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Abstract Sepsis and hypertension pose significant health risks, yet the optimal mean arterial pressure (MAP) target for resuscitation remains uncertain. This study investigates the association between average MAP (a-MAP) within the initial 24 h of intensive care unit admission and clinical outcomes in patients with sepsis and primary hypertension using the Medical Information Mart for Intensive Care (MIMIC) IV database. Multivariable Cox regression assessed the association between a-MAP and 30-day mortality. Kaplan–Meier and log-rank analyses constructed survival curves, while restricted cubic splines (RCS) illustrated the nonlinear relationship between a-MAP and 30-day mortality. Subgroup analyses ensured robustness. The study involved 8,810 patients. Adjusted hazard ratios for 30-day mortality in the T1 group (

Background and aim: Muscular atrophy is one of the most common age-related conditions characterized by the deterioration of skeletal muscle structures and impaired functions. It is associated with cellular senescence and chronic inflammation, which impair the function of muscle stem cells. Bazi Bushen (BZBS) is a patent compound Chinese medicine that has been shown to have anti-aging effects in various animal models. In this study, we investigated the effects and mechanisms of BZBS on muscular atrophy in naturally aged mice. Experimental procedure: A muscular atrophy model of naturally aged mice (18 months) was employed with administration of BZBS (2 g/kg/d, 1 g/kg/d) and nicotinamide mononucleotide (NMN, 200 mg/kg/d). After six months of drug administration, muscle weight loss, muscle function and muscle histopathology were measured to evaluate the therapeutic effect of BZBS. The expression of cellular senescence, inflammatory and satellite cell-related factors were used to assess the effects of BZBS in inhibiting cellular senescence, reducing inflammation and improving muscle atrophy. Results and conclusion: Compared with age matched natural aging mice, we found that BZBS improved muscle strength, mass, and morphology by reducing senescent cells, inflammatory cytokines, and intermyofiber fibrosis in aged muscle tissues. We also found that BZBS prevented the reduction of Pax7 positive stem cells and stimulated the activation and differentiation into myocytes. Our results suggest that BZBS might be a promising intervention in senile muscular atrophy.

Abstract Purpose Delirium has a significant impact on millions of people globally and is closely linked to an unfavorable prognosis for complications. Observational studies suggest that plasma metabolites may play significant roles as markers and effectors of delirium, but causal relationships have not yet been elucidated. Based on the most recent genome-wide association study (GWAS) data, our study aims to present novel insights into the genetic relationship between delirium and plasma metabolites. This investigation offers potential clues for utilizing plasma metabolites as predictors of delirium development. Methods We performed a thorough Mendelian randomization (MR) analysis to investigate the causal relationship between 1,091 individual metabolites and 309 metabolite ratios in plasma with respect to delirium. Inverse-variance weighting (IVW) was employed as the primary estimation method, while MR-Egger and weighed median methods were utilized to assess the robustness of the results. Sensitivity analyses encompassing the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test, Cochran Q test, leave-one-out analysis and MR Egger intercept analysis were also undertaken. Additionally, the MR Steiger test was performed to explore any potential reverse causal effect of metabolites on delirium. Results A total of 63 types of plasma metabolites associated with delirium were detected using the IVW method (p < 0.05). Among the known metabolites, our analysis revealed that two specific metabolites (1-palmitoyl-2-palmitoleoyl-gpc (16:0/16:1) and homovanillate) and a metabolite ratio (phosphate to oleoyl-linoleoyl-glycerol (18:1 to 18:2)) demonstrated a consistent and significant causal relationship with delirium across all analysis methods. Finally, no evidence of pleiotropy was detected in our analysis. Conclusions Our study has revealed a causal association between blood metabolites and the risk of delirium. homovanillate is known to be associated with immunity and redox, 1-palmitoyl-2-palmitoleoyl-gpc (16:0/16:1) and metabolite ratio (phosphate to oleoyl-linoleoyl-glycerol (18:1 to 18:2)) may play a role in lipid regulation. These findings may provide fresh insights into the identification of suitable diagnostic markers and potential treatment strategies focused on specific plasma metabolites in patients with delirium. However, further experiments are required to gain a comprehensive understanding of the underlying biological mechanisms involved.

Abstract Despite the importance of spliceosome core components in cellular processes, their roles in cancer development, including hepatocellular carcinoma (HCC), remain poorly understood. In this study, we uncover a critical role for SmD2, a core component of the spliceosome machinery, in modulating DNA damage in HCC through its impact on BRCA1/FANC cassette exons and expression. Our findings reveal that SmD2 depletion sensitizes HCC cells to PARP inhibitors, expanding the potential therapeutic targets. We also demonstrate that SmD2 acetylation by p300 leads to its degradation, while HDAC2-mediated deacetylation stabilizes SmD2. Importantly, we show that the combination of Romidepsin and Olaparib exhibits significant therapeutic potential in multiple HCC models, highlighting the promise of targeting SmD2 acetylation and HDAC2 inhibition alongside PARP inhibitors for HCC treatment.

Agricultural non-point source pollution threatens the quality of the ecological environment, human health, and safety. This study took the Sixth Drainage Ditch of the Yellow River Irrigation Area in Ningxia as the research area, set up a runoff water quality monitoring network, and comprehensively constructed an agricultural non-point source pollution monitoring model by combining the “source-sink” landscape theory, high-resolution remote sensing technology, and soil and water assessment tool (SWAT). The results showed that the simulation results of the flow and total nitrogen met the accuracy requirements. The R2 values of total nitrogen in the calibration and validation periods were both > 0.8, and Ens was > 0.9. The regional applicability of the model was good. Based on the simulation results, the following conclusions were drawn. (1) The temporal distribution of the pollution load was concentrated in May–October, with peaks in June and August, which is consistent with the irrigation period. (2) Spatially, the pollution load was mainly distributed in sub-basins 1 and 5. The area is dominated by cultivated land and has poor conditions that are prone to nitrogen and phosphorus loss. (3) By quantitatively identifying pollution sources, the results showed that agricultural irrigation accounted for approximately 92.88 % of total pollutants. Compared with traditional methods, the monitoring method proposed in this study systematically evaluates the potential for non-point source pollution in the region and builds a relatively complete real-time monitoring network, improving data quality and model reliability. In addition, the relationship between river network density and catchment area threshold was used to optimize the catchment area threshold in the SWAT model, and non-point source pollution parameters suitable for the basin were obtained, providing a data basis and theoretical support for the large-scale application of the model.

Abstract Background Dissolved organic matter (DOM) is the most active component of soil organic matter (SOM), playing a major role in regulating soil fertility and carbon cycling. However, the effects of different wolfberry (Lycium barbarum L.) planting ages on the chemical diversity of DOM and its interaction with soil physicochemical properties have not been comprehensively studied. In this context, we collected soil samples (0–10 cm) from wolfberry orchards at different planting ages (1, 4, 6, 10, and 13 years) and from a corn field (0 years) in the arid region of Northwest Ningxia in China to assess the changes in soil DOM quantity and quality using ultraviolet–visible absorbance, fluorescence spectroscopy, and parallel factor analysis. Results We found that the ages of the wolfberry plantation changed the contents of soil nutrients and SOM. In addition, significantly higher DOM concentrations were observed at wolfberry planting ages of 10 and 13 years than those in the control group (0 years) by 176.6 and 190.2%, respectively. The specific ultraviolet absorbance at 254 nm (SUVA254) and 254 nm to 365 nm ultraviolet absorbance ratio (E2/E3) values were decreased and increased, respectively, after wolfberry planting, indicating low aromatic and molecular weight compounds of soil DOM. The biogenic index (BIX) and fluorescence index (FI) of soil DOM ranged from 0.6 to 0.7 and 1.42 to 1.93, respectively, suggesting a combination of allochthonous and autochthonous sources. The short- and long-term wolfberry cultivations of 1 and 4 years decreased and increased the humification degrees of soil DOM, respectively. The contribution rate of the protein-like (C1) fluorescence intensity decreased, while that of the fulvic acid-like component (C3) increased with increasing wolfberry planting age, suggesting a change in the structure of soil DOM from protein-like to fulvic acids. In this study, total nitrogen (TN) and exchangeable Ca2+ were the main factors affecting the quantity and quality of soil DOM in the wolfberry orchards with different planting ages. Conclusions This study demonstrated that long-term wolfberry plantation enhances the accumulation of soil DOM and more complex compounds, thereby promoting soil organic carbon sequestration under different planting ages and land-use types in terrestrial ecosystems. Graphical Abstract

Abstract Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with a highly immunosuppressive tumor microenvironment and a typical pattern of disturbances in hepatic lipid metabolism. Long non‐coding RNAs are shown to play an important role in the regulation of gene expression, but much remains unknown between tumor microenvironment and lipid metabolism as a bridging molecule. Here, long intergenic nonprotein coding RNA 01116 (LINC01116) acts as this molecular which is frequently upregulated in HCC patients and associated with HCC progression in vitro and in vivo is identified. Mechanistically, LINC01116 stabilizes EWS RNA‐binding protein 1 (EWSR1) by preventing RAD18 E3 Ubiquitin Protein Ligase (RAD18) ‐mediated ubiquitination. The enhanced EWSR1 protein upregulates peroxisome proliferator activated receptor alpha (PPARA) and fatty acid binding protein1 (FABP1) expression, a long‐chain fatty acid (LCFA) transporter, and thus cancer cells outcompete T cells for LCFAs, especially linoleic acid, for seeding their own growth, leading to T cell malfunction and HCC malignant progression. In a preclinical animal model, the blockade of LINC01116 leads to enhanced efficacy of anti‐PD1 treatment accompanied by increased cytotoxic T cell and decreased exhausted T cell infiltration. Collectively, LINC01116 is an immunometabolic lncRNA and the LINC01116‐EWSR1‐PPARA‐FABP1 axis may be targetable for cancer immunotherapy.

Reducing methane emissions in the oil and gas industry is a top priority for the current international community in addressing climate change. Methane emissions from the energy sector exhibit strong temporal variability and ground monitoring networks can provide time-continuous measurements of methane concentrations, enabling the rapid detection of sudden methane leaks in the oil and gas industry. Therefore, identifying specific locations within oil fields to establish a cost-effective and reliable methane monitoring ground network is an urgent and significant task. In response to this challenge, this study proposes a technical workflow that, utilizing emission inventories, atmospheric transport models, and intelligent computing techniques, automatically determines the optimal locations for monitoring stations based on the input quantity of monitoring sites. This methodology can automatically and quantitatively assess the observational effectiveness of the monitoring network. The effectiveness of the proposed technical workflow is demonstrated using the Shengli Oilfield, the second-largest oil and gas extraction base in China, as a case study. We found that the Genetic Algorithm can help find the optimum locations effectively. Besides, the overall observation effectiveness grew from 1.7 to 5.6 when the number of site increased from 1 to 9. However, the growth decreased with the increasing site number. Such a technology can assist the oil and gas industry in better monitoring methane emissions resulting from oil and gas extraction.

In the field of image segmentation, there are still some technical problems, such as the segmentation accuracy of the image with intensity inhomogeneity is not high enough. Level set method has the advantages of solid theoretical foundation and stable algorithm for segmentation of small sample data, so far it has played a significant role in image segmentation. In this paper, with the level set method for the research framework, we present a new approach to segment noise and weak boundary images that is supported by an adaptive velocity correction function. Based on the properties analysis of noise and edge information, this correction function is replaced the original constant to largely improve the segmentation accuracy. In addition, on the basis of some theoretical analysis, we use the edge stop function constructed by entropy to effectively improve the accuracy of image segmentation. Finally, a large number of challenging image experiments show that the proposed segmentation model performs better than other classical models in segmentation accuracy.

Ageing is becoming an increasingly serious problem; therefore, there is an urgent need to find safe and effective anti-ageing drugs. Aims: To investigate the effects of Bazi Bushen capsule (BZBS) on the senescence of mesenchymal stem cells (MSCs) and explore its mechanism of action. Methods: Network pharmacology was used to predict the targets of BZBS in delaying senescence in MSCs. For in vitro studies, MSCs were treated with D-gal, BZBS, and NMN, and cell viability, cell senescence, stemness-related genes, and cell cycle were studied using cell counting kit-8 (CCK-8) assay, SA-β-galactosidase (SA-β-gal) staining, Quantitative Real-Time PCR (qPCR) and flow cytometry (FCM), respectively. Alkaline phosphatase (ALP), alizarin red, and oil red staining were used to determine the osteogenic and lipid differentiation abilities of MSCs. Finally, the expression of senescence-related genes and cyclin-related factors was detected by qPCR and western blotting. Results: Network pharmacological analysis suggested that BZBS delayed cell senescence by interfering in the cell cycle. Our in vitro studies suggested that BZBS could significantly increase cell viability (P

This research aimed to construct an emulsifier by the Maillard reaction at various times using cod fish skin collagen peptide (CSCP) and ι-carrageenan (ι-car) to stabilize an Antarctic krill oil (AKO) emulsion. This emulsion was then investigated for physicochemical stability, oxidative stability, and gastrointestinal digestibility. The emulsion stability index and emulsifying activity index of Maillard reaction products (MRPs) were increased by 36.32 % and 66.30 %, respectively, at the appropriate graft degree (25.58 %) compared with the mixture of ι-car and CSCP. In vitro digestibility suggested the higher release of free fatty acids (FFAs) of 10d-MRPs-AKO-emulsion, and the highest bioavailability of AST in 10d-MRPs-AKO was found to be 28.48 %. The findings of this study showed the potential of MRPs to improve peptide function, serve as delivery vehicles for bioactive chemicals, and possibly serve as a valuable emulsifier to be used in the food industry.

Based on the dynamic shock response of the material and structure, the hypervelocity impact processes and mechanisms of long composite rods with axial density/impedance gradients penetration into four-layer targets were studied through experiments and numerical simulation methods. The propagation law of the shock waves, together with the structural responses of the projectiles and targets, the formation and evolution of the fragment groups formed during the processes and their distributions were described. The damage of each target plate was quantitatively analysed by comparing the results of the experiment and numerical simulation. The results showed that the axial density/impedance gradient projectiles could decrease the impact pressure to a certain extent, and the degree of damage to the target plate decreased layer by layer when the head density/impedance of the projectile was high. When the head density/impedance of the projectile was low, the degree of target damage first increased layer by layer until the projectile was completely eroded and then it decreased. The results can provide a reference for the design and application of long rods with axial composite structure for velocities ranging from 6 to 10 Ma or greater.

It has always been a common demand to stay away from the harsh environment with narrow space, numerous devices, complex operation process, and hidden hazards, and realize intelligent unmanned mining in the coal industry. To achieve this goal, it is very necessary for us to develop an effective theory of vision computing for underground coalmine applications. Its main task is to build effective models or frameworks for perceiving, describing, recognizing and understanding the environment of underground coalmine, and let intelligent equipment get 3D environment information in coalmine from images or videos. To effectively develop this theory and make it better for intelligent development of coalmine, this paper first analyzed the similarities and differences about computer vision and visual computing in coalmine, and proposed its composition architecture. And then, this paper introduced in detail the key technologies involved in visual computing in coalmine including visual perception and light field computing, feature extraction and feature description, semantic learning and vision understanding, 3D vision reconstruction, and sense computing integration and edge intelligence, which is followed by typical application cases of visual computing in coalmines. Finally, the development trend and prospect of underground visual computing in coalmine was given. In this section, this paper focused on concluding the key challenges and introducing two valuable applications including coalmine Augmented Reality/Mixed Reality and parallel intelligent mining. With the breakthrough of underground vision computing, it will play a more and more important role in the intelligent development of coal mines.

Objective The thickened coracohumeral ligament (CHL) is an important part of the typical manifestations and magnetic resonance imaging of frozen shoulder. However, only a few clinical studies with limited cases on arthroscopic extra‐articular entire CHL release exist in the literature. This study was to evaluate the effect of arthroscopic extra‐articular entire CHL release for patients with recalcitrant frozen shoulder. Methods From February 2014 to February 2020, 81 cases of recalcitrant frozen shoulder patients treated with surgery in a single‐center shoulder department and followed for more than 2 years were analyzed. Arthroscopic 360° capsular release was performed with intra‐articular partial release (IPR group) or additional extra‐articular entire release (IPR + EER group) of CHL. The same rehabilitation program was performed after surgery in both groups. Visual analogue scale (VAS) for pain, range of motion (ROM), and the Constant–Murley scoring system was evaluated before operation, at 3 months after operation, 6 months after operation, and the final follow‐up. T‐test, Mann–Whitney U‐test and chi‐squared test were used to compared data. Results There were 39 patients in the IPR group, with an average follow‐up of 29.2 months. A total of Forty‐two patients in the IPR + EER group completed a mean follow‐up of 25.7 months. All incisions healed in stages. There were significant differences in Constant–Murley shoulder score, VAS score, and ROM before operation and at the final follow‐up in both groups (both P

Abstract The effects of velocity and gas type on foam flow through porous media have yet to be completely elucidated. Pressure drop and capillary pressure measurements were made at ambient conditions during a series of foam quality scan experiments in a homogenous sandpack while foam texture was simultaneously visualized. New insights into foam-flow behavior in porous media were discovered. Previously accepted “limiting” capillary pressure theory is challenged by the findings in this work, and the “limiting” terminology is replaced with the word “plateau” to reflect these novel observations. Plateau capillary pressure $${(P}_{c})$$ ( P c ) and transition foam quality were found to increase with velocity. Transition foam quality was found to depend mostly on liquid velocity rather than gas velocity and is physically linked to foam type (continuous vs. discontinuous) and texture (fine vs. coarse). Distinct rheological behaviors also arose in the low- and high-quality foam regimes as a function of velocity. Foam flow was found to be strongly shear thinning in the low-quality regime where foam texture was fine and discontinuous. In the high-quality regime, the rheology was weakly shear thinning to Newtonian for coarsely textured foam and continuous-gas flow respectively. When all other variables were held constant, at ambient conditions, CO2 foam was found to be weaker with also lower capillary pressures than N2 foam and the differences in gas solubility is a likely explanation.

Energy storage technology is one of the effective means to promote the consumption of new energy. It has the advantages of improving the flexibility and stability of power grid. Energy storage plays an important role in improving the peaking and valley filling function of the load side of the power grid. Based on the two-stage topology of the energy storage system, this paper establishes the mirror model of the practical application engineering of the energy storage system, and uses the data-driven method to establish the energy storage battery model. On this basis, the multi-objective control strategy is adopted for the peak regulating power of the energy storage system and the load state balance of the battery. The support vector machine algorithm is used to predict the daily load data of the power grid, and the constant power algorithm is proposed to control the battery control node signal. Finally, taking the battery compartment of the energy storage system as the simulation object, the effectiveness of the proposed control strategy is verified, which provides a theoretical basis for the topic research.

Abstract Differential composition analysis — the identification of cell types that have statistically significant changes in abundance between multiple experimental conditions — is one of the most common tasks in single cell omic data analysis. However, it remains challenging to perform differential composition analysis in the presence of flexible experimental designs and uncertainty in cell type assignment. Here, we introduce a statistical model and an open source R package, DCATS, for differential composition analysis based on a beta-binomial regression framework that addresses these challenges. Our empirical evaluation shows that DCATS consistently maintains high sensitivity and specificity compared to state-of-the-art methods.

PurposeThe senescence-accelerated prone mouse 8 (SAMP8) is a widely used model for accelerating aging, especially in central aging. Mounting evidence indicates that the microbiota-gut-brain axis may be involved in the pathogenesis and progression of central aging-related diseases. This study aims to investigate whether Bazi Bushen capsule (BZBS) attenuates the deterioration of the intestinal function in the central aging animal model.MethodsIn our study, the SAMP8 mice were randomly divided into the model group, the BZ-low group (0.5 g/kg/d BZBS), the BZ-high group (1 g/kg/d BZBS) and the RAPA group (2 mg/kg/d rapamycin). Age-matched SAMR1 mice were used as the control group. Next, cognitive function was detected through Nissl staining and two-photon microscopy. The gut microbiota composition of fecal samples was analyzed by 16S rRNA gene sequencing. The Ileum tissue morphology was observed by hematoxylin and eosin staining, and the intestinal barrier function was observed by immunofluorescence. The expression of senescence-associated secretory phenotype (SASP) factors, including P53, TNF-α, NF-κB, IL-4, IL-6, and IL-10 was measured by real-time quantitative PCR. Macrophage infiltration and the proliferation and differentiation of intestinal cells were assessed by immunohistochemistry. We also detected the inflammasome and pyroptosis levels in ileum tissue by western blotting.ResultsBZBS improved the cognitive function and neuronal density of SAMP8 mice. BZBS also restored the intestinal villus structure and barrier function, which were damaged in SAMP8 mice. BZBS reduced the expression of SASP factors and the infiltration of macrophages in the ileum tissues, indicating a lower level of inflammation. BZBS enhanced the proliferation and differentiation of intestinal cells, which are essential for maintaining intestinal homeostasis. BZBS modulated the gut microbiota composition, by which BZBS inhibited the activation of inflammasomes and pyroptosis in the intestine.ConclusionBZBS could restore the dysbiosis of the gut microbiota and prevent the deterioration of intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis. These results suggested that BZBS attenuated the cognitive aging of SAMP8 mice, at least partially, by targeting the microbiota-gut-brain axis.

This paper presents an in-depth analysis of the oscillation phenomenon occurring in multi-chip parallel automotive-grade power modules under short-circuit conditions and investigates three suppression methods. We tested and analyzed two commercial automotive-grade power modules, one containing two chips and the other containing a single chip, and found that short-circuit gate oscillations were more likely to occur in multi-chip parallel packaged modules than in single-chip packaged modules. Through experimental and simulation analyses, we observed that gate oscillations were mainly caused by the interaction between internal parasitic parameters of the module and the external drive circuit, and we found that high drive resistance and low common emitter inductance between parallel chips could effectively suppress gate voltage oscillations. We also analyzed the two mainstream suppression schemes, increasing the drive gate resistance and placing the drive capacitors in parallel. Unfortunately, we found that these suppression schemes were not ideal solutions because both schemes changed the switching characteristics of the power module. As an alternative, we propose a simple and effective solution that involves adding parallel connections between the parallel chips. Simulation calculations showed that this optimized method reduced the emitter inductance between parallel chips in the upper bridge arm by about 30% and in the lower bridge arm by 35%. Through short-circuit experiments conducted at different DC bus voltages, it has been verified that the new optimized solution effectively resolves gate oscillation issues without affecting the switching characteristics of the power module.

Chronic heart failure (CHF) is a key part of cardiovascular continuum. Under the guidance of the theory of vessel-collateral doctrine, the present study proposes therapeutic benefits of Qili Qiangxin (QLQX) capsules, an innovative Chinese medicine, on chronic heart failure. The studies show that multiple targets of the drug on CHF, including enhancing myocardial systole, promoting urine excretion, inhibiting excessive activation of the neuroendocrine system, preventing ventricular remodeling by inhibiting inflammatory response, myocardial fibrosis, apoptosis and autophagy, enhancing myocardial energy metabolism, promoting angiogenesis, and improving endothelial function. Investigation on the effects and mechanism of the drug is beneficial to the treatment of chronic heart failure (CHF) through multiple targets and/or signaling pathways. Meanwhile, it provides new insights to further understand other refractory diseases in the cardiovascular continuum, and it also has an important theoretical and practical significance in enhancing prevention and therapeutic effect of traditional Chinese medicine for these diseases.

Modern megacities offer convenient lifestyles to their citizens. However, agriculture is becoming increasingly vulnerable, especially during unexpected public health emergencies such as pandemics. Fortunately, the adaptability of terrace vegetables cultivation presents an opportunity to grow horticultural crops in residential spaces, bringing numerous benefits to citizens, including enhanced nutrition and recreational engagement in the cultivation process. Although certain planting skills and equipment have been developed, the citizens tend to sow some seeds with unknown pedigree, it is rare to find new plant varieties specifically bred for cultivation as terrace vegetables. To expand the genetic basis of new breeding materials, elite parents, and varieties (pre-breeding) for terrace cultivation, this review not only discusses the molecular breeding strategy for the identification, creation, and application of rational alleles for improving horticultural characteristics including plant architecture, flavor quality, and ornamental character, but also assesses the potential for terrace cultivation of some representative vegetable crops. We conclude that the process of pre-breeding specifically for terrace cultivation environments is vital for generating a genetic basis for urban terrace vegetable crops.

Molybdenum tailings, as one of the solid wastes which are produced by the exploitation of molybdenum mineral resources in the world, can not only solve the environmental pollution, but also make up for the shortage of natural sand resources by replacing concrete fine aggregate or cement with molybdenum tailings. It is one of the most economically and environmentally friendly resource utilization method of molybdenum tailings, due to it can able to meet the strategic requirements of green and sustainable development. In this paper, the research progress of application of molybdenum tailings in concrete is summarized. Firstly, the physical and chemical properties of molybdenum tailings are analyzed, and secondly, the working performance, mechanical performance and durability performance of molybdenum tailings concrete are discussed, finally the main problems existing in application of molybdenum tailings in concrete are suggested. This work is expected to be useful for the wide application of molybdenum tailings in concrete.

Cloud computing system has the characteristics of large-scale servers and a wide range of users.However, it also consumes a huge number of energy, resulting in high operating costs of cloud providers and high carbon emissions issue.Cloud computing is highly virtualized.How to allocate and manage the virtual resources to ensure efficient physical resource utilization and energy consumption control is a multi-parameter game problem, and it is also a research hotspot in this field.A virtual machine scheduling model and the corresponding SV-GA were proposed, which could calculate the contribution value of the physical machine participating in the work through the Shapley value, and modify the probability parameter of the mutation step in the genetic algorithm through the contribution value, so as to complete the task of virtual machine scheduling.The experimental results show that during the comparison with Max-Min, LrMmt and DE, the SV-GA shows its excellent performance in the multi-parameter game including migration time, times, SLA violation rate and energy consumption in the virtual machine scheduling process.

Cell type epigenetic and topographic information of primate brain is lacking. Here, authors identified transcriptional regulatory network, gradient expression pattern and disease vulnerability at cell type level in PFC, M1 and V1 of monkey brain by snRNAseq, snATAC-seq and Stereo-seq.

Abstract Growing evidence indicates that testosterone is a conspicuous marker for assessing male bone mineral density (BMD). However, research regarding testosterone levels and BMD is sparse and controversial for females. Hence, we aimed to investigate the association between testosterone levels and BMD among adult females aged 40–60 years in the United States. In this cross-sectional study, all participants were part of the National Health and Nutrition Examination Survey (2011–2016). A weighted general linear model was used to estimate the association between testosterone levels and lumbar BMD. Age, race, income level, education level, body mass index (BMI), blood urea nitrogen (BUN) level, serum uric acid (UA) level, serum calcium (Ca) level, serum phosphorus (P) level, the use of oral contraceptive pills, the use of hormone replacement therapy (HRT), smoking status, drinking status, and the use of corticosteroids were adjusted using a weighted multiple regression model. Subgroup analyses were performed using the same regression model. We included 2198 female participants in the study, and testosterone levels were positively associated with lumbar BMD after adjusting for all the covariates (β = 1.12, 95% CI 0.31, 1.93). In subgroup analyses, the associations in the fourth quartile of testosterone levels were stronger for the participants aged 40–50 years old (quartile 4, β = 42.92, 95% CI 7.53, 78.30 vs. quartile 1) and 50 to 60-year-old (quartile 4, β = 32.41, 95% CI 0.14, 64.69 vs. quartile 1). Similar results were found in other subgroups, including subgroups for race (Non-Hispanic Black, Other), income level (income ≤ 1.3, income > 3.5), education level (college or higher), BMI > 25 kg/m2, BUN levels ≤ 20 mg/dL, UA levels ≤ 6 mg/dL, Ca levels ≤ 10.1 mg/dL, P levels ≤ 5 mg/dL, drinking status, never smoker, never taking birth control pills, and HRT user. There was no interaction among the covariates in the association between lumbar BMD and testosterone levels (P for interaction > 0.05). In US adult females aged 40–60 years, the testosterone level was a positive predictor of the lumbar BMD after adjusting for covariates.

ABSTRACT Senecavirus A (SVA) is a type of nonenveloped single-stranded, positive-sense RNA virus. The VP2 protein is a structural protein that plays an important role in inducing early and late immune responses of the host. However, its antigenic epitopes have not been fully elucidated. Therefore, defining the B epitopes of the VP2 protein is of great importance to revealing its antigenic characterization. In this study, we analyzed B-cell immunodominant epitopes (IDEs) of the VP2 protein from the SVA strain CH/FJ/2017 using the Pepscan approach and a bioinformatics-based computational prediction method. The following four novel IDEs of VP2 were identified: IDE1, 41TKSDPPSSSTDQPTTT56; IDE2, 145PDGKAKSLQELNEEQW160; IDE3, 161VEMSDDYRTGKNMPF175; and IDE4, 267PYFNGLRNRFTTGT280. Most of the IDEs were highly conserved among the different strains. To our knowledge, the VP2 protein is a major protective antigen of SVA that can induce neutralizing antibodies in animals. Here, we analyzed the immunogenicity and neutralization activity of four IDEs of VP2. Consequently, all four IDEs showed good immunogenicity that could elicit specific antibodies in guinea pigs. A neutralization test in vitro showed that the peptide-specific guinea pig antisera of IDE2 could neutralize SVA strain CH/FJ/2017, and IDE2 was identified as a novel potential neutralizing linear epitope. This is the first time VP2 IDEs have been identified by using the Pepscan method and a bioinformatics-based computational prediction method. These results will help elucidate the antigenic epitopes of VP2 and clarify the basis for immune responses against SVA. IMPORTANCE The clinical symptoms and lesions caused by SVA are indistinguishable from those of other vesicular diseases in pigs. SVA has been associated with recent outbreaks of vesicular disease and epidemic transient neonatal losses in several swine-producing countries. Due to the continuing spread of SVA and the lack of commercial vaccines, the development of improved control strategies is urgently needed. The VP2 protein is a crucial antigen on the capsids of SVA particles. Furthermore, the latest research showed that VP2 could be a promising candidate for the development of novel vaccines and diagnostic tools. Hence, a detailed exploration of epitopes in the VP2 protein is necessary. In this study, four novel B-cell IDEs were identified using two different antisera with two different methods. IDE2 was identified as a new neutralizing linear epitope. Our findings will help in the rational design of epitope vaccines and further understanding of the antigenic structure of VP2.

Abstract Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Donafenib is a multi‐receptor tyrosine kinase inhibitor approved for the treatment of patients with advanced HCC, but its clinical effect is very limited. Here, through integrated screening of a small‐molecule inhibitor library and a druggable CRISPR library, that GSK‐J4 is synthetically lethal with donafenib in liver cancer is shown. This synergistic lethality is validated in multiple HCC models, including xenograft, orthotopically induced HCC, patient‐derived xenograft, and organoid models. Furthermore, co‐treatment with donafenib and GSK‐J4 resulted in cell death mainly via ferroptosis. Mechanistically, through integrated RNA sequencing (RNA‐seq) and assay for transposase‐accessible chromatin with high throughput sequencing (ATAC‐seq) analyses, that donafenib and GSK‐J4 synergistically promoted the expression of HMOX1 and increased the intracellular Fe2+ level is found, eventually leading to ferroptosis. Additionally, through cleavage under targets & tagmentation followed by sequencing (CUT&Tag‐seq), it is found that the enhancer regions upstream of HMOX1 promoter significantly increased under donafenib and GSK‐J4 co‐treatment. A chromosome conformation capture assay confirmed that the increased expression of HMOX1 is caused by the significantly enhanced interaction between the promoter and upstream enhancer under dual‐drug combination. Taken together, this study elucidates a new synergistic lethal interaction in liver cancer.

The research and development of new building materials such as phosphorous building gypsum is crucial to promote the utilisation of phosphogypsum resources by improving their value. This study developed a new type of shape-stabilised energy storage phosphorus building gypsum aggregate (ES-PBGA). The mechanical and thermal properties of ES-PBGA with Paraffin were investigated. The results indicate that the matrix of ES-PBGA had a good microstructure, and the optimal paraffin-embedding rate of ES-PBGA was 31.08%. The phase transition temperature and enthalpy of the endothermic and exothermic stages were 17.6 and 27.14 ℃, and 33.02 and 31.62 J/g, respectively. The cylinder pressure strength of ES-PBGA with paraffin (31.08%) was 4.32 MPa, which meets the requirements of artificial aggregate application. To verify the practicability of ES-PBGA, energy storage lightweight aggregate concrete was prepared with 0%, 25%, 50%, and 100% ES-PBGA to replace the lightweight shale ceramsite. The results show that ES-PBGA can improve the interface transition zone between cement-based materials and energy storage aggregates, thereby improving the strength, and has a relatively suitable thermal conductivity, thermal diffusion coefficient, and specific heat capacity. Furthermore, it is also a type of low-carbon energy storage aggregate, and its application in the field of energy storage composite building materials is a relatively new concept.

Superpixel segmentation has been widely used in the field of computer vision. The generations of PolSAR superpixels have also been widely studied for their feasibility and high efficiency. The initial numbers of PolSAR superpixels are usually designed manually by experience, which has a significant impact on the final performance of superpixel segmentation and the subsequent interpretation tasks. Additionally, the effective information of PolSAR superpixels is not fully analyzed and utilized in the generation process. Regarding these issues, a multiobjective evolutionary superpixel segmentation for PolSAR image classification is proposed in this study. It contains two layers, an automatic optimization layer and a fine segmentation layer. Fully considering the similarity information within the superpixels and the difference information among the superpixels simultaneously, the automatic optimization layer can determine the suitable number of superpixels automatically by the multiobjective optimization for PolSAR superpixel segmentation. Considering the difficulty of the search for accurate boundaries of complex ground objects in PolSAR images, the fine segmentation layer can further improve the qualities of superpixels by fully using the boundary information of good-quality superpixels in the evolution process for generating PolSAR superpixels. The experiments on different PolSAR image datasets validate that the proposed approach can automatically generate high-quality superpixels without any prior information.

With the active development of coal-related industries in Ningdong, problems such as land degradation caused by coal-based site expansion and soil pollution caused by coal-based solid waste discharge are getting progressively worse. The identification of space types and the proposal of risk management are the key basic issues of regional energy resource low-carbon development and ecological protection. This article proposes an index system for feature extraction at the regional and site scales. The spatial–temporal evolution trends and differences in Ningdong coal power base from 2003 to 2021 were identified and interpreted through feature recognition based on Landsat images at the regional scale. Accurate site type recognition was conducted based on 10 m resolution Sentinel-2 images from 2021. We utilized the PSR (pressure–state–response) model for a comprehensive assessment of risk management in Ningdong. The results of this study show that the coal site > the coal chemical site > the coal power site, and the risk of the coal power base is in a controllable state; thus, we put forward a zoning control strategy. Our data on the pollution risk management of large-scale coal-fired power generation complexes are of significant importance for site remediation and regional ecological restoration.

Abstract The incidence of hepatocellular carcinoma (HCC) is increasing in the world. However, its role and underlying molecular mechanism in HCC progression remain unclear. We found that CYB5A plays a key role in HCC metastasis by inhibiting the JAK1/STAT3 pathway through binding to STOML2. CYB5A combined with STOML2 can predict the outcome of patients. To demonstrate the effect of CYB5A on JAK1 inhibitor function, we applied Ruxolitinib in metastatic tumors with high CYB5A expression and found that it slowed disease progression and prolonged survival in mice. To the best of our knowledge, this study is the first to report the Ruxolitinib effect on the metastatic ability of HCC cells in vivo and in vitro.

Abstract Background Anovulation is one of the main causes of female infertility. This study will evaluate the effectiveness and safety of Bushen Culuan Decoction for anovulatory infertility caused by six diseases, including anovulatory abnormal uterine bleeding, polycystic ovarian syndrome, hyperprolactinemia, luteinized unruptured follicle syndrome, corpus luteum insufficiency, and premature ovarian insufficiency. Methods This is a randomized, double-blinded, double-dummy, parallel, positively controlled, adaptive, multicenter clinical trial. All participants will be randomly allocated by a central randomization system to the treatment group or the control group in a 1:1 ratio. The treatment group will undergo a 14-day treatment with Bushen Culuan Decoction 13 g three times a day and a 5-day treatment with clomiphene citrate placebo tablets 50 mg once a day starting on day 5 of every menstrual period. The control group will undergo a 14-day treatment with Bushen Culuan Decoction placebo 13 g three times a day and a 5-day treatment with clomiphene citrate tablets 50 mg once a day from day 5 in every menstrual period. The whole treatment will last through 3 menstrual periods or 6 menstrual periods, depending on whether ovulation is regained in the first 3 menstrual periods. All statistical analyses will be performed in SPSS 21.0 (SPSS, Chicago, Illinois, USA), and a p value

Bazi Bushen (BZBS), a traditional Chinese medicine, has been proven effective in the treatment of age-related disease in mouse models. However, whether its therapeutic effects are due to antiaging mechanism has not yet been explored. In the present study, we investigated the antiaging effects of BZBS in naturally aging mice by using behavioral tests, liver DNA methylome sequencing, methylation age estimation, and frailty index assessment. The methylome analysis revealed a decrease of mCpG levels in the aged mouse liver. BZBS treatment tended to restore age-associated methylation decline and prune the methylation pattern toward that of young mice. More importantly, BZBS significantly rejuvenated methylation age of the aged mice, which was computed by an upgraded DNA methylation clock. These results were consistent with enhanced memory and muscular endurance, as well as decreased frailty score and liver pathological changes. KEGG analysis together with aging-related database screening identified methylation-targeted pathways upon BZBS treatment, including oxidative stress, DNA repair, MAPK signaling, and inflammation. Upregulation of key effectors and their downstream effects on elevating Sod2 expression and diminishing DNA damage were further investigated. Finally, in vitro experiments with senescent HUVECs proved a direct effect of BZBS extracts on the regulation of methylation enzymes during cellular aging. In summary, our work has revealed for the first time the antiaging effects of BZBS by slowing the methylation aging. These results suggest that BZBS might have great potential to extend healthspan and also explored the mechanism of BZBS action in the treatment of age-related diseases.

ObjectiveThis study was conducted to develop and validate a radiomics-clinics combined model-based magnetic resonance imaging (MRI) radiomics and clinical features for the early prediction of radiation-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC).MethodsThis retrospective study was conducted using data from 130 patients with NPC (80 patients with and 50 patients without RTLI) who received radiotherapy. Cases were assigned randomly to training (n = 91) and testing (n = 39) datasets. Data on 168 medial temporal lobe texture features were extracted from T1WI, T2WI, and T1WI-CE MRI sequences obtained at the end of radiotherapy courses. Clinics, radiomics, and radiomics–clinics combined models (based on selected radiomics signatures and clinical factors) were constructed using machine learning software. Univariate logistic regression analysis was performed to identify independent clinical factors. The area under the ROC curve (AUC) was performed to evaluate the performance of three models. A nomogram, decision curves, and calibration curves were used to assess the performance of the combined model.ResultsSix texture features and three independent clinical factors associated significantly with RTLI were used to build the combined model. The AUCs for the combined and radiomics models were 0.962 [95% confidence interval (CI), 0.9306–0.9939] and 0.904 (95% CI, 0.8431–0.9651), respectively, for the training cohort and 0.947 (95% CI, 0.8841–1.0000) and 0.891 (95% CI, 0.7903–0.9930), respectively, for the testing cohort. All of these values exceeded those for the clinics model (AUC = 0.809 and 0.713 for the training and testing cohorts, respectively). Decision curve analysis showed that the combined model had a good corrective effect.ConclusionThe radiomics–clinics combined model developed in this study showed good performance for predicting RTLI in patients with NPC.

Type III polyketide synthase (PKS III) superfamily members are involved in plant secondary metabolism, which is important for plant development and resistance to biological and abiotic stress. However, the functions of most PKS III superfamily members in rice (Oryza sativa L.) remain unknown. Here, we identified PKS III genes in rice and performed phylogenetic analysis. This divided the 28 rice PKS III superfamily genes into six subgroups, the chalcone synthase (CHS) group and the CHS-like groups CHSL I–V. These PKS III genes share significant genomic synteny. CHS, CHSL I, and II genes are present in single copies in the rice genome, whereas CHSL III–V are present in gene clusters. The chromosomal regions harboring PKS III genes contain numerous transposable elements, which might underlie the duplication and expansion of the PKS III superfamily. Heatmap analysis indicated that PKS III genes in the same subgroup have similar expression patterns. We knocked out two anther-specific genes (OsPKS1 and OsPKS2) from subgroup CHSL II in rice to investigate their roles in male reproduction. The double knockout mutant ospks1/2 exhibited severer defects in exine and no-pollen phenotype, which is different from the partially abortive-pollen phenotype of the ospks1 and ospks2 single mutants. OsPKS1 is upregulated in ospks2 mutants and OsPKS2 is upregulated in ospks1 mutants, suggesting that the coordinated activities of OsPKS1 and OsPKS2 are essential for pollen development. Our findings provide new clues about the evolution of the PKS III superfamily and reveal the synergistic roles of OsPKS1 and OsPKS2 in regulating male reproduction in rice.

In this study, 27SiMn was selected as a substrate, and the powder was a self-made iron-based alloy. Further, the thermophysical properties of the material were predicted by the CALPHAD phase diagram algorithm. In order to verify the accuracy of the numerical model, 10 sets of experiments were set up. The agreement between the results from the model calculations and the experimental results was 92%. Through the study of energy distribution in the laser cladding process, it was found that about 10% of the laser energy was used to heat the substrate to form a melt pool, and at least 53% of the energy was radiated into the environment. Finally, the effects of the temperature gradient and solidification rate on the microstructure of the cladding layer were explored. The numerical simulation results are helpful in predicting the solidification rate, temperature distribution and microstructure of the melt pool, thereby reducing the cost of testing as well as the time for the experimental method of trial–error.

Drug–target interactions (DTIs) are considered a crucial component of drug design and drug discovery. To date, many computational methods were developed for drug–target interactions, but they are insufficiently informative for accurately predicting DTIs due to the lack of experimentally verified negative datasets, inaccurate molecular feature representation, and ineffective DTI classifiers. Therefore, we address the limitations of randomly selecting negative DTI data from unknown drug–target pairs by establishing two experimentally validated datasets and propose a capsule network-based framework called CapBM-DTI to capture hierarchical relationships of drugs and targets, which adopts pre-trained bidirectional encoder representations from transformers (BERT) for contextual sequence feature extraction from target proteins through transfer learning and the message-passing neural network (MPNN) for the 2-D graph feature extraction of compounds to accurately and robustly identify drug–target interactions. We compared the performance of CapBM-DTI with state-of-the-art methods using four experimentally validated DTI datasets of different sizes, including human (Homo sapiens) and worm (Caenorhabditis elegans) species datasets, as well as three subsets (new compounds, new proteins, and new pairs). Our results demonstrate that the proposed model achieved robust performance and powerful generalization ability in all experiments. The case study on treating COVID-19 demonstrates the applicability of the model in virtual screening.

The repair of critical-sized bone defects (CSBD) remains a significant challenge in clinical practice. Personalized 3D porous scaffolding is generally considered an ideal approach for directed regeneration of CSBD, which usually has irregular and complex 3D geometry. In this study, we designed a customized porous scaffold rabbit radius based on a body-centered cubic unit. Borate bioactive glass/polycaprolactone (BBG/PCL) composite scaffolds with different BBG contents (0%, 5%, 10%, 20%, and 40%) were fabricated using selective laser sintering. The pore geometry, porosity, mechanical strength, hydrophilicity, protein absorption, degradation behavior, in vitro cytocompatibility, and osteogenesis differentiation of the composite scaffolds were systematically characterized. The in vivo biological properties of the BBG/PCL composite scaffold for CSBD repair were assessed using a rabbit foreleg radius defect model. The results indicate that the BBG/PCL composite scaffold with 20% BBG content effectively promoted the proliferation of osteoblasts and repaired the rabbit radius defects. The mechanical strength of the scaffold was sufficient to maintain the integrity of the scaffold structure during a relatively long CSBD repair. Our results indicate that the BBG/PCL composite scaffold can be anticipated to be a promising biomaterial for CSBD repair.

The fundamental understanding of metal-organic frameworks (MOFs) is crucial since the relationship between the macroscopic properties of these materials and their molecular-level structures allows for the development of technological applications and improvements in current performance. The metal centers and attached functional groups dictate MOFs' dynamics, structure, and porosity. The development of the solid-state nuclear magnetic resonance (SSNMR) technique, capable of providing atomic-level information, enables the non-destructive characterization of the structure and dynamics of MOFs have become essential step in ameliorating our understanding and are often complementary to traditional methods. This review aims to briefly introduce the concepts of SSNMR and the methods employed when investigating the dynamics, structure, and mapping of functional groups of microporous materials, including MOFs. This review highlights the best experimental practices when working with these complex systems. The article scrutinizes the information on framework structures, active center, surface position, host-guest interaction, and intermediate interaction through different SSNMR spectrums. Despite all the recent technological advancements, the SSNMR still faces the challenges of large sample quantities, long experimental measurements and data analyses, and complex isotopic labeling, which are enlightened in this review.

PurposeTo compare the effectiveness and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab with those of TACE as well as apatinib among patients with unresectable hepatocellular carcinoma (HCC).Materials and methodsThe data of patients with unresectable HCC (uHCC) who received TACE-apatinib-camrelizumab combination (TACE + AC group) and TACE-apatinib combination (TACE + A group) were collected from two centers between January 2018 and January 2022. Propensity score matching (PSM) was conducted to diminish the bias between the two groups. The primary outcome measures of the study were overall survival (OS) and progression-free survival (PFS), and the secondary outcome measures were response rate (ORR), disease control rate (DCR), and adverse events (AEs).ResultsA total of 102 patients were enrolled in this study after PSM, with 34 patients in the TACE + AC group and 68 patients in the TACE + A group. Compared to the TACE + A group, TACE + AC had a significantly longer median OS (25.5 months, interquartile range [IQR], 23.5–33.0) than 18.5 months (IQR, 13.0–25.0; P = 0.001). Similarly, the PFS of the TACE + AC group was significantly improved (14.0 months, IQR, 9.0–NA) compared to that of the TACE + A group (5.0 months, IQR, 2.5–9.0; P = 0.001). The ORR rates (55.9% vs. 51.5%), and DCR rates (79.4% vs. 72.1%) were comparable between groups (P > 0.05). All treatment-related adverse events were tolerable and manageable, and no serious adverse events were observed.ConclusionTACE combined with apatinib plus camrelizumab demonstrated superior efficacy to TACE plus apatinib for patients with unresectable HCC. The two combination therapies showed similar safety profiles.

There is an increasing demand for the use of automotive sensors where complex working environments may easily lead to failure. Wire pull and shear test models based on finite-element analysis are established to evaluate their reliability by investigating the failure mode and mechanism of gold wire bonding. The effect of shear force position and pull force position on failure is also analyzed. The bonding failure was verified by experiments, which is consistent with the simulation result. The results show that: (1) The three-dimensional quantitative modeling reveals the process of bonding delamination and stress concentration. (2) The bonding–slip method (BSM) is adopted in the gold ball detaching process. The concept of three states, including deformation accumulation, cracking, and disengagement, was put forward to reveal the interface stress evolution trend according to the shear testing results. The results indicate that in the interface, the stress in the deformation accumulation state decreases from the tensile side (or compression side) to the center, and the stress in the cracking and disengagement states reduces gradually from the tensile side to the edge. When the interface is completely separated, the failed shear force concentrates on 42 g. The concept and theory proposed in this work can effectively reveal the failure mechanism of bonding interface and help to establish a new failure criterion.

Ag paste has been recognized as a promising substitute for Sn/Pb solder in SiC or GaN power electronic devices, owing to its ability to withstand high temperatures and facilitate low-temperature packing. The reliability of these high-power circuits is greatly influenced by the mechanical properties of sintered Ag paste. However, there exist substantial voids inside the sintered silver layer after sintering, and the conventional macroscopic constitutive models have certain limitation to describe the shear stress–strain relationship of sintered silver materials. To analyze the void evolution and microstructure of sintered silver, Ag composite pastes composed of micron flake silver and nano-silver particles were prepared. The mechanical behaviors were studied at different temperatures (0–125 °C) and strain rates (1 × 10−4–1 × 10−2) for Ag composite pastes. The crystal plastic finite element method (CPFEM) was developed to describe the microstructure evolution and shear behaviors of sintered silver at varied strain rates and ambient temperatures. The model parameters were obtained by fitting experimental shear test data to a representative volume element (RVE) model built on representative volume elements, also known as Voronoi tessellations. The numerical predictions were compared with the experimental data, which showed that the introduced crystal plasticity constitutive model can describe the shear constitutive behavior of a sintered silver specimen with reasonable accuracy.

Abstract The Hippo and mammalian target of rapamycin complex 1 (mTORC1) pathways are the two predominant pathways that regulate tumour growth and metastasis. Therefore, we explored the potential crosstalk between these two functionally relevant pathways to coordinate their tumour growth-control functions. We found that a Hippo pathway-related long noncoding RNA, HPR, directly interacts with Raptor, an essential component of mTORC1, to upregulate mTORC1 activation by impairing the phosphorylation of Raptor by AMPK. Knockdown or knockout of HPR in breast cancer and cholangiocarcinoma cells led to a reduction in tumour growth. Compared with HPR WT cells, HPR-overexpressing cells exhibited nuclear accumulation of YAP1, and significantly blocked the downregulation of mTORC1 signalling induced by energy stress. Thus, our study reveals a direct link between the Hippo and mTORC1 pathways in the control of tumour growth.

Abstract Surfactants are important components of oral care products. Sodium dodecyl sulfate (SDS) is the most common because of its foaming properties, taste and low cost. However, the use of ionic surfactants, especially SDS, is related to several oral mucosa conditions. Thus, there is a high interest in using non-ionic and amphoteric surfactants as they are less irritant. To better understand the performance of these surfactants in oral care products, we investigated their interaction with salivary pellicles i.e., the proteinaceous films that cover surfaces exposed to saliva. Specifically, we focused on pentaethylene glycol monododecyl ether (C12E5) and cocamidopropyl betaine (CAPB) as model nonionic and amphoteric surfactants respectively, and investigated their interaction with reconstituted salivary pellicles with various surface techniques: Quartz Crystal Microbalance with Dissipation, Ellipsometry, Force Spectroscopy and Neutron Reflectometry. Both C12E5 and CAPB were gentler on pellicles than SDS, removing a lower amount. However, their interaction with pellicles differed. Our work indicates that CAPB would mainly interact with the mucin components of pellicles, leading to collapse and dehydration. In contrast, exposure to C12E5 had a minimal effect on the pellicles, mainly resulting in the replacement/solubilisation of some of the components anchoring pellicles to their substrate.

In this article, a field deployable sensor was developed using a self-developed 4.58-µm continuous wave quantum cascade laser (CW-QCL) for the simultaneous detection of carbon monoxide (CO) and nitrous oxide (N2O), both of which have strong fundamental absorption bands in this waveband. The sensor is based on tunable diode laser absorption spectroscopy (TDLAS) technology, which combined a multi-pass gas cell (MPGC) with a 41 m optical path length to achieve high-precision detection. Meanwhile, the particle swarm optimization-kernel extreme learning machine (PSO-KELM) algorithm was applied for CO and N2O concentration prediction. In addition, the self-designed board-level QCL driver circuit and harmonic signal demodulation circuit reduce the sensor cost and size. A series of validation experiments were conducted to verify the sensor performance, and experiments showed that the concentration prediction results of the PSO-KELM algorithm are better than those of the commonly used back propagation (BP) neural networks and partial least regression (PLS), with the smallest root mean square error (RMSE) and linear correlation coefficient closest to 1, which improves the detection precision of the sensor. The limit of detection (LoD) was assessed to be 0.25 parts per billion (ppb) for CO and 0.27 ppb for N2O at the averaging time of 24 and 38 s. Field deployment of the sensor was reported for simultaneous detection of CO and N2O in the air.

Introduction : The homeostasis of intestinal epithelial cells (IECs) is disrupted in diabetes, leading to functional changes of the gastrointestinal tract and increasing the risk of diabetic enteropathy. Methods: The aim of this study is to explore the effect of autophagy on the expression of inflammatory factors under high glucose in vitro. The effect of glucose at different concentrations (5, 10, 30 and 50 Mm) on IEC-6 cells was analyzed. Dorsomorphin (AMPK antagonist) and GSK621 (AMPK agonist) were used to examine the relationship between the autophagy and the AMPK/ULK1 signaling pathway in IEC-6 cells. Results: Our results showed that the high glucose significantly inhibited the growth of IECs, and induced more shrinkage and necrosis of cells. Autophagy was inhibited by high glucose. Furthermore, the levels of cytokines, including IL-22, INF-γ, NOS2, and TNF-α, were significantly increased, which were positively correlated with glucose concentration. Additionally, we confirmed that Dorsomorphin down-regulated the expression of p-AMPK and autophagy protein compared with GSK621. Similar, cellular immunofluorescence also detected low autophagy expression. However, GSK621 and Rapamycin increased the level of autophagy and down-regulated the secretion of pro-inflammatory factors compared with Dorsomorphin. Conclusion: Therefore, our results demonstrate that AMPK mediated autophagy may regulate levels of inflammation in IECs and improve cell survival under high glucose.

The bending and pulling fatigue test is critical for inspecting cement concrete. The existing fatigue test equipment is expensive and non-conducive for the grassroots sector of construction units. The purpose of this study is to explore a scheme to modify an asphalt mixture rutting test machine to perform bending and pulling fatigue tests on cement concrete specimens. The test results show that (1) the fatigue life obtained from the fatigue test equipment for cement wheel load under the same stress level has a large dispersion, but the fatigue equation for the same group of specimens under different stress levels is fitted and found to be above 0.9; (2) the fatigue life of cement concrete obtained by cyclic loading using semi-positive sagittal loading waveform is shown by the Weibull data distribution model, and the fit is above 0.99; and (3) in a comparative study of the fatigue obtained from fatigue tests performed on other fatigue test equipment, the percentage of the absolute value of the average difference of the equation’s correlation coefficient is between 0.01% and 10.12%. In summary, the cement wheel load fatigue test equipment data is reliable, and the test scheme is reasonable. Thus, it can be used as a test scheme to examine the bending and tensile fatigue tests of cement concrete.

Abstract Background Renal cancer is a common malignant tumor with an increasing incidence rate. Methods In this study, based on the gene expression profiles, we analyzed the compositions of tumor-infiltrating immune cells (TIICs) in renal cancer and paracancerous samples using CIBERSORT. The proportions of 22 TIICs subsets in 122 paired renal carcinoma and paracancerous samples, and 224 Wilms tumor (WT) samples varied between intragroup and intergroup. Results After analyzed the difference of TIICs composition between renal cancer and paired paracancerous samples, we found that M0 macrophages and CD8 T cells were significantly elevated, while naive B cells were significantly decreased in renal cancer samples compared with paracancerous samples. Survival analysis showed that high overall TIICs proportion, the low proportion of resting mast cells and the high proportion of activated memory CD4 T cells were associated with poor prognosis of renal cancer patients. In addition, 3 clusters were identified by hierarchical clustering analysis, and they presented a distinct prognosis. Cluster 1 had superior survival outcomes, while cluster 2 had an inferior survival outcome. Conclusions Our study indicated that overall TIICs proportion, certain TIICs subset proportion, including resting mast cells and activated memory CD4 T cells, and distinct cluster patterns were associated with the prognosis of renal cancer, which was significant for the clinical surveillance and treatment of renal cancer.

The establishment of artificial grassland is crucial in restoring degraded grassland and resolving the forage–livestock conflict, and the application of organic fertilizer and complementary seeding of grass–legume mixture are effective methods to enhance grass growth in practice. However, its mechanism behind the underground is largely unclear. Here, by utilizing organic fertilizer in the alpine region of the Qinghai–Tibet Plateau, this study assessed the potential of grass–legume mixtures with and without the inoculation of Rhizobium for the restoration of degraded grassland. The results demonstrated that the application of organic fertilizer can increase the forage yield and soil nutrient contents of degraded grassland, and they were 0.59 times and 0.28 times higher than that of the control check (CK), respectively. The community composition and structure of soil bacteria and fungi were also changed by applying organic fertilizer. Based on this, the grass–legume mixture inoculated with Rhizobium can further increase the contribution of organic fertilizer to soil nutrients and thus enhance the restoration effects for degraded artificial grassland. Moreover, the application of organic fertilizer significantly increased the colonization of gramineous plant by native mycorrhizal fungi, which was ~1.5–2.0 times higher than CK. This study offers a basis for the application of organic fertilizer and grass–legume mixture in the ecological restoration of degraded grassland.

Premature ovarian insufficiency (POI) can result in lower fertility and shorten the female reproductive span. Bushen-Culuan Decoction (BCD) is a traditional Chinese medication utilized for treating POI for many years. We previously observed that BCD protects against further deterioration of the ovarian reserve of POI patients, however, the underlying mechanism has not been well studied. Our investigation seeks to evaluate the effect of BCD on POI induced by Tripterygium wilfordii polyglycosidium (TWP) and the likely mechanistic pathways, which we hypothesize may involve the Nrf2/ARE pathway. The body weights, estrous cycle, serum hormone levels, histological follicular analysis and quantification, levels of oxidative stress biomarkers in the ovarian tissue of POI mice models were evaluated. Western blotting and RT-PCR enabled quantification of the components of the Nrf2/ARE pathway. Our results showed that BCD restored hormonal profiles and estrous cycles of POI mice similar to those observed in healthy controls. BCD reduced the numbers of atretic follicles while increasing the number of primordial follicles. BCD facilitated lower 8-OHdG and MDA levels while increasing levels of key antioxidant enzymes including GSH-Px, CAT, and SOD. Furthermore, TWP increased Bach 1, Nrf2, and Keap 1 expressions at the translational level, while decreased that of HO-1. BCD treatment also promoted nuclear translocation rates of Bach 1 and Nrf2, suppressed Keap 1 protein expression, as well as raised HO-1 protein expression. Taken together, BCD likely augments ovarian reserve by activating the Nrf2/ARE signaling pathway, which stimulated higher levels of antioxidants and suppressed oxidative stress. BCD may be an important therapeutic compound in POI.