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Zinc (Zn)-based biodegradable metals (BMs) fabricated through conventional manufacturing methods exhibit adequate mechanical strength, moderate degradation behavior, acceptable biocompatibility, and bioactive functions. Consequently, they are recognized as a new generation of bioactive metals and show promise in several applications. However, conventional manufacturing processes face formidable limitations for the fabrication of customized implants, such as porous scaffolds for tissue engineering, which are future direction towards precise medicine. As a metal additive manufacturing technology, laser powder bed fusion (L-PBF) has the advantages of design freedom and formation precision by using fine powder particles to reliably fabricate metallic implants with customized structures according to patient-specific needs. The combination of Zn-based BMs and L-PBF has become a prominent research focus in the fields of biomaterials as well as biofabrication. Substantial progresses have been made in this interdisciplinary field recently. This work reviewed the current research status of Zn-based BMs manufactured by L-PBF, covering critical issues including powder particles, structure design, processing optimization, chemical compositions, surface modification, microstructure, mechanical properties, degradation behaviors, biocompatibility, and bioactive functions, and meanwhile clarified the influence mechanism of powder particle composition, structure design, and surface modification on the biodegradable performance of L-PBF Zn-based BM implants. Eventually, it was closed with the future perspectives of L-PBF of Zn-based BMs, putting forward based on state-of-the-art development and practical clinical needs.

Abstract Acute myeloid leukemia (AML) exhibits pronounced heterogeneity and chemotherapy resistance. Aberrant programmed cell death (PCD) implicated in AML pathogenesis suggests PCD-related signatures could serve as biomarkers to predict clinical outcomes and drug response. We utilized 13 PCD pathways, including apoptosis, pyroptosis, ferroptosis, autophagy, necroptosis, cuproptosis, parthanatos, entotic cell death, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, and disulfidptosis to develop predictive models based on 73 machine learning combinations from 10 algorithms. Bulk RNA-sequencing, single-cell RNA-sequencing transcriptomic data, and matched clinicopathological information were obtained from the TCGA-AML, Tyner, and GSE37642-GPL96 cohorts. These datasets were leveraged to construct and validate the models. Additionally, in vitro experiments were conducted to substantiate the bioinformatics findings. The machine learning approach established a 6-gene pan-programmed cell death-related genes index (PPCDI) signature. Validation in two external cohorts showed high PPCDI associated with worse prognosis in AML patients. Incorporating PPCDI with clinical variables, we constructed several robust prognostic nomograms that accurately predicted prognosis of AML patients. Multi-omics analysis integrating bulk and single-cell transcriptomics revealed correlations between PPCDI and immunological features, delineating the immune microenvironment landscape in AML. Patients with high PPCDI exhibited resistance to conventional chemotherapy like doxorubicin but retained sensitivity to dasatinib and methotrexate (FDA-approved drugs for other leukemias), suggesting the potential of PPCDI to guide personalized therapy selection in AML. In summary, we developed a novel PPCDI model through comprehensive analysis of diverse programmed cell death pathways. This PPCDI signature demonstrates great potential in predicting clinical prognosis and drug sensitivity phenotypes in AML patients.

This article aimed to establish an amplified luminescent proximity homogeneous assay linked immune sorbent assay (AlphaLISA) for detecting quinolones (QNS) residues in milk. The EDC/NHS active ester method was used to connect 6-aminocaproic acid as the spacer arm on the norfloxacin molecule to prepare biotin-modified norfloxacin hapten (Biotin-6AS-NOR), and QNS monoclonal antibody was coupled on the receptor microsphere. Biotin-6AS-NOR could compete with QNS in the sample to bind quinolone antibodies. A competitive indirect AlphaLISA for QNS residues in milk was established by optimizing the parameters including QNS antibody coupling amount on receptor microspheres, Biotin-6AS-NOR, the dosage of donor/receptor microspheres, and dilution schemes for milk samples. By using the 1:5 milk sample dilution scheme, the limit of detection and the limit of quantification of the established AlphaLISA for QNS in milk were 0.19 ng/mL and 0.46 ng/mL, respectively. The recovery values ranged from 85.97% and 110.11%, and the intraday and interday variation were both less than 10%. The cross-reactivity values for norfloxacin, enrofloxacin, ciprofloxacin, ofloxacin, pefloxacin, ofloxacin, and lomefloxacin were all higher than 70%. In conclusion, the established AlphaLISA showed high sensitivity, accuracy and good repeatability, without the need of tedious wash steps throughout the detection process; therefore, it is easy to achieve automated detection of chemical hazards residue in milk and has high application and promotion value.

Abstract In chronic kidney disease (CKD), renal fibrosis is an unavoidable result of various manifestations. However, its pathogenesis is not yet fully understood. Here, we revealed the novel role of Homeobox D10 (HOXD10) in CKD-related fibrosis. HOXD10 expression was downregulated in CKD-related in vitro and in vivo fibrosis models. UUO model mice were administered adeno-associated virus (AAV) containing HOXD10, and HOXD10 overexpression plasmids were introduced into human proximal tubular epithelial cells induced by TGF-β1. The levels of iron, reactive oxygen species (ROS), lipid ROS, the oxidized glutathione/total glutathione (GSSG/GSH) ratio, malonaldehyde (MDA), and superoxide dismutase (SOD) were determined using respective assay kits. Treatment with AAV–HOXD10 significantly attenuated fibrosis and renal dysfunction in UUO model mice by inhibiting NOX4 transcription, ferroptosis pathway activation, and oxidative stress. High levels of NOX4 transcription, ferroptosis pathway activation and profibrotic gene expression induced by TGF-β1/erastin (a ferroptosis agonist) were abrogated by HOXD10 overexpression in HK-2 cells. Moreover, bisulfite sequencing PCR result determined that HOXD10 showed a hypermethylated level in TGF-β1-treated HK-2 cells. The binding of HOXD10 to the NOX4 promoter was confirmed by chromatin immunoprecipitation (ChIP) analysis and dual-luciferase reporter assays. Targeting HOXD10 may represent an innovative therapeutic strategy for fibrosis treatment in CKD.

Abstract As the global data strategy deepens and data elements accelerate integrating and flowing more rapidly, the demand for data security and privacy protection has become increasingly prominent. Confidential computing emerges as a crucial security technology to solve security and privacy problem, and it is also a hot subject of in contemporary security technologies. Leveraging collaborative security in both hardware and software, it builds a trusted execution environment to ensure confidentiality and integrity protection for data in use. This paper provides a comprehensive overview of the development process of confidential computing, summarizing its current research status and issues, which focuses on the security requirements for data security and privacy protection. Furthermore, it deeply analyses the common technical features of confidential computing, and proposes a trusted confidential computing architecture based on collaborative hardware and software trust. Then, it elaborates on the research status and issues of confidential computing from four aspects: hardware security, architecture and key technologies, applications, and standards and evaluation. Finally, this paper provides a synthesis and outlook for the future development of confidential computing. In summary, confidential computing is currently in a rapidly developing stage and will play an important role in cyber security in the future.

Background Diabetes has emerged as a critical global public health issue. The burden of diabetes is escalating in developing countries, including China. For individuals with diabetes, making informed and rational decisions regarding health-seeking behaviour is crucial to prevent or delay the occurrence of complications. However, prevalent irrational health-seeking behaviours among Chinese patients with diabetes have led to a low treatment rate of only 32.2%. In this study, we explore the subjective experiences of elderly patients with diabetes related to their decision-making experience for seeking healthcare, providing valuable insights for targeted intervention, and provide theoretical basis for establishing an efficient medical and health service system.Methods A qualitative study using descriptive phenomenology research methodology was adopted to explore the decision-making experience of elderly diabetes patients in seeking healthcare services. A purposive sampling approach, specifically maximum variation sampling, was employed to conduct semistructured in-depth interviews with 11 eligible participants between January and February 2023. Data analysis was carried out using QSR Nvivo 12.0 software and Colaizzi’s seven-step analysis method.Results Four themes emerged: ‘lack of disease risk perception and negative coping styles’, ‘ huge medical and economic burden’, ‘lack of family and social support’ and ‘Dissatisfaction with medical services’.Conclusion The health-seeking behavioural decision-making level of elderly diabetic patients is relatively low. Medical and healthcare professionals should formulate targeted intervention measures aimed at improving their disease cognition level, changing their coping styles and enhancing their health-seeking behavioural decision-making level to improve their health outcomes. Meanwhile, policymakers should plan and allocate medical resources in a targeted manner based on the needs and expectations of patients.

BackgroundOsteoporosis (OP) and sarcopenia are prevalent musculoskeletal conditions among the elderly. Nevertheless, the causal relationship between sarcopenia and OP remains a subject of controversy and uncertainty. In this study, we employed cross-sectional analysis and Mendelian randomization (MR) to investigate the intricate relationship between sarcopenia and OP.MethodsThe cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2020, which involved in 116,876 participants. It assessed the correlation between sarcopenia, osteoporosis (OP), and bone mineral density (BMD) using Chi-square tests, T-tests, and a multiple logistic regression model. Additionally, we conducted Mendelian randomization (MR) analysis to investigate the causal effects of sarcopenia-related characteristics (ALM) on OP. We employed IVW, sensitivity analysis, heterogeneity testing, and other methods for MR. The ALM data was sourced from the UK Biobank (n=450,243), while the aggregated data on OP was obtained from GWAS statistics (n=53,236).ResultsIn this cross-sectional analysis, we observed that in the multivariate logistic regression model, without adjusting for any variables, OP emerged as a risk factor for sarcopenia [OR 95% CI = 1.90 (1.13-3.18), P = 0.02]. Following adjustments for gender, age, BMI, and biochemical variables, OP retained its status as a risk factor for sarcopenia [OR 95% CI = 3.54 (1.91-6.54), P < 0.001]. Moreover, after accounting for all variables, OP emerged as an independent risk factor for sarcopenia [OR 95% CI = 4.57 (1.47-14.22), P = 0.01].In the MR analysis, we uncovered that femoral neck BMD (FN BMD), lumbar spine BMD (LS BMD), and forearm bone mineral density (FA BMD) exerted a direct causal influence on ALM [FA BMD: OR 95% CI = 1.028 (1.008, 1.049), p = 0.006; FN BMD: OR (95% CI) = 1.131 (1.092, 1.170), p = 3.18E-12; LS BMD: OR (95% CI) = 1.080 (1.062, 1.098), p = 2.86E-19].ConclusionOur study has revealed a positive correlation between OP and the prevalence of sarcopenia. It suggests a potentially robust causal relationship between OP and sarcopenia. Notably, OP appears to be associated with a higher likelihood of losing ALM, and a significant loss of ALM may contribute to a decline in LS BMD.

Abstract Global riverine nitrous oxide (N2O) emissions have increased more than 4-fold in the last century. It has been estimated that the hyporheic zones in small streams alone may contribute approximately 85% of these N2O emissions. However, the mechanisms and pathways controlling hyporheic N2O production in stream ecosystems remain unknown. Here, we report that ammonia-derived pathways, rather than the nitrate-derived pathways, are the dominant hyporheic N2O sources (69.6 ± 2.1%) in agricultural streams around the world. The N2O fluxes are mainly in positive correlation with ammonia. The potential N2O metabolic pathways of metagenome-assembled genomes (MAGs) provides evidence that nitrifying bacteria contain greater abundances of N2O production-related genes than denitrifying bacteria. Taken together, this study highlights the importance of mitigating agriculturally derived ammonium in low-order agricultural streams in controlling N2O emissions. Global models of riverine ecosystems need to better represent ammonia-derived pathways for accurately estimating and predicting riverine N2O emissions.

Abstract. Background:. Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. Methods:. This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. Results:. A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P

Abstract Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.

Miniaturized fiber-optic magnetic field sensors have attracted considerable interest owing to their superiorities in anti-electromagnetic interference and compactness. However, the intrinsic thermodynamic properties of the material make temperature cross-sensitivity a challenging problem in terms of sensing accuracy and reliability. In this study, an ultracompact multicore fiber (MCF) tip sensor was designed to discriminatively measure the magnetic field and temperature, which was subsequently evaluated experimentally. The novel 3D printed sensing component consists of a bowl-shaped microcantilever and a polymer microfluid-infiltrated microcavity on the end-facet of an MCF, acting as two miniaturized Fabry-Perot interferometers. The magnetic sensitivity of the microcantilever was implemented by incorporating an iron micro ball into the microcantilever, and the microfluid-infiltrated microcavity enhanced the capability of highly sensitive temperature sensing. Using this tiny fiber-facet device in the two channels of an MCF allows discriminative measurements of the magnetic field and temperature by determining the sensitivity coefficient matrix of two parameters. The device exhibited a high magnetic field intensity sensitivity, approximately 1805.6 pm/mT with a fast response time of ~ 213 ms and a high temperature sensitivity of 160.3 pm/℃. Moreover, the sensor had a low condition number of 11.28, indicating high reliability in two-parameter measurements. The proposed 3D printed MCF-tip probes, which detect multiple signals through multiple channels within a single fiber, can provide an ultracompact, sensitive, and reliable scheme for discriminative measurements. The bowl-shaped microcantilever also provides a useful platform for incorporating microstructures with functional materials, extending multi-parameter sensing scenarios and promoting the application of MCFs.

Abstract Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory tract infection in humans, especially in infants and the elderly. The identification and structural resolution of the potent neutralizing epitopes on RSV fusion (F) protein enable an “epitope-focused” vaccine design. However, the display of RSV F epitope II on the surface of the widely-used human hepatitis B virus core antigen (HBcAg) has failed to induce neutralizing antibody response in mice. Here, we used the hepadnavirus core protein (HcAg) from different mammalian hosts as scaffolds to construct chimeric virus-like particles (VLPs) presenting the RSV F epitope II. Mouse immunization showed that different HcAg-based chimeric VLPs elicited significantly different neutralizing antibody responses, among which the HcAg derived from roundleaf bat (RBHcAg) is the most immunogenic. Furthermore, RBHcAg was used as the scaffold platform to present multiple RSV F epitopes, and the immunogenicity was further improved in comparison to that displaying a single epitope II. The designed RBHcAg-based multiple-epitope-presenting VLP formulated with MF59-like adjuvant elicited a potent and balanced Th1/Th2 immune response, and offered substantial protection in mice against the challenge of live RSV A2 virus. The designed chimeric VLPs may serve as the potential starting point for developing epitope-focused vaccines against RSV. Our study also demonstrated that RBHcAg is an effective VLP carrier for presenting foreign epitopes, providing a promising platform for epitope-focused vaccine design.

Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A three-dimensional (3D)-printed porous Ti6Al4V scaffold (3DTi) is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants, including a lower elasticity modulus, stronger bone-implant interlock, and larger drug-loading space. Simvastatin is a multitarget drug with anti-tumor and osteogenic potential; however, its efficiency is unsatisfactory when delivered systematically. Here, simvastatin was loaded into a 3DTi using a thermosensitive poly (lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and osteogenic effects. Newly constructed simvastatin/hydrogel-loaded 3DTi (Sim-3DTi) was comprehensively appraised, and its newfound anti-osteosarcoma mechanism was explained. Specifically, in a bone defect model of rabbit condyles, Sim-3DTi exhibited enhanced osteogenesis, bone in-growth, and osseointegration compared with 3DTi alone, with greater bone morphogenetic protein 2 expression. In our nude mice model, simvastatin loading reduced tumor volume by 59%–77 % without organic damage, implying good anti-osteosarcoma activity and biosafety. Furthermore, Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both in vivo and in vitro. Sim-3DTi is a promising osteogenic bone substitute for osteosarcoma-related bone defects, with a ferroptosis-mediated anti-osteosarcoma effect.

Background The Minqin Oasis, which is located in Wuwei City, Gansu Province, China, faces a very serious land desertification problem, with about 94.5% of its total area desertified. Accordingly, it is crucial to implement ecological restoration policies such as cropland abandonment in this region. In abandoned croplands, abiotic factors such as soil properties may become more important than biotic factors in driving vegetation succession. However, the connections between soil properties and vegetation succession remain unclear. To fill this knowledge gap, this study investigated these connections to explore major factors that affected vegetation succession, which is meaningful to designing management measures to restore these degraded ecosystems. Methods This study investigated seven 1–29-year-old abandoned croplands using the “space for time” method in Minqin Oasis. Vegetation succession was classified into different stages using a canonical correlation analysis (CCA) and two-way indicator species analysis (Twinspan). The link between soil properties and vegetation succession was analyzed using CCA. The primary factors shaping community patterns of vegetation succession were chosen by the “Forward selection” in CCA. The responses of dominant species to soil properties were analyzed using generalized additive models (GAMs). Results Dominant species turnover occurred obviously after cropland abandonment. Vegetation succession can be classified into three stages (i.e., early, intermediate, and late successional stages) with markedly different community composition and diversity. The main drivers of vegetation succession among soil properties were soil salinity and saturated soil water content and they had led to different responses of the dominant species in early and late successional stages. During the development of vegetation succession, community composition became simpler, and species diversity decreased significantly, which was a type of regressive succession. Therefore, measures should be adopted to manage these degraded, abandoned croplands.

ObjectivesThis study aims to: 1) Explore the mobility experiences of seniors with slow walking speeds (SSWS) in urban neighborhoods; and 2) Investigate their environmental barriers and supports.MethodsGo-along interviews were conducted with 36 SSWS residing in urban neighborhoods of Chongqing City, China. The mobility patterns and built environment factors influencing their mobility were revealed through cartographic analysis and thematic analysis.ResultsSSWS primarily focused their activities within a 400-meter radius of their homes. Built environment themes included topography, neighborhood services, sidewalks, seating, traffic safety, weather, greenery, and lighting. Significant mobility barriers included long stairs, steep slopes, fast-moving objects on sidewalks, road crossings, and fast traffic. Available handrails, nearby food-service places, ample seating, and greenery were identified as supportive factors for their mobility.ConclusionThis study stands out as the first to specifically examine the mobility of SSWS within the built environment. We suggest that SSWS should be taken into account when establishing a benchmark for general design frameworks. These improvements not only contribute to the mobility of slow walkers but also have positive impacts on the broader population.

In this study, high-throughput sequencing and metabolomics analysis were conducted to analyze the microbial and metabolites of dry-cured Sanchuan ham, Laowo ham, Nuodeng ham, and Heqing ham that have fermented for two years produced from western Yunnan China. Results showed that at the genus level, the dominant bacteria in the four types of ham were Halomonas and Staphylococcus, while the dominant fungi were Aspergillus and Yamadazyma. A total 422 different metabolites were identified in four types of ham, mainly amino acids, peptides, fatty acids, and their structural analogs, which were involved in pantothenate and coenzyme A biosynthesis, caffeine, and tyrosine metabolism. The dominant microorganisms of the four types of ham were mainly related to the metabolism of fatty acids and amino acids. This research enhances the identification degree of these four types of dry-cured ham and provides a theoretical basis for developing innovative and distinctive ham products.

Abstract Background Several studies have previously reported the normal values of corneal volume (CV) in various populations, whereas little is known about the CV distribution in healthy young Chinese adults. Our study aimed to investigate the distribution of CV and its relationships with other ocular biometric parameters among healthy young Chinese adults. Methods A total of 1645 eyes from 1645 students at Dali University in Yunnan Province, China, were analyzed. Pentacam was used to measure CV. Central corneal thickness (CCT) and biomechanically corrected intraocular pressure (bIOP) were evaluated by Corvis-ST. Other biometrical parameters, including axial length (AL), keratometry, and white-to-white (WTW) distance, were measured using IOL Master. Results The mean age of the study population was 19.01 ± 0.92 years, and 68.81% of them were women. The CV was normally distributed in the whole sample, with a mean value of 61.23 ± 3.22 mm3. CV and CCT were significantly smaller in the Yi ethnic group than in the Han ethnic group (p

Abstract Invariant natural killer T (iNKT) cells, a unique T cell population, lend themselves for use as adoptive therapy due to diverse roles in orchestrating immune responses. Originally developed for use in cancer, agenT-797 is a donor-unrestricted allogeneic ex vivo expanded iNKT cell therapy. We conducted an open-label study in virally induced acute respiratory distress syndrome (ARDS) caused by the severe acute respiratory syndrome-2 virus (trial registration NCT04582201). Here we show that agenT-797 rescues exhausted T cells and rapidly activates both innate and adaptive immunity. In 21 ventilated patients including 5 individuals receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO), there are no dose-limiting toxicities. We observe an anti-inflammatory systemic cytokine response and infused iNKT cells are persistent during follow-up, inducing only transient donor-specific antibodies. Clinical signals of associated survival and prevention of secondary infections are evident. Cellular therapy using off-the-shelf iNKT cells is safe, can be rapidly scaled and is associated with an anti-inflammatory response. The safety and therapeutic potential of iNKT cells across diseases including infections and cancer, warrants randomized-controlled trials.

Objective To investigate associations of changes in waist circumference (WC) and body mass index (BMI) with the variation of fasting blood glucose among middle aged and elderly residents with high cardiovascular risk. MethodsTotally 71 758 urban/rural permanent residents aged 35 years or older were recruited at 8 districts/counties of 3 municipalities, Jiangsu province for a baseline survey conducted during 2015 as a part of the ‘Early Screening and Comprehensive Intervention on Cardiovascular Diseases among High-Risk Populations in China’. Out of those residents surveyed, 12 369 individuals with initial records of fasting blood glucose (FBG) and at high-risk of cardiovascular diseases were followed up annually in 2017, 2018, and 2019 to observe changes in their FBG levels over time. The generalized estimating equation (GEE) was used to explore associations of the changes in WC and BMI with the variations of FBG among the participants. ResultsOf the 9 952 participants successfully followed up 3 045 (30.6%), 2 130 (21.4%), and 4 777 (48.0%) had normal WC, pre-central obesity, and obesity and 56 (0.6%), 2 669 (26.8%), 4 540 (45.6%), and 2 687 (27.0%) were assessed as having underweight, normal weight, overweight, and obesity respectively at the baseline survey. After adjusting for gender, age, education, place of residence, smoking, alcohol drinking, hypertension, diabetes mellitus, dyslipidemia, baseline WC, baseline BMI, and follow-up sequence, the results of GEE analysis revealed that compared to those with normal WC, the participants having declined WC were at a decreased risk of abnormal FBG (odds ratio [OR] = 0.911, 95% confidence interval [95%CI]: 0.867 – 0.958) but the participants having elevated WC were at an increased risk of abnormal FBG (OR = 1.070, 95%CI: 1.022 – 1.120); the results also showed that every one centimeter increase in baseline WC and one unit increase in baseline BMI were associated with 0.011 mmol/L (β = 0.027, 95%CI: 0.013 – 0.041) and 0.027 mmol/L (β = 0.027, 95%CI: 0.013 – 0.041) increase in FBG. Further subgroup analysis demonstrated that every one centimeter increase in baseline WC was associated with 0.011/0.010, 0.014/0.005, and 0.007/0.021 mmol/L increase in FBG for the participants being male/female, living in urban/rural regions, and with/without diabetes (all P < 0.001); while, every one unit increase in baseline BMI was associated with 0.030, 0.026/0.024, and 0.031 mmol/L increase in FBG for the participants being female, living in urban/rural regions, and having diabetes, respectively (all P < 0.05). ConclusionThere are positively linear associations of changes in WC and BMI with the variation of FBG among middle aged and elderly populations with high cardiovascular risk.

Objective To explore the status quo of ICU nurses' knowledge, attitude and practice of physical restraints use in general hospitals in Guangxi, and to provide a theoretical basis for clinical training and quality control. Methods A simple random sampling method was used to select ICU nurses from Grade III and Grade II hospitals in Guangxi, including 2 Grade III hospitals and 3 Grade II hospitals, with a total of 201 ICU nurses. The knowledge, attitude and practice status of nurses on physical restraints use were investigated by using a physical restraints knowledge, attitude and behavior questionnaire, and the influencing factors were analyzed. Results The total score and scores of knowledge dimension, attitude dimension, and behavior dimension were (135. 08±18. 07), (68. 70±9. 49), (20. 73±4. 82), (45. 66±8. 95), respectively, indicating a low-to-medium level awareness of physical restraints among ICU nurses in general hospitals in Guangxi. There were statistically significant differences in the level of knowledge, attitude and practice of ICU nurses with different hospital levels, ICU working years, and ICU specialist qualifications (P＜0. 05). Conclusion ICU nurses in Guangxi have a more positive attitude towards physical restraint, and their knowledge and behavior level need to be strengthened urgently. ICU managers should improve the physical restraint training mechanism, types and teams of ICU nurses, strengthen relevant knowledge and skills training according to the different characteristics of nurses, build positive attitudes and emotions through enhanced knowledge, promote behavioral changes, and improve the development of physical restraint specialization. (目的 探讨广西壮族自治区ICU护士身体约束知信行现状, 为临床开展相关的培训及质控提供理论依据。方法 采用简单随机抽样法, 选取广西壮族自治区三级甲等、二级甲等共5所医院的ICU护士共201名作为研究对象, 采用“ICU护士实施身体约束知信行评估量表”调查护士对患者实施身体约束的知识、态度和行为现状, 并分析影响因素。结果 广西壮族自治区ICU护士身体约束知信行总分、知识维度、态度维度、行为维度得分分别为(135. 08±18. 07)分、(68. 70±4. 82)分、(45. 66±8. 95)分, 整体上为中等偏低水平。不同医院等级、ICU工作年限、有无ICU专科资质的ICU护士身体约束知信行水平差异有统计学意义(P＜0. 05)。结论 广西壮族自治区ICU护士身体约束态度较为积极, 知识及行为水平亟待加强。ICU管理者应健全ICU护士身体约束培训机制、种类和队伍, 根据护士的不同特征强化相关知识与技能培训, 通过增强知识建立积极态度和情感, 促使行为改变, 促进身体约束专科化发展。)

Abstract Background The objective of this study was to evaluate the effects of glutamine on the growth performance and systemic innate immune response in broiler chickens challenged with Salmonella pullorum. A total of 600 one-day-old Arbor Acres broiler chickens were assigned randomly to 6 dietary treatments with 10 replicates for a 21-day feeding experiment. The experimental treatments were as follows: the control treatment (birds fed the basal diet), the Gln1 treatment, and the Gln 2 treatment (birds fed the basal diet supplemented with 0.5%, and 1.0% Glutamine, respectively). At 3 d of age, half of the birds from each treatment were challenged oral gavage with 2.0 × 104 CFU/mL of S. pullorum suspension (1.0 mL per bird) or an equivalent amount of sterile saline alone, which served as a control. Results The results showed that S. pullorum infection had adverse effects on the average daily feed intake, average daily gain, and feed conversion ratio of broiler chickens compared with those of the CON treatment on d 7, decreased the spleen and bursa of fabricius relative weights (except on d 21), serum immunoglobulin A (IgA),immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations, and spleen melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology gene 2 (LGP2) mRNA expression levels, and increased the mRNA expression levels of spleen Nodinitib-1 (NOD1), Toll-like receptors 2,4 (TLR2, TLR4), DNA-dependent activator of IFN-regulatory factors (DAI), mitochondrial antiviral-signaling protein (MAVS), P50, P65, and RelB on d 4, 7, 14, and 21. Supplementation with Gln improved the relative weights of the spleen and bursa of Fabricius (except on d 21), increased the serum IgA, IgG, and IgM concentrations and the mRNA expression levels of spleen MDA5 and LGP2, and decreased the mRNA expression levels of spleen NOD1, TLR2, TLR4, DAI, MAVS, P50, P65, and RelB of S. pullorum-challenged broiler chickens. Conclusion These results indicate that Gln might stimulate the systemic innate immune responses of the spleen in broiler chickens challenged with S. pullorum.

Shell–tube heat exchangers are commonly used equipment in large-scale industrial systems of wastewater heat exchange to reclaim the thermal energy generated during industrial processes. However, the internal surfaces of the heat exchanger tubes often accumulate fouling, which subsequently reduces their heat transfer efficiency. Therefore, regular cleaning is essential. We aim to detect circle holes on the end surface of the heat exchange tubes to further achieve automated positioning and cleaning tubes. Notably, these holes exhibit a regular distribution. To this end, we propose a circle-permutation-aware object detector for heat exchanger cleaning to sufficiently exploit prior information of the original inputs. Specifically, the interval prior to the extraction module extracts interval information among circle holes based on prior statistics, yielding prior interval context. The following interval prior fusion module slices original images into circle domain and background domain maps according to the prior interval context. For the circle domain map, prior-guided sparse attention using prior a circle–hole diameter as the step divides the circle domain map into patches and performs patch-wise self-attention. The background domain map is multiplied by a hyperparameter weak coefficient matrix. In this way, our method fully leverages prior information to selectively weigh the original inputs to achieve more effective hole detection. In addition, to adapt the hole shape, we adopt the circle representation instead of the rectangle one. Extensive experiments demonstrate that our method achieves state-of-the-art performance and significantly boosts the YOLOv8 baseline by 5.24% mAP50 and 5.25% mAP50:95.

Patchiness is known to affect soil water and soil temperature, and may trigger or accelerate alpine meadow degradation. However, there is a lack of direct evidence concerning the role of the size and type of patches on soil conditions. Here, we estimated the effects of typical patch types on the critical factors of soil water and soil temperature through an in situ survey and then analyzed the potential impacts of patchiness on alpine meadow degradation. The results showed that (1) the soil water storage (SWS) of typical patch types was remarkably different, and vegetation patches had higher SWS than bare patches; (2) with abundant precipitation, the isolated vegetation patch (IV) had higher SWS than the original vegetation patch (OV), accompanied by a decrease in the SWS of the surrounding medium bare patch (MP); (3) patchiness significantly altered the surface soil temperature, with the IV having the highest soil temperature (ST), followed by the OV and bare patches; and (4) the maximum mean value of evapotranspiration was observed in IV (3.85 mm/day), about 12.78% and 46.66% higher than in the bare patches and OV. Our findings indicated that patchiness intensified the heterogeneity of soil water and soil temperature. The IV could absorb soil water from surrounding MP for excessive evapotranspiration through constant high ST, potentially inducing or aggravating degradation. Increasing the connectivity of IV and preventing the transition of OV to IV is important for the stability and restoration of alpine meadow.

Introduction:Ganoderma lucidum: (G. lucidum, Lingzhi) is a medicinal and edible homologous traditional Chinese medicine that is used to treat various diseases, including Alzheimer’s disease and mood disorders. We previously reported that the sporoderm-removed G. lucidum spore extract (RGLS) prevented learning and memory impairments in a rat model of sporadic Alzheimer’s disease (sAD), but the effect of RGLS on depression-like behaviors in this model and its underlying molecular mechanisms of action remain unclear.Method: The present study investigated protective effects of RGLS against intracerebroventricular streptozotocin (ICV-STZ)-induced depression in a rat model of sAD and its underlying mechanism. Effects of RGLS on depression- and anxiety-like behaviors in ICV-STZ rats were assessed in the forced swim test, sucrose preference test, novelty-suppressed feeding test, and open field test.Results: Behavioral tests demonstrated that RGLS (360 and 720 mg/kg) significantly ameliorated ICV-STZ-induced depression- and anxiety-like behaviors. Immunofluorescence, Western blot and enzyme-linked immunosorbent assay results further demonstrated that ICV-STZ rats exhibited microglia activation and neuroinflammatory response in the medial prefrontal cortex (mPFC), and RGLS treatment reversed these changes, reflected by the normalization of morphological changes in microglia and the expression of NF-κB, NLRP3, ASC, caspase-1 and proinflammatory cytokines. Golgi staining revealed that treatment with RGLS increased the density of mushroom spines in neurons. This increase was associated with elevated expression of brain-derived neurotrophic protein in the mPFC.Discussion: In a rat model of ICV-STZ-induced sAD, RGLS exhibits antidepressant-like effects, the mechanism of which may be related to suppression of the inflammatory response modulated by the NF-κB/NLRP3 pathway and enhancement of synaptic plasticity in the mPFC.

Introduction:Ganoderma lucidum (G. lucidum, Lingzhi) has long been listed as a premium tonic that can be used to improve restlessness, insomnia, and forgetfulness. We previously reported that a rat model of sporadic Alzheimer’s disease (sAD) that was induced by an intracerebroventricular injection of streptozotocin (ICV-STZ) showed significant learning and cognitive deficits and sleep disturbances. Treatment with a G. lucidum spore extract with the sporoderm removed (RGLS) prevented learning and memory impairments in sAD model rats.Method: The present study was conducted to further elucidate the preventive action of RGLS on sleep disturbances in sAD rats by EEG analysis, immunofluorescence staining, HPLC-MS/MS and Western blot.Results: Treatment with 720 mg/kg RGLS for 14 days significantly improved the reduction of total sleep time, rapid eye movement (REM) sleep time, and non-REM sleep time in sAD rats. The novelty recognition experiment further confirmed that RGLS prevented cognitive impairments in sAD rats. We also found that RGLS inhibited the nuclear factor-κB (NF-κB)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammatory pathway in the medial prefrontal cortex (mPFC) in sAD rats and ameliorated the lower activity of γ-aminobutyric acid (GABA)-ergic neurons in the parabrachial nucleus (PBN).Discussion: These results suggest that inhibiting the neuroinflammatory response in the mPFC may be a mechanism by which RGLS improves cognitive impairment. Additionally, improvements in PBN-GABAergic activity and the suppression of neuroinflammation in the mPFC in sAD rats might be a critical pathway to explain the preventive effects of RGLS on sleep disturbances in sAD.

BackgroundSarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort.MethodsWe analyzed 1999–2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII’s association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness.ResultsOver a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25–1.98), cardiovascular(1.61, 1.00–2.58), cancer(2.13, 1.32–3.44), and respiratory disease mortality(3.21, 1.66–6.19) in fully adjusted models. Subgroup analyses revealed SII’s association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models.ConclusionOur study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population.

Siamese network-based visual tracking algorithms have achieved excellent performance in recent years, but challenges such as fast target motion, shape and scale variations have made the tracking extremely difficult. The regression of anchor-free tracking has low computational complexity, strong real-time performance, and is suitable for visual tracking. Based on the anchor-free siamese tracking framework, this paper firstly introduces balance factors and modulation coefficients into the cross-entropy loss function to solve the classification inaccuracy caused by the imbalance between positive and negative samples as well as the imbalance between hard and easy samples during the training process, so that the model focuses more on the positive samples and the hard samples that make the major contribution to the training. Secondly, the intersection over union (IoU) loss function of the regression branch is improved, not only focusing on the IoU between the predicted box and the ground truth box, but also considering the aspect ratios of the two boxes and the minimum bounding box area that accommodate the two, which guides the generation of more accurate regression offsets. The overall loss of classification and regression is iteratively minimized and improves the accuracy and robustness of visual tracking. Experiments on four public datasets, OTB2015, VOT2016, UAV123 and GOT-10k, show that the proposed algorithm achieves the state-of-the-art performance.

Abstract Background Few previous studies have introduced general techniques to overcome the “chopstick effect” in laparoendoscopic single-site surgery (LESS). We aim to investigate and highlight the key ergonomic methodologies for gynaecologic LESS based on the surgeon’s hands-on performance. Methods The first author surgeon A reviewed and analyzed the LESS procedures performed by herself and how she taught surgeon B from January 2021 to April 2022. The procedures were classified based on technical difficulty and learning periods, and the hands-on technical skills of LESS module were evaluated. Results Surgeon A conducted 580 LESS procedures, which were divided into the novice (n = 48) and intermediate (n = 33) periods, and the remaining cases were included in the routine period. We formed a special ergonomic LESS operating methodology: Maintain good LESS laparoscopic spatial sensation, keep hand-eye coordination, well cooperation between the main surgeon and the assistant; Experienced multiport laparoscopy surgery (MPS) skills, improve basic LESS technique: grasp, lift, transfer, place, blunt separating, coagulation and cutting. Coordination location, orientation, movements, and flexion or extension of shoulders, arms, elbow, wrist and finger joints; Maintain strength, tension and ambidexterity postures with joint and muscular efforts to control instruments. Surgeon B learned the above experiences by performing 39 LESS procedures under the guidance of surgeon A. Conclusion This educational research sheds light on the common challenges faced in LESS and presents the importance of ergonomic hands-on performance skills in improving surgical outcomes, which could serve as a guide for future training and education in LESS.

Abstract Architected materials that consist of multiple subelements arranged in particular orders can demonstrate a much broader range of properties than their constituent materials. However, the rational design of these materials generally relies on experts’ prior knowledge and requires painstaking effort. Here, we present a data-efficient method for the high-dimensional multi-property optimization of 3D-printed architected materials utilizing a machine learning (ML) cycle consisting of the finite element method (FEM) and 3D neural networks. Specifically, we apply our method to orthopedic implant design. Compared to uniform designs, our experience-free method designs microscale heterogeneous architectures with a biocompatible elastic modulus and higher strength. Furthermore, inspired by the knowledge learned from the neural networks, we develop machine-human synergy, adapting the ML-designed architecture to fix a macroscale, irregularly shaped animal bone defect. Such adaptation exhibits 20% higher experimental load-bearing capacity than the uniform design. Thus, our method provides a data-efficient paradigm for the fast and intelligent design of architected materials with tailored mechanical, physical, and chemical properties.

Objective The high hip center (HHC) technique has been proposed for the treatment of patients with developmental dysplaisa of the hip (DDH) who have an acetabular bone defect. However, the importance of global femoral offset (FO) in the application of this technique has not been sufficiently appreciated. Our goals were to confirm that the HHC technique is feasible in the treatment of patients with DDH and to assess the function of global FO in this procedure. Methods We retrospectively analyzed 73 patients who underwent total hip arthroplasty using high hip center technique for unilateral DDH at our hospital between January 2014 and June 2019. According to global FO, the patients were split into three groups: increased FO group (increment greater than 5 mm), restored FO group (restoration within 5 mm) and decreased FO group (reduction greater than 5 mm). Patients' medical records and plain radiographs were reviewed. One‐way ANOVA was used to compare radiographic outcomes and Harris hip score (HHS). Paired t‐test was used to assess preoperative and postoperative HHS and leg length discrepancy. Trochanteric pain syndrome, Trendelenburg sign and postoperative limp was evaluated with Fisher's exact test. Results The average follow‐up time was 7.5 ± 1.4 years. The patients' HHS and leg length discrepancy were significantly improved (p

Deep-sea mining, as a critical direction for the future development of mineral resources, places significant importance on the mechanical characteristics of its transportation pipelines for the safety and efficiency of the entire mining system. This paper establishes a simulation model of the deep-sea mining system based on oceanic environmental loads and the mechanical theory of deep-sea mining transportation pipelines. Through a static analysis, the effective tension along the pipeline length, the maximum values of bending moment, and the minimum values of bending radius are determined as critical points for the dynamic analysis of pipeline mechanical characteristic monitoring. A dynamic simulation analysis of the pipeline’s mechanical characteristics was conducted, and simulation sensor data were obtained as inputs for the prediction model construction. A prediction model of pipeline mechanical characteristics based on the BP neural network was constructed, with the model’s prediction correlation coefficients all exceeding 0.95, enabling an accurate prediction of pipeline state parameters.

Compared to the traditional wet-mate underwater power supply method, Magnetic Coupling Resonant Wireless Power Transfer (MCR-WPT) technology boasts advantages such as excellent insulation, high safety, and convenient operation, showing promising application prospects in the field of power supply for underwater vehicles and other mobile underwater devices. In order to explore the transmission characteristics of this technology underwater, this article first establishes a traditional mathematical model, and then modifies the underwater model through analysis of changes in coil self-inductance and mutual inductance, as well as the impact of eddy current losses. Using the modified mathematical model of the underwater MCR-WPT system, the transmission characteristics are analyzed, and simulations and experimental validations are performed using MATLAB R2022a software. In the study of frequency characteristics, it is found that the system operates optimally when both ends of the circuit work at the resonant state; that is, when finput = fresonance = 100 kHz, the output performance is at its best, and the optimal resonant frequency significantly improves power and transmission efficiency. When the input frequency is less than 87.3 kHz or greater than 122.9 kHz, the output power decreases to less than half of the maximum power. In the investigation of load effects, the optimal load for maximizing system output power was identified, but the load that maximizes transmission efficiency is different from this optimal load. This study provides strong theoretical support and guidance for improving the performance of underwater wireless power transmission systems.

Emerging pollutants such as microplastics in water environments readily accumulate microorganisms on their surfaces, forming biofilms and concentrating antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). Consequently, microplastic biofilms have attracted the attention of researchers. Horizontal gene transfer (HGT) of ARGs is one of the primary ways that bacteria acquire antibiotic resistance. Most studies focus on the effects of nanomaterials on suspended bacteria, but microplastic biofilms as hotspots for horizontal gene transfer also warrant significant investigation. This study primarily explored and compared the effects of nano-titanium dioxide on the conjugation transfer frequency of ARGs in suspended bacteria and microplastic biofilms. Nano-titanium dioxide could promote ARG conjugation in both suspended bacteria and microplastic biofilms, with a greater effect on the former. The mechanism involved nano-titanium dioxide promoting the production of reactive oxygen species (ROS) in suspended and biofilm bacteria, increasing the synthesis of outer membrane proteins, enhancing the cell membrane permeability, and elevating the expression levels of conjugation-related genes, thereby facilitating the conjugation transfer of ARGs. Biofilm bacteria, being heavily encased and protected by extracellular polymeric substances (EPS), exhibit greater resistance to external environmental pressure, resulting in the weaker impact of nano-titanium dioxide on biofilm bacteria compared to suspended bacteria. This study reveals the risk of ARG conjugation transfer within microplastic biofilms induced by nanomaterials, providing valuable insights into the risks of microplastic and antibiotic resistance dissemination in water environments.

Magnetically coupled resonant wireless power transfer (MCR-WPT) technology offers longer effective transmission distances and higher efficiency compared to traditional charging methods, making it better suited to the prolonged and efficient operation of autonomous underwater vehicles. This paper first establishes a traditional mathematical model and then refines it while analyzing the variations in the self-inductance and mutual inductance of underwater coils. To further enhance the system’s performance, a multi-objective optimization of the coupling mechanism is conducted. An orthogonal experiment is employed to determine the effects of various influencing factors on the coils’ self-inductance and mutual inductance. Subsequently, an RBF neural network is used to create a regression prediction model based on the results of the orthogonal experiment. The NSGA-II algorithm is then applied for the multi-objective optimization of the coupling mechanism, resulting in a Pareto front solution set. The optimized efficiency is 93.35%, representing an approximately 6% improvement over the original system, with the power density increasing from 1.267×106 W/m3 before optimization to 4.782×106 W/m3 after optimization. Significant enhancement in system performance is achieved.

Abstract Background Evidence links gamma‐glutamyl transferase (GGT) to mortality in the general population. However, the relationship of GGT with all‐cause and cause‐specific mortality risk has been little explored in type 2 diabetes mellitus (T2DM) patients. Methods We recruited 20 340 community‐dwelling T2DM patients between 2013 and 2014 in Jiangsu, China. Cox regression models were used to assess associations of GGT with all‐cause and specific‐cause mortality. Restricted cubic splines were used to analyze dose–response relationships between GGT and mortality. Stratified analysis was conducted to examine potential interaction effects by age, sex, smoking status, body mass index (BMI), diabetes duration, and dyslipidemia. Results During a median follow‐up period of 7.04 years (interquartile range: 6.98–7.08), 2728 deaths occurred, including 902 (33.09%) due to cardiovascular disease (CVD), and 754 (27.58%) due to cancer. GGT concentrations were positively associated with all‐cause, CVD, and cancer mortality. Multivariable hazard ratios (HRs) for the highest (Q5) vs. the lowest quintile (Q1) were 1.63 (95% confidence intervals [CI]: 1.44–1.84) for all‐cause mortality, 1.87 (95% CI: 1.49–2.35) for CVD mortality, and 1.43 (95% CI: 1.13–1.81) for cancer mortality. Effect modification by BMI and dyslipidemia was observed for all‐cause mortality (both p for interaction

Abstract Background Myopia is prevalent in children and adolescents. Understanding the effect of multiple behaviors and their latent patterns on ocular biometric parameters may help clinicians and public health practitioners understand the behavioral risk pattern of myopia from a person-centered perspective. The purpose of this study was to identify the patterns of four major behavioral risk factors associated with myopia, including time spent outdoors, digital screen time, sleep duration, and performance of Chinese eye exercises. The study also examined the relationships between these behavioral patterns and myopia as well as ocular biometric parameters in a sample of Chinese college students. Methods This study included 2014 students from the Dali University Students Eye Health Study. The average age of the subjects was 19.0 ± 0.9 years old, ranging from 15.7 to 25.1 years old. Each participant’s refractive status was measured using an autorefractor without cycloplegia and ocular biometric parameters were measured using an IOL Master. Behavioral risk factors were collected using a pre-designed self-administered questionnaire. Latent class analysis (LCA) was performed to identify cluster patterns of various behaviors. Results The prevalence of myopia was 91.8% in this population. The 2-class model was selected for the LCA based on goodness-of-fit evaluation metrics. Among the overall study sample, 41.1% and 58.9% were assigned into the high-risk and low-risk class, respectively. The risk of myopia [odds ratio (OR) = 2.12, 95% confidence interval (CI) = 1.52–3.14], high myopia (OR = 1.43, 95% CI = 1.14–1.78) and axial length/corneal radius (AL/CR) ratio of more than 3.0 (OR = 1.82, 95% CI = 1.22–2.72) were significantly higher in the high-risk compared with low-risk class. Conclusions Chinese university students showed differential risks of myopia and could be subdivided into high- and low-risk clusters based on four behavioral variables.

Abstract Uterine leiomyosarcoma (uLMS) is an aggressive mesenchymal neoplasm associated with a poor prognosis. Systemic chemotherapy is the standard therapy for patients with uLMS. However, it is unclear which treatment regimen results in the most favorable clinical outcome. We performed a meta‐analysis and meta‐regression analysis to assess the efficiency of different treatments received by patients with advanced, metastatic, and relapsing uLMS by evaluating the objective response rate (ORR) and disease control rate (DCR) as primary endpoints. The frequentist random effects meta‐analysis model was used to compare the outcomes of different treatment regimens for advanced uLMS. A meta‐regression analysis was performed to estimate the association between the study‐specific hazard ratios and specific demographic variables. A meta‐analysis of 51 reports including 1664 patients was conducted. Among patients who received adjuvant chemotherapy (916 patients; 55%), gemcitabine and docetaxel were the most frequently used drugs. First‐line monotherapy with alkylating agents (pooled ORR = 0.48; 95% confidence interval [CI]: 0.44–0.52) and second‐line monotherapy with protein kinase inhibitors (pooled ORR = 0.45; 95% CI: 0.39–0.52) resulted in favorable prognoses. The combinations of anthracycline plus alkylating therapy (pooled DCR = 0.74; 95% CI: 0.67–0.79) and of gemcitabine plus docetaxel (pooled DCR = 0.70; 95% CI: 0.63–0.75) showed the greatest benefits when used as first‐line and second‐line chemotherapies, respectively. Subgroup meta‐analysis results revealed that dual‐regimen therapies comprising anthracycline plus alkylating therapy and gemcitabine plus docetaxel are practical therapeutic choices for International Federation of Gynecology and Obstetrics stages III–IVb with distant metastases when assessed by computed tomography (p = 0.001). Furthermore, neoadjuvant chemotherapy and local radiotherapy resulted in favorable outcomes for patients with earlier stages of distant relapsed uLMS (p

BackgroundNeutrophil extracellular traps (NETs) play a key role in thrombus formation in patients with coronavirus disease 2019 (COVID-19). However, the existing detection and observation methods for NETs are limited in their ability to provide quantitative, convenient, and accurate descriptions of in situ NETs. Therefore, establishing a quantitative description of the relationship between NETs and thrombosis remains a challenge.ObjectiveWe employed morphological observations of blood cells and statistical analyses to investigate the correlation between the NETs/neutrophilic segmented granulocyte ratio and mortality risk in patients with COVID-19.MethodsPeripheral blood samples were collected from 117 hospitalized patients with COVID-19 between November 2022 and February 2023, and various blood cell parameters were measured. Two types of smudge cells were observed in the blood and counted: lymphatic and neutral smudge cells. Statistical data analysis was used to establish COVID-19 mortality risk assessment indicators.ResultsMorphological observations of neutrophilic smudge cells revealed swelling, eruption, and NETs formation in the neutrophil nuclei. Subsequently, the NETs/neutrophilic segmented granulocyte ratio (NNSR) was calculated. A high concentration of NETs poses a fatal risk for thrombus formation in patients. Statistical analysis indicated that a high NNSR was more suitable for evaluating the risk of death in patients with COVID-19 compared to elevated fibrinogen (FIB) and D-dimer (DD) levels.ConclusionObserving blood cell morphology is an effective method for the detection of NETs, NNSR are important markers for revealing the mortality risk of patients with COVID-19.

To study the decolorization and deproteinization conditions of Balanophora japonica polysaccharide by hydrogen peroxide and Sevag method, and to optimize the process. Based on single factor experiments, the response surface methodology was used to design a three factor and three level experiments to optimize the decolorization conditions of Balanophora japonica polysaccharides using the decolorization rate of polysaccharides as an index. Using protein removal rate and polysaccharide retention rate as indicators, a response surface experiment was designed at the factor level of Sevag reagent ratio (chloroform:n-butanol), sample solution: Sevag reagent and oscillation time to obtain the optimal process conditions. Results showed that, under the condition of pH8, the optimal decolorization process was as follows: The dosage of hydrogen peroxide was 20%, the decolorization time was 46 min, and the decolorization temperature was 60 ℃. Under this condition, the decolorization rate of polysaccharides was 84.21%. The optimal deproteinization conditions were chloroform:n-butanol 5:1, sample solution:Sevag reagent 4:1, and shock time 15 min, under this condition, the polysaccharide retention rate was 81.03%, and the protein removal rate was 40.44%. The decolorization and deproteinization of Balanophora japonica polysaccharide by hydrogen peroxide and Sevag method was stable, feasible and simple, and would be suitable for decolorization and deproteinization of Balanophora japonica polysaccharide.

Abstract Background Globoid cell leukodystrophy (GLD) is a devastating neurodegenerative disease characterized by widespread demyelination caused by galactocerebrosidase defects. Changes in GLD pathogenesis occurring at the molecular level have been poorly studied in human-derived neural cells. Patient-derived induced pluripotent stem cells (iPSCs) are a novel disease model for studying disease mechanisms and allow the generation of patient-derived neuronal cells in a dish. Results In this study, we identified gene-expression changes in iPSCs and iPSC-derived neural stem cells (NSCs) from a patient with GLD (K-iPSCs/NSCs) and normal control (AF-iPSCs/NSCs), in order to investigate the potential mechanism underlying GLD pathogenesis. We identified 194 (K-iPSCs vs. AF-iPSCs) and 702 (K-NSCs vs. AF-NSCs) significantly dysregulated mRNAs when comparing the indicated groups. We also identified dozens of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway terms that were enriched for the differentially expressed genes. Among them, 25 differentially expressed genes identified by RNA-sequencing analysis were validated using real-time quantitative polymerase chain reaction analysis. Dozens of pathways involved in neuroactive ligand–receptor interactions, synaptic vesicle cycle signaling, serotonergic synapse signaling, phosphatidylinositol–protein kinase B signaling, and cyclic AMP signaling were identified as potential contributors to GLD pathogenesis. Conclusions Our results correspond to the fact that mutations in the galactosylceramidase gene may disrupt the identified signaling pathways during neural development, suggesting that alterations in signaling pathways contribute to GLD pathogenesis. At the same time, our results demonstrates that the model based on K-iPSCs is a novel tool that can be used to study the underlying molecular basis of GLD.

The agro-pastoral transitional zone in northern China is an important agricultural and pastoral production base. This study focuses on the eastern section of the agro-pastoral transitional zone in northern China. Combined with spatio-temporal analysis, stepwise regression, and gray relation analysis, we analyzed the average annual growth rate, spatio-temporal changes, and influencing factors of agricultural and pastoral production in the study area during 2000–2020. The results show that, in the past 20 years, the agricultural and pastoral production of the 50 municipal districts and counties has significantly changed, among which the agricultural production of 38 municipal districts and counties has shown an extremely significant increase. Generally, the growth rate of agricultural production is higher than that of pastoral production. Agricultural and pastoral production in the study area is influenced by socio-economic and land use/cover factors, with an average correlation degree of 0.79 and 0.88, respectively. Climate change affects agricultural production in agricultural counties, with a correlation degree of 0.85. The results of this research provide valuable insights into understanding the long-term temporal and spatial changes in agricultural and pastoral production and help to develop sound agriculture and pastoral management practices in the eastern section of the agro-pastoral transitional zone in Northern China.

Accurate three-dimensional (3D) cloud structure measurements are critical for assessing the influence of clouds on the Earth’s atmospheric system. This study extended the MODIS (Moderate-Resolution Imaging Spectroradiometer) cloud vertical profile (64 × 64 scene, about 70 km in width × 15 km in height) retrieval technique based on conditional generative adversarial networks (CGAN) to construct seamless 3D cloud fields for the MODIS granules. Firstly, the accuracy and spatial continuity of the retrievals (of 7180 samples from the validation set) were statistically evaluated. Then, according to the characteristics of the retrieval error, a spatially overlapping-scene ensemble generation method and a bidirectional ensemble binning probability fusion (CGAN-BEBPF) technique were developed, which improved the CGAN retrieval accuracy and support to construct seamless 3D clouds for the MODIS granules. The CGAN-BEBPF technique involved three steps: cloud masking, intensity scaling, and optimal value selection. It ensured adequate coverage of the low reflectivity areas while preserving the high-reflectivity cloud cores. The technique was applied to retrieve the 3D cloud fields of Typhoon Chaba and a multi-cell convective system and the results were compared with ground-based radar measurements. The cloud structures of the CGAN-BEBPF results were highly consistent with the ground-based radar observations. The CGAN-EBEPF technique retrieved weak ice clouds at the top levels that were missed by ground-based radars and filled the gaps of the ground-based radars in the lower levels. The CGAN-BEBPF was automated to retrieve 3D cloud radar reflectivity along the MODIS track over the seas to the east and south of mainland China, providing valuable cloud information to support maritime and near-shore typhoons and convection prediction for the cloud-sensitive applications in the regions.

Alpine grasslands are vital in regulating carbon balance on the Qinghai-Tibetan Plateau (QTP) because of the large soil organic carbon (SOC) stocks, while persistent disturbance from the endemic small semifossorial herbivore, plateau pika (Ochotona curzoniae, hereafter pika), may break this balance. Pika affect the soil microclimate by creating a heterogeneous underlying surface, which is expected to alter soil microbial communities and eventually SOC stocks. However, our knowledge regarding the potential influence mechanism is still limited. Here, we investigated vegetation biomass, soil properties and soil microbes among 4 different surfaces (i.e., original vegetation, new pika pile, old pika pile and bare patch) of typical alpine grasslands to reveal soil microbial communities and the associated effect on SOC in response to pika bioturbation. Our results showed that pika bioturbation increased both bacterial and fungal diversity and their phyla abundance for SOC decomposition. Vegetation biomass, electrical conductivity and NH4+-N accounted for the variation in both bacterial and fungal community compositions and diversity. SOC stocks were 15–30% lower in pika piles and bare patches than in the original vegetation, which was mainly attributed to the reduced soil organic matter input from vegetation and the enhanced SOC consumption by soil microbial communities. Overall, we conclude that pika bioturbation altered the diversity and composition of soil microbial communities, which was associated with SOC loss and positive carbon feedback in alpine grasslands. Our findings provide insights into the role of small semifossorial herbivores in the carbon cycle of global grasslands.

The first full demonstration of a high-efficiency phase-locking mechanism was accomplished in the millimeter-wave (mm wave) bands. Two modular Ka-band coaxial magnetrons were fabricated and phase-locked. The coaxial magnetron consisted of a conventional structure and a carefully designed coupling port that included an RF window. The coupling ports of two magnetrons were connected by coupling bridges to phase lock the coaxial magnetrons in zero-phase and π-phase difference mode, reaching phase-locking efficiencies of 93.4% and 95.6%, respectively. Two phase-locking modes were both verified by a mode detection system based on a symmetrical E-plane T-junction and a high bandwidth, high sample rate oscilloscope. Signals from the oscilloscope confirmed that phase-locking occurred after 25 ns and was reproducible from pulse to pulse. With higher power and more coaxial magnetrons in arrays, 1 MW may be achievable at Ka-band.

Summary: Tubulointerstitial abnormalities contribute to the progression of diabetic kidney disease (DKD). However, the underlying mechanism of the pathobiology of tubulointerstitial disease is largely unknown. Here, we showed that MYCT1 expression was downregulated in in vitro and in vivo DKD models. Adeno-associated virus (AAV)-Myct1 significantly attenuated renal dysfunction and tubulointerstitial fibrosis in diabetic db/db mice and downregulated Sp1 transcription and TGF-β1/SMAD3 pathway activation. In human proximal tubular epithelial cells, high glucose-induced high expression of SP1 and TGF-β1/SMAD3 pathway activation as well as overaccumulation of extracellular matrix (ECM) were abrogated by MYCT1 overexpression. Mechanistically, the binding of VDR to the MYCT1 promoter was predicted and confirmed using dual-luciferase reporter and ChIP analysis. VDR transcriptionally upregulates MYCT1. Our data reveal MYCT1 as a new and potential therapeutic target in treating DKD.

Abstract An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures. Biodegradable Zn metals are revolutionary materials for orthopedic implants. In this study, pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion (L-PBF) technology. First, the mechanical properties, corrosion behavior, and biocompatibility of the pure Zn porous scaffolds were characterized in vitro. The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks. The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone, as well as relatively suitable degradation rates for bone regeneration. A benign host response was observed using hematoxylin and eosin (HE) staining of the heart, liver, spleen, lungs, and kidneys. Moreover, the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo. This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.

Abstract In this post hoc subgroup analysis of 200 patients enrolled in China from the phase III PHOENIX trial (N = 838, NCT01855750), addition of ibrutinib to rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP) did not improve event‐free survival (EFS) versus placebo+R‐CHOP in the intent‐to‐treat (ITT; n = 200, hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0·509–1.349; p = 0.4495) or activated B‐cell‐like (ABC; n = 141 [based on available gene‐expression profiling data], HR = 0.86, 95% CI: 0.467–1.570; p = 0.6160) subpopulations. However, ibrutinib+R‐CHOP improved EFS (HR = 0·50, 95% CI: 0.251–1.003) and progression‐free survival (PFS; HR = 0.48, 95% CI: 0.228–1.009) versus placebo+R‐CHOP in patients aged