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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.

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.

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.

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.

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.

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.

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.

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.

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/).

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.

Abstract Hypertensive vascular remodeling is defined as the changes in vascular function and structure induced by persistent hypertension. Maresin‐1 (MaR1), one of metabolites from Omega‐3 fatty acids, has been reported to promote inflammation resolution in several inflammatory diseases. This study aims to investigate the effect of MaR1 on hypertensive vascular remodeling. Here, we found serum MaR1 levels were reduced in hypertensive patients and was negatively correlated with systolic blood pressure (SBP). The treatment of MaR1 reduced the elevation of blood pressure and alleviated vascular remodeling in the angiotensin II (AngII)‐infused mouse model. In addition, MaR1‐treated vascular smooth muscle cells (VSMCs) exhibited reduced excessive proliferation, migration, and phenotype switching, as well as impaired pyroptosis. However, the knockout of the receptor of MaR1, leucine‐rich repeat‐containing G protein‐coupled receptor 6 (LGR6), was seen to aggravate pathological vascular remodeling, which could not be reversed by additional MaR1 treatment. The mechanisms by which MaR1 regulates vascular remodeling through LGR6 involves the Ca2+/calmodulin‐dependent protein kinase II/nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 signaling pathway. Overall, supplementing MaR1 may be a novel therapeutic strategy for the prevention and treatment of hypertension.

Summary: Here, we describe a protocol based on semi-site-specific primer PCR (3SP-PCR) to access unknown flanking DNA sequences. We specify the guidelines for designing primers for 3SP-PCR. We also describe experimental procedures for the 3SP-PCR, along with PCR product purification and subsequent sequencing and analysis.For complete details on the use and execution of this protocol, please refer to Wei et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

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.

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.

[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.

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.

Objective： Optimize the preparation process of salt-soluble porcine liver protein and improve the utilization rate of porcine liver by-products. Methods： Taking the extraction rate as the index, the effects of NaCl concentration, pH, extraction time and solid-liquid ratio on the extraction rate of SSLP were analyzed, and the optimal preparation process was determined by orthogonal rotation optimization test. Taking water soluble liver proteins （WSLP） as the control, the functional characteristics （solubility, foaming, foam stability, emulsification, emulsification stability, etc.） of SSLP were compared and analyzed, and Fourier transform infrared spectroscopy （FT-IR） was used, the structural changes were analyzed by low field nuclear magnetic resonance （LF-NMR） and differential scanning calorimetry （DSC）. Results： The optimum extraction process of SSLP was NaCl concentration 0.4 mol/L, pH 8, extraction time 12.95 h, solid-liquid ratio 1∶4.6 (g/mL), and the extraction rate was 10.60%. FT-IR analysis showed that the absorption peak of characteristic functional groups of SSLP was obvious and in the secondary structure β-The relative content of corner was 39.91%, α-The relative content of helix was 13.55%, β-The relative content of folding was 21.32%, and the relative content of random curl was 25.23%; LF-NMR analysis showed that SSLP had higher bound water and higher water retention; DSC results showed that the denaturation temperature of SSLP was 78.68 ℃. Conclusion： SSLP prepared under optimal process conditions has better solubility, foaming, emulsification and emulsification stability than WSLP, which is a high-quality source for the development of pig liver protein products.

An aqueous enzymatic–ultrasound cavitation extraction (AEUCE) method was developed to separate Sapium sebiferum seed kernel oil. In this process, neutral proteinase was screened as the propriate enzyme. The Plackett–Burman and Box–Behnken designs were employed to optimize AEUCE. We determined the optimal extraction conditions, producing an oil yield of 84.22 ± 3.17 %. Gas chromatography–mass spectrometry (GC–MS) analysis indicated that the S. sebiferum seed kernel oil was abundant in unsaturated fatty acids (>92 %) and that the compositions of the fatty acid profiles extracted by AEUCE were similar to those obtained from Soxhlet extraction, but their contents were slightly different. The physicochemical properties analysis showed that the oil extracted by AEUCE was comparable to that obtained from Soxhlet extraction. The results showed that the developed AEUCE is an efficient technique that can separate high-quality plant oils. The S. sebiferum seed kernel oil obtained from this extraction method is a promising substitute for vegetable oils used in biodiesel production.

AbstractPurpose This study aimed to develop a postoperative MRI-based fibrosis scoring system and to assess its correlation with anorectal function in locally advanced rectal cancer (LARC) cases administered neoadjuvant chemoradiotherapy (nCRT).Methods Pathologically confirmed LARC cases administered nCRT and radical resection were assessed retrospectively. Based on postoperative magnetic resonance imaging (MRI) findings, anastomotic fibrosis score (AFS) and perirectal fibrosis score (PFS) were determined to evaluate the extent of fibrosis. The Wexner continence score for anorectal function was obtained 2 years postoperatively and assessed for correlation with MRI fibrosis scores. The cases were divided into 2 groups by the median Wexner score. Univariable and multivariable analyses were adopted for building a nomogram model, whose diagnostic performance was estimated by receiver operating characteristic (ROC) and decision curve analyses (DCA).Results Finally, 144 patients with LARC were included in cohort 1 (training set). 52 patients were enrolled in cohort 2 (external validation set). Spearman correlation analysis indicated that AFS and PFS were positively correlated with the Wexner score. Univariable and multivariable analyses revealed age, tumor height, AFS, and PFS were independent predictors of anorectal function. The nomogram model achieved a good diagnostic performance, with AUCs of 0.800 and 0.827 in the training and validation sets, respectively; its predicting value was also confirmed by DCA.Conclusion The present study showed AFS and PFS derived from postoperative MRI are positively correlated with Wexner score. In addition, the new scoring system was effective in predicting anorectal function in LARC cases administered nCRT.

AbstractThis work aimed to investigate the effects of curcumin (Cur) encapsulated in triblock copolymer nanomicelles on lncRNA GAS5 expression and NF-κB signalling pathway in ischemic stroke rats. Using polycaprolactone (PCL), polyethylene (mPEG), polyglutamic acid (PLG), and Cur as raw materials, Cur-PLG-mPEG-PCL nanoparticles were prepared. Its morphology, particle size, and Zeta potential were analyzed. Then seventy-two SD rats were randomly divided into control (Ctrl) group, model group, model + blank nanomicelles (M + BNM) group, model +80 mg/mL Cur (M + C) group, model +40 mg/mL Cur-nanomicelles (M + CNM (40 mg/mL)) group, and model +80 mg/mL Cur nanomicelle (M + CNM (80 mg/mL)) group. The results showed that mean particle size of Cur-PLG-mPEG-PCL was (148.27 ± 27.44) nm, and mean Zeta potential was (−1.97 ± 0.21) mV. The evaluation time of intelligent optimization algorithm based on Single Shot MultiBox Detector (SSD) was significantly shortened, and average EEG power spectrum of ischemic cerebral pawns was significantly lower than that of the control group at θ, α, β, and γ bands for 4h (p

Abstract Background Contact sports athletes and military personnel who suffered a repetitive mild traumatic brain injury (rmTBI) are at high risk of neurodegenerative diseases such as advanced dementia and chronic traumatic encephalopathy (CTE). However, due to the lack of specific biological indicators in clinical practice, the diagnosis and treatment of rmTBI are quite limited. Methods We used 2-methacryloyloxyethyl phosphorylcholine (MPC)-nanocapsules to deliver immunoglobulins (IgG), which can increase the delivery efficiency and specific target of IgG while reducing the effective therapeutic dose of the drug. Results Our results demonstrated that MPC-capsuled immunoglobulins (MPC-n (IgG)) significantly alleviated cognitive impairment, hippocampal atrophy, p-Tau deposition, and myelin injury in rmTBI mice compared with free IgG. Furthermore, MPC-n (IgG) can also effectively inhibit the activation of microglia and the release of inflammatory factors. Conclusions In the present study, we put forward an efficient strategy for the treatment of rmTBI-related cognitive impairment and provide evidence for the administration of low-dose IgG.

Aiming at the problem that the non-stationary of airborne bistatic radar clutter reduces the performance of traditional clutter suppression algorithm, this paper first formulates airborne bistatic radar clutter model, and then analyzes the bistatic radar clutter characteristics in four typical combat scenarios. In addition, in order to reduce the computation burden of the STAP algorithm, a three-dimensional cross-beam clutter suppression algorithm is proposed, which uses the transformation matrix to convert the space-time two-dimensional data into azimuth-elevation-Doppler three-dimensional data. By eliminating auxiliary beam clutter data, only the main beam clutter data which plays a major role in dual-basis clutter suppression is retained to form a three-dimensional cross-beam for local adaptive clutter suppression. The proposed algorithm can greatly reduce the amount of calculation and the demand of training samples, while trying to ensure that the clutter suppression performance does not degrade. The effectiveness of the proposed algorithm is verified by analyzing the clutter suppression effect and computation amount of various algorithms in typical combat scenarios. Therefore, the algorithm has great potential in the applications of airborne bistatic and non-stationary clutter suppression.

IntroductionGliomas have emerged as the predominant brain tumor type in recent decades, yet the exploration of non-apoptotic cell death regulated by the pan-optosome complex, known as pan-apoptosis, remains largely unexplored in this context. This study aims to illuminate the molecular properties of pan-apoptosis-related genes in glioma patients, classifying them and developing a signature using machine learning techniques.MethodsThe prognostic significance, mutation features, immunological characteristics, and pharmaceutical prediction performance of this signature were comprehensively investigated. Furthermore, GPX8, a gene of interest, was extensively examined for its prognostic value, immunological characteristics, medication prediction performance, and immunotherapy prediction potential. ResultsExperimental techniques such as CCK-8, Transwell, and EdU investigations revealed that GPX8 acts as a tumor accelerator in gliomas. At the single-cell RNA sequencing level, GPX8 appeared to facilitate cell contact between tumor cells and macrophages, potentially enhancing microglial migration. ConclusionsThe incorporation of pan-apoptosis-related features shows promising potential for clinical applications in predicting tumor progression and advancing immunotherapeutic strategies. However, further in vitro and in vivo investigations are necessary to validate the tumorigenic and immunogenic processes associated with GPX8 in gliomas.

Summary: Cardiac dysfunction is a well-recognized complication of sepsis and seriously affects the prognosis of sepsis patients. IL-30 has been reported to exert anti-inflammatory effects in various diseases. However, the role of IL-30 in sepsis-induced myocardial dysfunction (SIMD) remains unclear. Here, we explored the protective role of IL-30 in cecum ligation and puncture (CLP)-induced SIMD mice. IL-30 expression increased in the cardiac tissues of septic mice and was mainly derived from macrophages. IL-30 deletion or neutralization aggravated sepsis-induced cardiac dysfunction and injury, whereas recombinant IL-30 treatment significantly ameliorated it. Mechanistically, IL-30 deficiency exerts pro-inflammatory effects by promoting Ly6Chigh macrophage polarization and pyroptosis. Inhibiting NLRP3 with MCC950 significantly reversed cardiac dysfunction, macrophage polarization and pyroptosis aggravated by IL-30 deficiency. Recombinant IL-30 inhibited pro-inflammatory macrophage polarization and pyroptosis in vivo and vitro. Taken together, these results suggest that IL-30 protects against SIMD by inhibiting pro-inflammatory macrophage polarization and pyroptosis.

The efficacy of the available genome-walking methods is restricted by low specificity, high background, or composite operations. We herein conceived bridging PCR, an efficient genome-walking approach. Three primers with random sequences, inner walker primer (IWP), bridging primer (BP), and outer walker primer (OWP), are involved in bridging PCR. The BP is fabricated by splicing OWP to the 5′-end of IWP’s 5′-part. A bridging PCR set is constituted by three rounds of amplification reactions, sequentially performed by IWP, BP plus OWP, and OWP, respectively pairing with three nested sequence-specific primers (SSP). A non-target product arising from IWP alone undergoes end-lengthening mediated by BP. This modified non-target product is a preferentially formed hairpin between the lengthened ends, instead of binding with shorter OWP. Meanwhile, a non-target product, triggered by SSP alone or SSP plus IWP, is removed by nested SSP. As a result, only the target DNA is accumulated. The efficacy of bridging PCR was validated by walking the gadA/R genes of Levilactobacillus brevis CD0817 and the hyg gene of rice.

Genome-walking has been frequently applied to molecular biology and related areas. Herein, a simple but reliable genome-walking technique, termed semi-site-specific primer PCR (3SP-PCR), is presented. The key to 3SP-PCR is the use of a semi-site-specific primer in secondary PCR that partially overlaps its corresponding primary site-specific primer. A 3SP-PCR set comprises two rounds of nested amplification reactions. In each round of reaction, any primer is allowed to partially anneal to the DNA template once only in the single relaxed-stringency cycle, creating a pool of single-stranded DNAs. The target single-stranded DNA can be converted into a double-stranded molecule directed by the site-specific primer, and thus can be exponentially amplified by the subsequent high-stringency cycles. The non-target one cannot be converted into a double-strand due to the lack of a perfect binding site to any primer, and thus fails to be amplified. We validated the 3SP-PCR method by using it to probe the unknown DNA regions of rice hygromycin genes and Levilactobacillus brevis CD0817 glutamic acid decarboxylase genes.

Abstract Background Long non-coding RNA (lncRNA) LINC00460 is an onco-lncRNA in a variety of cancers, including pancreatic cancer (PC). This study is aimed to investigate the regulatory mechanisms of LINC00460 in PC. Methods The tumor and adjacent normal tissues were collected from 73 PC patients. The expression of LINC00460, miR-503-5p, and ANLN was detected using qRT-PCR. We then analyzed the proliferation, migration, invasion, and apoptosis/cell cycle of PC cells by performing the MTT/EdU, transwell, and flow cytometry assays, respectively. The xenograft tumor model were utilized to confirm the effect of LINC00460 knockdown on PC through anti-PD-1 therapy in vivo, and the sensitivity of PANC-1 cells to the cytotoxicity of CD8+ T cells in vitro. Western blotting was used to determine the protein levels. A co-culture model was utilized to explore the effects of exosomes on macrophages. Results LINC00460 was up-regulated in PC tissues and cells. LINC00460 knockdown suppressed cell proliferation, migration, and invasion, facilitated cell apoptosis and G0/G1 phase arrest, and inhibited the tumor growth through anti-PD-1 therapy. Both miR-503-5p down-regulation and ANLN up-regulation reversed the effects of LINC00460 knockdown on inhibiting the proliferation, migration and invasion, and on promoting the apoptosis, G0/G1 phase arrest, and the sensitivity of PC cells to the cytotoxicity of CD8+ T cells. Exosomes were uptaken by the ambient PC cells. PANC-1 cells-derived exosomal LINC00460-induced M2 macrophage polarization accelerates the cell migration and invasion. Conclusions LINC00460 silencing attenuates the development of PC by regulating the miR-503-5p/ANLN axis and exosomal LINC00460-induced M2 macrophage polarization accelerates the migration and invasion of PANC-1 cells, thus LINC00460 may act as a possible therapeutic target for treating PC.

Abstract Our previous studies showed that dysregulation of the long noncoding RNA (lncRNA) HOXA11-AS plays an important role in the development of glioma. However, the molecular mechanism of HOXA11-AS in glioma remains largely unknown. In this study, we explore the molecular mechanisms underlying abnormal expression and biological function of HOXA11-AS for identifying novel therapeutic targets in glioma. The expression of HOXA11-AS, and the relationship between HOXA11-AS and the prognosis of glioma patients were analyzed using databases and glioma samples. Transcriptomics, proteomics, RIP, ChIRP, luciferase, and ChIP assays were used to explore its upstream and downstream targets in glioma. The role of HOXA11-AS in regulating the sensitivity of glioma cells to reactive oxygen species (ROS) was also investigated in vitro and in vivo. We found that HOXA11-AS was significantly upregulated in glioma, and was correlated with the poor prognosis of glioma patients. Ectopic expression of HOXA11-AS promoted the proliferation, migration, and invasion of glioma cells in vitro and in vivo. Mechanistically, HOXA11-AS acted as a molecular sponge for let-7b-5p in the cytoplasm, antagonizing its ability to repress the expression of CTHRC1, which activates the β-catenin/c-Myc pathway. In addition, c-Myc was involved in HOXA11-AS dysregulation via binding to its promoter region to form a self-activating loop. HOXA11-AS, functioned as a scaffold in the nucleus, also recruited transcription factor c-Jun to the Tpl2 promoter, which activates the Tpl2-MEK1/2-ERK1/2 pathway to promote ROS resistance in glioma. Importantly, HOXA11-AS knockdown could sensitize glioma cells to ROS. Above, oncogenic HOXA11-AS upregulates CTHRC1 expression as a ceRNA by adsorbing let-7b-5p, which activates c-Myc to regulate itself transcription. HOXA11-AS knockdown promotes ROS sensitivity in glioma cells by regulating the Tpl2-MEK1/2-ERK1/2 axis, demonstrating that HOXA11-AS may be translated to increase ROS sensitivity therapeutically.

Abstract Various PCR-based genome-walking methods have been developed to acquire unknown flanking DNA sequences. However, the specificity and efficacy levels, and the operational processes, of the available methods are unsatisfactory. This work proposes a novel walking approach, termed differential annealing-mediated racket PCR (DAR-PCR). The key to DAR-PCR is the use of primer-mediated intra-strand annealing (ISA). An ISA primer consists of a 5’ root homologous to the known sequence and a heterologous 3’ bud. In the single low-stringency cycle, the ISA primer anneals to a site on an unknown region and extends towards the sequence-specific primer (SSP) 1 site, thereby forming a target single-stranded DNA bound by the SSP1 complement and the ISA primer. In the subsequent more stringent cycles, its complementary strand is accumulated, owing to the differential annealing between the moderate-stringency ISA primer and the high-stringency SSP1. The accumulation of this strand provides an opportunity for ISA mediated by the ISA primer root. A loop-back extension subsequent to ISA occurs, creating a racket-like DNA with the known region positioned at both ends of the unknown sequence. This DNA is exponentially amplified during the secondary PCR driven by an SSP pair inner to SSP1. DAR-PCR was validated as an efficient walking method by determining unknown flanking sequences in Lactobacillus brevis and Oryza sativa.

2D transition metal ditellurides exhibit nontrivial topological phases, but the controlled bottom-up synthesis of these materials is still challenging. Here, the authors report the layer-by-layer growth of large-area bilayer and trilayer 1T’ MoTe2 films, showing thickness-dependent ferroelectricity and nonlinear Hall effect.

In this article, we consider a two-dimensional inverse heat conduction problem that determines the surface temperature distribution from measured data at the fixed location. This problem is severely ill-posed, i.e., the solution does not depend continuously on the data. A quasi-boundary value regularization method in conjunction with the a posteriori parameter choice strategy is proposed to solve the problem. A Hölder-type error estimate between the approximate solution and its exact solution is also given. The error estimate shows that the regularized solution is dependent continuously on the data.

Stargardt disease (STGD) is the most common form of inherited retinal genetic disorders and is often caused by mutations in ABCA4. Gene therapy has the promise to effectively treat monogenic retinal disorders. However, clinically approved adeno-associated virus (AAV) vectors do not have a loading capacity for large genes, such as ABCA4. Self-assembly nanoparticles composed of (1-aminoethyl)iminobis[N-(oleoylcysteinyl-1-amino-ethyl)propionamide (ECO; a multifunctional pH-sensitive/ionizable amino lipid) and plasmid DNA produce gene transfection comparable with or better than the AAV2 capsid. Stable PEG-ECO/pGRK1-ABCA4-S/MAR nanoparticles produce specific and prolonged expression of ABCA4 in the photoreceptors of Abca4−/− mice and significantly inhibit accumulation of toxic A2E in the eye. Multiple subretinal injections enhance gene expression and therapeutic efficacy with an approximately 69% reduction in A2E accumulation in Abca4−/− mice after 3 doses. Very mild inflammation was observed after multiple injections of the nanoparticles. PEG-ECO/pGRK1-ABCA4-S/MAR nanoparticles are a promising non-viral mediated gene therapy modality for STGD type 1 (STGD1).

Background Sympathetic hyperactivity contributes to pathological remodeling after myocardial infarction (MI). However, the mechanisms underlying the increase in sympathetic activity remain unknown. Microglia are the predominant immune cells in the central nervous system and can regulate sympathetic neuron activity through neuroimmune response in the hypothalamic paraventricular nucleus. The present study aimed to investigate whether microglia‐mediated neuroimmune response can regulate sympathetic activity and cardiac remodeling after MI. Methods and Results PLX3397 (pexidartinib) was used to deplete central microglia via intragastric injection or intracerebroventricular injection. After that, MI was induced by ligation of the left anterior descending coronary artery. Our study showed that MI resulted in the activation of microglia in the paraventricular nucleus. Microglia depletion, which was induced by PLX3397 treatment via intragastric injection or intracerebroventricular injection, improved cardiac function, reduced infarction size, and attenuated cardiomyocyte apoptosis, fibrosis, pathological electrical remodeling, and myocardial inflammation after MI. Mechanistically, these protective effects were associated with an attenuated neuroimmune response in the paraventricular nucleus, which contributed to the decrease of sympathetic activity and attenuation of sympathetic remodeling in the heart. However, intragastric injection with PLX3397 obviously depleted macrophages and induced neutrophil and T‐lymphocyte disorders in the heart, blood, and spleen. Conclusions Microglia depletion in the central nervous system attenuates pathological cardiac remodeling after MI by inhibiting neuroimmune response and sympathetic activity. Intragastric administration of PLX3397 leads to serious deleterious effects in peripheral immune cells, especially macrophages, which should be a cause for concern in animal experiments and clinical practice.

Abstract Background CARs are engineered receptors comprising an immunoglobulin single‐chain variable fragment (scFv) that identifies and binds to the target antigen, a transmembrane domain, and an intracellular T‐cell signaling domain. CD19 is a B lineage‐specific transmembrane glycoprotein and is expressed in more than 95% of B‐cell malignancies. Streptavidin (SA) is a homo‐tetrameric protein derived from Streptomyces avidinii, which can bind four biotin molecules with an extremely high affinity at a Kd value of 10‐15 M. Aims The aim of the study is to generate a novel soluble multimeric fusion protein, sCD19‐streptavidin (sCD19‐SA) for functional detection and selective expansion of CD19‐targeted CAR‐T cells. Methods The fusion proteins CD19‐SA was expressed in CHO cells and purified by use of Ni‐nitrilotriacetic acid agarose beads. Results A novel fusion protein (sCD19‐SA) was generated, consisting of the extracellular domain of human CD19 and the core region of SA, and could be used to functionally detect CD19‐targeted CAR‐T cells. Furthermore, this protein was demonstrated to form multimers to activate CAR‐T cells to induce their selective expansion. Importantly, sCD19‐SA‐stimulated CD19‐targeted CAR‐T cells could improve antitumor effects in vivo. Conclusions Our study has highlighted the potential of utilizing antigen‐SA fusion proteins such as sCD19‐SA for CAR‐T therapy for the functional detection of CAR expression and selective expansion of CAR‐T cells.

The upper wind has a major impact on the safety of the launch vehicle, and the wind speed 3 hours before launching is a determinant for the eventual schedule. If the maximum aerodynamic load generated by the upper wind does not exceed the threshold, the rocket can be launched as planned, otherwise it will be considered to postpone the launch. The deviation of the upper wind 3 hours before and at the launch time should be investigated. Taking the upper wind dataset with an interval of 3.5 hours (December 2014 to December 2020) to analyze the wind difference, and a forecast model for the wind of 0.5 hours after the launch is established using WRF model and the wind data of 3 hours before the launch. It shows that the characteristics of upper wind speed and direction difference within 3.5 hours are related to altitude, season, and the average upper wind speed. Although the maximum wind speed deviation range is -24.00-26.00 m·s-1, for two-thirds of the cases the deviation is within 10 m·s-1, which mainly occur in the middle and upper troposphere with altitude of [6.5 km, 11.5 km). The absolute value of the maximum wind direction deviation range is 10.00°-180°, mainly in the [30°, 60°) interval, and this mostly occurs in the middle and lower troposphere with altitude of [1.5 km, 6.5 km). The average absolute deviation of the upper wind speed within 3.5 hours shows an increasing trend with the increase of average upper wind speed 3 hours before the launch, but the relative error and the wind direction deviation decreases, indicating that when the upper wind is strong, the wind direction is less prone to short-term changes. The upper wind deviation within 3.5 hours varies with the seasons, for example, the absolute deviation of winter wind speed is greater than that of summer, but the absolute deviation of wind direction in winter is smaller than that of summer. Using the forecast model results of wind 0.5 hours after the launch can help to avoid the risk of rocket launch in advance.

Objective To analyze the risk factors for prognosis of patients with malignant bowel obstruction (MBO) using multiple factors, and establish the nomogram model for predicting the survival of patients with MBO. Methods The clinical data of 203 patients with MBO from June 2013 to June 2019 who were followed up in our hospital were analyzed retrospectively. Results A total of 143 (70.4%) patients have been followed up. It was shown with univariate analysis that indexes of gender, age, platelet, C-reactive protein, and total protein levels, comorbidities, the treatment with somatostatin, enteral nutrition, and parenteral nutrition, length of hospital were not related to the survival of patients with MBO. There were some factors including late TNM stage of tumor (P

Abstract Non-coding RNAs (ncRNAs) account for the majority of the widespread transcripts of mammalian genomes. They rarely encode proteins and peptides, but their regulatory role is crucial in numerous physiological and pathological processes. The m6A (N6-methyladenosine) modification is one of the most common internal RNA modifications in eukaryotes and is associated with all aspects of RNA metabolism. Accumulating researches have indicated a close association between m6A modification and ncRNAs, and suggested m6A-modified ncRNAs played a crucial role in tumor progression. The correlation between m6A modification and ncRNAs offers a novel perspective for investigating the potential mechanisms of cancer pathological processes, which suggests that both m6A modification and ncRNAs are critical prognostic markers and therapeutic targets in numerous malignancies. In the present report, we summarized the interaction between m6A modification and ncRNA, emphasizing how their interaction regulates pathological processes in cancer.

Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions (IUAs). Evidence shows that apoptosis occurs in a majority of grafted stem cells, and apoptotic bodies (ABs) play a critical role in compensatory tissue regeneration. However, the therapeutic potential of AB-based therapy and its mechanism have not been explored in detail. Here, a cell-free therapeutic strategy was developed by incorporating mesenchymal stem cell-derived ABs into a hyaluronic acid (HA) hydrogel to achieve endometrial regeneration and fertility restoration. Specifically, we found that the ABs could induce macrophage immunomodulation, cell proliferation, and angiogenesis in vitro. The HA hydrogel promoted the retention of ABs and facilitated their continuous release. In a murine model of acute endometrial damage and a rat model of IUAs, in situ injection of the AB-laden HA hydrogel could efficiently reduce fibrosis and promote endometrial regeneration, resulting in the fertility restoration. Consequently, ABs show good potential as therapeutic vesicles, and the AB-laden HA hydrogel appears to be a clinically feasible and cell-free alternative for endometrial regeneration and IUA treatment.

Summary: Here we describe a protocol for wristwatch PCR, an approach based on wristwatch-like structure formed between walking primers to obtain unknown flanks. We specify the criteria for designing wristwatch primers and gene-specific primers. We detail how to set wristwatch primer permutations to obtain personalized walking outcomes and improve walking efficiency. We describe experimental procedures for isolating a DNA of interest using three rounds of nested wristwatch PCR as well as the subsequent steps for DNA purification, cloning, and sequencing.For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Esophageal squamous cell carcinoma (ESCC) is a common subtype of esophageal cancer with high incidence. Surgery remains the main strategy for treatment of ESCC at early stage. However, the treatment outcome is unsatisfactory. Therefore, finding new therapeutics is of great importance. In the present study, we measured the level of NEDD4L, an ubiquitin protein ligase, in clinical samples and investigated the effects of NEDD4L on cell viability, cell cycle progression, and glutamine metabolism in TE14 cells determined by CCK-8 assay, flow cytometry and biochemical analysis, respectively. The results show that NEDD4L is significantly decreased in ESCC specimens, and its decreased expression is associated with a poor clinical outcome. Overexpression of NEDD4L significantly inhibits cell viability, cell cycle progression, and glutamine metabolism in TE14 cells. Mechanistic study indicates that NEDD4L regulates tumor progression through ubiquitination of c-Myc and modulation of glutamine metabolism. NEDD4L inhibits cell viability, cell cycle progression, and glutamine metabolism in ESCC by ubiquitination of c-Myc to decrease the expressions of GLS1 and SLC1A5. Our findings highlight the importance of NEDD4L/c-Myc signaling in ESCC.

China's convenience food industry is developing rapidly. In recent years, the development of new product standards for convenience food has been continuously strengthened. Besides the approved industry standards such as “convenience dishes”, there are a number of industry standards currently being approved for development plan, which will effectively guide and standardize the industry's high-quality and healthy development. But on the whole, the product standard in this field needs to be revised and the product standard system needs to be further improved. By analyzing and interpreting the current standards and the standard system and the main contents of the newly formulated standards, this paper sorts out the main problems in the formulation and implementation of the standards, and puts forward the direction and suggestions for the construction of the standard system and its future revision, to facilitate the food industry’s product research and development, production and supervision to provide a technical basis.

Abstract Background Previous studies reported that transnasal ileus tube was a new and useful method for rapid relief of small intestinal obstruction. However, no study reported the impacts of the transnasal ileus tube for Crohn’s disease combined with intestinal obstruction. We aimed to describe the strategy to the small intestine obstruction caused by Crohn’s disease on the basis of transnasal ileus tube insertion. Methods From November 2019 to November 2021, the data of 6 hospitalized patients with CD, diagnosed and conservatively treated in The Second Hospital of Nanjing, were not relived and retrospectively collected. After the insertion of transnasal ileus tube, demographic information, clinical features and treatment data were extracted from medical records. Results Six Crohn’s disease patients with intestinal obstruction were included. Half of them were male. The patients aged from 29 to 70 years. Five patients had chronic intestinal obstruction more than one year. Three patients had intestinal surgery history. One patient had colonic abdominal fistula and anastomotic fistula, when she took intermittent usage of sulfsalazine and steroid. On admission, all the patients had abdominal pain, distention and mass. Five patients had anemia, low albumin and cholinesterase. All CDAI scores were more than 400. Compared to 19 patients with incomplete intestinal obstruction improved by nasogastric decompression tube, 6 patients with intestinal obstruction catheter had significant difference in time for relieving abdominal pain and distension (p = 0.003), time for alleviating abnormal mass (p ≤ 0.01), drainage volume (p = 0.004), and preoperative CDAI score (p = 0.001). Compared with X-ray image before insertion, complete remission of obstruction of 5 patients were observed in intestinal cavity after insertion. After 1–2 months nutrition, all the patients had small intestine resection and ileostomy, half of them underwent colectomy and fistula repair, and 4 patients were performed enterolysis at the same time, the residual small intestine length ranging from 250 to 400 cm. 1 patient had permanent ileostomy;1 patient had abdominal infection after operation. The typical manifestations of acute and chronic inflammation, transmural inflammation, pseudopolyps and serous fiber hyperplasia could be seen in pathological findings of patients 1 to 5. All the patients continued enteral nutrition after surgery. Four patients were treated with infliximab or vedolizumab. Conclusion The current intestinal obstruction catheter which is used to treat patients with Crohn's combined obstruction can afford quick clinical remission, longer nutrition time, and suitable preoperative CDAI score for operation, which is worthy of wildly being used.

Male Infertility Oxidative System (MiOXSYS) has been proposed as a rapid and promising technology for the evaluation of sperm oxidative stress. In this case–control study, 134 men with normal sperm parameters (NSP) and 574 men with abnormal sperm parameters (ASP), according to the World Health Organization sperm assessment references values established in 2010, were enrolled. Conventional sperm parameters were evaluated in all patients. Sperm static oxido-reduction potential (sORP) was assessed using the MiOXSYS. Sperm DNA integrity was measured in 604 patients. To ensure that sperm concentration was not a confounding factor in the sORP index ratio, sperm and seminal fluid sORP from 57 randomly selected additional patients were also measured using the MiOXSYS. sORP index (mV/106 sperm/ mL) was higher in patients with ASP and seemed to correlate with conventional sperm parameters. Although receiver-operating characteristic analysis revealed that a sORP index cut-off of 0.79 could differentiate normal from ASP with 57.7% sensitivity and 73.1% specificity, these values are much lower than those found in the literature. These values also need to be higher to be applicable in a clinical setting. Furthermore, absolute sORP (mV) was not different in the presence or absence of spermatozoa. sORP index relationships with sperm parameters seem rather be due to sperm concentration, denominator of the sORP index ratio. The establishment of a reliable method using the absolute sORP value, independent of sperm concentration, needs to be addressed. Other oxidative stress biomarkers could be used to validate this method.

The tether deployment of a tethered satellite system involves the consideration of complex dynamic properties of the tether, such as large deformation, slack, and even rebound, and therefore, the dynamic modelling of the tether is necessary for performing a dynamic analysis of the system. For a variable-length tether element, the absolute nodal coordinate formulation (ANCF) in the framework of the arbitrary Lagrange-Euler (ALE) description was used to develop a precise dynamic model of a tethered satellite. The model considered the gravitational gradient force and Coriolis force in the orbital coordinate frame, and it was validated through numerical simulation. In the presence of dynamic constraints, a deployment velocity of the tether was obtained by an optimal procedure. In the simulation, rebound behavior of the tethered satellite system was observed when the ANCF-ALE model was employed. Notably, the rebound behavior cannot be predicted by the traditional dumbbell model. Furthermore, an improved optimal deployment velocity was developed. Simulation results indicated that the rebound phenomenon was eliminated, and smooth deployment as well as a stable state of the station-keeping process were achieved. Additionally, the swing amplitude in the station-keeping phase decreased when a deployment strategy based on the improved optimal deployment velocity was used.

With the increasing amount of space debris, it is necessary to develop space debris active cleaning technology. The space netted pocket system is a flexible mechanism system which can be used to capture a non-cooperative target flexibly due to the advantages of having a stable structure, strong adaptability and a large capture range. In this paper, the dynamics of the space netted pocket system capturing a non-cooperative target are investigated. The dynamics model of the space netted pocket system is established based on the absolute nodal coordinate formulation (ANCF). The mathematic model of the closing rope is modeled using an ANCF flexible cable dynamics model. Then, the contact collision force model is presented to describe the collision characteristics during the space netted pocket system capturing the target. Finally, the dynamic characteristics of the space netted pocket system capturing the non-cooperative target are analyzed and discussed for different capturing strategies. The simulation results indicate that the target is captured successfully and the target contacts and collides with the rope net in the capturing process, which is subjected to contact and collision forces.

With the occurrence of information leakage events of online ride-hailing, the information security of Internet of Vehicles has been highly valued by the society. Once the information of the Internet of Vehicles is exposed by the online ride-hailing platform or stolen by hackers, it will pose a fatal threat to the personal and property safety of users, and even cause a major information security accident to the whole society. Based on a post-quantum cryptography system, this paper proposes a practical privacy protection scheme for ride-hailing route information, which can present the complete statistical aggregation operation of the route and the frequency from the starting point to the destination without the visibility of the ride-hailing platform, and ensure the data privacy security of a single vehicle. Compared with representative multi-vehicle aggregation solutions, we not only guarantee message privacy, confidentiality, integrity, forward and backward security, anti-man in attack and anti-redial attack, but also achieve multi-dimensional aggregation, CCA security and anti-quantum attack. Through the analysis of the experiment, the cost of our scheme is reasonable. Therefore, the scheme is more practical in this scenario.

To solve the problem of space debris, a film capture pocket system is designed in this paper. The film capture pocket is more flexible and reliable, compared with the space rope net. The film capture pocket system contains many flexible structures that are prone to large deformation and vibration during movement. The deformation causes large disturbances to the service spacecraft. It is necessary to establish an accurate rigid-flexible coupling dynamic model for quantitative analysis of disturbances. First, a film dynamic model is developed using high-order absolute nodal coordinate formulation. Second, an attitude tracking control law is designed by using the fast nonsingular terminal sliding mode controller and fixed time dilation observer (FxESO). Finally, combining dynamics and control principles, a virtual prototype of spacecraft with film capture pocket system is established. The simulation results show that higher-order absolute nodal coordinate formulation elements have better convergence, compared to ABAQUS finite element analysis. Meanwhile, the dynamic model simulates the deformation and vibration states of large flexible structures, during the spacecraft maneuver. The FxESO can estimate and compensate the complex disturbance. The error under fast nonsingular terminal sliding mode + FxESO control law converge more rapidly than the nonsingular terminal sliding mode + expansion observer control law. The final spacecraft attitude tracking error is about 10−4, indicating the effectiveness of the controller.

Tumor immune microenvironment plays an important role in tumorigenesis and metastasis. Polo-like kinases 4 (PLK4) is a crucial regulatory factor in the process of cell cycle, and its abnormal regulation often leads to a variety of diseases including tumorigenesis. We have previously explored the function of PLK4 in sensitizing chemotherapy in glioma, but there are few studies on the correlation between PLK4 and tumor immune microenvironment. PLK4 was found to be highly expressed in various types of cancers, including glioma and closely related to histological and genetic features in public databases. Kaplan-Meier survival analysis and Cox regression analysis revealed that higher PLK4 expression is associated with poorer prognosis. GO and KEGG functional enrichment analysis showed that PLK4 expression level was significantly correlated with regulation of immune microenvironment, cell cycle and genomic instability. Immune infiltration analysis showed that high expression of PLK4 resulted in reduced infiltration of macrophages. M1 macrophage infiltration assays showed that PLK4 knockdown GBM cell lines promoted the recruitment of M1-type macrophages via altering expression of chemokines. And in intracranial tumor mouse models, PLK4 inhibition increased tumor-infiltrating M1 macrophages. In summary, our results demonstrated the correlation between high PLK4 expression level and malignant progression of gliomas, and the possible involvement of PLK4 in regulation of cell cycle, cell proliferation and macrophages infiltration in gliomas.