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To address organic dye pollution and agricultural waste comprehensive utilization, the biochar (ZB) was prepared using Rosa roxburghii residue as the material for preparation. Three modified biochars (ZBO, ZBS, and ZBH) were created using NaOH, Na2S, and H3PO4 as modifying agents. The morphology, structure, pore size, and elemental composition of biochars were characterized and analyzed by a combination of FTIR, SEM-EDS, and N2 adsorption–desorption techniques. Furthermore, the adsorption performance of the as-prepared biochars was investigated in the adsorption of RhB and MB dye process. The experimental findings showed that adsorption equilibrium for these dyes was achieved in 180 min. Moreover, the dye adsorption on biochars followed a pseudo-second-order kinetic equation. For the biochar (ZB), the Langmuir equation proved to be more appropriate than the Freundlich equation. In contrast, the Freundlich equation was more apt for the modified biochars. More importantly, Pearson's correlation analysis revealed that the adsorption rate and capacity of RhB positively correlated with the specific pore volume, t-plot micropore area, and BET surface area, but a negative one with the pore size. The MB adsorption showed the opposite correlations. This study reveals a novel biochar for adsorbing organic dyes, which provides a strategy for the treatment of Rosa roxburghii residue.

Abstract Background Circular RNAs (circRNAs) can influence a variety of biological functions and act as a significant role in the progression and recurrence of glioblastoma (GBM). However, few coding circRNAs have been discovered in cancer, and their role in GBM is still unknown. The aim of this study was to identify coding circRNAs and explore their potential roles in the progression and recurrence of GBM. Methods CircSPECC1 was screened via circRNAs microarray of primary and recurrent GBM samples. To ascertain the characteristics and coding ability of circSPECC1, we conducted a number of experiments. Afterward, through in vivo and in vitro experiments, we investigated the biological functions of circSPECC1 and its encoded novel protein (SPECC1-415aa) in GBM, as well as their effects on TMZ sensitivity. Results By analyzing primary and recurrent GBM samples via circRNAs microarray, circSPECC1 was found to be a downregulated circRNA with coding potential in recurrent GBM compared with primary GBM. CircSPECC1 suppressed the proliferation, migration, invasion, and colony formation abilities of GBM cells by encoding a new protein known as SPECC1-415aa. CircSPECC1 restored TMZ sensitivity in TMZ-resistant GBM cells by encoding the new protein SPECC1-415aa. The m6A reader protein IGF2BP1 can bind to circSPECC1 to promote its expression and stability. Mechanistically, SPECC1-415aa can bind to ANXA2 and competitively inhibit the binding of ANXA2 to EGFR, thus resulting in the inhibition of the phosphorylation of EGFR (Tyr845) and its downstream pathway protein AKT (Ser473). In vivo experiments showed that the overexpression of circSPECC1 could combine with TMZ to treat TMZ-resistant GBM, thereby restoring the sensitivity of TMZ-resistant GBM to TMZ. Conclusions CircSPECC1 was downregulated in recurrent GBM compared with primary GBM. The m6A reader protein IGF2BP1 could promote the expression and stability of circSPECC1. The sequence of SPECC1-415aa, which is encoded by circSPECC1, can inhibit the binding of ANXA2 to EGFR by competitively binding to ANXA2 and inhibiting the phosphorylation of EGFR and AKT, thereby restoring the sensitivity of TMZ-resistant GBM cells to TMZ.

Objective To construct a Type 1 diabetes model in miniature pigs and explore postoperative care strategies for effectively prolonging the survival time of the model pigs. Methods Seven Banna miniature pigs were selected for pancreatectomy. Glucose, vitamins, and antibiotics were administered for 3-5 days after surgery to aid recovery. Blood glucose and urine glucose levels were measured twice a day in the morning and evening to adjust insulin supplementation accordingly. The model pigs were observed daily and records were kept, including orexis, psychosis, weakness, skin ulcer, and feces and urine. Body weight was measured weekly until the death of the model animals. Based on the model pigs' condition, glucose injection and Ringer's lactate solution were administered to supplement nutrition and correct electrolyte imbalances. Results All seven Banna miniature pigs showed typical symptoms of diabetes: random blood glucose levels higher than 11.1 mmol/L after pancreatectomy, far exceeding the average blood glucose level of 6.0 mmol/L in normal pigs; positive urine glucose; and progressive weight loss. These features indicated the successful construction of Type 1 diabetes model. Additionally, Type 1 diabetic pigs that survived more than 8 weeks showed progressive hair loss and skin ulceration. Euthanasia was performed on model pigs when they were unable to stand or even eat independently, and pathological examination and HE staining were conducted on tissues collected from affected organs such as the liver, kidneys, and skin. Pathological sections revealed liver congestion, massive glycogen accumulation, ballooning degeneration of hepatocytes, and progressive liver fibrosis, along with glomerular congestion, vacuolar degeneration in renal tubular epithelial cells, proteinuria, dermal congestion, thinning of vascular walls, and varying degrees of parakeratosis and dyskeratosis in the liver, kidneys, and skin tissues due to prolonged hyperglycemia. The average survival time of the constructed Banna miniature pig diabetes model was 44 d, with a maximum survival time of 121 d. Conclusion Type 1 diabetes model can be constructed successfully in Banna miniature pigs through pancreatectomy. With meticulous postoperative care, a long-term Type 1 diabetes model with significant complications can be achieved, providing a stable large-animal model for Type 1 diabetes treatment strategies.

Abstract Genome-scale metabolic models (GEMs) can facilitate metabolism-focused multi-omics integrative analysis. Since Yeast8, the yeast-GEM of Saccharomyces cerevisiae, published in 2019, has been continuously updated by the community. This has increased the quality and scope of the model, culminating now in Yeast9. To evaluate its predictive performance, we generated 163 condition-specific GEMs constrained by single-cell transcriptomics from osmotic pressure or reference conditions. Comparative flux analysis showed that yeast adapting to high osmotic pressure benefits from upregulating fluxes through central carbon metabolism. Furthermore, combining Yeast9 with proteomics revealed metabolic rewiring underlying its preference for nitrogen sources. Lastly, we created strain-specific GEMs (ssGEMs) constrained by transcriptomics for 1229 mutant strains. Well able to predict the strains’ growth rates, fluxomics from those large-scale ssGEMs outperformed transcriptomics in predicting functional categories for all studied genes in machine learning models. Based on those findings we anticipate that Yeast9 will continue to empower systems biology studies of yeast metabolism.

Abstract Glioblastoma (GBM) represents a primary malignant brain tumor. Temozolomide resistance is a major hurdle in GBM treatment. Proteins encoded by circular RNAs (circRNAs) can modulate the sensitivity of multiple tumor chemotherapies. However, the impact of circRNA-encoded proteins on GBM sensitivity to temozolomide remains unknown. Herein, we discover a circRNA (circCOPA) through the circRNA microarray profile in GBM samples, which can encode a novel 99 amino acid protein (COPA-99aa) through its internal ribosome entry site. Functionally, circCOPA overexpression in GBM cells inhibits cell proliferation, migration, and invasion in vitro and growth in vivo. Rather than itself, circCOPA mainly functions as a suppressive effector by encoding COPA-99aa. Moreover, we reveal that circCOPA is downregulated in GBM tissues and high expression of circCOPA is related to a better prognosis in GBM patients. Mechanistically, a heteromer of SFPQ and NONO is required for double-strand DNA break repair. COPA-99aa disrupts the dimerization of NONO and SFPQ by separately binding with the NONO and SFPQ proteins, thus resulting in the inhibition of proliferation or invasion and the increase of temozolomide-induced DNA damage in GBM cells. Collectively, our data suggest that circCOPA mainly contributes to inhibiting the GBM malignant phenotype through its encoded COPA-99aa and that COPA-99aa increases temozolomide-induced DNA damage by interfering with the dimerization of NONO and SFPQ. Restoring circCOPA or COPA-99aa may increase the sensitivity of patients to temozolomide.

To address the issue of severe mine pressure manifestations and difficult-to-control deformation in deep coal seam roadways, an orthogonal numerical simulation experiment was conducted based on the Kastner formula.This experiment examined five factors affecting the stability of roadway surrounding rock: height-to-width ratio, lateral pressure coefficient, depth, cross-sectional shape, and surrounding rock strength.Sensitivity of each factor to roadway deformation and damage was studied using variance analysis and intuitive analysis charts.The stress distribution patterns of elliptical and rectangular roadways under different lateral pressure coefficients and height-to-width ratios were analyzed using the plane elasticity complex variable function theory.Optimal designs for the height-to-width ratio and shape of elliptical and rectangular roadways were developed.The results showed that the main factors affecting the stability of surrounding rock are the strength of the surrounding rock and the lateral pressure coefficient, while depth, cross-sectional shape, and height-to-width ratio are secondary factors.Elliptical roadways exhibit the smallest difference in surrounding rock stress under isotropic stress ratios.Rectangular roadways have lower stress concentration when the width is 5 m and the height-to-width ratio is approximately 0.6.For areas with rapid stress increase in rectangular roadways, an optimized rounded rectangular roadway was designed considering bearing characteristics and cross-sectional utilization, and a calculation formula for the corner radius was established.The optimization performance of this design was verified through numerical simulation.

Abstract Background Artificially sweetened beverages (ASB) are consumed globally, but their impact on overall health remains uncertain. We summarized published associations between ASB intake with all-cause and cause-specific mortality. Methods We searched Medline, Embase, Web of Science, and Cochrane CENTRAL databases until August 2023. Random effect meta-analysis was conducted to calculate pooled risk ratios (RRs) and 95% confidence intervals (95%CIs) for highest versus lowest categories of ASB consumption in relation to all-cause and cause-specific mortality. Linear and non-linear dose-response analyses were also performed. Results Our systematic review and meta-analysis included 11 prospective cohort studies. During a median/mean follow-up period of 7.0 to 28.9 years, 235,609 deaths occurred among 2,196,503 participants. Intake of ASB was associated with higher risk of all-cause and CVD mortality with pooled RRs (95%CIs) of highest vs. lowest intake categories of 1.13 (1.06, 1.21) (I2 = 66.3%) for all-cause mortality and 1.26 (1.10, 1.44) (I2 = 52.0%) for CVD mortality. Dose-response analysis revealed a non-linear association of ASB with all-cause mortality (p non−linearity = 0.01), but a linear positive association with CVD mortality (p non−linearity = 0.54). No significant association was observed for ASB intake and cancer mortality. Moreover, a secondary meta-analysis demonstrated that replacing 1 serving/day of sugary sweetened beverages (SSB) with ASB was associated with 4–6% lower risk of all-cause and CVD mortality. Per NutriGrade, the evidence quality for associations between ASB intake with all-cause and CVD mortality was moderate. Conclusions Higher intake of ASB was associated with higher risk of all-cause and CVD mortality, albeit a lower risk than for SSB. Systematic review registration PROSPERO registration no. CRD42022365701.

The amount of rural sewage varies greatly, which easily affects the normal operation of sewage treatment facilities. The application of waste bricks to construct rural sewage treatment type household manholes can realize front pollution control, improve the stability of the rural sewage treatment system, and realize the resource utilization of rural construction wastes, which has a broad prospect. However, the influencing factors and parameter selection of this technology are not clear, which affects its popularization and application. To solve the above problems,this study adopted small and pilot devices, combined with material characterization, single factor analysis and response surface analysis to study the influence of waste brick particle size, pollution control effect and parameter optimization process of waste brick-based rural sewage treatment type household manholes. It was found that waste brick-based rural sewage treatment type household manholes had good sewage treatment effects, and waste brick fragments with particle size of 0.5-

IntroductionT cell Antigen Coupler (TAC) T cells harness all signaling subunits of endogenous T cell receptor (TCR) to trigger T-cell activation and tumor cell lysis, with minimal release of cytokines. Some of the major obstacles to cellular immunotherapy in solid tumors include inefficient cell infiltration into tumors, lack of prolonged cellular persistence, and therapy-associated toxicity.MethodsTo boost the cytotoxic potential of TAC-T cells against solid tumors, we generated a novel NECTIN-4-targeted TAC-T variant, NECTIN-4 TAC28-T, which integrated the co-stimulatory CD28 cytoplasmic region, and compared the anti-tumor activities between NECTIN-4 TAC-T cells and NECTIN-4 TAC28-T cells in vitro and vivo.ResultsWe demonstrated NECTIN-4 TAC28-Tcells could be effectively activated by NECTIN-4 protein-coated magnetic beads (NECTIN-4-beads), and further revealed that the incorporated CD28 co-stimulatory domain enhanced their activation and proliferation capabilities. Notably, NECTIN-4 TAC28-T cells exhibited better anti-tumor effects both in vitro and in vivo than the original NECTIN-4 TAC-T cells.DiscussionOur data highlighted that NECTIN-4 TAC28-T cells may represent a promising, safe and effective cell therapy for NECTIN-4-overexpressing solid tumors.

IntroductionExtensive trauma frequently disrupts endometrial regeneration by diminishing endometrial stem cells/progenitor cells, affecting female fertility. While bone marrow mesenchymal stem cell (BMSC) transplantation has been suggested as an approach to address endometrial injury, it comes with certain limitations. Recent advancements in endometrial epithelial organoids (EEOs) have displayed encouraging potential for endometrial regeneration. Therefore, this study aims to explore whether EEOs surpass BMSCs in their ability to repair injured endometrium and to examine whether the restoration process involves the integration of EEOs into the endometrial tissue of the recipient.MethodsWe developed rat EEOs (rEEOs) mimicking the features of the rat endometrium. Subsequently, we created a rat model of endometrial injury to compare the effects of rEEOs and rat BMSCs (rBMSCs) on endometrial regeneration and reproductive recovery. Bulk RNA-sequencing analysis was conducted to further investigate the capacity of rEEOs for endometrial regeneration and to identify discrepancies between rEEOs and rBMSCs. Additionally, to track the fate of the transplanted cells in vivo, we transplanted green fluorescent protein (GFP) -labelled rEEOs or red fluorescent protein (RFP) -labelled rBMSCs.ResultsIn a rat model of endometrial injury, we observed that fertility recovery in rats transplanted with rEEOs was more comparable to that of normal rats than in those treated with rBMSC. rEEOs possess a high concentration of endometrial epithelial stem/progenitor cells and secrete vascular endothelial growth factor (VEGF)-A to promote endometrial neovascularization. Significantly, we observed that cells from GFP-labelled rEEOs could integrate and differentiate into functional glands within the injured endometrium of recipient rats.DiscussionEEOs offer a transformative approach to address the challenges of endometrial trauma. Their remarkable regenerative potential holds promise for the restoration of damaged endometrium. As we venture into the future, the concept of utilizing patient-specific EEOs for transplantation emerges as a tantalizing prospect. However, the EEOs in our experiments were mainly cultured in Matrigel, which has barriers to clinical translation as a biomaterial, a new biomaterial to be explored. Secondly, our experiments have been successful only in rat models, and more efforts need to be made before clinical translation.

Accumulating evidence has revealed that chronic unresolved inflammation can cause significant tissue damage and can be a key mediator of advanced heart failure (HF). Resolvin (Rv) D2, a member of specialized pro-resolving lipid mediators (SPMs), plays a protective role in various diseases by facilitating resolution. However, whether RvD2 participates in the pathogenesis of HF is still unclear. Our study demonstrated that RvD2 treatment mitigated cardiac remodeling and improved cardiac function in HF mice induced by pressure overload. The absence of G protein-coupled receptor 18 (GPR18), an endogenous receptor for RvD2, abolished the beneficial effects of RvD2 on HF. Additionally, RvD2 inhibited inflammatory responses and Ly6Chigh macrophage polarization during both early and late inflammatory stages involved in HF. Further investigation revealed that bone marrow transplantation from Gpr18 deficient mice into WT mice blocked the protective effects of RvD2 in HF mice. Moreover, Gpr18 deficiency impeded RvD2's capacity to downregulate inflammatory responses and Ly6Chigh macrophage polarization. Consistent with experiments in vivo, RvD2 treatment in bone marrow-derived macrophages (BMDMs) reduced inflammatory responses through its receptor GPR18. Mechanistically, RvD2 suppressed the phosphorylation of STAT1 and NF-κB p65, and the effects of RvD2 were reversed by the application of STAT1 or NF-κB p65 agonists in BMDMs. In conclusion, RvD2/GPR18 axis improved cardiac remodeling and function in pressure overload-induced HF mice by modulating macrophage phenotype via STAT1 and NF-κB p65 pathways. Our findings underscore the anti-inflammatory potential of RvD2/GPR18 axis, suggesting that RvD2/GPR18 axis may be a potential strategy for the treatment of HF.

BackgroundBovine paratuberculosis is a chronic infectious disease of ruminants primarily caused by Mycobacterium avium subsp. paratuberculosis (MAP). It is essentially a chronic granulomatous enteritis characterized by intractable diarrhea, progressive lethargy, and thickening of the intestinal mucosa with the formation of crumpled pouches. Bovine paratuberculosis not only adversely affects milk production and the quality of dairy products but also poses a significant threat to the economic development of dairy farming and human food security. This systematic review and meta-analysis was conducted to assess the prevalence of MAP infection among cattle herds in mainland ChinaResultsA total of 62 studies with data from 102,340 cattle in 24 provinces in China were selected after matching the assessment criteria. In China, the overall estimated prevalence of MAP infection in cattle was 8%(7727/102340). Interestingly, the MAP infection rate in cattle in southern China was estimated to be 2% (6/281), which was significantly lower compared with other regions of China, and the highest infection rate was 12% (1914/16008) in eastern China. MAP infection rates were related to age, average herd size, type of use, season, detection method, and sample type. Moreover, the MAP infection rate in cattle did not correlate with the publication date of the studies.ConclusionThe analysis identified age, average herd size, type of use, and season as significant potential risk factors associated with PTB pool positivity. In addition, the detection method and sample type can also potentially affect the incidence of detected PTB.

AI large model is leading the hot ICT(information and communications technology) industry in the next decade. Intelligent computing center network is a communication base to support the distributed training of AI large model, and it is one of the key factors to determine the efficiency of AI clusters. The data volume and the number of parameters of AI large model are expanding continuously, which brings the network of intelligent computing centers serious challenges, and also brings an opportunity for intergenerational innovation of key network technologies. In the process of AI large model training and inferencing, providing high performance and high security transmission of data are the two core requirements of AI business for intelligent computing network. Efficient load balancing, congestion control technologies and network security protocols are the key network technologies. To address the challenge brought by large-scale AI business, global scheduling ethernet (GSE) was proposed as a corresponding solution, and realistic test environment was built to compare the performance of GSE and RoCE. The test results show that GSE significantly improves JCT compared with RoCE network.

Abstract The high cost of establishing a cell and tissue culture facility has denied students an opportunity to practice proper aseptic techniques during their studies. An in-house application named AsepticTech Virtual Reality (VR) was developed to simulate a cell and tissue culture facility for students to train their aseptic techniques virtually. However, the performance gain associated with the application will be limited by the student’s willingness to use the application. Therefore, this study aims to investigate the driving factors behind students’ intention to use AsepticTech VR. A total of 55 biomedical undergraduates were granted access to AsepticTech VR. After using the application, the students completed a Technology Acceptance Model (TAM) questionnaire. It measures seven latent constructs that are believed to influence the students’ behavioral intention to use the application, namely Perceived Usefulness (PU), Perceived Ease of Use (PEU), Attitude Towards Use (ATU), Behavioral Intention (BI), Perceived Enjoyment (PENJ), Perceived Health Risk (PHR) and Self-Efficacy (SE). The questionnaire was preliminarily evaluated on its validity and reliability using Confirmatory Factor Analysis (CFA), Average Variance Extracted (AVE), Composite Reliability (CR), and Cronbach’s alpha. Subsequently, the interactions between the seven latent variables were analyzed via path analysis. Findings of the path analysis suggested that ATU is the most influential factor on BI, followed by PENJ and SE. In turn, ATU was positively and significantly influenced by PENJ, whereas PHR exerted a significant negative influence on ATU. This study revealed that enjoyment and comfort are the principal factors influencing students’ acceptance of AsepticTech VR. This study also identifies other determinants that influence users’ acceptance of AsepticTech VR and paves guidance for the future development of the application.

In order to improve the recognition accuracy of radar targets and the recognition performance under incomplete angular domain data, a high resolution range profile (HRRP) recognition algorithm based on time series forest is proposed. The basic principle of time series forest algorithm and the basic steps of HRRP target recognition are introduced in detail. The experimental results of measured HRRP data show that compared with k-nearest neighbors(KNN), support vector machine(SVM), random forest(RF), convolutional neural network(CNN), long short-term memory(LSTM) and other classical target recognition algorithms, the proposed algorithm has better recognition performance and better angular domain promotion ability. Under the condition of training only 1/2 and 1/3 angular domain data, the average recognition rate of the full angular domain data is better than 85%, which is an average increase of 5.2% compared with the above method.

A prominent cause of cancer-related fatalities with a poor prognosis is lung adenocarcinoma (LUAD). KIF5A, a crucial member of the kinesin superfamily, is linked to drug resistance in malignancies. This work aims to investigate the mechanism of KIF5A in docetaxel (DTX) resistance in LUAD cells. The results of bioinformatics analysis, qRT-PCR and western blot analysis show that KIF5A, which is involved in the glycolysis pathway, is highly expressed in LUAD and is positively correlated with glycolysis-related genes. We further verify that silencing of KIF5A inhibits DTX resistance, glycolysis, and lactate production in LUAD cells via cell counting kit-8 (CCK-8), flow cytometry, Seahorse XFe 96, lactate, and glucose assays. Mechanistically, KIF5A promotes DTX resistance in LUAD, and this effect is attenuated upon the addition of an LDHA inhibitor. Chromatin immunoprecipitation and dual-luciferase reporter assays reveal that FOXP3 transcriptionally activates KIF5A. Knockdown of FOXP3 reduces lactate production and enhances DTX sensitivity in LUAD, which is restored upon simultaneous overexpression of KIF5A. Our findings reveal that FOXP3 increases DTX resistance in LUAD cells by enhancing lactate production through the upregulation of KIF5A level. In conclusion, our study provides a novel treatment target for improving chemosensitivity in LUAD.

Critically ill patients are at high risk for hospital acquired infections, which can significantly increase the mortality rate and treatment costs for these patients. Therefore, in the process of treating the primary disease, strict prevention and control of new hospital infections is an essential component of the treatment for critically ill patients. The treatment of critically ill patients involves multiple steps and requires a concerted effort from various aspects such as theory, management, education, standards, and supervision to achieve effective prevention and control of hospital infections. However, there is currently a lack of unified understanding and standards for hospital infection prevention and control. To address this, in March 2024, a group of experts in critical care medicine, infectious diseases, and hospital infection from China discussed the current situation and issues of hospital infection control in the intensive care unit together. Based on a review of the latest evidence-based medical evidence from both domestic and international sources, 2024 Expert Consensus on Hospital Acquired Infection Control Principles in the Department of Critical Care Medicine was formed, aiming to provide a basis for the development of hospital infection prevention and control strategies in the field of critical care medicine.

With the development of nuclear industry technology, the use of nuclear fuel is gradually increasing and the amount of produced spent fuel is increasing. During the reprocessing process of spent fuel, a large amount of low concentration tritium-containing purified water is generated. China’s backup spent fuel reprocessing plants are established in inland areas and use air carrying emission technology with certain shortcomings such as limited increase in air carrying capacity, and the air after carrying may experience re-condensation due to temperature and humidity imbalance, resulting in environmental pollution. In response to the low emission efficiency and poor environmental adaptability of the existing tritium-containing purified water air carrier technology, which could not effectively meet the practical needs of spent fuel reprocessing development, a two-step air carrier tritium-containing purified water system was proposed in this paper based on LiBr refrigeration drive solution dehumidification and efficient humidification. A prototype of the two-step tritium-containing purified water air carrier system was established with carrier capacity larger than 2 t/d, and its operational characteristics under different conditions were systematically studied based on the criteria of safety and efficient discharge. The results show that no condensation phenomenon occurs at the outlet of the carrier air, indicating that the experimental prototype is able to safely and efficiently discharge tritium-containing purified water under environmental conditions of air temperature ranging from 3 ℃ to 50 ℃ and air relative humidity ranging from 0 to 90%. Under the standard condition with an air temperature of 22 ℃ and air relative humidity of 47%, the carrier capacity of the experimental prototype is 100.8 kg/h, which is 298.4% higher than the one-step method. Under the high relative humidity condition with an air temperature of 25 ℃ and air relative humidity of 90%, the carrier capacity of the experimental prototype is 119.9 kg/h, which is 508.6% higher than the one-step method. Under the low temperature condition with an air temperature of 3 ℃ and air relative humidity of 70%, the carrier capacity of the experimental prototype is 17.4 kg/h. Under the high temperature condition with an air temperature of 50 ℃ and air relative humidity of 20%, the carrier capacity of the experimental prototype is 96.0 kg/h, which is 60.0% higher than the one-step method. The above results indicate that the two-step method can significantly expand the environmental adaptation range for safe discharge of tritium-containing purified water, and the emission efficiency is high. The results in this paper can provide reference for the application of tritium-containing purified water discharge.

Abstract Prodrugs have been explored as an alternative to conventional chemotherapy; however, their target specificity remains limited. The tumor microenvironment harbors a range of microorganisms that potentially serve as tumor-targeting vectors for delivering prodrugs. In this study, we harness bacteria-cancer interactions native to the tumor microbiome to achieve high target specificity for prodrug delivery. We identify an oral commensal strain of Lactobacillus plantarum with an intrinsic cancer-binding mechanism and engineer the strain to enable the surface loading of anticancer prodrugs, with nasopharyngeal carcinoma (NPC) as a model cancer. The engineered commensals show specific binding to NPC via OppA-mediated recognition of surface heparan sulfate, and the loaded prodrugs are activated by tumor-associated biosignals to release SN-38, a chemotherapy compound, near NPC. In vitro experiments demonstrate that the prodrug-loaded microbes significantly increase the potency of SN-38 against NPC cell lines, up to 10-fold. In a mouse xenograft model, intravenous injection of the engineered L. plantarum leads to bacterial colonization in NPC tumors and a 67% inhibition in tumor growth, enhancing the efficacy of SN-38 by 54%.

Multi-criteria priority ranking involves determining priorities through calculations for a multitude of tasks as per potentially conflicting criteria, to aid decision-makers in efficient allocation of resources and prioritization of tasks based on their criticality. This process is essential for optimizing resource allocation and improving overall work efficiency. Over the past two decades, the field of priority ranking has seen the development of numerous mature classic methods through continuous modifications and expansions. Furthermore, new sorting methods rooted in advancing technologies in the era of big data have also emerged. To assist decision-makers in evaluating and selecting the most suitable multi-criteria prioritization methods for priority ranking needs in specific application scenarios, this paper first elucidates differences across various multi-criteria prioritization methods regarding criteria substitutability, advantages and disadvantages, data input/output requirements, and applicable scenes. It further categorizes existing multi-criteria task prioritization methods into four main types: full aggregation methods, inferiority ranking methods, reference level methods, and data processing-based prioritization methods. Additionally, it discusses in detail the basic principles, implementation steps, latest research findings, and pros and cons of representative methods within each category. Finally, this paper summarizes current research hotspots, including the analytic hierarchy process, fuzzy theory, and AI-assisted ranking technologies, while suggesting future research pathways covering AI-assisted big data ranking optimization, ranking stability enhancement, and intelligent preference identification.

Objective To optimize the operational steps and processes in mouse cervical heterotopic heart transplantation by modifying the conventional cuff technique for vascular anastomosis and consequently establish a more stable cervical heterotopic heart transplantation model in mice. Methods C57BL/6 male mice (6~8 weeks old, weighing 20~24 g) were categorized into control (conventional cuff technique) and experimental groups (our "Anchoring Node" technique). Time for each surgical step, frequencies of vascular everting and vascular trimming, and the reasons for failure were recorded and compared between the 2 groups. Postoperative survival of heart allograft was determined by daily observation and touching, and the mice with the survival time >48 h were considered as successful model establishment. On the 7th and 14th days after surgery, HE staining was used to observe the pathologic changes in the vascular tissues at anastomosis. The expression of troponin T (cTnT) in the heart on the 7th day was detected with immunofluorescence assay. Results ① In the 25 hearts from each group, 2 hearts from the experimental group and 8 from the control group failed, and the survival rate of heart allografts was 92% and 68%, respectively. In the experimental group, arterial and venous everting occurred at an average of 1.16 times, with an average frequency of trimming of 0.04 times, while in the control group, arterial and venous everting was 2.00 and 2.28 times, respectively, with an average frequency of trimming of 0.21 and 0.46 times, respectively. ② Significant differences were observed in the overall duration for cervical heterotopic heart transplantation (77.22±3.82 vs 87.49±8.01 min), vascular separation plus cannulation (30.06±2.68 vs 36.50±6.67 min), and cervical anastomosis (7.31±1.08 vs 12.34±2.58 min) between the experimental and control groups (all P < 0.05). ③HE staining displayed that vascular patency was observed in the experimental group on the 7th and 14th days after surgery. ④cTnT staining indicated no massive myocardial necrosis was seen in both groups. Conclusion Based on conventional cuff technique for mouse cervical heterotopic heart transplantation, our modified "Anchoring Node" technique ensures the stability and efficiency of one-man microscopic operation with controllable quality, with the advantages of longer postoperative survival of heart allograft, high patency rate of anastomotic vessels, good cardiac function, and fewer postoperative complications.

Decision-makers in GIS often need to combine multiple spatial algorithms and operations to solve geospatial tasks. While professionals can understand and solve these tasks by using GIS tools sequentially, developing workflows for various tasks can be inefficient, as even slight differences in tasks require corresponding adjustments in the workflow. Recently, large language models (e.g., ChatGPT) presented a strong performance in semantic understanding and reasoning. Especially, AutoGPT can further extend the capabilities of large language models (LLMs) by automatically reasoning and calling externally defined tools. Inspired by these studies, we attempt to increase the efficiency of developing workflows for handling geoprocessing tasks by integrating the semantic understanding ability inherent in LLMs with mature tools within the GIS community. Specifically, we develop a new framework called GeoGPT that can conduct geospatial data collection, processing, and analysis in an autonomous manner. In this framework, a LLM is used to understand the demands of users, and then think, plan, and execute defined GIS tools sequentially to output final effective results. In this process, our framework is user-friendly, accepting natural language instructions as input and adapting to various geospatial tasks, which can serve as an assistant for GIS professionals. A systemic evaluation and several cases, including geospatial data crawling, spatial query, facility siting, and mapping, validate the effectiveness of our framework. Though limited cases are presented in this paper, GeoGPT can be further extended to various tasks by equipping with more GIS tools, and we think the paradigm of “foundational plus professional” implied in GeoGPT provides an effective way to develop next-generation GIS in this era of large foundation models.

The MCrAlY(M=Ni, Co or NiCo)has become a widely used bond-coat material of thermal barrier coatings (TBCs) due to its advantages of high-temperature oxidation resistance and high thermal expansion coefficient, with the continuous increase in turbine inlet temperature of aero engines and gas turbines. However, the stress distribution at the interface between the bond and top coating in thermal barrier coatings becomes more complicated under a high-temperature service environment. The failure of the bond-coat leads to the spalling of the top coating, which limits the development of the thermal protection coating field. The development process of the bond-coat was briefly described.The failure behavior of the bond-coat interface due to high-temperature phase transition, increased thermal and growth stresses, and S-element diffusion was focused on, and the failure mechanism of the bond-coat interface was analyzed. The research on improving the bond-coat interface failure at home and abroad was summarized. The synergistic strengthening of MCrAlY by rare earth and nanoparticles is proposed, which provides a research direction for the future optimization design of thermal bond-coat systems.

Traceability is an important tool in the harmonization and standardization of reporting laboratory results, making them comparable across measurement systems. Driven by International Standardization Organization (ISO) 15189 accreditation requirements, medical laboratories have entered the era of metrological traceability. Although calibrators are a key component in the entire metrological traceability system, there is controversy over internal quality control (IQC) materials. It has been proposed that trueness materials supplied by the system's manufacturer with metrological traceability can be used to confirm that the performance of the measuring system is properly unbiased. This article focuses on the implementation challenges and operational hurdles of applying traceability concepts to IQC materials for trueness verification in medical laboratories regarding the most recent 2022 edition of ISO 15189 standard requirements for IQC and metrological traceability. There are practical considerations concerning the acquiring of IQC materials. We must acknowledge the limitations and restrictions that manufacturers and laboratories face before the recommendations can be applied in routine practices.

The realization of higher coupling strengths between coupled resonant modes enables exploration of compelling phenomena in diverse fields of physics and chemistry. In this study, we focus on the modal coupling between localized surface plasmon resonance (LSPR) of Au nanoparticles (Au-NPs) and Fabry–Pérot mode (p-NiO/Au film). The effects of nanoparticle size, projected surface coverage (PSC), interparticle distance (IPD), and arrangement to the coupling strength between the two modes are theoretically investigated using finite-difference time-domain (FDTD) method. Au-NPs/p-NiO/Au film (ANA) nanostructures with NPs size of 10 nm, 30 nm, and 50 nm are considered. Numerical calculations point to larger size and higher projected surface coverage (also smaller IPD) of NPs as pre-eminent factors in enhancing the strength of modal coupling. ANA nanostructure with NPs size of 30 nm (ANA-30) and 50 nm (ANA-50) are experimentally fabricated via a facile air–liquid interface self-assembly. The fabricated nanodevices exhibit immense Rabi splitting energies of 655 meV (ANA-30) and 770 meV (ANA-50), and thus fulfill the ultrastrong coupling condition with remarkable splitting energy to bare (plasmon) energy ratio of 0.35 (ANA-30) and 0.4 (ANA-50). The physical insights presented in this study, together with the simple and scalable fabrication process, establish a viable approach to realize stronger coupling between LSPR and Fabry–Pérot mode in metal NPs/dielectric/metal film systems. This will be vital to take advantage of the promising performance enhancements of plasmonic-based nanostructures under strongly coupled regimes in areas such as solar to fuel conversion, sensing, opto-electronics, and quantum applications.

Abstract Although CD19-specific chimeric antigen receptor (CAR) T cells are curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), disease relapse with tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T cells could overcome a suppressive milieu, but the clinical safety and efficacy of this CAR-T therapy remain unclear. Here we report the preclinical development of CD19-specific CAR-T cells capable of expressing interleukin (IL)-7 and chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement (referred to as 7 × 19 CAR-T cells) and results from a phase 1 and expansion phase trial of 7 × 19 CAR-T cell therapy in patients with R/R LBCL (NCT03258047). In dose-escalation phase, there were no dose-limiting toxicities observed. 39 patients with R/R LBCL received 7 × 19 CAR-T with doses ranged from 0.5 × 106–4.0 × 106 cells per kg body weight. Grade 3 cytokine release syndrome occurred in 5 (12.8%) patients and ≥ grade 3 neurotoxicity in 4 (10.3%) patients. The overall response rate at 3 months post-single infusion was 79.5% (complete remission, 56.4%; partial response, 23.1%). With a median follow-up of 32 months, the median progression-free survival was 13 months, and median overall survival was not reached, with an estimated rate of 53.8% (95% CI, 40.3% to 72.0%) at two years. Together, these long-term follow-up data from the multicenter clinical study suggest that 7 × 19 CAR-T cells can induce durable responses with a median overall survival of greater than 2 years, and have a manageable safety profile in patients with R/R LBCL.

IDH wild-type glioblastoma (GBM) intrinsic subtypes have been linked to different molecular landscapes and outcomes. Accurate prediction of molecular subtypes of GBM is very important to guide clinical diagnosis and treatment. Leveraging machine learning technology to improve the subtype classification was considered a robust strategy. Several single machine learning models have been developed to predict survival or stratify patients. An ensemble learning strategy combines several basic learners to boost model performance. However, it still lacked a robust stacking ensemble learning model with high accuracy in clinical practice. Here, we developed a novel integrative stacking ensemble model framework (ecGBMsub) for improving IDH wild-type GBM molecular subtype classification. In the framework, nine single models with the best hyperparameters were fitted based on extrachromosomal circular DNA (eccDNA) molecular profiling. Then, the top five optimal single models were selected as base models. By randomly combining the five optimal base models, 26 different combinations were finally generated. Nine different meta-models with the best hyperparameters were fitted based on the prediction results of 26 different combinations, resulting in 234 different stacked ensemble models. All models in ecGBMsub were comprehensively evaluated and compared. Finally, the stacking ensemble model named “XGBoost.Enet-stacking-Enet” was chosen as the optimal model in the ecGBMsub framework. A user-friendly web tool was developed to facilitate accessibility to the XGBoost.Enet-stacking-Enet models (https://lizesheng20190820.shinyapps.io/ecGBMsub/).

Abstract Universal newborn hearing screening (UNHS) and audiological diagnosis are crucial for children with congenital hearing loss (HL). The objective of this study was to analyze hearing screening techniques, audiological outcomes and risk factors among children referred from a UNHS program in Beijing. A retrospective analysis was performed in children who were referred to our hospital after failing UNHS during a 9-year period. A series of audiological diagnostic tests were administered to each case, to confirm and determine the type and degree of HL. Risk factors for HL were collected. Of 1839 cases, 53.0% were referred after only transient evoked otoacoustic emission (TEOAE) testing, 46.1% were screened by a combination of TEOAE and automatic auditory brainstem response (AABR) testing, and 1.0% were referred after only AABR testing. HL was confirmed in 55.7% of cases. Ears with screening results that led to referral experienced a more severe degree of HL than those with results that passed. Risk factors for HL were identified in 113 (6.1%) cases. The main risk factors included craniofacial anomalies (2.7%), length of stay in the neonatal intensive care unit longer than 5 days (2.4%) and birth weight less than 1500 g (0.8%). The statistical data showed that age (P

"Objective To investigate the predictive value of hemoglobin glycation index (HGI) for endpoint events in patients with acute decompensated heart failure (ADHF). Methods A total of 1 420 patients with ADHF who were admitted to the Department of Cardiology, Nanjing Drum Tower Hospital from September 1, 2010, to September 1, 2019, were included in this study, and the corresponding HGI values were calculated. The patients were divided into three groups based on the tertiles of HGI ［group T1（HGI≤0.499%， n=473），group T2（0.499%＜HGI≤1.108%， n=474），group T3（HGI＞1.108%， n=473）］. The endpoints included all-cause mortality, cardiovascular mortality, and major adverse cardiovascular and cerebrovascular events (MACCE). The occurrence rates of the endpoints in the three groups were evaluated by Kaplan-Meier curves, and the predictive value of HGI for the endpoints was assessed by the multivariable COX proportional hazards model. Results During a follow-up period of 60 months, all-cause mortality was 25.28%, cardiovascular mortality was 13.03%, and MACCE incidence rate was 58.59% in the study cohort. The adjusted Kaplan-Meier curves showed that all-cause mortality and cardiovascular mortality decreased with increasing HGI values (P＜0.05). There was no significant difference in incidence rate of MACCE among three groups (P>0.05). In the adjusted multivariate COX proportional hazaras model, the increase in HGI was significantly associated with a decrease in all-cause mortality (HR=0.501, 95%CI: 0.336-0.747, P=0.001) and cardiovascular mortality (HR=0.438, 95%CI: 0.255-0.754, P=0.003). Conclusion Increased HGI values are significantly associated with decreased all-cause mortality and cardiovascular mortality in patients with ADHF, but not with the occurrence of MACCE. "

The 6061-T651 aluminum alloy was strengthened by torsional deformation with the torsion angles of 90°, 180° and 360°. The quasi-static and dynamic compressive properties of the samples before and after torsional deformation were investigated. The results show that the grain size of the samples remains unchanged at first with the increase of the torsion angle, and then begins to decrease. However, the Kernel average misorientation(KAM) value continues to increase with the increase of the torsion angle. The quasi-static and dynamic compression experiments show a slight increase in the yield strength of the samples with the increase of the torsion angle. For the same torsion angle, the dynamic yield strength is significantly higher than the yield strength at quasi-static loading. The strain rate experiment shows that the yield strength of the sample increases with the increase of strain rate, but compared with the untorsional sample, the strain rate sensitivity of the 360° torsional sample is significantly reduced. Based on the experimental data, the parameters in the Cowper-Symonds constitutive model were fitted. The stress-strain curves obtained from this model are in good agreement with the experimental results.

In this article, we investigate a spherically symmetric backward heat conduction problem, starting from the final temperature. This problem is severely ill posed: the solution (if it exists) does not depend continuously on the final data. A conditional stability result of its solution is given. Further, we propose a quasi-boundary value regularization method to solve this ill-posed problem. Two Hölder type error estimates between the approximate solution and its exact solution are obtained under an a priori and an a posteriori regularization parameter choice rule, respectively.

It is of great practical significance for real-time health monitoring to reconstruct other position responses by using limited measuring point information of wing box structure in complex navigation with harsh bearing conditions. The nonlinear relationship between the responses is obtained by training the back propagation neural network, and the response reconstruction method based on neural network is established and verified by numerical simulation through finite element analysis. The method is applied to the response reconstruction, damage location and judgment analysis of typical load-bearing structures of wing boxes under measured random excitation environment.The results show that the root mean square relative error of the predicted response power spectral density reconstructed by this method is less than 1.90 dB and the main frequency error is less than 10%. The damage or fault of the key measuring point e of the wing box occurred 3 s after the intercepted fragment data, and its fault characteristic frequency is about 240 Hz. The method is feasible to response reconstruction prediction and health monitoring analysis.

Background and purpose: The incidence of deep venous thrombosis (DVT) for patients with breast cancer after surgery is 2.00%-6.40%. The purpose of this study was to evaluate the correlation between postoperative DVT complications and surgical timing in breast cancer patients with coronavirus disease 2019 (COVID-19) infection, in order to guide clinical decision-making. Methods: From December 20, 2022 to March 20, 2023, 317 patients with breast cancer diagnosed with COVID-19 and with signs and symptoms of infection turning negative in Shandong Institute of Cancer Prevention and Treatment (Shandong Cancer Hospital), Shandong First Medical University (Shandong Academy of Medical Sciences) were enrolled. The control group included 329 patients with breast cancer who underwent surgery between May 1, 2019 and September 30, 2019 in the same hospital. Patients were grouped according to the interval between the date of COVID-19 infection and the date of surgery, and the interval time and postoperative DVT occurrence were analyzed. Results: Among 317 patients with breast cancer who underwent surgery after COVID-19 infection, 17 (5.36%), 29 (9.15%), 31 (9.78%), 50 (15.78%) and 190 (59.90%) underwent surgery after 0-2, 3-4, 5-6, 7-8 and 8 weeks, respectively. The incidence of postoperative DVT was 11.76%, 3.45%, 3.23%, 6.00% and 1.58%, respectively. The incidence of postoperative DVT in 329 patients without COVID-19 infection was 1.21%, and the incidence of postoperative DVT in patients receiving operation within 2 weeks of COVID-19 infection was significantly higher (OR=10.556; 95% CI: 1.095-303.313, P=0.03), the incidence of postoperative DVT in patients undergoing operation 3-8 weeks following COVID-19 infection was 4.55%. Multivariate analysis showed that COVID-19 infection interval was an independent predictor of DVT (OR=2.795; 95% CI: 0.692-11.278, P=0.024). All 10 patients with DVT after breast cancer surgery were recovered without serious complications such as pulmonary embolism, and the follow-up adjuvant anti-tumor therapy was not affected after symptomatic treatment. Conclusion: The incidence of DVT after breast cancer surgery within 8 weeks of COVID-19 infection is significantly higher than that of uninfected patients, especially the incidence of DVT in patients undergoing surgery within 2 weeks of COVID-19 infection is as high as 11.76%. Elective surgery for breast cancer within 2 weeks of COVID-19 infection should be avoided. Although the incidence of DVT in patients undergoing surgery 3 weeks after COVID-19 infection is still slightly high, surgical treatment can be recommended considering the urgency of breast cancer treatment, the good prognosis of DVT and the lack of influence on subsequent adjuvant therapy. However, detailed records of COVID-19 infection history of patients, early prevention and close monitoring should be made, and postoperative DVT should be treated.

With the growth of network traffic, communication services have higher and higher requirements on the performance of Dense Wavelength Division Multiplexing (DWDM). In order to improve the transmission efficiency, the transmission spectrum gradually expands to the C+L band transmission, and Super C Band transmission emerges as the times require. In order to solve this problem, this paper proposes an Erbium-Doped Fiber Amplifier (EDFA) structure for Super C Band transmission. Based on the Giles model, the characteristics of the EDFA in Super C Band are analyzed. A multi-stage pumping mechanism is used to design an EDFA that amplify in the Super C Band range. The results show that the EDFA can achieve a flat gain of 26 dB and an output power of 16.7 dBm when the light is incident at -9.3 dBm. The noise figure is less than 5 dB, and the ripple is less than 0.1 dB. And according to the requirement, when the incident light is in the range of -15～-3.5 dBm, the adjustable gain of 7～26 dB can be achieved by adjusting the pump power and the value of Variable Optical Attenuator (VOA). The EDFA can be used in the area of 5G transmission, optical fiber communication between data centers, etc.

The precise segmentation of different regions of the prostate is crucial in the diagnosis and treatment of prostate-related diseases. However, the scarcity of labeled prostate data poses a challenge for the accurate segmentation of its different regions. We perform the segmentation of different regions of the prostate using U-Net- and Vision Transformer (ViT)-based architectures. We use five semi-supervised learning methods, including entropy minimization, cross pseudo-supervision, mean teacher, uncertainty-aware mean teacher (UAMT), and interpolation consistency training (ICT) to compare the results with the state-of-the-art prostate semi-supervised segmentation network uncertainty-aware temporal self-learning (UATS). The UAMT method improves the prostate segmentation accuracy and provides stable prostate region segmentation results. ICT plays a more stable role in the prostate region segmentation results, which provides strong support for the medical image segmentation task, and demonstrates the robustness of U-Net for medical image segmentation. UATS is still more applicable to the U-Net backbone and has a very significant effect on a positive prediction rate. However, the performance of ViT in combination with semi-supervision still requires further optimization. This comparative analysis applies various semi-supervised learning methods to prostate zonal segmentation. It guides future prostate segmentation developments and offers insights into utilizing limited labeled data in medical imaging.

Steel reinforcement in marine concrete structures is vulnerable to chloride-induced corrosion, which compromises its structural integrity and durability. This study explores the combined effect of the alloying element Cr and the smart corrosion inhibitor LDH-NO2 on enhancing the corrosion resistance of steel reinforcement. Employing a machine learning approach with a support vector machine (SVM) algorithm, a predictive model was developed to estimate the polarization resistance of steel, considering Cr content, LDH-NO2 dosage, environmental pH, and chloride concentration. The model was rigorously trained and validated, demonstrating high accuracy, with a correlation coefficient exceeding 0.85. The findings reveal that the addition of Cr and application of LDH-NO2 synergistically improve corrosion resistance, with the model providing actionable insights for selecting effective corrosion protection methods in diverse concrete environments.

[Objective] The slope vegetation restoration effect and dominant ecological factors in the working area of DG hydropower station in Xizang Autonomous Region were studied in order to provide a theoretical basis and technical support to increase the success rate of vegetation restoration, control soil erosion, and improve the ecological environment in the work area. [Methods] Five different types of slope (slag accumulation, soil, soil/rock mixed, rock, and concrete ) were taken as the research objects, and the relative soil water content, air temperature, slope and slope aspect were selected as ecological factors. After in-situ monitoring, sampling and analyzing the entropy-weight method was used to calculate the weight scores of vegetation characteristics (species diversity, species richness, and vegetation coverage) and soil fertility (organic matter, available phosphorus, available nitrogen, and available potassium). Then the comprehensive-evaluation method was used to calculate the comprehensive score that was then combined with the range analysis to select the most dominant ecological factor. [Results] The highest comprehensive score of vegetation restoration (10.000 0) was obtained for the slag accumulation slope and the soil slope, and the effect of vegetation restoration was the best for these two slopes. The comprehensive score of vegetation restoration for the concrete slope was only 5.369 0, and the effect of vegetation restoration was poor. Different types of slope had different effects on vegetation restoration because of different ecological factors. The impact of ecological factors followed the order of relative soil water content>slope>air temperature>slope aspect for the soil/rock mixed slope; relative soil water content>air temperature>slope>slope aspect for the rock slope; relative soil water content>slope aspect>slope>air temperature for the soil slope, concrete slope, and slag accumulation slope. Hence, relative soil water content was the most dominant ecological factor for all slopes. [Conclusion] The main ecological factor affecting slope vegetation restoration in the working area of DG hydropower station in Xizang Autonomous Region is soil relative humidity. There are great differences in the combination of optimal ecological factors for vegetation restoration in different types of slopes, among which the relative soil water content and slope of soil-rock mixed slope, rock slope, soil slope, concrete slope and residue accumulation body slope are the same, and the differences are mainly reflected in slope aspect and air temperature.

Abstract Optimizing several properties simultaneously based on small data-driven machine learning in complex black-box scenarios can present difficulties and challenges. Here we employ a triple-objective optimization algorithm deduced from probability density functions of multivariate Gaussian distributions to optimize the γ′ volume fraction, size, and morphology in CoNiAlCr-based superalloys. The effectiveness of the algorithm is demonstrated by synthesizing alloys with desired γ/γ′ microstructure and optimizing γ′ microstructural parameters. In addition, the method leads to incorporating refractory elements to improve γ/γ′ microstructure in superalloys. After four iterations of experiments guided by the algorithm, we synthesize sixteen alloys of relatively high creep strength from ~120,000 candidates of which three possess high γ′ volume fraction (>54%), small γ′ size (77%).

Objective·To investigate the effect of C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD)-related poly-glycine-arginine (poly-GR) on mitochondrial morphology and function, and analyze the rescue effect of metformin on mitochondrial damage induced by poly-GR and its underlying mechanism.Methods·SK-N-SH cells stably overexpressing 50 repeated glycine-arginine sequences [(GR)50] or green fluorescent protein (GFP) were constructed by lentivirus infection, which were respectively named as (GR)50-SK cell line and GFP CTRL-SK cell line. (GR)50 expression in (GR)50-SK cells was verified by Western blotting. GFP expression in GFP GTRL-SK cells was observed by fluorescence microscope. Propidium iodide (PI) staining was used to detect the apoptosis levels of (GR)50-SK and GFP CTRL-SK cells. Immunofluorescence (IF) staining was performed to determine the subcellular location of (GR)50. Reactive oxygen species (ROS) level of mitochondria was evaluated by staining cells with MitoSOX Red followed by observing the intensity of red fluorescence under fluorescence microscope. The mitochondrial morphology of (GR)50-SK and GFP CTRL-SK cells was observed by transmission electron microscopy. Western blotting was used to detect protein kinase B (PKB, also known as AKT) and its phosphorylation levels in (GR)50-SK and GFP CTRL-SK cells. SC79 was used to activate AKT in (GR)50-SK cells, and MitoSOX Red staining and PI staining were used to analyze mitochondrial ROS and apoptosis levels after phosphorylated AKT increased. Metformin was used to treat (GR)50-SK and GFP CTRL-SK cells, respectively, and the apoptosis levels, mitochondrial ROS levels, mitochondrial morphology, AKT and its phosphorylation levels, and ATP concentrations of the two cells were detected by the above methods and ATP detection kit, respectively.Results·Western blotting showed that the construction of (GR)50-SK cells was successful, and fluorescence microscopy showed that the construction of GFP CTRL-SK cells was also successful. PI staining results showed that the apoptosis level of (GR)50-SK cells was higher than that of the GFP CTRL-SK cells (P=0.016). IF staining results showed that there was partial co-localization of (GR)50 in the mitochondria of (GR)50-SK cells. Compared with GFP CTRL-SK cells, the mitochondrial morphology and structure of (GR)50-SK cells were significant abnormalities, with a significantly increased ROS levels. The AKT levels in (GR)50-SK cells were similar to those in the GFP CTRL-SK cells, but there was a significant decrease in phosphorylated AKT levels. After (GR)50-SK cells were treated with SC79, the AKT phosphorylation level was significantly upregulated, and ROS level and apoptosis level were significantly downregulated. Metformin could significantly up-regulate the phosphorylated AKT levels in (GR)50-SK cells, but had no effect on AKT levels; it could reshape the morphology and structure of some mitochondria, reduce ROS levels, increase ATP production (P=0.000), and down-regulate the level of cell apoptosis (P=0.000).Conclusion·(GR)50 can cause mitochondrial morphology and function abnormalities by down-regulating AKT phosphorylation, and promote cell apoptosis. Metformin can effectively reduce the occurrence of the above pathological events induced by (GR)50.

This paper mainly discusses the formation and development of the core literacy of sports majors. Then, this paper establishes the factor model that affects the professional quality of youth sports employing multiple linear regression analysis. First, this paper uses factor analysis to observe 19-factor patterns. After the maximum variance rotation method, four dimensions were determined from the factor loading matrix, and confirmatory factor analysis was performed. Finally, this paper uses the multiple linear regression method to establish young students’ core literacy education model. This paper analyzes the model and draws the influence of four factors of school, family, society and individual on adolescents.

High-throughput sequencing technology was used to analyze the microbial community of fermented grains for Fuhexiangxing baijiu during mechanized and traditional stack fermentation. The results showed that microbial exchange, succession and enrichment occurred during the fermentation process. In both fermented grains, the microbial communities were composed of four major bacterial genera including Bacillus, Weissella, Acetobacter and Ralstonia, and six major fungal genera including Aspergillus, Lichtheimia, Candida, Pichia, Wickerhamomyces and Saccharomyces. The diversity of bacteria was significantly higher in mechanized than traditional stack fermentation, while the diversity of fungi was significantly lower in traditional than mechanized stack fermentation. Moreover, bacterial diversity was lower on the surface than in the interior of fermented grains, whereas fungal diversity was higher on the surface than in the interior of fermented grains. These results provide a basis for continuous optimization of the mechanized brewing process of Fuhexiangxing baijiu and for improving the quality of base baijiu.

Boron neutron capture therapy (BNCT) is an advanced radiation therapy technique that is rapidly developing in the field of cancer treatment. This technique, an atomic-level binary targeted therapy, kills cancer cells by causing a 10B(n, α)7Li nuclear reaction within the cancer cells, and its clinical implementation requires professional technology and device support. The core elements of BNCT include appropriate neutron sources and neutron capture drugs. Compared with traditional radiotherapy techniques, BNCT shows outstanding advantages in treating locally recurrent tumors, such as central nervous system tumors and head and neck tumors. Furthermore, it can better protect normal organs, especially for tumors that have already significantly invaded surrounding organs, demonstrating its promising future prospects. This article mainly elaborates on the technical principles, core elements, and clinical applications of BNCT, in hope of providing reference for clinical diagnosis and treatment.

Background While global newborn hearing screening programmes (NHSP) are far from the optimal level, the combined hearing and genetic screening has emerged as an innovative approach of early healthcare interventions. There is a clear need for economic evaluation to establish whether newborn deafness gene screening (NDGS), currently mandated by many cities in China, is a good investment.Methods A decision-tree model was constructed to simulate a hypothetical 10-million Chinese newborn cohort over a lifetime with three strategies: (1) no screening, (2) NHSP (standard screening) and (3) NHSP+NDGS (combined screening). The presence of permanent congenital hearing loss (PCHL) and genetic mutation were assigned at birth and held constant for all strategies. Input parameters were obtained from the Cohort of Deafness-gene Screening study and literature review. The government contract price for genetic screening was US$77/child. Outcomes of interest included the number of early diagnosed PCHL, prelingual deafness, total deafness, special education referral, incremental cost-effectiveness ratio (ICER) and benefit–cost ratio (BCR).Results Both standard and combined screening strategies were more effective and more costly than ‘no screening’. Compared with standard screening, combined screening led to 9112 (28.0%) more PCHL cases early detected, avoiding 4071 (66.9%) prelingual deafness cases and 3977 (15.6%) special education referrals. The ICER and BCR for combined screening were US$ 4995/disability-adjusted life-year (95% uncertainty interval, 2963 to 9265) and 1.78 (1.19 to 2.39), from healthcare sector perspective. Combined screening would dominate standard screening from societal perspective. Moreover, it remained cost-effective even in pessimistic scenarios.Conclusions Our findings have particular implication for the ‘scale-up’ of genetic screening at the national level in China. The model may serve as a feasible example for hearing screening strategies in other countries, as well as genetic screening for other diseases.

Background Dilated cardiomyopathy (DCM) is the leading cause of heart failure with a poor prognosis. Recent studies suggest that endothelial to mesenchymal transition (EndMT) may be involved in the pathogenesis and cardiac remodeling during DCM development. EDIL3 (epidermal growth factor‐like repeats and discoidin I‐like domains 3) is an extracellular matrix glycoprotein that has been reported to promote EndMT in various diseases. However, the roles of EDIL3 in DCM still remain unclear. Methods and Results A mouse model of DCM and human umbilical vein endothelial cells were used to explore the roles and mechanisms of EDIL3 in DCM. The results indicated that EndMT and EDIL3 were activated in DCM mice. EDIL3 deficiency attenuated cardiac dysfunction and remodeling in DCM mice. EDIL3 knockdown alleviated EndMT by inhibiting USP10 (ubiquitin specific peptidase 10) dependent Smad4 deubiquitination in vivo and in vitro. Recombinant human EDIL3 promoted EndMT via reinforcing deubiquitination of Smad4 in human umbilical vein endothelial cells treated with IL‐1β (interleukin 1β) and TGF‐β (transforming growth factor beta). Inhibiting USP10 abolished EndMT exacerbated by EDIL3. In addition, recombinant EDIL3 also aggravates doxorubicin‐induced EndMT by promoting Smad4 deubiquitination in HUVECs. Conclusions Taken together, these results indicate that EDIL3 deficiency attenuated EndMT by inhibiting USP10 dependent Smad4 deubiquitination in DCM mice.