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Virtual Reality (VR) is increasingly recognized as a promising tool to enhance learning, yet research on the use of VR instructional approaches for online learning remains limited. The present study aims to address this research gap by examining the effects of VR instructional approaches and textual cues on learning. We conducted an educational VR study using a 2 x 2 + 1 between-subjects design involving 67 secondary vocational students. Participants learned computer assembly online and were exposed to either vicarious experience or direct manipulation instructional approaches, with or without textual cues. A control group received traditional online instruction using slides. We collected retention, transfer learning outcomes, cognitive load, and learning experience of students. The findings indicated that while vicarious VR had no effects on long-term retention, transfer, and learning experience, there were significant positive effects on the immediate acquisition of knowledge. Textual cues did not affect learning in general. However, for immediate knowledge gain, they did provide a positive boost to learning in VR involving direct manipulation, while they were unnecessary in vicarious VR experiences. This study contributes to how the cueing principle can be extended to educational VR contexts and expands the knowledge of vicarious VR learning.

Responding to a recent call for interdisciplinary research into 'night studies', the present study attempts to put the nighttime at the centre of the sociolinguistic enquiry, seeking to explore how the nocturnal linguistic landscape (LL) differs from the diurnal LL by drawing on Singapore's Chinatown as the research site. A total of 1091 LL items constitute the database. Altogether 808 LL items were collected during the daytime and 283 of these LL items were found to be illuminated during nighttime site visits. The quantitative analysis reveals that the nocturnal LL differs from the diurnal LL in several ways: at the top-down level, the nocturnal LL shows a strong monolingual English tendency, while the diurnal LL has a tendency towards multilingualism; at the bottom-up level, fewer languages are used in the nocturnal signs than in the diurnal signs and Chinese is used as the prominent language in nocturnal signs, whereas English has a leading position in the diurnal signs. Our findings complicate previous scholarly understanding of bilingual and multilingual configurations in Singapore, suggesting that the LL has its own unique representation at night. The potential for integrating nighttime as a new dimension to examine LL is discussed .

Digital media literacy education has become shared responsibility of all educators, school-based initiatives are considered to be a crucial component of digital media literacy education. This 10-week intervention study explores the effects of digital media literacy (DML) course on students' digital media literacy. The participants were 58 fifth graders (M = 11.5 years) from two classes in Beijing. An analysis of covariance (ANCOVA) and structural equation modeling (SEM) were performed to examine the effects of the DML course on the digital media literacy of primary school students. The results provided evidence that the DML course positively impacts students' citizenship participation, but has no significant influence on students' technical skills, critical understanding, or creation and communication. The findings also explained a positive relationship between teacher's scaffolding support and students' digital media literacy.

Researchers have found that violent online game addiction has become a serious global problem that negatively affects younger people. This study used a cross-sectional research design to examine the effects of violent online game contact on individuals' academic procrastination. We further explored the mediating role of emotional self-regulation and the moderating role of peer communication in the link between violent online game contact and academic procrastination. A sample of 1132 students completed self-reported questionnaires regarding violent online game contact, emotional self-regulation, peer communication, and academic procrastination. Participants were randomly selected from Guangdong Province, China. Results indicated that violent online game contact was positively correlated with academic procrastination, while emotional self-regulation indirectly affected the relationship. Peer communication played a moderating role in the indirect effect between emotional self-regulation and academic procrastination. The general pattern of this mechanism illustrates that as peer communication increased, the effects of emotional self-regulation on academic procrastination decreased. The findings elucidate how and for whom violent online game exposure is related to academic procrastination. This research demonstrates that violent game contact is an important factor affecting academic procrastination, clarifies the role of peer communication and emotional self-regulation, and provides practical suggestions for preventing academic procrastination in the field of school psychology.

Computer programming and municipal engineering (ME) students' specialised knowledge are still poorly integrated, leading to limited improvement of students' programming abilities. This paper describes an effective attempt in ME at Xi'an University of Architecture and Technology (XAUAT). Students were divided into several teams and required to develop software tools for ME design problems using Visual C++ 6.0. In this teaching approach, students need to identify the solutions by integrating knowledge in mathematics, physics, chemistry, basic engineering science, and ME. Moreover, students should develop programmes with friendly interfaces, essential prompts, and reliable results. The example programmes, positive feedback from the survey, and better performance in the final examination proved that the students' abilities of knowledge application and problem-solving had been developed, and their motivation in learning programming had been improved.

Abstract Background Human papillomavirus (HPV) infection significantly contributes to the global cancer burden. Understanding the factors influencing male clinical interns’ willingness to promote HPV vaccination is crucial for developing effective public health strategies in China. Methods This study employed a stratified random sampling method to select 1,980 male clinical interns from five provinces in China between January and March 2024. Data were collected on participants’ demographic characteristics, HPV-related clinical experience, and knowledge. The Theory of Planned Behavior framework, encompassing attitudes, subjective norms, and perceived behavioral control, was used to examine factors influencing the willingness to promote the HPV vaccine. Logistic regression analyses were conducted to identify factors associated with the willingness to promote the HPV vaccine. Results Among the respondents, 72.29% were willing to encourage others to receive the HPV vaccine. Significant factors influencing this willingness included older age (OR = 3.065, P ≤ 0.001), higher monthly household income (OR = 1.449, P = 0.025), participation in the diagnosis and treatment of HPV-related diseases (OR = 3.458, P ≤ 0.001), positive attitude towards the vaccine (OR = 13.503, P = 0.004), and strong perceived behavioral control (OR = 2.364, P = 0.006). Conclusion This study highlights the critical role of practical experience and targeted education in promoting HPV vaccination among male clinical interns in China. Enhancing the training and education of this group is essential for improving HPV vaccine advocacy and supporting public health efforts to reduce HPV-related diseases.

Abstract In this study, we successfully established a novel gallbladder cancer cell line, designated as GBC-X1, derived from a primary tumor of a gallbladder cancer patient. By comprehensively analyzing the cell line’s phenotype, molecular characteristics, biomarkers, and histological characteristics, we confirmed that GBC-X1 serves as a valuable model for investigating the pathogenesis of gallbladder cancer and developing therapeutic agents. GBC-X1 has been continuously cultured for one year, with over 60 stable passages. Morphologically, GBC-X1 exhibits typical features of epithelial tumors. The population doubling time of GBC-X1 is 32 h. STR analysis validated a high consistency between GBC-X1 and the patient’s primary tumor. Karyotype analysis revealed an abnormal hypertetraploid karyotype for GBC-X1, characterized by representative karyotypes of 98, XXXX del (4) p (12) del (5) p (21) der (10). Under suspension culture conditions, GBC-X1 efficiently forms tumor balls, while subcutaneous inoculation of GBC-X1 cells into NXG mice leads to xenograft formation with a rate of 80%. Drug sensitivity testing demonstrated that GBC-X1 is resistant to oxaliplatin and sensitive to 5-FU, gemcitabine, and paclitaxel. Immunohistochemistry revealed positive expression of CK7, CK19, E-cadherin, MMP-2, CD44, SOX2, and TP53 in GBC-X1 cells, weak positive expression of Vimentin, and a Ki67 positive rate of 35%. Our research highlights GBC-X1 as a novel gallbladder cancer cell line and emphasizes its potential as an effective experimental model for investigating the pathogenesis of gallbladder cancer and drug development.

Walnut kernels, selected as the raw material, underwent hydrolysis with protein-glutaminase (PG) following pulping. This process laid the foundation for producing set-type walnut yogurt, involving steps such as blending, homogenization, sterilization, and fermentation. The study investigated the impact of protein-glutaminase and five distinct starter cultures labeled I~V on the quality of walnut yogurt. This was evaluated by examining the yogurt's fermentation characteristics, physicochemical indicators, and microstructure. Furthermore, walnut yogurt developed under these optimal conditions was compared to traditional milk yogurt to assess its quality and characteristics. The findings revealed a significant improvement in the fermentation characteristics and textural parameters of yogurt fermented by walnut milk following enzymatic hydrolysis compared to non-enzymatic walnut milk. The optimal conditions were identified as 0.2% enzyme concentration and a 40-minute reaction time, with the pH, acidity, hardness, and consistency of walnut yogurt being 4.3, 55°T, 85.30 g, and 583.96 g·s, respectively. Walnut yogurt developed using starter culture I exhibited the highest acidity level, maintaining minimal fluctuation over a 21-day storage period. In contrast, yogurts prepared with alternative starter cultures demonstrated varying degrees of stratification and sedimentation. The yogurt fermented with culture I showed superior viscoelastic properties, presenting a denser gel network. Conversely, yogurts fermented with cultures IV and V displayed reduced apparent viscosity, lower values of G' (storage modulus), and G'' (loss modulus), along with a looser gel structure. Additionally, walnut yogurt produced with starter culture I maintained bacterial counts exceeding 106 CFU/mL throughout the storage duration. Despite walnut yogurt requiring further refinement in aspects such as consistency, water-holding capacity, and whey release rate compared to milk yogurt, the overall impact of PG was positive, enhancing the gelation quality of walnut yogurt. The yogurt prepared with starter culture I (Lactobacillus bulgaricus and Streptococcus thermophilus) was notably improved, receiving favorable overall assessments.

Abstract Mandarin Chinese is typologically unusual among the world’s languages in having flexible word order despite a near absence of inflectional morphology. These features of Mandarin challenge conventional linguistic notions such as subject and object and the divide between syntax and semantics. In the present study, we tested monolingual processing of argument structure in Mandarin verb-final sentences, where word order alone is not a reliable cue. We collected participants’ responses to a forced agent-assignment task while measuring their electroencephalography data to capture real-time processing throughout each sentence. We found that sentence interpretation was not informed by word order in the absence of other cues, and while the coverbs BA and BEI were strong signals for agent selection, comprehension was a result of multiple cues. These results challenge previous reports of a linear ranking of cue strength. Event-related potentials showed that BA and BEI impacted participants’ processing even before the verb was read and that role reversal anomalies elicited an N400 effect without a subsequent semantic P600. This study demonstrates that Mandarin sentence comprehension requires online interaction among cues in a language-specific manner, consistent with models that predict crosslinguistic differences in core sentence processing mechanisms.

Abstract Effectively controlling the selective conversion of CO2 photoreduction to C2 products presents a significant challenge. Here, we develop a heterojunction photocatalyst by controllably implanting Au nanoparticles and single atoms into unsaturated Mo atoms of edge-rich MoS2, denoted as Aun/Au1-CMS. Photoreduction of CO2 results in the production of CH3COOH with a selectivity of 86.4%, which represents a 6.4-fold increase compared to samples lacking single atoms, and the overall selectivity for C2 products is 95.1%. Furthermore, the yield of CH3COOH is 22.4 times higher compared to samples containing single atoms and without nanoparticles. Optical experiments demonstrate that the single atoms domains can effectively capture photoexcited electrons by the Au nanoparticles, or the local electric field generated by the nanoparticles promotes the transfer of photogenerated electrons in MoS2 to Au single atoms, prolonging the relaxation time of photogenerated electrons. Mechanistic investigations reveal that the orbital coupling of Au5d and Mo4d strengthens the oxygen affinity of Mo and carbon affinity of Au. The hybridized orbitals reduce energy splitting levels of CO molecular orbitals, aiding C–C coupling. Moreover, the Mo−Au dual-site stabilize the crucial oxygen-associated intermediate *CH2CO, thereby enhancing the selectivity towards CH3COOH. The cross-scale heterojunctions provide an effective strategy to simultaneously address the kinetical and thermodynamical limitations of CO2-to-CH3COOH conversion.

Abstract Lattice oxygen in metal oxides plays an important role in the reaction of diesel oxidation catalysts, but the atomic-level understanding of structural evolution during the catalytic process remains elusive. Here, we develop a Mn2O3/SmMn2O5 catalyst using a non-stoichiometric exsolution method to explore the roles of lattice oxygen in NO oxidation. The enhanced covalency of Mn–O bond and increased electron density at Mn3+ sites, induced by the interface between exsolved Mn2O3 and mullite, lead to the formation of highly active lattice oxygen adjacent to Mn3+ sites. Near-ambient pressure X-ray photoelectron and absorption spectroscopies show that the activated lattice oxygen enables reversible changes in Mn valence states and Mn-O bond covalency during redox cycles, reducing energy barriers for NO oxidation and promoting NO2 desorption via the cooperative Mars-van Krevelen mechanism. Therefore, the Mn2O3/SmMn2O5 exhibits higher NO oxidation activity and better resistance to hydrothermal aging compared to a commercial Pt/Al2O3 catalyst.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Background and aim: A surplus of glucocorticoids (GC) is a main cause of non-traumatic osteonecrosis of the femoral head (ONFH), and Jintiange (JTG), as one of the traditional Chinese medicines (TCM), also plays an instrumental role in the alleviation of bone loss simultaneously. Therefore, JTG was thought to be able to reverse GC-induced ONFH (GC-ONFH) to a certain extent. Experimental procedure: In vivo, the effect of JTG on trabeculae in the subchondral bone of the femoral head was investigated using micro-computed tomography (micro-CT), TdT-mediated dUTP nick end labeling (TUNEL) and histological staining; in vitro, proliferation, viability, apoptosis, and senescence of purified bone mesenchymal stem cells (BMSCs) were examined to demonstrate the direct impact of JTG on these cells. Meanwhile after using a series of interventions, the function of JTG on BMSC differentiation could be assessed by measuring of osteogenic and adipogenic markers at levels of protein and mRNA. Results: Our final results demonstrated that with the involvement of Wnt/β-catenin pathway, JTG was able to significantly promote osteogenesis, restrain adipogenesis, delay senescence in BMSCs, reduce osteoclast number, weaken apoptosis, and enhance proliferation of osteocytes, all of which could mitigate the progression of subchondral osteonecrosis. Conclusion: According to the results of experiments in vitro and vivo, JTG was deemed to relieve the early GC-ONFH using the prevention of destruction of subchondral bone, which was contributed to regulating the differentiation of BMSCs and the number of osteoclasts.

Earthquakes are major catastrophes that cause great life and economic losses to human society and environment. This paper reviews and synthesizes relevant studies, drawing from a systematic examination of 4229 articles from the Web of Science core collection (1982–2023). Employing the CiteSpace visualization and analysis tool, current research and emerging trends in seismic risk assessment are discussed and analyzed. This paper provides a holistic overview of principal contributions, knowledge sources, interdisciplinary characteristics, and principal research topics in this field. Additionally, we propose key technologies that are in urgent need of enhancement, including data availability, quantity and quality of data, interpretability of machine learning models, performance improvement of machine learning methods and application of foundation models, as well as real-time risk assessment techniques. These insights support both theoretical understanding and practical applications of seismic risk assessment and damage analysis.

MgAl2O4 ceramics possess outstanding mechanical properties, making them promising for use as reinforcing or interfacial modulating phase in Al-based metal composites. The challenge lies in the insufficient interatomic potential parameters to accurately characterize the MgAl2O4/Al interfacial interactions, which hampers a detailed understanding of the interfacial strengthening mechanisms at the atomic level. Since the pair potential satisfies the requirements for computational efficiency and accuracy, it has been widely used for investigating the interfacial properties of composite materials. In this study, the interatomic potential parameters for Al–Mg and Al–Al bonds were derived from Buckingham potential, while those for Al–O bonds were obtained from Morse potential via first principles calculations. The uniaxial tensile mechanical properties and interface-dislocation strengthening mechanisms of MgAl2O4/Al interface configuration were explored through molecular dynamics simulations. The analyses reveal that the strength enhancement of the MgAl2O4/Al interface is due to the generation of a large number of immovable 1/6 stair-rod dislocations therein. The thickness of MgAl2O4 layer significantly influences the mechanical properties. Below a thickness of 20 Å, the presence of movable dislocations reduces the strengthening effect. Conversely, increasing the thickness of MgAl2O4 encourages the emergence of immovable dislocations and increases the flow stress, while the corresponding yield strain decreases. These insights open up new prospects in the development of aluminum metal matrix composites with enhanced performance.

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

Abstract For enhancing the accuracy of cargo box position and angle recognition on the conveyor platform, this paper proposes a cargo box attitude detection and adjustment method based on instance segmentation and image processing. This approach involves generating Mask data through target detection of the cargo box using Mask R-CNN. Using image processing algorithms to generate a minimum rectangle according to the Mask data, and the minimum rectangle data is aligned with the Bbox data of Maks R-CNN. The position and angle of the cargo box are detected based on the minimum rectangular data, and the conveyor platform is adjusted to control the cargo box attitude using the Bbox data. Nine attitude acquisition and comparison experiments were conducted on the cargo box using an angle sensor, and the deviation of the method was consistently $$

Abstract Cryogenic electron microscopy (cryo-EM) has revolutionized structural biology, enabling efficient determination of structures at near-atomic resolutions. However, a common challenge arises from the severe imbalance among various conformations of vitrified particles, leading to low-resolution reconstructions in rare conformations due to a lack of particle images in these quasi-stable states. We introduce CryoTRANS, a method that predicts high-resolution maps of rare conformations by constructing a self-supervised pseudo-trajectory between density maps of varying resolutions. This trajectory is represented by an ordinary differential equation parameterized by a deep neural network, ensuring retention of detailed structures from high-resolution density maps. By leveraging a single high-resolution density map, CryoTRANS significantly improves the reconstruction of rare conformations and has been validated on four real-world datasets: alpha-2-macroglobulin, actin-binding protein complexes, SARS-CoV-2 spike glycoprotein, and the 70S ribosome. CryoTRANS can also predict high-resolution structures in cryogenic electron tomography maps using a high-resolution cryo-EM map.

Abstract Tissue-derived extracellular vesicles (EVs) are emerging as pivotal players to maintain organ homeostasis, which show promise as a next-generation candidate for medical use with extensive source. However, the detailed function and therapeutic potential of tissue EVs remain insufficiently studied. Here, through bulk and single-cell RNA sequencing analyses combined with ultrastructural tissue examinations, we first reveal that in situ liver tissue EVs (LT-EVs) contribute to the intricate liver regenerative process after partial hepatectomy (PHx), and that hepatocytes are the primary source of tissue EVs in the regenerating liver. Nanoscale and proteomic profiling further identify that the hepatocyte-specific tissue EVs (Hep-EVs) are strengthened to release with carrying proliferative messages after PHx. Moreover, targeted inhibition of Hep-EV release via AAV-shRab27a in vivo confirms that Hep-EVs are required to orchestrate liver regeneration. Mechanistically, Hep-EVs from the regenerating liver reciprocally stimulate hepatocyte proliferation by promoting cell cycle progression through Cyclin-dependent kinase 1 (Cdk1) activity. Notably, supplementing with Hep-EVs from the regenerating liver demonstrates translational potential and ameliorates insufficient liver regeneration. This study provides a functional and mechanistic framework showing that the release of regenerative Hep-EVs governs rapid liver regeneration, thereby enriching our understanding of physiological and endogenous tissue EVs in organ regeneration and therapy.

Abstract Background Cardiovascular disease (CVD) is a major health concern for middle-aged and older adults, with lifestyle and metabolic risk factors well-studied. However, the role of psychosocial factors in CVD remains underexplored. Objective This study aims to delve into the connection between psychosocial factors and the occurrence of CVD. Methods We utilized data from the UK Biobank, a large-scale study covering adults aged 38 to 73 recruited from various centers across the UK between 2006 and 2010. We employed Cox proportional hazards models to analyze the relationship between social isolation, loneliness, and incident CVD. CVD diagnoses were confirmed through hospital records and death-register data. Additionally, we conducted mediation analyses to assess the impact of low-grade inflammation. Results The study encompassed 427,942 participants free from CVD, 55.8% of whom are women. High levels of social isolation and loneliness were linked to a higher risk of CVD (HRs 1.11, 95% CI 1.06–1.16; HRs 1.17, 95% CI 1.11–1.23). Depression also emerged as a predictor of CVD onset (HRs 1.25, 95% CI 1.19–1.31), with each psychosocial factor independently contributing to increased CVD risk. Mediation analyses pinpointed inflammation as a crucial mediator, especially for loneliness (indirect effect proportion: 4.7%). Conclusions This study underscores the significance of psychosocial factors in relation to CVD. Integrating assessments for social isolation, loneliness, and depression into routine healthcare could potentially aid in CVD prevention among middle-aged and elderly individuals. Lay summary This study underscores the significance of psychosocial factors in relation to CVD, emphasizing the association between social isolation or loneliness and the heightened risk of CVD. Graphical abstract

Abstract Aim This study aimed to discover risk factors for death in patients with critical COVID-19 infection in order to identify patients with a higher risk of death at an early stage. Methods We retrospectively analyzed the clinical data of patients with critical COVID-19 infection from April 2022 to June 2022. Data were collected from the electronic medical records. Propensity matching scores were used to reduce the effect of confounding factors, such as patient baseline variables. Independent risk factors affecting patient prognosis were assessed using univariate logistic regression and multivariate logistic regression analysis. Restricted cubic spline curves were used to assess the relationship between independent and dependent variables. Results The data of 132 patients with critical COVID-19 infection were included in the study. Of the 132 patients, 79 survived and 53 died. Among laboratory indicators, patients who died had higher proportions of abnormalities in procalcitonin, aspartate aminotransferase (AST), creatinine, cardiac troponin I, and myoglobin. Univariate and multivariate logistic regression analyses suggested that abnormal AST (OR = 4.98, P = 0.02), creatinine (OR = 7.93, P = 0.021), and myoglobin (OR = 103.08, P = 0.002) were independent risk factors for death. After correction for AST and creatinine, a linear relationship between myoglobin and risk of death in patients was found using restricted cubic splines. Conclusion High myoglobin level is an independent risk factor for death and is therefore a prognostic marker in elderly patients with severe COVID-19 infection.

Abstract Objective Bibliometrics was employed in this study to determine the research trends in the worldwide application of 3D printing technology to treat bone tumors over the previous 10 years. Methods Published from 2013 to 2022, the papers related to bone tumors treated with 3D printing were located in Web of Science Core Collection (WoSCC), PubMed, and Scopus. The screened articles were included in this bibliometric study. From these papers in WoSCC, information on annual publications, journals, keywords, countries, authors, institutions, and cited references were extracted and visualized with CiteSpace (version 6.1.R6) software to investigate the state of bone tumor treatment using 3D printing as well as research hotspots. The Carrot2 online visualization tool and Vosviewer software (version 1.6.20) were employed to visualize the publications from PubMed and Scopus, respectively, in order to ascertain the most popular research topics from both databases. Results A total of 606, 233, and 364 publications were obtained from WoSCC, PubMed, and Scopus, respectively, between the years 2013 and 2022. In WoSCC, the peak number of publications was found in 2021, with 145 publications published. Acta Biomaterialia (11 publications) and World Neurosurgery (10 publications) were the most prolific journals, and Biomaterials was the journal cited the most (244 times). Yong Zhou was the most productive author with 14 publications, while Kwok-Chuen Wong (69 citations) and William F Enneking, (69 citations) possessed the most citations. The country with the largest quantity of publications was China (207). Among all institutions, Shanghai Jiao Tong University produced the most publications (29). Rapid prototyping was the keyword with the strongest citation burst (4.73). ‘Reconstruction’, ‘surgery’, ‘resection’, and ‘design’ caught the significant attention of researchers. 3D-printed materials, pelvic reconstruction, mandibular reconstruction, computer-assisted surgical techniques, photothermal therapy, and in vitro experiments were recognized as hot subjects and trends in current research. The most frequently occurring topics in Scopus are not significantly different from those found in WoSCC. The most prevalent research areas in PubMed encompass implant, patient-specific, bioceramic, models, and pelvic.

Abstract The free-field switching of the perpendicular magnetization by the out-of-plane polarized spin current induced spin-orbit torque makes it a promising technology for developing high-density memory and logic devices. The materials intrinsically with low symmetry are generally utilized to generate the spin current with out-of-plane spin polarization. However, the generation of the out-of-plane polarized spin current by engineering the symmetry of materials has not yet been reported. Here, we demonstrate that paramagnetic CaRuO3 films are able to generate out-of-plane polarized spin current by engineering the crystal symmetry. The non-uniform oxygen octahedral tilt/rotation along film’s normal direction induced by oxygen octahedral coupling near interface breaks the screw-axis and glide-plane symmetries, which gives rise to a significant out-of-plane polarized spin current. This spin current can drive field-free spin-orbit torque switching of perpendicular magnetization with high efficiency. Our results offer a promising strategy based on crystal symmetry design to manipulate spin current and could have potential applications in advanced spintronic devices.

Abstract Background Unicompartmental knee arthroplasty (UKA) has been proved to be a successful treatment for osteoarthritis patients. However, the stress shielding caused by mismatch in mechanical properties between human bones and artificial implants remains as a challenging issue. This study aimed to properly design a bionic porous tibial implant and evaluate its biomechanical effect in reconstructing stress transfer pathway after UKA surgery. Methods Voronoi structures with different strut sizes and porosities were designed and manufactured with Ti6Al4V through additive manufacturing and subjected to quasi-static compression tests. The Gibson-Ashby model was used to relate mechanical properties with design parameters. Subsequently, finite element models were developed for porous UKA, conventional UKA, and native knee to evaluate the biomechanical effect of tibial implant with designed structures during the stance phase. Results The internal stress distribution on the tibia plateau in the medial compartment of the porous UKA knee was found to closely resemble that of the native knee. Furthermore, the mean stress values in the medial regions of the tibial plateau of the porous UKA knee were at least 44.7% higher than that of the conventional UKA knee for all subjects during the most loading conditions. The strain shielding reduction effect of the porous UKA knee model was significant under the implant and near the load contact sites. For subject 1 to 3, the average percentages of nodes in bone preserving and building region (strain values range from 400 to 3000 μm/m) of the porous UKA knee model, ranging from 68.7 to 80.5%, were higher than that of the conventional UKA knee model, ranging from 61.6 to 68.6%. Conclusions The comparison results indicated that the tibial implant with designed Voronoi structure offered better biomechanical functionality on the tibial plateau after UKA. Additionally, the model and associated analysis provide a well-defined design process and dependable selection criteria for design parameters of UKA implants with Voronoi structures.

Abstract With the area of perovskite films and devices increases, the performance tends to deteriorate, which can be attributed to the accumulation of defects at the bottom surface without proper passivation. Here, we introduce the 1-(4-Fluorophenyl)−2-pyrrolidone molecule (FPP) as additive in large-area blade-coating perovskite films. During the top-down crystallization process, the FPP molecule form an intermediate phase with the perovskite components and subsequently self-deposit at the bottom surface. Consequently, the crystallization kinetics of the large-area thin films are regulated, and the bottom surface is effectively and uniformly passivated in one single-step processing. By employing this self-deposited passivation method (SDP), the efficiency decrease caused by the expansion of the device area has been significantly suppressed and the devices yield power conversion efficiency of 23.41% (0.09 cm2), 22.43% (1 cm2), and 20.75% (24 cm2). The method is compatible for commercial manufacturing with scaling up solar cell area and holding high efficiency.

Abstract The high‐voltage pulse discharge technology, which is based on the electrohydraulic effect, can generate powerful, controllable, and repetitive electrohydraulic shock waves (EHSWs) in underground confined space, so it has been applied in the petroleum industry to improve the permeable of the reservoir. In this paper, a numerical model based on LS‐DYNA is built to study the damage analysis of the cement sheath and rock subjected to EHSWs during perforation completion. The results show that the stress state of the cement sheath and rock surrounding the perforation hole is determined by the shock pressure from both the perforation hole and the wellbore; the damage of the cement sheath and rock is mainly caused by tensile stress; the damage zone of the cement sheath is mainly distributed on the inner surface and near the perforation hole, while the damage zone of rock is distributed near the perforation hole; after multiple discharges, the damage of cement sheath and rock gradually accumulates, and the damage zone eventually forms a vertical plane along perforation holes. Overall, these results provide guidance for the safe application of the high‐voltage pulse discharge technology in the oil field.

Abstract Objective High‐risk types of diffuse gliomas in adults include isocitrate dehydrogenase (IDH) wild‐type glioblastomas and grade 4 astrocytomas. Achieving noninvasive prediction of high‐risk molecular subtypes of gliomas is important for personalized and precise diagnosis and treatment. Methods We retrospectively collected data from 116 patients diagnosed with adult diffuse gliomas. Multiple high‐risk molecular markers were tested, and various habitat models and whole‐tumor models were constructed based on preoperative routine and diffusion kurtosis imaging (DKI) sequences to predict high‐risk molecular subtypes of gliomas. Feature selection and model construction utilized Least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). Finally, the Wilcoxon rank‐sum test was employed to explore the correlation between habitat quantitative features (intra‐tumor heterogeneity score，ITH score) and heterogeneity, as well as high‐risk molecular subtypes. Results The results showed that the habitat analysis model based on DKI performed remarkably well (with AUC values reaching 0.977 and 0.902 in the training and test sets, respectively). The model's performance was further enhanced when combined with clinical variables. (The AUC values were 0.994 and 0.920, respectively.) Additionally, we found a close correlation between ITH score and heterogeneity, with statistically significant differences observed between high‐risk and non‐high‐risk molecular subtypes. Interpretation The habitat model based on DKI is an ideal means for preoperatively predicting high‐risk molecular subtypes of gliomas, holding significant value for noninvasively alerting malignant gliomas and those with malignant transformation potential.

Abstract This study was focused on a specific blue‒green pigment applied on the edges of the green blocks of wall paintings in the Kizil Grottoes, the earliest Buddhist cave complex in China containing many wall paintings. Based on in situ portable XRF analyses, μ-Raman spectroscope, elemental analysis (SEM–EDS and EPMA-WDS) and μ-XRPD analyses, the pigment was proven to be lavendulan [NaCaCu5(AsO4)4Cl·5H2O], which has not been reported in ancient wall painting studies before. Lavendulan was found to coexist with atacamite [Cu2(OH)3Cl] in some of the samples in the study and showed a nanoneedle-like morphology. Further investigations of lavendulan revealed that it was probably not originally used as a pigment but was generated by the transformation of atacamite under the influence of arsenates [As(V)] and Na+. This phenomenon and the related mechanism were discovered in this study and are discussed in this paper. As an important cultural heritage site in the Silk Road, the Route Network of the Chang’an-Tianshan Corridor and the Kizil Grottoes are listed as UNESCO World and Natural Heritage sites. The pigment types and preservation conditions of wall paintings are similar to those of many wall paintings found along the Silk Road, and further attention should be given to this discolouration mechanism for heritage site conservation.

Abstract Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation EGFR TKI with remarkable antitumor effects that has undergone New Drug Application (NDA) submission in China. Despite substantial progress, acquired resistance to EGFR-TKIs remains a significant challenge, impeding the long-term effectiveness of therapeutic approaches. In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition of BCAT1 impaired the growth of resistant cells and partially re-sensitized tumor cells to EGFR TKIs. Mechanistically, upregulated BCAT1 in resistant cells reprogrammed branched-chain amino acid (BCAA) metabolism and promoted alpha ketoglutarate (α-KG)-dependent demethylation of lysine 27 on histone H3 (H3K27) and subsequent transcriptional derepression of glycolysis-related genes, thereby enhancing glycolysis and promoting tumor progression. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC.

Abstract Background Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. Methods The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People’s Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. Results The overall HPV infection rate at the First People’s Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20–29 age group and 13.84% in the 30–39 age group, followed by a gradual increase to 14.64% in the 40–49 age group, 16.65% in the 50–59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. Conclusion There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

Abstract The HBV core protein (HBc) is an important viral protein of HBV that plays an indispensable role in the lifecycle of HBV, including capsid assembly and transport, reverse transcription and virus release. In recent years, evidence has shown that HBc may be involved in the malignant progression of HCC. Thus, HBc is an attractive target for antiviral agents and provides a new strategy for the treatment of HBV-related HCC. Here, we identified a novel anti‐HBc compound—colchicine, an alkaloid compound—that promoted selective autophagic degradation of HBc through the AMPK/mTOR/ULK1 signalling pathway. We further confirmed that colchicine promoted the selective autophagy of HBc by enhancing the binding of HBc to the autophagy receptor p62. Finally, we evaluated the effects of colchicine on HBV replication and HBc-mediated HCC metastasis in vitro and in vivo. Our research indicated that the inhibitory effects of colchicine on HBV and HBV-related HCC depend on the selective autophagic degradation of HBc. Thus, colchicine is not only a promising therapeutic strategy for chronic hepatitis B but also a new treatment for HBV-related HCC.

Abstract Background Fifteen-and-a-Half Syndrome is an uncommon clinical presentation characterized by the coexistence of one-and-a-half syndrome and bilateral facial palsy. In this study, we provide a comprehensive description of symptom evolution and imaging changes in a patient with Fifteen-and-a-Half Syndrome. Case presentation A 54-year-old male presented with sudden onset of one-and-a-half syndrome, which gradually progressed to fifteen-and-a-half syndrome. The final diagnosis was confirmed to be pontine infarction which occurred at the midline of the pontine tegmentum. Conclusion This case highlights the diverse and progressive early clinical manifestations associated with Fifteen-and-a-half Syndrome. Currently, all reported cases of this syndrome are linked to brainstem infarction; however, early differential diagnosis is crucial to ensure prompt initiation of appropriate treatment for affected patients.

Abstract Background The increase in the number of substitutions allowed in football from three to five has profoundly influenced the game. The impact of the rule change on the FIFA World Cup needs further verification. Methods A total of 2,151 team substitution opportunities and 2,410 substitutions in 384 matches from six FIFA World Cups (2002–2022) were analyzed to assess its impact. One-way ANOVA was used to assess differences in average substitution times among the six FIFA World Cups. Factors affecting the time of substitutions were explored using Generalized Linear Mixed Models. Results In each FIFA World Cup, over 92% of substitutions occurred during half-time and the second half, with a higher proportion in knockout stage matches than group stage matches. Group stage substitutions tended to happen earlier, particularly when teams were losing. As allowed substitutions increased, multiple substitutions in one opportunity rose from 4% to 38%. Of the 2,410 substitutions in the six FIFA World Cups, 21.45% were offensive, 63.65% were neutral and 14.90% were defensive. Winning teams made the highest percentage of defensive substitutions, while drawing or losing teams made the highest percentage of offensive substitutions. Match status significantly affected the time of the first three substitutions, and the presence of extra time significantly affected the time of the fourth substitution. Conclusion Analysis of substitutions in FIFA World Cups (2002–2022) reveals: Most substitutions occur during halftime and the second half; Substitutions are earlier in group stages, especially for losing teams; Increased allowed substitutions lead to more multiple-player substitutions; Defensive substitutions are more common when winning, while offensive ones are frequent when drawing or losing; Match status, ranking gap, extra time, game round, and substitution rules significantly influence the time of team substitutions.

The professional certification of engineering education is an important measure in training the engineering talents in new era. Its education concept happens to coincide with the goal of ''curriculum ideological and political education (CIPE)'' of specialized courses. Under the background of engineering certification of food science and engineering, this paper summarized the curriculum characteristics of Food Machinery and Equipment, explored the ideological and political elements of the curriculum, and analyzed the relationship between the objectives of curriculum and CIPE based on the Outcomes-based Education (OBE) concept. Besides, the strategies for the integration of CIPE with the professional certification system of engineering education were discussed. The evaluation and continuous improvement plan for CIPE were also set up based on the OBE concept. This study would provide basis and supports for further improving the level of CIPE in specialized courses, and implementing the fundamental task of morality cultivation.

Purpose: In the military, neck pain is second to low back pain among musculoskeletal disorders. However, the prevalence and related factors of neck pain in military personnel have not been systematically investigated, which may lead to the lack of neck pain prevention and the generation of additional medical expenses, posing challenges to medical care. This review aimed to obtain the prevalence and related factors for neck pain in military personnel in an attempt to provide directions for prevention and intervention. Methods: We searched PubMed, Embase, and Cochrane databases in December 2021. Two researchers independently screened studies according to eligibility criteria and assessed study quality. Results: We screened titles and abstracts of 503 articles, and 17 articles met the inclusion criteria. Sixteen articles received moderate to high-quality evaluations. Neck pain is common in the military, with 1-year prevalence as high as 83% and lifetime prevalence as high as 78%. Old age (OR = 5.0), poor neck mobility (OR = 3.61), shoulder pain (OR = 4.9), low back pain (OR = 2.3), high-G pilots (OR = 1.6), longer flight time (OR = 2.53), type of aircraft (OR = 3.93), and use of helmets and night vision systems (OR = 1.9) may be associated with the prevalence of neck pain. Conclusion: Neck pain is highly prevalent in military personnel and exhibits a substantial lifetime prevalence rate. The high prevalence rate of neck pain in the military is related to many individual-related factors and work-related factors. The in-depth assessment and prevention of specific factors is an important direction of future research.

Abstract Disruption of the alveolar barrier can trigger acute lung injury. This study elucidated the association of methyltransferase‐like 3 (METTL3) with Streptococcus pneumoniae (SP)‐induced apoptosis and inflammatory injury of alveolar epithelial cells (AECs). AECs were cultured and then infected with SP. Furthermore, the expression of METTL3, interleukin (IL)‐10, IL‐6, tumor necrosis factor‐alpha (TNF‐α), monocyte chemoattractant protein‐1 (MCP‐1), long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), mucin 19 (MUC19), N6‐methyladenosine (m6A), and NEAT1 after m6A modification were detected by qRT‐PCR, Western blot, and enzyme‐linked immunosorbent, m6A quantification, and methylated RNA immunoprecipitation‐qPCR analyses, respectively. Moreover, the subcellular localization of NEAT1 was analyzed by nuclear/cytosol fractionation assay, and the binding between NEAT1 and CCCTC‐binding factor (CTCF) was also analyzed. The results of this investigation revealed that SP‐induced apoptosis and inflammatory injury in AECs and upregulated METTL3 expression. In addition, the downregulation of METTL3 alleviated apoptosis and inflammatory injury in AECs. METTL3‐mediated m6A modification increased NEAT1 and promoted its binding with CTCF to facilitate MUC19 transcription. NEAT1 or MUC19 overexpression disrupted their protective role of silencing METTL3 in AECs, thereby increasing apoptosis and inflammatory injury. In conclusion, this is the first study to suggest that METTL3 aggravates SP‐induced cell damage via the NEAT1/CTCF/MUC19 axis.

The unique continuous extrusion-based severe plastic deformation approaches were proposed recently to process high-performance magnesium (Mg) alloys, while the in-depth deformation mechanisms under such complicated thermomechanical conditions were not well understood. In the present work, the fundamental deformation behaviors of AZ61 Mg alloy from 25 to 400 °C were firstly examined under uniaxial compression deformation. Then the deformation mechanisms and microstructural characteristics of AZ61 Mg alloy during continuous expansion extrusion forming (CEEF) were systematically investigated by microstructural observations, finite element and cellular automata simulations. The results showed that the continuous evolutions of temperature, larger strain level and complex stress state with strain rate range of 0 ∼ 5.98 s−1 during CEEF brought the distinctive dynamic recrystallization behaviors and texture development in AZ61 Mg alloy, which were different to that of uniaxial compression deformation. In details, a remarkable grain refinement was achieved via CEEF processing due to the simultaneous actions of continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX). Gradually enhanced CDRX were observed from center to edge region, which had significant effects on the texture distribution and texture strength. The c-axis of most grains rotated under distinctive shear strain following parabolic metal flow, resulting in stable fiber texture. In addition, the evolution of the internal texture of the alloy led to an obvious increase in the Schmid factor for the activation of basal 〈c + a〉 slip system.

Objective To verify the function of exosomes from 293T cells over-expressing membrane-localized IL-3 in vitro, so as to lay a foundation for in vivo function verification in animal models of Alzheimer′s disease. Methods Using the patented structure of the group, a recombinant IL-3 lentiviral vector was constructed and virus-infected 293T cells were packaged. Stable cell strain over-expressing IL-3 was screened. The membrane localization of IL-3 was verified by flow cytometry and immuno-fluorescence. Il-3-exosomes were purified by ultra filtration centrifugation, the exosmic morphology was observed by transmission electron microscope, the size distribution and concentration of exosomes were detected by nano-flow analysis, and the expression of IL-3 and exosome related marker proteins were detected by Western blot. The effect of BV-2 on the phagocytosis of Aβ amyloid was detected by immuno-fluorescence. Results Through vector construction, virus infection, screening and verification of puromycin, 293T cell strain with stable over-expression membrane-anchored IL-3 was obtained. The purified exosomes were collected and the structures of double-layer membrane vesicles with a diameter of 50-100 nm were observed under transmission electron microscope. Western blot results proved the presence of CD63, ALIX, TSG101 and other exosome marker proteins and these molecules were rich in IL-3 as compared with the control, that suggested the successful purification of IL-3-exosomes. The results of immuno-fluorescence assay showed that IL-3-exosomes promoted the phagocytosis of Aβ amyloid by BV-2 cells in vitro. Conclusions The gene modified 293T cell exosomes membrane-anchored expression of IL-3 can play a role of both IL-3 and exosomes in vitro, which promote the phagocytosis of microglia, there for provides a new idea for the clinical treatment of Alzheimer′s disease.

To clarify the mechanical characteristics of tight sandstone in the Cretaceous Bashijiqike Formation of Kuqa Depression in Tarim Basin, and address field issues in deep and ultra-deep oil and gas exploration and development, triaxial compression experiments were used to quantitatively study the patterns of changes in rock mechanical properties influenced by confining pressure, fluid, and loading rate, with a preliminary analysis of their causes. The results showed that the maximum principal stress difference and elastic modulus of the sandstone samples increased significantly with confining pressure. The micro-reason was that the increase in confining pressure reduced the distance between particles inside the rock, enhancing the rock's cohesion and making particle dispersion less likely. Sandstone samples exhibited a progression from brittleness under low confining pressure to brittle-ductile transformation, and to ductile deformation under high confining pressure. Compared with dry sandstone samples, the reduction in the elastic modulus of samples soaked in pure water, 150 g/L solution, 250 g/L solution, and 350 g/L solution were 67.71%, 61.45%, 64.69%, and 57.32%, respectively, with pure water soaking causing the greatest reduction. Increasing fluid salinity could mitigate the weakening trend in rock mechanical parameters. Crystallization on crystal surfaces and changes in the electric double layer thickness were important controlling factors for these patterns. At lower loading rates, the values for maximum principal stress difference, elastic modulus, and Poisson's ratio of the sandstone samples were smaller, but they increased faster with increasing loading rates. When the loading rate reached a certain critical value (around 0.05 mm/min in this experiment), the rate of increase in rock mechanical parameters slowed down.

To enhance the development efficiency of ultra-deep fault-controlled carbonate reservoirs, large-scale rock mechanical experiments were conducted to reveal the deformation and connectivity mechanisms of high-angle to near-vertical fault surfaces. Based on the mechanical and flow coupling principles of high-pressure water injection production, geomechanical modeling was employed to clarify the current in-situ stress field and fault activity distribution patterns in fault-controlled carbonate reservoirs. Significant differences were found in fault activities in different directions and in the connectivity of fracture and cavity bodies in different parts. The development effects of different wellbore trajectories were then analyzed, and an integrated geological and engineering working method was proposed to scientifically guide the design of wellbore trajectories and the optimization of water injection schemes. The results show: ① Large-scale fractured bodies and high-angle fracture systems in strike-slip fault deformation are key factors affecting reservoir quality. High-pressure water injection can activate existing fractures on one hand, and on the other hand, it can extend and expand based on existing fractures, even generating new fractures, promoting the interconnection of fault-controlled fracture and cavity bodies in both vertical and horizontal directions; ② During the high-pressure water injection process, coupling changes between mechanics and flow occur inside the fault body, improving the seepage environment, and increasing oil and gas recovery rate through cyclic lifting; ③ According to the shape and the occurrence of the fault body, and the dynamic shear deformation connectivity of the fault surface, the best well point and well trajectory for directional wells can be selected, and the water injection scheme can be optimized; ④ In the fault-controlled oil reservoir test area of Tarim Basin, the recovery rate was increased by 5% through high-pressure water injection. This method provides a good theoretical basis and technical support for the efficient development of ultra-deep fault-controlled reservoirs.