coefficient is used to characterize the adhesion between particles, a mechanical model of coal dust particles deposited at the bottom of the well is established, and the corresponding calculation formula for the outlet flow rate of the coal dust cleaning nozzle is derived. The fluid mechanics parameters of the bottom of the well coal dust cleaning under different conditions are obtained, and the numerical simulation method is used to simulate the whole process of jet flushing of the bottom of the well coal dust deposited, and the effect of the bottom of the well jet flushing of coal dust deposits is analyzed, providing a theoretical basis for the bottom of the well coal dust flushing process.

Abstract Background Direct-acting antivirals (DAAs) show high cure rates in treating chronic hepatitis C virus (HCV). However, the effect of DAAs on patients infected with genotype 2 (GT2) is difficult to determine despite the availability of several DAA regimens. Methods A systematic search of six databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Clinicaltrial.gov) was conducted through April 20, 2022. We considered the sustained virological response 12 weeks after treatment (SVR12) as the efficacy outcome, and adverse events (AEs) as the safety outcome. By calculating the mean SVR12 and the proportion of AEs among patients, we considered the intervention effect for each DAA regimen. The random effect model was then used in all meta-analyses. This systematic review and meta-analysis aimed to summarize the evidence on efficacy and safety of DAAs in patients infected with HCV GT2. The Bayesian Markov Chain Monte Carlo (MCMC) network metanalysis was used to indirectly compare regimen in GT2 patients. Results Among 31 articles included (2,968 participants), consisting of 1,387 treatment-naive patients and 354 patients with cirrhosis. The overall pooled SVR12 rate was 94.62% (95% CI: 92.43-96.52%) among the participants who received all doses of treatment. Meta-analysis results of AEs revealed that fatigue was the most common AE (14.0%, 95% CI: 6.4-21.6%), followed by headache (13.1%, 95% CI: 9.2-17.1%), whereas death and serious adverse events were uncommon. Conclusions We compared DAA-based treatments indirectly using meta-analysis and found the combination of Sofosbuvir plus Velpatasvir and Glecaprevir plus Pibrentasvir, each administered over a 12-week period, were identified as the most effective and relatively safe in managing chronic hepatitis C virus genotype 2 (HCV GT2) infection. Both treatments achieved a SVR12 of 100% (95% CI 99–100%).

Abstract Autoimmune attack toward pancreatic β cells causes permanent loss of glucose homeostasis in type 1 diabetes (T1D). Insulin secretory granules store and secrete insulin but are also thought to be tissue messengers for T1D. Here, we show that the crinophagic granules (crinosome), a minor set of vesicles formed by fusing lysosomes with the conventional insulin dense-core granules (DCG), are pathogenic in T1D development in mouse models. Pharmacological inhibition of crinosome formation in β cells delays T1D progression without affecting the dominant DCGs. Mechanistically, crinophagy inhibition diminishes the epitope repertoire in pancreatic islets, including cryptic, modified and disease-relevant epitopes derived from insulin. These unconventional insulin epitopes are largely undetectable in the MHC-II epitope repertoire of the thymus, where only canonical insulin epitopes are presented. CD4+ T cells targeting unconventional insulin epitopes display autoreactive phenotypes, unlike tolerized T cells recognizing epitopes presented in the thymus. Thus, the crinophagic pathway emerges as a tissue-intrinsic mechanism that transforms insulin from a signature thymic self-protein to a critical autoantigen by creating a peripheral-thymic mismatch in the epitope repertoire.

Abstract Background Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients’ quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. Purpose Investigate the effects of tDCS on pain and physical function in patients with KOA. Methods Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. Results Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. Conclusions The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.

In this study, high-resolution TEM was utilized to provide a detailed characterization of the precipitates in CuCrZr alloys induced by cryogenic treatment. Building on these findings, first-principles computational models were developed to investigate the mechanical properties of various precipitates and their interfacial bonding characteristics with the matrix. The results demonstrated that cryogenic treatment generated two submicron-sized secondary phases in the matrix: pure Cr particles with a BCC structure and Cu5Zr particles with an FCC structure. Additionally, we observed that nano-sized pure Cr particles were dispersed throughout the matrix and exhibited an orientation relationship of (−111) Cu//(0–11) Cr and [0–11] Cu//[−1−1-1] Cr. First-principles calculations revealed that all the above precipitates exhibited higher modulus and hardness compared to the matrix, with Cr particles being particularly notable. Additionally, the adhesion strength of the Cr/Cu interface was exceptional, surpassing that of the fully coherent CuSlab and CuTwin. Furthermore, the analysis of the electronic properties of the interface revealed that the strengthening effect could be attributed to the higher charge density and localized nature of the Cr atoms near the interface. In summary, precipitates with high hardness and strong adhesion to the matrix can more effectively hinder dislocation movement, which is crucial for enhancing the mechanical properties of the alloys.

Abstract Background As a currently incurable but preventable disease, the prevention and early diagnosis of Alzheimer’s disease (AD) has long been a research hotspot. Amyloid deposition has been shown to be a major pathological feature of AD. Notably, not all the people with amyloid-beta (Aβ) pathology will have significant cognitive declines and eventually develop AD. Therefore, the aim of this study was to explore the risk factors for cognitive decline in Aβ-positive participants. Methods We included 650 non-demented participants who were Aβ-positive at baseline from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Mixed effects and COX regression models were applied to assess 37 potential risk factors. Mixed effects models were employed to assess the temporal associations between potential risk factors and four cognitive assessment scales. COX regression models were used to assess the impact of potential risk factors on cognitive diagnosis conversion. Univariate and multivariate analyses were applied to the above models. Additionally, we used the Cochran-Armitage trend test to examine whether the incidence of cognitive decline increased with the number concurrent of risk factors. Results Six factors (low diastolic pressure, low body mass index, retired status, a history of drug abuse, Parkinsonism, and depression) were the identified risk factors and four factors (a history of urinary disease, musculoskeletal diseases, no major surgical history, and no prior dermatologic-connective tissue diseases) were found to be suggestive risk factors. The incidence of cognitive decline in the Aβ-positive participants gradually increased as the number of concurrent risk factors increased (p for trend = 0.0005). Conclusions Our study may facilitate the understanding of the potential pathological processes in AD and provide novel targets for the prevention of cognitive decline among participants with Aβ positivity.

Abstract Cerium oxide (CeO2) nanospheres have limited enzymatic activity that hinders further application in catalytic therapy, but they have an “oxidation switch” to enhance their catalytic activity by increasing oxygen vacancies. In this study, according to the defect-engineering strategy, we developed PtCuOX/CeO2-X nanozymes as highly efficient SOD/CAT mimics by introducing bimetallic copper (Cu) and platinum (Pt) into CeO2 nanospheres to enhance the oxygen vacancies, in an attempt to combine near-infrared (NIR) irradiation to regulate microenvironment for osteoarthritis (OA) therapy. As expected, the Cu and Pt increased the Ce3+/Ce4+ ratio of CeO2 to significantly enhance the oxygen vacancies, and simultaneously CeO2 (111) facilitated the uniform dispersion of Cu and Pt. The strong metal-carrier interaction synergy endowed the PtCuOX/CeO2-X nanozymes with highly efficient SOD/CAT-like activity by the decreased formation energy of oxygen vacancy, promoted electron transfer, the increased adsorption energy of intermediates, and the decreased reaction activation energy. Besides, the nanozymes have excellent photothermal conversion efficiency (55.41%). Further, the PtCuOX/CeO2-X antioxidant system effectively scavenged intracellular ROS and RNS, protected mitochondrial function, and inhibited the inflammatory factors, thus reducing chondrocyte apoptosis. In vivo, experiments demonstrated the biosafety of PtCuOX/CeO2-X and its potent effect on OA suppression. In particular, NIR radiation further enhanced the effects. Mechanistically, PtCuOX/CeO2-X nanozymes reduced ras-related C3 botulinum toxin substrate 1 (Rac-1) and p-p65 protein expression, as well as ROS levels to remodel the inflammatory microenvironment by inhibiting the ROS/Rac-1/nuclear factor kappa-B (NF-κB) signaling pathway. This study introduces new clinical concepts and perspectives that can be applied to inflammatory diseases. Graphical Abstract

Objective To investigate the effect and mechanism of emodin on cell proliferation in OSCC. Methods CAL-27 cells and SCC-15 cells were intervened with different concentrations of emodin, and the proliferative activity of the cells was detected by CCK-8 method, and the appropriate concentration was screened for follow-up experiments. The colony formation experiment helped detect the colony formation ability. The expressions of PCNA, Beclin1 and LC3 were detected using Western blot. After treating the cells with rapamycin and emodin, the cell proliferation activity and the colony formation ability were examined. PCNA, Beclin1 and LC3 expressions were detected. The tumor formation experiment helped detect the effect of emodin on tumor weight and volume in nude mice. The liver and kidney structure in nude mice was observed using HE staining. Moreover, the PCNA and Beclin1 protein expression was detected by IHC. Results Emodin could significantly decrease the proliferative activity and aggregation ability of CAL-27 cells in a concentration-dependent manner. Emodin could down-regulate the PCNA, Beclin1, and LC3Ⅱ/LC3Ⅰ expression levels. RAPA could reverse the inhibitory effect of emodin on cell proliferation. Emodin had no significant hepatorenal toxicity and could reduce the volume and mass of the tumor and down-regulate the expression of PCNA and Beclin1 protein inside the tumor. Moreover, the expression of PCNA and Beclin1 in tumor showed a certain positive correlation. Conclusion Emodin can inhibit oral squamous cell proliferation, and its effect may be associated with autophagy inhibition.

Objective Numerous iron deposits hosted in Carboniferous marine volcanic rocks occurred in the Beishan Orogenic Belt, Eastern Tianshan.The Biyushan iron deposit, located at the northwestern margin of Inner Mongolia, is a typical iron deposit hosted in Carboniferous marine volcanic rocks. Methods In this study, we utilized field observation, microscope imaging, and scanning electron microscopy to charaterize the mineral assemblages of iron ores and microtextures of magnetite and apatite, in order to decipher the genesis of iron ores. Results Our preliminary work has revealed that iron ores in the Biyushan deposit commonly have a mineral assemblage of magnetite-apatite, with apatite having abundant monazite inclusions due to the dissolution-reprecipitation processes.In addition, magnetite grains commonly have high Ti contents with ilmenite exsolution.Thus, the mineral assemblage of iron ores and mineralogical features of apatite and magnetite are similar to these of typical Kiruna-type deposits. Conclusion Based on our preliminary analysis of geological characteristics, we suggest that the Biyushan iron deposit in Inner Mongolia is likely a Kiruna-type iron deposit hosted in submarine volcanic rocks that has not yet been documented.Therefore, these findings can guide future exploration of iron oxide-apatite deposits in this region.

Abstract Introduction Self-medication was remarkably popular during the COVID-19 pandemic. In older populations, the risk of self-medication is higher. Pharmacists are well positioned to provide public health education and disease prevention. This study aims to explore the self-medication patterns and intention to seek pharmacist guidance among older adults in Macao. Methods A face-to-face cross-sectional survey was subsequently performed in March-April 2023 among older adults in Macao. The questionnaire was designed based on the Theory of Planned Behavior (TPB) framework. Multiple logistic regression was used to analyze predictors of self-medication behavior and multiple linear regression analysis to determine whether the TPB construct was the predictor of older adults’ intention to seek guidance from pharmacists. Results A total of 412 participants completed the questionnaire. The self-medication rate among older adults in Macao was 64.2%. The most commonly used types of medications were over-the-counter and traditional Chinese medicine, mainly from government anti-pandemic packages. The majority of individuals engaged in self-medication to treat COVID-19 symptoms or prevent COVID-19 infection. The prevalent reasons for self-medication were the perceived non-seriousness of the illness. 85 years old or older and university degree were significantly associated with self-medication behavior. Older adults had moderate intention to seek pharmacist guidance on medication use. The average scores (standard deviation) were 3.43 (1.10) for Attitude, 2.69 (0.99) for Subjective Norm, 3.56 (1.04) for Perceived Behavioral Control, and 3.07 (1.43) for Intention. Attitude, Subjective Norm, and Perceived Behavioral Control were all strong predictors of intention, which explained 53% of the variance in intention. In demographic factors, age was identified as a significant predictor of intentions. Conclusions Self-medication was widely practiced in Macao during the COVID-19 pandemic. To better control the risks associated with self-medication, the role of pharmacists is paramount. Enhancing the recognition and trust of pharmacists within society, modifying pharmacy management models, and strengthening pharmacists’ self-perception of their profession are all pivotal directions areas to further enhance their role.

Clubroot disease is a severe threat to Brassica crops globally, particularly in western Canada. Genetic resistance, achieved through pyramiding clubroot resistance (CR) genes with different modes of action, is the most important strategy for managing the disease. However, studies on the CR gene functions are quite limited. In this study, we have conducted investigations into the temporal, structural, and interacting features of a newly cloned CR gene, Rcr1, using CRISPR/Cas9 technology. For temporal functionality, we developed a novel CRISPR/Cas9-based binary vector, pHHIGR-Hsp18.2, to deliver Rcr1 into a susceptible canola line (DH12075) and observed that early expression of Rcr1 is critical for conferring resistance. For structural functionality, several independent mutations in specific domains of Rcr1 resulted in loss-of-function, highlighting their importance for CR phenotype. In the study of the interacting features of Rcr1, a cysteine protease gene and its homologous allele in canola were successfully disrupted via CRISPR/Cas9 as an interacting component with Rcr1 protein, resulting in the conversion from clubroot resistant to susceptible in plants carrying intact Rcr1. These results indicated an indispensable role of these two cysteine proteases in Rcr1-mediated resistance response. This study, the first of its kind, provides valuable insights into the functionality of Rcr1. Further, the new vector pHHIGR-Hsp18.2 demonstrated an inducible feature on the removal of add-on traits, which should be useful for functional genomics and other similar research in brassica crops.

Abstract The advancements in tactile sensor technology have found wide-ranging applications in robotic fields, resulting in remarkable achievements in object manipulation and overall human-machine interactions. However, the widespread availability of high-resolution tactile skins remains limited, due to the challenges of incorporating large-sized, robust sensing units and increased wiring complexity. One approach to achieve high-resolution and robust tactile skins is to integrate a limited number of sensor units (taxels) into a flexible surface material and leverage signal processing techniques to achieve super-resolution sensing. Here, we present a magnetic skin consisting of multi-direction magnetized flexible films and a contactless Hall sensor array. The key features of the proposed sensor include the specific magnetization arrangement, K-Nearest Neighbors (KNN) clustering algorithm and convolutional neural network (CNN) model for signal processing. Using only an array of 4*4 taxels, our magnetic skin is capable of achieving super-resolution perception over an area of 48400 mm2, with an average localization error of 1.2 mm. By employing neural network algorithms to decouple the multi-dimensional signals, the skin can achieve multi-point and multi-scale perception. We also demonstrate the promising potentials of the proposed sensor in intelligent control, by simultaneously controlling two vehicles with trajectory mapping on the magnetic skin.

IntroductionThe east-west trending Khondalite Belt, located on the northern margin of the North China Craton, is linked to the Paleoproterozoic Columbia supercontinent’s evolution. However, the relationship between the Khondalite Belt formation and orogenic processes remains unclear.MethodsField investigations, petrology, zircon U-Pb dating, whole-rock geochemistry, and electron probe mineral thermobarometry.ResultsGarnet-bearing pyroxenite and serpentinite-like dunite in the ultramafites have zircon U-Pb ages of (1947 ± 17) Ma and (1960 ± 25) Ma, respectively. The rocks show characteristics of subalkaline tholeiitic basalt series, with low SiO2 (35.79%–50.77%), TiO2 (0.01%–0.71%), Al2O3 (0.17%–3.39%), and alkalis (0.02%–2.01%), but high Fe2O3 (12.92%–15.06%). These rocks are enriched in light rare earth elements with slight depletion of Eu, enriched in large ion lithophile elements (Rb and K), and depleted in high field strength elements (P, Zr, and Hf).DiscussionThese metamorphic environments imply that the conditions for ultramafites formation were insufficient to induce granulite-facies metamorphism in the surrounding rocks, indicating that granulite-facies metamorphism in the Khondalite Belt is not closely related to post-orogenic extension in the Inner Mongolia-Northern Hebei orogenic belt.

IntroductionAs adolescent smoking rates rise, its impact on cognitive function has drawn greater attention. This study explores whether exercise can mitigate the negative effects of smoking on executive function in male college students.MethodsSixty male college students were divided into four groups (n = 15 each): sedentary smokers, sedentary nonsmokers, athletic smokers, and athletic nonsmokers. All participants completed the Eriksen flanker task, with prefrontal cortex activation measured using functional near-infrared spectroscopy. After the baseline test, all sedentary students engaged in 33 min of high-intensity interval training, followed by the same procedures as in the pre-test.ResultsIn the flanker task, college athletes exhibited superior executive function compared to sedentary students, with higher accuracy (p = 0.042), faster reaction times (p = 0.002), and more pronounced brain activation (p = 0.048). Post-exercise, reaction times improved significantly in sedentary groups (p < 0.05). Smoking impaired executive function both before and after exercise, with smokers showing lower accuracy (p < 0.001), slower reaction times (p < 0.001), and diminished brain activation (p < 0.001) compared to nonsmokers.DiscussionEngaging in acute aerobic exercise may improve executive function in sedentary smokers. Exercise may help mitigate smoking-related declines in executive function among college students.

The emergence of metadevices has provided an unprecedented ability to manipulate electromagnetic waves, especially in the terahertz band where natural materials are scarce. However, most metadevices have fixed and singular functions after fabrication, making them challenging to adapt to various application scenarios. The paper proposes a reconfigurable multifunctional metadevices platform that integrates metal waveguide arrays with 3D printed structures, capable of independently and simultaneously manipulating the polarisation, phase, and amplitude of two orthogonally polarised terahertz waves. For proof-of-concept experimental demonstration, metadevices featuring polarisation selection, beam deflection, and dual-channel imaging functions are designed, fabricated, and characterised. By replacing the 3D printed structures, reconfiguration between different functions is achieved, with a control efficiency exceeding 60%. Compared to traditional semiconductor processing methods, this modular design approach is not only more cost-effective but also more adaptable, making it highly suitable for applications requiring large-scale metadevices.

This study comprehensively examines how combining γ-irradiation and enzymatic modification influences the microstructure and physicochemical properties of dietary fiber (DF) obtained from defatted rice bran. The resulting yields of soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) were measured at 13.38 ± 0.40 g/100 g and 52.19 ± 0.97 g/100 g, respectively. The modifications led to a diminish in particle size, an increase in specific surface area, and an improvement in water-holding capacity, oil-holding capacity, swelling capacity, glucose adsorption capacity, and cholesterol adsorption capacity. Furthermore, the modified DF exhibited enhanced anti-digestive properties and probiotic activity. Cluster and principal component analysis results revealed that the modified SDF exhibited superior functional properties. Correlation analysis indicated a noticeable relationship between the monosaccharide composition of DF and its functional characteristics. These findings suggest that γ-irradiation combined with enzymatic modification represents a viable approach for enhancing the quality of rice bran DF.

This paper investigates the tightening and anti-loosening performance of phosphated spring washers (i.e., PSW) and galvanized spring washers (i.e., GSW), considering three torques and comparing them with galvanized flat washers (i.e., GFW). Subsequently, a finite element model of the spring washer connecting bolt was established and validated, further investigating the force performance of the spring washer and the stress distribution in the thread area. Finally, a quantitative evaluation method for the anti-loosening performance of spring washers was proposed. The results show that the preload of GSW is maximum after the nut is tightened, and the loss of preload can be supplied by the flattened spring washer. At the same time, the inner ring of the spring washer is sticking, while the outer ring is sliding. Similarly, the contact pressure of the washer decreases radially. During the lateral vibration process, the decrease curve of preload consists of three stages: initial stage, stable stage, and loosening rotation stage. Specifically, GSW has the best anti-loosening performance, because the wear of the zinc layer increases friction. More importantly, the spring washer compensates for the gap between the nut contact surface during transverse vibration, ensuring uniform force distribution in the threaded area and effectively improving the anti-loosening performance.

Aim Comparing the anxiety and depression severity and their impact on subsequent birth outcomes in pregnant women before and during Omicron wave in Shanghai in 2022.Methods The depression-anxiety symptoms networks were compared between the pregnant women during the outbreak period (outbreak group; n = 783) and a matched control group of pregnant women before the outbreak (pre-outbreak group; n = 783). The impact of baseline mental state on follow-up pregnancy and neonatal outcomes was also explored by logistic regression.Findings Levels of depression and anxiety between the two groups were not significant different. Network analysis showed that central symptom "trouble relaxing" and bridge symptom "depressed mood" shared by both groups. Different symptom associations in different periods of the pandemic. Total scores and sub-symptom scores of prenatal depressive and anxious severities increased the odds ratios of maternal and neonatal syndromes. The influence of mental state on gestational and neonatal outcomes differed across different pandemic periods.Conclusion The Omicron wave did not have a significant negative impact on the depressive and anxious mood in pregnant women. Targeting central and bridge symptoms intervention may be effective in reducing their adverse effects on co-occurring of anxious and depressive mood and birth outcomes.

IntroductionLong COVID (LC) poses a persistent challenge in clinical practice due to limited understanding of its etiology. LC is hypothesized to stem from aberrant immune responses in COVID-19. Vaccinations, which boost immune cells to restore function, could help ease LC symptoms.MethodsTo exclude the impact of vaccination, we examined the immune cell profiles of recovering COVID-19 patients before vaccines were available. White blood cell differentials were monitored in ninety-twohealthy unvaccinated controls. Seventy-six unvaccinated COVID-19 patients were monitored upon admission and on the 50th day post-symptom onset (DPSO50). Peripheral lymphocyte subsets were analyzed using flow cytometry.ResultsMild cases showed no significant changes in lymphocyte counts or subsets from admission to DPSO50. By DPSO50, severe and critical cases showed almost complete recovery from lymphopenia, with critical cases having CD19+ B-cell counts approximately 45% lower than the mild group. Severe and critical cases exhibited reduced B-cell frequencies, with critical cases displaying around 48% higher natural killer (NK) cell counts. In mild cases, NK cell counts negatively correlated with B-cell counts (r=-0.528, p=0.02). Additionally, critical cases showed positive correlations between NK cell counts and CD4+ T-cell counts (r=0.83, p

IntroductionArc-continent collision contributes to the accretion of continental crust in the Central Asian Orogenic Belt. The Chegendalai ophiolitic mélange, located between the Bainaimiao arc and the North China Craton, is important to understanding the early Paleozoic evolution of the South Bainaimiao Ocean and arc-continent collision processes.MethodsIn this study, we provide Early Paleozoic geochronological and geochemical data from the Chegendalai ophiolitic mélange and island arc magmatic rocks in northern Damaoqi.ResultsZircon U-Pb dating of ultrabasic rocks and diabase porphyrite from the Chegendalai ophiolitic mélange yielded ages of 424 Ma and 431.9 Ma, respectively. Schist has an age of 421 Ma. Zircon U-Pb ages of island arc magmatic rocks are 425.7 Ma for tonalite, and 431 ± 11 Ma and 433.2 ± 4.4 Ma for granodiorite. Gabbro and ultrabasic rocks were formed in a volcanic arc basalt or mid-ocean ridge setting, displaying a tholeiitic basalt signature. These rocks likely derived from the lithospheric mantle with assimilation of crustal materials. Intermediate-acid magmatic rocks in northern Damaoqi are geochemically classified as I-type granites and exhibit characteristics of adakites.DiscussionThese rocks formed by partial melting of subducted plates and interactions with crustal and mantle wedges in a volcanic arc setting. Based on these results, we propose a three-stage evolution model for the South Bainaimiao Ocean: (i) Initial subduction during the Ordovician (∼450 Ma), where the Bainaimiao arc separated the South Bainaimiao Ocean from the PaleoAsian Ocean, with the former acting as a branch ocean basin of the latter; (ii) Northward subduction from the Ordovician to Late Silurian (450–424 Ma), with the South Bainaimiao Ocean subducting northward. The subducted slab partially melted and interacted with the crust-mantle wedge, leading to the formation of subduction-related island arc magmatic rocks; (iii) Closure during the Late Silurian (424–421 Ma), marked by the collision of the Bainaimiao arc with the North China Craton in an arc-continent collision, ending orogenesis with the Xibiehe Formation.

IntroductionPlatelets are hyperactived during acute COVID-19, promoting clotting and modulating immune-cell responses. Immune thrombocytopenia in adults can manifest as an uncommon complication resulting from various viral infections or as a rare adverse event associated with vaccination. However, their role in convalescent COVID-19 patients remains underexplored. This study examines platelet dynamics early in the pandemic, 48 days post-symptom onset, in unvaccinated patients.MethodsThis longitudinal study included 298 unvaccinated COVID-19 patients (17 mild, 281 moderate) from multiple centers. Clinical evaluations and peripheral lymphocyte subset analyses via flow cytometry were conducted upon admission and on day 48 post-symptom onset (DPSO 48).ResultsAt DPSO 48, 5.3% of moderate COVID-19 patients exhibited high platelet counts (>300×109/L), associated with elevated total T-cells (26.4%), CD4 T-cells (24.4%), CD8 T-cells (36.9%), and Tregs (33.9%) compared to patients with normal platelet counts. However, the CD4/CD8 T-cell ratio and T-cell subset frequencies remained unaffected, indicating ongoing T-cell homeostasis restoration. Additionally, a significant positive correlation (r=0.636, p=0.03) was found between platelet counts and B cells in patients with elevated platelet counts.DiscussionPlatelets may play a pivotal role in immune regulation during the recovery phase of COVID-19. Targeting platelets and their secreted mediators could improve immune balance in patients with immune disorders, highlighting a potential therapeutic approach for enhancing recovery in post-COVID-19 patients.

Deep convolutional neural networks (CNNs) have achieved remarkable success in various computer vision tasks. However, the lack of interpretability in these models has raised concerns and hindered their widespread adoption in critical domains. Generating activation maps that highlight the regions contributing to the CNN's decision has emerged as a popular approach to visualize and interpret these models. Nevertheless, existing methods often produce activation maps contaminated with irrelevant background noise or incomplete object activation, limiting their effectiveness in providing meaningful explanations. To address this challenge, we propose Union Class Activation Mapping (UnionCAM), an innovative visual interpretation framework that generates high-quality class activation maps (CAMs) through a novel three-step approach. UnionCAM introduces a weighted fusion strategy that adaptively combines multiple CAMs to create more informative and comprehensive activation maps. First, the denoising module removes background noise from CAMs by using adaptive thresholding. Subsequently, the union module fuses the denoised CAMs with region-based CAMs using a weighted combination scheme to obtain more comprehensive and informative maps, which we refer to as fused CAMs. Lastly, the activation map selection module automatically selects the optimal CAM that offers the best interpretation from the pool of fused CAMs. Extensive experiments on ILSVRC2012 and VOC2007 datasets demonstrate UnionCAM's superior performance over state-of-the-art methods. It effectively suppresses background noise, captures complete object regions, and provides intuitive visual explanations. UnionCAM achieves significant improvements in insertion and deletion scores, outperforming the best baseline. UnionCAM makes notable contributions by introducing a novel denoising strategy, adaptive fusion of CAMs, and an automatic selection mechanism. It bridges the gap between CNN performance and interpretability, providing a valuable tool for understanding and trusting CNN-based systems. UnionCAM has the potential to foster responsible deployment of CNNs in real-world applications.

BackgroundDermatomyositis (DM) is an autoimmune disease that primarily affects the skin and muscles. It can lead to increased mortality, particularly when patients develop associated malignancies or experience fatal complications such as pulmonary fibrosis. Identifying reliable biomarkers is essential for the early diagnosis and treatment of DM. This study aims to identify and validate pivotal diagnostic biomarker for DM through integrated bioinformatics analysis and clinical sample validation.MethodsGene expression datasets GSE46239 and GSE142807 from the Gene Expression Omnibus (GEO) database were merged for analysis. Differentially expressed genes (DEGs) were identified and subjected to enrichment analysis. Advanced machine learning methods were utilized to further pinpoint hub genes. Weighted gene co‐expression network analysis (WGCNA) was also conducted to discover key gene modules. Subsequently, we derived intersection gene from these methods. The diagnostic performance of the candidate biomarker was evaluated using analysis with dataset GSE128314 and confirmed by immunohistochemistry (IHC) in skin lesion biopsy specimens. The CIBERSORT algorithm was used to analyze immune cell infiltration patterns in DM, then the association between the hub gene and immune cells was investigated. Gene set enrichment analysis (GSEA) was performed to understand the biomarker’s biological functions. Finally, the drug-gene interactions were predicted using the DrugRep server.ResultsInterferon-stimulated gene 15 (ISG15) was identified by intersecting DEGs, advanced machine learning-selected genes and key module genes from WGCNA. ROC analysis showed ISG15 had a high Area under the curve (AUC) of 0.950. IHC findings confirmed uniformly positive expression of ISG15, particularly in perivascular regions and lymphocytes, contrasting with universally negative expression in controls. Further analysis revealed that ISG15 is involved in abnormalities in various immune cells and inflammation-related pathways. We also predicted three drugs targeting ISG15, supported by molecular docking studies.ConclusionOur study identifies ISG15 as a highly specific diagnostic biomarker for DM, ISG15 may be closely related to the pathogenesis of DM, demonstrating promising potential for clinical application.

Abstract The utilization of single atoms (SAs) as trifunctional electrocatalyst for nitrogen reduction, oxygen reduction, and oxygen evolution reactions (NRR, ORR, and OER) is still a formidable challenge. Herein, we devise one‐pot synthesized palladium SAs stabilized on nitrogen‐doped carbon palladium SA electrocatalyst (Pd‐SA/NC) as efficient trifunctional electrocatalyst for NRR, ORR, and OER. Pd‐SA/NC performs a robust catalytic activity toward NRR with faradaic efficiency of 22.5% at −0.25 V versus reversible hydrogen electrode (RHE), and the relative Pd utilization efficiency is enhanced by 17‐fold than Pd‐NP/NC. In addition, the half‐wave potential reaches 0.876 V versus RHE, amounting to a 58‐time higher mass activity than commercial Pt/C. Moreover, the overpotential at 10 mA cm−2 is as low as 287 mV for Pd‐SA/NC, outperforming the commercial IrO2 by 360 times in turnover frequency at 1.6 V versus RHE. Accordingly, the assembled rechargeable zinc‐air battery (ZAB) achieves a maximum power density of 170 mW cm−2, boosted by 2.3 times than Pt/C–IrO2. Two constructed ZABs efficiently power the NRR‐OER system to electrochemically generate ammonia implying its superior trifunctionality.

Abstract The rapid development of ocean exploration and underwater robot technology has put forward new requirements for underwater sensing methods, which can be used for hydrodynamic characteristics perception, underwater target tracking, and even underwater cluster communication. Here, inspired by the specialized undulated surface structure of the seal whisker and its ability to suppress vortex‐induced vibration, a multidirectional hydrodynamic sensor based on biomimetic whisker array structure and magnetic 3D self‐decoupling theory is introduced. The magnetic‐based sensing method enables wireless connectivity between the magnetic functional structures and electronics, simplifying device design and endowing complete watertightness. The 3D self‐decoupling capability enables the sensor, like a seal or other organisms, to perceive arbitrary whisker motions caused by the action of water flow without complex calibration and additional sensing units. The whisker sensor is capable of detecting a variety of hydrodynamic information, including the velocity (RMSE

Abstract Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next‐generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26–2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67–4.50) and in a biobank meta‐analysis (OR, 1.16; 95% CI, 1.04–1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9‐edited HEK293T cell lines show that loss‐of‐function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/− mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein‐stimulated pancreatitis models, Sec16a+/− mice display heightened pancreatic inflammation and fibrosis compared to wild‐type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.

Background and objective: The use of mesenchymal stem cells for heart failure treatment has gained increasing interest. However, most studies have relied on a single injection approach, with no research yet confirming the effects of multiple administrations. The present trial aims to investigate the safety and efficacy of multi-intravenous infusion of umbilical cord-mesenchymal stem cells (UC-MSCs) in patients with heart failure and reduced ejection fraction (HFrEF). Methods: The PRIME-HFrEF trial is a single-center, prospective, randomized, triple-blinded, placebo-controlled trial of multi-intravenous infusion of UC-MSCs in HFrEF patients. A total of 40 patients meeting the inclusion criteria for HFrEF were enrolled and randomized 1:1 to the MSC group or the placebo group. Patients enrolled will receive intravenous injections of either UC-MSCs or placebo every 6 weeks for three times. Both groups will be followed up for 12 months. The primary safety endpoint is the incidence of serious adverse events. The primary efficacy endpoint is a change in left ventricular ejection fraction (LVEF) measured by left ventricular opacification (LVO) with contrast echocardiography and magnetic resonance imaging (MRI) at 12 months. The secondary endpoints include a composite of the incidence of death and re-hospitalization caused by heart failure at the 12th month, serum NT-proBNP, growth stimulation expressed gene 2 (ST2), and a change of right ventricular structure and function. Conclusions: The PRIME-HFrEF study is designed to shed new light on multiple UC-MSC administration regimens for heart failure treatment.