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Abstract The biological role and precise molecular mechanisms of Notch receptor 3 (NOTCH3) in the malignant progression of bladder cancer (BLCA) remain unclear. In this study, we found that NOTCH3 was significantly upregulated and associated with poor prognosis in BLCA patients. Functional experiments demonstrated that NOTCH3 knockdown inhibited BLCA cell proliferation, migration, invasion and significantly suppressed tumor growth and metastasis in vivo as well. Mechanically, chromatin immunoprecipitation and dual-luciferase reporter assays confirmed that NOTCH3 could promote the transcription of secreted phosphoprotein 1 (SPP1), a potential downstream target gene of NOTCH3, by binding to the CSL elements in the SPP1 promoter. Moreover, we also found that targeting NOTCH3 inhibited BLCA growth and metastasis by suppressing the SPP1-PI3K/AKT axis. Our study highlights the critical role of NOTCH3-SPP1-PI3K/AKT axis in the malignant progression of BLCA, suggesting that NOTCH3 may be a potential therapeutic target for BLCA.

The general purpose plugin for deep reinforcement learning is a type of algorithm that can be attached to most native algorithms and is compatible with other kinds of plugins. Under different environments, the original algorithm forms different variants after adding appropriate plugins, and achieves better results in training speed and stability. According to the commonness of the general plugins in the training process, the variants were divided into six categories, including the general network model, intrinsic reward, experience replay, self-play, imitation learning, and curriculum learning. The general plugins commonly used in these six kinds of algorithms were reviewed, and their application scenarios and main functions in deep reinforcement learning were also briefly introduced. The future research priorities were put forward: 1) to improve the efficiency of experience utilization; 2)to design and train a general neural network architecture; 3)to improve the efficiency of algorithm exploration in sparse reward environment; 4)to improve the ability of the algorithm to deal with various emergencies in reality.

Abstract Background Heart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. Methods The active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model. Results We initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated. Conclusions Mechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF. Graphical Abstract

The occurrence of hyperuricemia (HUA; elevated serum uric acid) in athletes is relatively high despite that exercise can potentially reduce the risk of developing this condition. Although recent studies have shown the beneficial properties of DAG in improving overall metabolic profiles, a comprehensive understanding of the effect of DAG in modulating HUA in athletes is still lacking. In this study, we leveraged combinatorial lipidomics and metabolomics to investigate the effect of replacing TAG with DAG in the diet of athletes with HUA. A total of 1,074 lipids and metabolites from 94 classes were quantitated in serum from 33 athletes, who were categorized into responders and non-responders based on whether serum uric acid levels returned to healthy levels after the DAG diet intervention. Lipidomics and metabolomics analyses revealed lower levels of xanthine and uric acid in responders, accompanied by elevated plasmalogen phosphatidylcholines and diminished acylcarnitine levels. Our results highlighted the mechanisms behind how the DAG diet circumvented the risk and effects associated with high uric acid via lowered triglycerides at baseline influencing the absorption of DAG resulting in a decline in ROS and uric acid production, increased phospholipid levels associated with reduced p-Cresol metabolism potentially impacting on intestinal excretion of uric acid as well as improved ammonia recycling contributing to decreased serum uric acid levels in responders. These observed alterations might be suggestive that successful implementation of the DAG diet can potentially minimize the likelihood of a potentially vicious cycle occurring in high uric acid, elevated ROS, and impaired mitochondrial metabolism environment.

Purpose: Myofibroblastic cancer-associated fibroblasts (myCAFs) are important components of the tumor microenvironment closely associated with tumor stromal remodeling and immunosuppression. This study aimed to explore myCAFs marker gene biomarkers for clinical diagnosis and therapy for patients with bladder cancer (BC). Materials and Methods: BC single-cell RNA sequencing (scRNA-seq) data were obtained from the National Center for Biotechnology Information Sequence Read Archive. Transcriptome and clinical data were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Subsequently, univariate Cox and LASSO (Least Absolute Shrinkage and Selection Operator regression) regression analyses were performed to construct a prognostic signature. Immune cell activity was estimated using single-sample gene set enrichment analysis whilst the TIDE (tumor immune dysfunction and exclusion) method was employed to assess patient response to immunotherapy. The chemotherapy response of patients with BC was evaluated using genomics of drug sensitivity in cancer. Furthermore, Immunohistochemistry was used to verify the correlation between MAP1B expression and immunotherapy efficacy. The scRNA-seq data were analyzed to identify myCAFs marker genes. Results: Combined with bulk RNA-sequencing data, we constructed a two-gene (COL6A1 and MAP1B) risk signature. In patients with BC, the signature demonstrated outstanding prognostic value, immune infiltration, and immunotherapy response. This signature served as a crucial guide for the selection of anti-tumor chemotherapy medications. Additionally, immunohistochemistry confirmed that MAP1B expression was significantly correlated with immunotherapy efficacy. Conclusions: Our findings revealed a typical prognostic signature based on myCAF marker genes, which offers patients with BC a novel treatment target alongside theoretical justification.

Basalt fiber-reinforced polymer (BFRP) has high mechanical strengths as a repairing material but exhibits low ductility. This paper investigates the damage process of reinforced concrete beams repaired using BFRP sheets, aimed at understanding the underlying mechanisms of achieving structural ductility when BFRP sheets are used. The damage process was assessed using digital image correlation (DIC) and acoustic emission (AE) techniques applied to monitor surface and internal damages of three full-scale concrete beams subjected to four-point bending. A beam was first loaded to crack, then repaired with BFRP sheets, and finally reloaded to failure. Surface strain fields and cracks were monitored using a DIC method, and cracking events were monitored using AE sensors deployed at different positions of the beams. The AE signals were analyzed to assess the damage process. The test results indicated that (1) tensile cracks predominated throughout the loading process; (2) the BFRP sheets hindered the widening of cracks and promoted the generation of fine cracks; and (3) the development of concrete cracks promoted interfacial debonding at steel-concrete and BFRP-concrete interfaces. A combination of different types of cracks and interfacial debonding helped the repaired beam achieve ductile flexural behaviors.

Continuous remodeling of the heart can result in adverse events such as reduced myocardial function and heart failure. Available evidence indicates that ferroptosis is a key process in the emergence of cardiac disease. P2 family purinergic receptor P2X7 receptor (P2X7R) activation plays a crucial role in numerous aspects of cardiovascular disease. The aim of this study was to elucidate any potential interactions between P2X7R and ferroptosis in cardiac remodeling stimulated by angiotensin II (Ang II), and P2X7R knockout mice were utilized to explore the role of P2X7R and elucidate its underlying mechanism through molecular biological methods. Ferroptosis is involved in cardiac remodeling, and P2X7R deficiency significantly alleviates cardiac dysfunction, remodeling, and ferroptosis induced by Ang II. Mechanistically, Ang II interacts with P2X7R directly, and LYS-66 and MET-212 in the in the ATP binding pocket form a binding complex with Ang II. P2X7R blockade influences HuR-targeted GPX4 and HO-1 mRNA stability by affecting the shuttling of HuR from the nucleus to the cytoplasm and its expression. These results suggest that focusing on P2X7R could be a possible therapeutic approach for the management of hypertensive heart failure.

Nowadays, the intricate nature of synthetic aperture radar (SAR) ship scenes, coupled with the presence of multiscale targets, poses a significant challenge in detection accuracy. Furthermore, to reduce the financial outlay on hardware, there is also a considerable challenge in lightweighting the model. In order to resolve the aforementioned concerns, we propose a cross-spatial multiscale lightweight network, designated as DEPDet. First, a new efficient multiscale detection backbone network DEMNet is redesigned. To improve the feature extraction capability of the network, a cross-spatial multiscale convolution (CSMSConv) is designed and a new CSMSConv module CSMSC2F is constructed. Meanwhile, we introduce an efficient multiscale attention module. DEMNet is capable of more effectively extracting information pertaining to multiscale ships. Moreover, to enhance the fusion of features at diverse scales, we design a new path aggregation feature pyramid network DEPAFPN, which combines deformable convolution and CSMSC2F. Finally, we introduce partial convolution to construct a lightweight detection head module PCHead, which can be employed to extract spatial features with greater efficiency. The publicly available SAR ship datasets, SAR Ship Detection Dataset and High-Resolution SAR Image Dataset, are employed for the purpose of conducting experiments. The mean average precision (mAP) obtained was 98.2% (+1.4%) and 91.6% (+1.6%), respectively. The F1 obtained 0.950 (+1.7%) and 0.871 (+1.4%), respectively. Concurrently, the Params decreased from 3.2M to 2.1M, a decrease of approximately 34%. The floating-point operations (FLOPs) decreased from 8.7G to 4.5G, a decrease of approximately 48%. The experimental results indicate that the network achieves an effective balance between detection accuracy and lightweight effect with good generalization and extensibility.

Abstract Sepsis is a common acute and severe medical condition with a high mortality rate. Anoikis, an emerging form of cell death, plays a significant role in various diseases. However, the role of anoikis in sepsis remains poorly understood. Based on the datasets from Gene Expression Omnibus and anoikis-related genes from GeneCards, the differentially expressed anoikis-related genes (DEARGs) were identified. Based on hub genes of DEARGs, a novel prognostic risk model was constructed, and the pattern of immune infiltration was investigated by CIBERSORT algorithm. And small molecule compounds targeting anoikis in sepsis were analyzed using Autodock. Of 23 DEARGs, CXCL8, CFLAR, FASLG and TP53 were significantly associated with the prognosis of sepsis (P

Urothelial carcinoma (UC) with testicular metastasis is extremely rare, and its modes of metastasis, prognosis, and treatment are unclear. In this report, we present an extraordinarily rare case of testicular metastasis arising from UC 8 years after surgery. The patient underwent left orchiepididymectomy and received immunotherapy postoperatively. After a 6-month follow-up, there were no signs of recurrence. Moreover, the clinical characteristics, metastasis pattern, and treatment plan were also summarized based on 14 earlier reported cases of UC with testicular metastasis.

Muscle-invasive urothelial cancer (MUC), characterized by high aggressiveness and significant heterogeneity, is currently lacking highly precise individualized treatment options. We used a computational pipeline to synthesize multiomics data from MUC patients using 10 clustering algorithms, which were then combined with 10 machine learning algorithms to identify molecular subgroups of high resolution and develop a robust consensus machine learning-driven signature (CMLS). Through multiomics clustering, we identified three cancer subtypes (CSs) that are related to prognosis, with CS2 exhibiting the most favorable prognostic outcome. Subsequent screening enabled identification of 12 hub genes that constitute a CMLS with robust predictive power for prognosis. The low-CMLS group exhibited a more favorable prognosis and greater responsiveness to immunotherapy and was more likely to exhibit the “hot tumor” phenotype. The high-CMLS group had a poor prognosis and lower likelihood of benefitting from immunotherapy, but dasatinib and romidepsin may serve as promising treatments for them. Comprehensive analysis of multiomics data can offer important insights and further refine the molecular classification of MUC. Identification of CMLS represents a valuable tool for early prediction of patient prognosis and for screening potential candidates likely to benefit from immunotherapy, with broad implications for clinical practice.

Grease lubrication is cost-effective and low-maintenance for motorized spindles, but standard steel bearings can fail at high speeds. This study focuses on high-speed full ceramic ball bearings lubricated with grease. The coefficient of friction torque in the empirical formula is corrected by establishing the heat generation model of full ceramic ball bearing and combining it with experiments. A simulation model of grease flow is established to study the influence of grease filling amount on grease distribution. The simulation model of the temperature field of a full ceramic ball bearing is established to analyze the influence of rotating speed on bearing heat generation, and experiments verify the calculation results of the theoretical model. The results show that an optimal grease filling amount of 15~25% ensures even distribution without accumulation. Additionally, when the amount of grease is constant, the outer ring temperature increases with higher rotating speeds. The test results show that when the grease filling is 0.9~1.2 g, it accounts for about 9~12% of the volume of the bearing cavity, and the temperature of the outer ring is the lowest. At a rotation speed of 24,000 rpm, the outer ring temperature of the grease-lubricated bearing is 50.1 °C, indicating a reasonable range for use in motorized spindles. It provides a theoretical basis for the optimization design of macro-structural parameters of full ceramic ball bearings in the future, which can minimize heat generation and maximize bearing capacity.

It is important to eliminate the fishy odor and improve the aroma quality of seafood. In this study, the Saccharina japonica (S. japonica) seedling, which is a new food material, was investigated for the effects of fermentation with Saccharomyces cerevisiae (S. cerevisiae) through sensory evaluation, GC–MS, and odor activity value (OAV) analysis. GC–MS analysis revealed the presence of 43 volatile compounds in the unfermented S. japonica seedling, with 1-octen-3-ol, hexanal, and trans-2,4-decadienal identified as the main contributors to its fishy odor. After fermentation with S. cerevisiae, 26 volatile compounds were identified in the S. japonica seedling. Notably, the major malodorous fish compounds, including 1-octen-3-ol, hexanal and trans-2,4-decadienal, were no longer present. The results indicate that fermentation with S. cerevisiae is an effective method for removing fishy malodor compounds and enhancing the volatile components with fruity, sweet, green, and floral notes in the Saccharina japonica seedling. This process facilitates the elimination of fishy malodor and enhance the fruity, sweet, green, and floral notes of S. japonica seeding and other seaweeds.

Abstract Purpose The clinical outcomes of using a tubular microdiscectomy for lumbar disc herniation were evaluated by comparison with conventional microdiscectomy. Methods All of the comparative studies published in the PubMed, Cochrane Library, Medline, Web of Science, and EMBASE databases as of 1 May 2023 were included. All outcomes were analysed using Review Manager 5.4. Results This meta-analysis included four randomized controlled studies with a total of 523 patients. The results showed that using tubular microdiscectomy for lumbar disc herniation was more effective than conventional microdiscectomy in improving the Oswestry Disability Index (P 0.05) between the tubular microdiscectomy and conventional microdiscectomy groups. Conclusions Based on our meta-analysis, it was found that the tubular microdiscectomy group had better outcomes than the conventional microdiscectomy group in terms of Oswestry Disability Index. However, there were no significant differences between the two groups in terms of operating time, intraoperative blood loss, hospital stay, Visual Analogue Scale, reoperation rate, postoperative recurrence rate, dural tear incidence, and complications rate. Current research suggests that tubular microdiscectomy can achieve clinical results similar to those of conventional microdiscectomy. PROSPERO registration number is: CRD42023407995.

The objective of this work was to completely replace margarine with peanut diacylglycerol oil/ethyl cellulose-glycerol monostearate oleogel (DEC/GMS) oleogel, and evaluate its effect on starch digestibility of cakes. The in vitro digestibility analysis demonstrated that the DEC/GMS-6 cake exhibited a 26.36% increase in slowly digestible starch (SDS) and resistant starch (RS) contents, compared to cakes formulated with margarine. The increased SDS and RS contents might mainly be due to the hydrophobic nature of OSA-wheat flour, which could promote the formation of lipid-amylose complexes with GMS and peanut diacylglycerol oil. XRD pattern suggested that the presence of GMS in DEC-based oleogels facilitated the formation of lipid-amylose complexes. The DSC analysis revealed that the addition of GMS resulted in a significant increase in gelatinization enthalpy, rising from 249.7 to 551.9 J/g, which indicates an improved resistance to gelatinization. The FTIR spectra indicated that the combination of GMS could enhance the hydrogen bonding forces and short-range ordered structure in DEC-based cakes. The rheological analysis revealed that an increase in GMS concentration resulted in enhanced viscoelasticity of DEC-based cake compared to TEC-based cakes. The DEC-based cakes exhibited a more satisfactory texture profile and higher overall acceptability than those of TEC-based cakes. Overall, these findings demonstrated that the utilization of DEC-based oleogel presented a viable alternative to commercial margarine in the development of cakes with reduced starch digestibility.

Abstract Tenderness and color affect meat quality. Our previous results indicated that cranberry powder can partially replace NaNO2 in fried beef meatballs processing without compromising on its quality, especially the color. In this research, the effect of different protease enzymes combined with 10 g/kg cranberry powder for improving the quality, characteristics of fried beef meatballs were investigated. Addition of protease together with cranberry powder, the tenderness, a* value, and sensory score of fried beef meatballs were improved as a whole compared with sole 10 g/kg cranberry powder addition, indicating that protease had a beneficial effect on improving the quality of fried beef meatballs. Among the different proteases screened, the fried beef meatballs prepared with 80 U/g bromelain had a relatively higher a* value (13.06) and tenderness (12.61), and the overall acceptability (6) was the highest. Meanwhile, this combination exhibited lower shear stress and cooking loss, with higher water‐holding capacity and protein content. The effects of marination time on the physicochemical properties of fried beef meatballs were also investigated. Marinating for 8 h displayed the best effect with the highest a* value, the lowest shear force. The current study provides a potential solution for the quality improvement of fried beef meatballs.

Phthalate acid ester hydrolases are of promise for the microbial degradation of phthalate acid ester plasticizers, however, only a small number of PAE hydrolases have been characterized. Here, the authors report the structural and functional characterization of MehpH, a monoalkyl phthalate (MBP) hydrolase that degrades MBP to phthalic acid and butanol.

Flexible thermoelectric generators (FTEGs), which can overcome the energy supply limitations of wearable devices, have received considerable attention. However, the use of toxic Te-based materials and fracture-prone electrodes constrains the application of FTEGs. In this study, a novel Ag2Se and Poly (3,4-ethylene dioxythiophene): poly (styrene sulfonate) (PEDOT:PSS)/multi-walled carbon nanotube (MWCNT) FTEG with a high output performance and good flexibility is developed. The thermoelectric columns formulated in the work are environmentally friendly and reliable. The key enabler of this work is the use of embedded EGaIn electrodes, which increase the temperature difference collected by the thermoelectric column, thereby improving the FTEG output performance. Additionally, the embedded EGaIn electrodes could be directly printed on polydimethylsiloxane (PDMS) molds without wax paper, which simplifies the preparation process of FTEGs and enhances the fabrication efficiency. The FTEG with embedded electrodes exhibits the highest output power density of 25.83 μW/cm2 and the highest output power of 10.95 μW at ΔT = 15 K. The latter is 31.6% higher than that of silver-based FTEGs and 2.5% higher than that of covered EGaIn-based FTEGs. Moreover, the prepared FTEG has an excellent flexibility (>1500 bends) and output power stability (>30 days). At high humidity and high temperature, the prepared FTEG maintains good performance. These results demonstrate that the prepared FTEGs can be used as a stable and environmentally friendly energy supply for wearable devices.

Summary: ALDH1A1 is one of the classical stem cell markers for bladder cancer. Lysine 2-hydroxyisobutyrylation (Khib) is a newfound modification to modulate the protein expression, and the underlying mechanisms of how ALDH1A1 was regulated by Khib modification in bladder cancer remains unknown. Here, ALDH1A1 showed a decreased K260hib modification, as identified by protein modification omics in bladder cancer. Decreasing ALDH1A1 expression significantly suppressed the proliferation, migration and invasion of bladder cancer cells. Moreover, K260hib modification is responsible for the activity of ALDH1A1 in bladder cancer, which is regulated by HDAC2/3. Higher K260hib modification on ALDH1A1 promotes protein degradation through chaperone-mediated autophagy (CMA), and ALDH1A1 K260hib could sensitize bladder cancer cells to chemotherapeutic drugs. Higher ALDH1A1 expression with a lower K260hib modification indicates a poor prognosis in patients with bladder cancer. Overall, we demonstrated that K260hib of ALDH1A1 can be used as a potential therapeutic target for bladder cancer treatment.

Non-dairy creamers have been widely used for coffee whitening and texture improvement. To avoid the intake of trans fatty acids from partially hydrogenated oil, coconut oil-based diacylglycerol (CO-DAG) was applied in non-dairy creamer as core material. In this study, effects of DAG content (30, 50, 70, 90%) on the characteristics of CO-DAG were evaluated, including rheological and thermodynamic properties. The CO-DAG with a content of 50% exhibited a wide plastic range and contained mixture of β and β' polymorphic forms. Using CO-DAG (50%) as core material, the physicochemical properties of non-dairy creamer were characterized and compared with commercial products. The results indicated that CO-DAG-based non-dairy creamers showed similar encapsulation efficiency (92.74%) and thermal stability to commercial products. Furthermore, CO-DAG-based non-dairy creamer showed higher whiteness index (54.20) than commercial non-dairy creamers (50.22) when applied to black coffee. Overall, it is anticipated that CO-DAG-based non-dairy creamers have great potentials in coffee whitening.

Abstract Purpose Cancer cells require a supply of amino acids, particularly essential amino acids such as branched-chain amino acids (BCAAs, i.e., valine, leucine, and isoleucine), to meet the increased nutrient demands of malignant tumors. The cell-autonomous and non-autonomous roles of altered BCAA supply have been implicated in cancer progression. The critical proteins involved in BCAA uptake, transport, metabolism, etc. serve as potential therapeutic biomarkers in human cancers. Here, we summarize the potential anti-tumor mechanism of BCAA by exploring the chain reaction triggered by increased BCAA supply in the tumor. Method A system-wide strategy was employed to provide a generic solution to establish the links between BCAA and cancer based on comprehensive omics, molecular experimentation, and data analysis. Results BCAA over-supplementation (900 mg/kg) significantly inhibited tumor growth and reduced tumor burden, with isoleucine having the most pronounced effect. Surprisingly, isoleucine inhibited tumor growth independently of mTORC1 activation, a classical amino acid sensor. Exploratory transcriptome analysis revealed that Phosphatase and tensin homolog (PTEN) is the critical factor in the anti-tumor effect of isoleucine. By inhibiting PTEN ubiquitination, isoleucine can promote PTEN nuclear import and maintain PTEN nuclear stability. Interestingly, this process was regulated by isoleucine-tRNA ligase, cytoplasmic (IARS), a direct target of isoleucine. We demonstrated the enhanced interaction between IARS and PTEN in the presence of excess isoleucine. At the same time, IARS knockout leads to loss of isoleucine tumor suppressor ability. Conclusion Overall, our results provide insights into the regulation of the IARS-PTEN anti-tumor axis by isoleucine and reveal a unique therapeutic approach based on enhancing cellular isoleucine supply.

This paper proposed a wedge concrete fixed pier device based on self-locking to solve the problems existing in the fixed pier of water supply pipeline in utility tunnels. The system converted the horizontal thrust, originally applied to the weld seam in the pipeline, into oblique downward pressure by bending the pipeline upward. When the pipeline was bent upward at an angle equal to twice the horizontal angle of the wedge concrete fixed pier, then the fixed pier achieved the variable pressure-bearing effect in the horizontal direction through the self-locking between the concrete pier and the bottom plate of the utility tunnels. In addition, this avoided the damage to the fixed pier device, caused by the instantaneous pipeline internal pressure exceeding the maximum bearing thrust of the weld seam. The wedge fixed pier could be poured twice when the pipeline entered the utility tunnels, saving the rework cost of pouring the concrete again due to the changes of the design positioning of the water supply pipeline. As long as the area of the built-in steel fittings in the wedge concrete exceeded a certain range, the wedge concrete pier would not be crushed.

Abstract Background Adrenocortical carcinoma (ACC) is a rare endocrine neoplasm, which is characterized by poor prognosis and high recurrence rate. Novel and reliable prognostic and metastatic biomarkers are lacking for ACC patients. This study aims at screening potential prognostic biomarkers and therapeutic targets of ACC through bioinformatic methods and immunohistochemical (IHC) analysis. Methods In the present study, by using the Gene Expression Omnibus (GEO) database we identified differentially expressed genes (DEGs) in ACC and validated these DEGs in The Cancer Genome Atlas (TCGA) ACC cohort. A DEGs-based signature was additionally constructed and we assessed its prognosis and prescient worth for ACC by survival analysis and nomogram. Immunohistochemistry (IHC) was used to verify the relationship between hub gene–GMNN expressions and clinicopathologic outcomes in ACC patients. Results A total of 24 DEGs correlated with the prognosis of ACC were screened from the TCGA and GEO databases. Five DEGs were subsequently selected in a signature which was closely related to the survival rates of ACC patients and GMNN was identified as the core gene in this signature. Univariate and multivariate Cox regression showed that the GMNN was an independent prognostic factor for ACC patients (P

Continental shale oil to be studied urgently is an important unconventional “source rock oil and gas” and key domain of “exploring petroleum inside source kitchens”. Based on the “source rock oil and gas” theory and the thought of “exploring petroleum inside source kitchens”, this paper established the ”six determination” exploration workflow for continental shale oil (i.e., determining the background, source rock, reservoir, play, resources, and sweet spot), which geological characteristics and exploration workflow are significantly different from conventional hydrocarbon. A case study was conducted by the workflow in the Kong 2 member (Ek2) of the Cangdong sag in the Bohai Bay Basin, China. Semi-deep to deep lacustrine facies belts and many gentle slope structures (belts) were widespread during Kongdian Formation depositing, thus providing favorable conditions for the formation and large-area accumulation of shale oil. Ek2 developed broader-distributed, and thick-bedded dark mudstone and oil shale, which exhibit high TOC, a good kerogen type, and great hydrocarbon-generating potential. Siltstone to fine sandstone and mud to micritic dolomite reservoirs were found within the low-dip slopes and central zone, which are thick, overlapped, abundant high-angle fractures, and exhibit low porosity and ultra-low permeability. Sandstone-type and dolomite-type shale oil of Ek2 characterized source–reservoir integration and five types of sources–reservoir configurations. They mainly overlapped at the front end of the braided river delta in the slope zone and in the sag center, where are superimposed vertically, and are connected horizontally with conventional structural–lithological oil pools in the up-dip slope. The median geological resources of the two classes shale oil were 5.26×108/t, with the remaining resources accounting for 90% of the total and moderate buried depths, thus the exploration potential is great. Several special exploration wells have obtained industrial oil flow. There are two types of sweet spots: low permeability sandstone layers and interbedded layers of oil shale and dolomite. A few favorable sweet spots were identified as targets for subsequent exploration. Then, three aspects of thinking and recommendations to solve the next exploration direction and technical problems were proposed, which will provide important reference and theoretical guidance for the further exploration of the same type of shale system in China and the world.

Antimicrobial toxins are secreted by bacteria to kill rival species. Here the authors report the mechanism of inhibition of EsaD, a toxin secreted by some S. aureus strains to kill competitors that lack the antitoxin EsaG, showing marked mechanistic differences to other Type II toxin-antitoxin systems.

Identifying snow phenomena in images from automatic weather station (AWS) is crucial for live weather monitoring. In this paper, we propose a convolutional neural network (CNN) based model for snow identification using images from AWS cameras. The model combines the attention mechanism of the DANet model with the classical residual network ResNet-34 to better extract the features of snow cover in camera images. To improve the generalizability of the model, we also use images from public datasets in addition to images taken by cameras from unmanned weather stations. Our results show that the proposed model achieved a POD of 91.65%, a FAR of 7.34% and a TS score of 85.45%, demonstrating its effectiveness in snow identification. This study has the potential to facilitate more efficient and effective weather monitoring in a variety of locations.

The application feedback on existing silicon nitride ceramic bearings and RCF experimental research all indicate that the primary failure mode of silicon nitride ceramic bearings is material spalling on the contact surface. Spalling failure occurs due to the initiation and propagation of cracks under rolling contact. However, silicon nitride ceramic bearings, owing to their unique manufacturing method, inevitably exhibit defects and cracks. Therefore, as silicon nitride ceramic bearings are increasingly prevalent, reducing the probability of spalling failure is crucial for extending their service life. This can only be achieved by gaining a clear understanding of the crack initiation and expansion mechanisms in silicon nitride ceramic bearings. This paper is based on silicon nitride rolling friction experiments. It involves the joint simulation of Franc3D-V8.4 and ABAQUS2020, wherein the crack front SIFs are calculated for each load contact position of the surface crack on the silicon nitride ceramic bearing ring during cyclic movement. The study also delves into the determination of the maximum effective stress intensity factors and explores the influence of the initial crack depth on the cycle life and direction of crack propagation. The research yields several valuable conclusions. The findings of this research offer theoretical guidance for formulating grinding technologies for silicon nitride rings and adjusting and controlling working parameters of silicon nitride ceramic ball bearings. These insights are crucial for enhancing the reliability and longevity of silicon nitride ceramic bearings in practical applications.

Abstract Considering the under-maintenance and over-maintenance of existing equipment maintenance methods, this paper studies a Condition Based Maintenance method for silk dryers. The entropy method is used to eliminate the influence of subjective factors to more objectively reflect the weight of different input parameters; optimizing the number of nodes in the hidden layer of the network to improve the prediction accuracy; and using the GA-BP neural network to establish a state prediction model of the equipment to solve the disadvantages of the BP neural network, for example, unstable prediction, easily falling into local optimum, and slow global search ability. Simulation experiments show that this method can effectively compensate for the shortcomings of the existing maintenance methods, and provide an effective scientific basis for dryer state maintenance.

Abstract The latest research on hybrid networks of decode‐and‐forward (DF) relay and intelligent reflecting surface (IRS) is limited to just a single relay. To harvest multiple relay gains, this paper proposes a hybrid communication networks that combines multiple DF relays with an IRS. The authors formulate and address the joint optimization problem to maximize the end‐to‐end transmission rate by jointly optimizing the reflect beam forming, the best relay selection and the power allocation, subject to total transmit power constraint. Moreover, to better exploit the degrees of freedom, it is proposed that the source also transmits signals in the second time slot. While the optimization problem is difficult to solve, the authors propose some efficient approaches to make the problem tractable. First, power allocation problem is simplified by applying Cauchy‐Schwarz inequality and introducing equivalent channel gain, second, non‐convex rank‐one constraint is overcome by utilizing semidefinite relaxation (SDR) approach, then the slacked non‐convex constraint is overcome by applying first‐order Taylor expansion approximation. The simulation results demonstrate that our proposed joint optimization scheme for hybrid networks of multiple DF relays with an IRS has significant performance improvement over the other optimization schemes, such as the optimization scheme for hybrid networks of single DF relay and an IRS.

IntroductionLung adenocarcinoma (LUAD), as the most frequent pathological subtype of non−small cell lung cancer, is often characterized by poor prognosis and low 5-year survival rate. Exploriton of new biomarkers and accurate molecular mechanisms for effectively predicting the prognosis of LUAD patients is still necessary. Presently, BTG2 and SerpinB5, which play important roles in tumors, are studied as a gene pair for the first time with the aim of exploring whether they can be used as potential prognostic markers.MethodsUsing the bioinformatics method to explore whether BTG2 and SerpinB5 can become independent prognostic factors, and explore their clinical application value and whether they can be used as immunotherapeutic markers. In addition, we also verify the conclusions obtained from external datasets, molecular docking, and SqRT-PCR.ResultsThe results show that compared with normal lung tissue, BTG2 expression level was down-regulated and SerpinB5 was up-regulated in LUAD. Additionally, Kaplan–Meier survival analysis demonstrate that the prognosis of low expression level of BTG2 was poor, and that of high expression level of SerpinB5 was poor, suggesting that both of them can be used as independent prognostic factors. Moreover, the prognosis models of the two genes were constructed respectively in this study, and their prediction effect was verified by external data. Besides, ESTIMATE algorithm reveals the relationship between this gene pair and the immune microenvironment. Furthermore, patients with a high expression level of BTG2 and a low expression level of SerpinB5 have higher immunophenoscore for CTLA-4 and PD-1 inhibitors than patients with a low expression level of BTG2 and a high expression level of SerpinB5, indicating that such patients have a more obvious effect of immunotherapy.DiscussionCollectively, all the results demonstrate that BTG2 and SerpinB5 might serve as potential prognostic biomarkers and novel therapeutic targets for LUAD.

Diacylglycerol (DAG)-based edible oils have attracted increasing research interest owing to their health-promoting properties. Recent animal and human studies showed that an increased 1,2-DAG content in the liver and skeletal muscle may cause insulin resistance. However, earlier studies using animal models or humans reported that dietary DAGs with a 1,2-DAGs to 1,3-DAGs ratio of approximately 3:7 could improve insulin sensitivity in type 2 diabetic patients. This conflict raises the question of whether there is a link between the ingested DAGs and endogenous DAGs during their metabolism. To make a contribution to this field, this review provides an overview of the metabolic pathways of ingested DAGs and biological roles of DAGs (ingested and endogenous) in the change of insulin sensitivity. Accordingly, strategies for further investigations on the metabolism of DAGs are proposed.

Membrane-free acoustic sensors based on new principle and structure are becoming a research hotspot, because of many advantages, e.g., their wide bandwidth and high sensitivity. It is proposed that a membrane-free acoustic sensor employs a semi-buried optical waveguide ring resonator (SOWRR) as a sensing element. Using air as the upper cladding medium, the excited evanescent field in the air cladding medium would be modulated by acoustic wave. On this basis, the acoustic sensing model is established. Taking high Q factor and resonance depth as design criteria, the optimal design parameters are given. The optimal values of the air/SiO2: Ge/SiO2 waveguide resonator length and coupling spacing are obtained as 50 mm and 5.6 μm, respectively. The Q factor of the waveguide resonator of this size is as high as 8.33 × 106. The theoretical simulation indicates that the frequency response ranges from 1 Hz to 1.58 MHz and that the minimum detectable sound pressure is 7.48 µPa using a laser with linewidth of 1 kHz. Because of its advantages of wide bandwidth and high sensitivity, the membrane-free sensor is expected to become one of the most promising candidates for the next-generation acoustic sensor.

As a typical representative of micro/nano-textured silicon, black silicon has excellent light absorption properties and is gradually surfacing as a substitute for standard silicon in photoelectric devices. Black silicon overcomes the limitations of traditional silicon-based devices, which are unable to achieve infrared light detection at wavelengths >1100 nm and have low quantum efficiency and sensitivity in ultraviolet light detection. In this article, the recent theoretical and experimental breakthroughs in near-infrared and ultraviolet detection using black silicon are summarized in detail. First, black silicon and the techniques for its fabrication are introduced. Then, the application of enhanced black silicon photodetectors within or above the bandgap limit and black silicon fabricated using different methods in infrared detection is discussed. In principle, infrared detection using black silicon is achieved by jointly utilizing element doping, localized surface plasmon resonance effect, and heterojunction formation. In addition, the application of black silicon in ultraviolet detection is also introduced. Ultraviolet detection is realized by an induced junction and the self-built electric field between black silicon and aluminum oxide. Finally, the increasingly growing potential of black silicon in near-infrared and ultraviolet detection applications, such as infrared night vision imaging, signal detection, ultraviolet light intensity monitoring, and national defense early warning, is further discussed.

This study aimed to investigate the nutritional value of five commercial meal-replacement shakes, and mainly focused on the lipid digestion fates and fat-soluble vitamin bioavailability. Four out of five samples exhibited a low lipolysis level (37.33–61.42%), aligning with the intended objectives of these products. Although the remaining sample rich in diacylglycerol (DAG) had a higher lipolysis level (80.83%), the inherent low-calorie nature of DAG might compensate for this drawback. The release level of individual fatty acid was largely determined by the glycerolipid composition. Moreover, the strong positive correlation between lipid hydrolyzed products amounts and the fat-soluble vitamin bioavailability was observed. Surprisingly, one out of five samples can provide enough vitamin A and vitamin E for consumers as a total replacement of one or two regular meals. Consequently, the meal-replacement shakes hold the potential to emerge as healthy products for this fast-paced era if the composition and structure were carefully designed and calculated.

Abstract Because of the complex etiology, the treatment of gastric cancer is a formidable challenge for contemporary medical. The current treatment method focuses on traditional surgical procedures, supplemented by other treatments. Among these other treatments, Traditional Chinese Medicine (TCM) plays an important role. Here, we used the systems pharmacology approach to reveal the potential molecular mechanism of PRGRC on gastric cancer which composes of Pinellia ternata (Thunb.) Breit., Rheum palmatum L., Gentiana scabra Bunge, Radix Aucklandiae and Citrus aurantium L. This approach combines pharmacokinetics analysis with pharmacodynamics evaluation for the active compounds screening, targets prediction and pathways assessing. Firstly, through pharmacokinetic evaluation and target prediction models, 83 potential compounds and 184 gastric cancer-related targets were screened out. Then, the results of network analysis suggested that the targets of PRGRC were mainly involved two aspects: apoptosis and inflammation. Finally, we verified the reliability of the above analysis at the cellular level by using naringenin and luteolin with good pharmacokinetic activity as representative compounds. Overall, we found that PRGRC could influence the development of gastric cancer from a multi-scale perspective. This study provided a new direction for analyzing the mechanism of TCM.

Abstract Background Targeting tumor microenvironment (TME) may provide therapeutic activity and selectivity in treating cancers. Therefore, an improved understanding of the mechanism by which drug targeting TME would enable more informed and effective treatment measures. Glycyrrhiza uralensis Fisch (GUF, licorice), a widely used herb medicine, has shown promising immunomodulatory activity and anti-tumor activity. However, the molecular mechanism of this biological activity has not been fully elaborated. Methods Here, potential active compounds and specific targets of licorice that trigger the antitumor immunity were predicted with a systems pharmacology strategy. Flow cytometry technique was used to detect cell cycle profile and CD8+ T cell infiltration of licorice treatment. And anti-tumor activity of licorice was evaluated in the C57BL/6 mice. Results We reported the G0/G1 growth phase cycle arrest of tumor cells induced by licorice is related to the down-regulation of CDK4-Cyclin D1 complex, which subsequently led to an increased protein abundance of PD-L1. Further, in vivo studies demonstrated that mitigating the outgrowth of NSCLC tumor induced by licorice was reliant on increased antigen presentation and improved CD8+ T cell infiltration. Conclusions Briefly, our findings improved the understanding of the anti-tumor effects of licorice with the systems pharmacology strategy, thereby promoting the development of natural products in prevention or treatment of cancers.

The cold-adapted and/or salt-tolerant enzymes from marine microorganisms were confirmed to be meritorious tools to enhance the efficiency of biocatalysis in industrial biotechnology. We purified and characterized a dextranase CeDex from the marine bacterium Cellulosimicrobium sp. THN1. CeDex acted in alkaline pHs (7.5–8.5) and a broad temperature range (10–50°C) with sufficient pH stability and thermostability. Remarkably, CeDex retained approximately 40% of its maximal activities at 4°C and increased its activity to 150% in 4 M NaCl, displaying prominently cold adaptation and salt tolerance. Moreover, CeDex was greatly stimulated by Mg2+, Na+, Ba2+, Ca2+ and Sr2+, and sugarcane juice always contains K+, Ca2+, Mg2+ and Na+, so CeDex will be suitable for removing dextran in the sugar industry. The main hydrolysate of CeDex was isomaltotriose, accompanied by isomaltotetraose, long-chain IOMs, and a small amount of isomaltose. The amino acid sequence of CeDex was identified from the THN1 genomic sequence by Nano LC–MS/MS and classified into the GH49 family. Notably, CeDex could prevent the formation of Streptococcus mutans biofilm and disassemble existing biofilms at 10 U/ml concentration and would have great potential to defeat biofilm-related dental caries.

α-Tocopherol has been widely used in medicine, cosmetics, and food industry as a nutritional supplement and antioxidant. However, α-tocopherol showed low bioaccessibility, and there is a widespread α-tocopherol deficiency in society today. The preparation of oil-in-water emulsions with high safety and low-calorie property is necessary. The aim of this research was to investigate the effects of different protein emulsifiers (whey protein isolate (WPI), soy protein isolate (SPI), and sodium casein (SC)) on the properties of emulsions delivery system, and diacylglycerol (DAG) was picked as a low-accumulated lipid. The interfacial changes, microstructural alterations, and possible interactions of the protein-stabilized DAG emulsions were investigated during the in vitro digestion. The results show that different proteins affect the degree of digestibility and α-tocopherol bioaccessibility of the emulsions. Both WPI- and SPI-coated emulsions showed good digestibility and α-tocopherol bioaccessibility (77.64 ± 2.93%). This might be due to the strong hydrolysis resistance of WPI (β-lactoglobulin) and the good emulsification ability of SPI. The SC-coated emulsion showed the lowest digestibility and α-tocopherol bioaccessibility, this might be due to the emulsification property of hydrolysis products of SC and the potential interaction with calcium ions. This study provides new possibilities for the application of DAG emulsions in delivery systems.

Abstract Background Discordance between traditional cytogenetic and molecular cytogenetic tests is rare but not uncommon. The explanation of discordance between two genetic methods is difficult but especially important for genetic counseling, particularly for prenatal genetic diagnosis. Case presentation Two unrelated fetuses were diagnosed with cardiac defects by prenatal ultrasound examination, and invasive cordocentesis was performed to obtain cord blood samples for prenatal genetic diagnosis. For both fetuses, chromosomal microarray analysis (CMA) detected a novel approximately 27-Mb mosaic duplication with a high copy number of approximately six to seven copies on chromosome 8q24.1q24.3 that was not identified by karyotyping. To exclude artificial errors and validate laboratory detection results, multiple procedures including copy number variation sequencing, fluorescence in situ hybridization, and short tandem repeat and single-nucleotide polymorphism genotype comparison were performed, confirming the discordant results between CMA and karyotyping. The potential causes of discordance between CMA and karyotyping using fetal blood lymphocytes are discussed; we suggest that extrachromosomal DNA or cell-free DNA fragmentation originating from certain tumor tissues with 8q24.1q24.3 duplication might deserve further investigation. Conclusions This study may be helpful for prenatal evaluation and genetic counseling for subsequent patients with similar mosaic 8q24.1q24.3 duplications. Additionally, more cases and further research are needed to understand whether mosaic 8q24.1q24.3 duplication is associated with certain genetic disorders and to investigate the causes of discordance between molecular and morphological methods.

Abstract In lime concretion black soil, a two-factor (tillage and irrigation) split block experiment from 2015 to 2017 was conducted to identify whether their combination is suitable for the improvement of winter wheat yield and water use efficiency. The main treatments were subsoiling (SS) and rotary tillage (RT), with secondary treatments of three irrigation regimes: no irrigation during the whole growth period (W0), irrigation at jointing stage (W1), and irrigation at both jointing and anthesis stages (W2). In combination with a soil column experiment, the contribution of the root system in different soil layers to yield was clarified. The results indicated that both tillage and irrigation significantly influenced the spatiotemporal distributions of the root systems and yield components, while tillage produced the strongest effect. Compared with RT, SS significantly promoted the root penetration and delayed root senescence in deep soil layers. With increasing soil depth, each root configuration parameter (dry root weight density, DRWD; root length density, RLD; root surface area per unit area, RSA; root volume per unit area, RV) gradually decreased, and the peak appearance times of each root parameter in RT and three parameters (RLD, RSA and RV) in SS were postponed from heading to anthesis and from anthesis to filling stage, respectively. The average post-peak attenuation values at soil layers from 60 to 100 cm in W1 were less than those in W0 and W2. SSW1 generated the highest grain yields, with an average increase of 31.88% compared with the yield in RTW0. Root systems at three soil layers (0–40 cm, 40–80 cm and below 80 cm) differentially contributed to grain yields with 78.32%, 12.09% and 9.59%, respectively. The growth peak of the deep root system in SSW1 was postponed to the filling stage, and the post-peak attenuation declining rates were also slowed. Therefore, SSW1 is an effective cultivation method improving grain yields and water use efficiency in lime concretion black soil.

Bladder cancer is one of the concerning malignancies worldwide, which is lacking effective targeted therapy. Gene therapy is a potential approach for bladder cancer treatment. While, a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment in vivo. In this study, we confirmed that the bladder cancer had CD44 overexpression and small interfering RNAs (siRNA) with high interfere to Bcl2 oncogene were designed and screened. Then hyaluronic acid dialdehyde (HAD) was prepared in an ethanol-water mixture and covalently conjugated to the chitosan nanoparticles (CS-HAD NPs) to achieve CD44 targeted siRNA delivery. The in vitro and in vivo evaluations indicated that the siRNA-loaded CS-HAD NPs (siRNA@CS-HAD NPs) were approximately 100 nm in size, with improved stability, high siRNA encapsulation efficiency and low cytotoxicity. CS-HAD NPs could target to CD44 receptor and deliver the therapeutic siRNA into T24 bladder cancer cells through a ligand-receptor-mediated targeting mechanism and had a specific accumulation capacity in vivo to interfere the targeted oncogene Bcl2 in bladder cancer. Overall, a CD44 targeted gene delivery system based on natural macromolecules was developed for effective bladder cancer treatment, which could be more conducive to clinical application due to its simple preparation and high biological safety.

This paper applies the elitist genetic algorithm to the electric vehicle routing problem with time window. In initialization, the paper proposes an improved neighbor routing initialization method for adaptive elitist genetic algorithm. The improved neighbor routing method is used to select the nearest EV customer as the next route to be scheduled and make the route start from the suitable first customer in the initialization of the elitist GA. It makes the scheduled route begins with a neighboring directionality, which can be inherited in selection, crossover, and mutation operations. For effective convergence, new adaptive crossover probability and mutation probability are provided to make the algorithm converge faster. Experimental studies on randomly distributed customers and Solomon benchmark cases show the effective performance of the algorithm. The algorithm is demonstrated in the simulation of a U.S. Postal Service system.

Graphene silicon devices have attracted significant attention due to their outstanding electronic and optical properties. By electrically tuning the Fermi level of the monolayer graphene sheet, electro-optic (EO) modulators have been widely analyzed. Despite significant progress has been achieved on high-speed modulation with integrated graphene silicon waveguides, it remains challenging to realize a high modulation efficiency since the light absorption in graphene is limited. Here, we propose and experimentally demonstrate a high efficiency EO modulator using a graphene-assisted tapered silicon ring resonator, where the tapered zone is covered by a graphene/graphene capacitor. This graphene-assisted tapered zone strongly enhances the graphene-light interaction that the achieved static and dynamic modulation (1KHz) depths are up to 26 dB and 12 dB, respectively. Physical mechanism of the modulation based on this nanostructure is also discussed in detail. The proposed nanostructure provides a promising alternative method for high-performance EO modulator, which is essential for the on-chip optical communication, optical computing and optical signal processing.

Current studies indicated that immune-associated genes (IAGs) have important roles in the occurrence and development of bladder cancer (BC). The current work aims to identify the prognostic values of IAGs in BC and establish a prognostic signature based on IAGs. RNA sequencing data and protein expression data were used to identify differentially expressed IAGs in BC. An IAGs based signature was further constructed and the prognostic and predictive values of the signature were evaluated by survival analysis and nomogram. RNA isolation and reverse transcription-quantitative PCR (RT-qPCR) were further performed to investigate the expression levels of IAGs in BC cells and were used to explore the relationship between IAGs and M2 tumour-associated macrophages (TAMs) secreted transforming growth factor-β1 (TGF-β1) in BC cells. We selected five IAGs to develop an IAGs signature model, which were significantly related to survival outcomes of BC patients. RT-qPCR showed that five IAGs were significantly differentially expressed and three IAGs were positively correlated with M2 TAMs secreted TGF-β1 in T24 cells. We identified and validated an IAGs based signature to predict the prognosis of BC patients. Furthermore, M2 TAMs may promote the expression of IAGs in BC via the TGF-β1 signalling pathway.

Background: Diabetic cardiomyopathy (DCM), the main complication of diabetes mellitus, presents as cardiac dysfunction by ventricular remodeling. In addition, the inhibition of P2X7 purinergic receptors (P2X7R) alleviates cardiac fibrosis and apoptosis in Type 1 diabetes. However, whether exercise training improves cardiac remodeling by regulating P2X7R remains unknown.Methods: Db/db mice spontaneously induced with type 2 diabetes and high-fat diet (HFD) and mice with streptozotocin (STZ)-induced type 2 diabetes mice were treated by 12-week treadmill training. Cardiac functions were observed by two-dimensional echocardiography. Hematoxylin-eosin staining, Sirius red staining and transmission electron microscopy were respectively used to detect cardiac morphology, fibrosis and mitochondria. In addition, real-time polymerase chain reaction and Western Blot were used to detect mRNA and protein levels.Results: Studying the hearts of db/db mice and STZ-induced mice, we found that collagen deposition and the number of disordered cells significantly increased compared with the control group. However, exercise markedly reversed these changes, and the same tendency was observed in the expression of MMP9, COL-I, and TGF-β, which indicated cardiac fibrotic and hypertrophic markers, including ANP and MyHC expression. In addition, the increased Caspase-3 level and the ratio of Bax/Bcl2 were reduced by exercise training, and similar results were observed in the TUNEL test. Notably, the expression of P2X7R was greatly upregulated in the hearts of db/db mice and HFD + STZ-induced DM mice and downregulated by aerobic exercise. Moreover, we indicated that P2X7R knock out significantly reduced the collagen deposition and disordered cells in the DM group. Furthermore, the apoptosis levels and TUNEL analysis were greatly inhibited by exercise or in the P2X7R−/− group in DM. We found significant differences between the P2X7R−/− + DM + EX group and DM + EX group in myocardial tissue apoptosis and fibrosis, in which the former is significantly milder. Moreover, compared with the P2X7R−/− + DM group, the P2X7R−/− + DM + EX group represented a lower level of cardiac fibrosis. The expression levels of TGF-β at the protein level and TGF-β and ANP at the genetic level were evidently decreased in the P2X7R−/− + DM + EX group.Conclusion: Aerobic exercise reversed cardiac remodeling in diabetic mice at least partly through inhibiting P2X7R expression in cardiomyocytes.

Unevenness is one of the important parameters for evaluating yarn quality, but the current prediction accuracy of yarn unevenness is low. One of the important reasons is that there are few sample dataset for yarn unevenness prediction. For this problem, this paper applies generalized regression neural network to predict the unevenness of the yarn. Then, the generalized regression neural network is optimized by using particle swarm optimization, fruit fly optimization algorithm, and gray wolf optimizer, respectively. Finally, the optimized models were experimentally validated for their effectiveness. The experimental results show that the generalized regression neural network optimized by gray wolf optimizer has the best effect and the fastest optimization speed; the generalized regression neural network optimized by particle swarm optimization algorithm has the middle optimization speed; the generalized regression neural network optimized by fruit fly optimization algorithm has the worst effect and the slowest optimization speed.

Abstract Background Bladder cancer (BC) is a commonly diagnosed malignant tumor in the urinary system, with a high morbidity and a high recurrence rate. Current studies indicated that metabolism-associated genes (MAGs) having critical roles in the etiology of BC. The present study aims to identify differentially expressed MAGs and construct a MAGs based prognostic risk signature for BC by using The Cancer Genome Atlas (TCGA) database and proteomics data. Methods RNA-sequence data from the TCGA database and proteomics data from our BC samples were used to identify differentially expressed MAGs and construct a MAGs based prognostic signature in BC. Subsequently, survival analysis and nomogram were used to evaluate the prognostic and predictive value of the MAGs based signature in BC. RNA isolation and reverse transcription‑quantitative PCR (RT-qPCR) were further performed to investigate the expression levels of MAGs in BC cells and explore the relationship between MAGs and M2 tumor associated macrophages (TAMs) secreted transforming growth factor-β1 (TGF-β1) in BC cells. Results A total of 23 differentially expressed MAGs were identified and five MAGs were finally used to construct a MAGs based signature. Survival analysis revealed that the MAGs based signature was closely correlated with the survival outcomes of patients with BC. A nomogram with the MAGs based signature risk score and clinical features was also constructed to facilitate the individualized prediction of BC patients. RT-qPCR showed that five MAGs were significantly differentially expressed and the expression levels of three MAGs were positively correlated with M2 TAMs secreted TGF-β1 in T24 cells. Conclusions Our study identified novel prognostic MAGs and constructed a MAGs based signature, which can be used as an independent factor in evaluating the prognosis of patients with BC. Furthermore, M2 TAMs may promote the expression of MAGs via the TGF-β1 signaling pathway in the microenvironment of BC. Further clinical trials and experimental explorations are needed to validate our observations in BC.

As the gas station is an important part of urban natural gas transmission and distribution system, the level of its construction management has a very significant impact on construction quality, project schedule, investment benefit and safe operation of gas station after it is put into service. An important way to improve the construction management of gas station is to constantly innovate the construction management methods and the technical means. Taking a large gas station in Tangshan Harbour Economic Development Zone as research object, where the Building Information Modeling(BIM) technology was applied to the construction management of gas station for the first time, research on the application of BIM technology in the station planning and design, simulation of complex process construction, integrated management of pipeline network, cost control and facility management of gas station was carried out, and a construction management method of gas station based on BIM was proposed. The practice shows that BIM technology can significantly improve the construction management level of gas station, and ensure the realization of construction quality target, schedule target and investment benefit of the station, which further provides reference for the construction management of similar project.

Abstract Low-rank coal reservoirs of Badaowan Formation and Xishanyao Formation are mainly developed in Junggar Basin. This paper discussed their features and coalbed methane (CBM) exploration potential based on geological survey, coal samples testing and mathematical fitting analysis. The pores are mainly small-micro- and large pores, and the porosity is 3.25–27.4% with an average of 9–10.51%; and macro-cracks and micro-fissures are well developed leading to a great variation of the permeability. The shallow coal reservoirs are mostly undersaturated, and the gas saturation tends to increase toward the deep coalbed. The J2x has a stronger methane adsorption and storage capacity than that of J1b and better physical properties, making CMB recovery easier. The coalbed reservoirs in middle-east of southern margin, eastern part and hinterland of Junggar Basin reach methane-rich to extremely methane-rich coalbeds and have strong ability to adsorb and store CBM. Coal seam gas shows generally, and the measured gas-bearing property is good. Low-rank CBM accounts for the majority of CBM resources in the basin. According to Langmuir volume, the gas provinces are classified into four types of blocks, i.e., CBM-poor ( 20 m3/t). The relatively CBM-rich blocks cover block of well Qing 1 to Qi 8, Changji–Urumqi–Fukang area and slope belt of northwest margin to basin hinterland; while the CBM-rich blocks include most of eastern Junggar Basin. Since 2005, a series of special exploration and research of CBM have been carried out successively, and significant progress has been made in exploration of deep and shallow combination, conventional (gas) and unconventional (gas) combination. Recently shallow CBM exploration has achieved gas extraction at Dahuangshan coal mine, industrial gas flow wells in western Baiyanghe, and breakthrough of deep CBM exploration in Baijiahai area has been made, which confirmed the great development potential of low-rank CBM. The southern margin and the east of Junggar Basin have become the new frontier of low-rank CBM exploration in China.