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Abstract Drug resistance remains a significant challenge in cancer treatment. Recently, the interactions among various cell types within the tumor microenvironment (TME) have deepened our understanding of the mechanisms behind treatment resistance. Therefore, this review aims to synthesize current research focusing on infiltrating cells and drug resistance suggesting that targeting the TME could be a viable strategy to combat this issue. Numerous factors, including inflammation, metabolism, senescence, hypoxia, and angiogenesis, contribute to drug resistance could be a viable strategy to combat this issue. Overexpression of STAT3 is commonly associated with drug-resistant cancer cells or stromal cells. Current research often generalizes the impact of stromal cells on resistance, lacking specificity and statistical robustness. Thus, future research should take notice of this issue and aim to provide high-quality evidence. Despite the existing limitations, targeting the TME to overcome therapy resistance hold promising and valuable potential.

To investigate the changes of phenolic metabolite during different grains fermentation stages of Chinse Baijiu, the ultra-performance liquid chromatography-quadrupole time of-flight mass spectrometry (UHPLC-QTOF-MS) was applied to identify and analyze the different phenolic metabolites, combined with principal component analysis and partial least squares discriminant analysis. Results indicated that significant differences in phenolic metabolites during different fermentation stages were found. Among the 231 phenolic metabolites detected, 36, 31, 19, 23, 14, and 50 differential phenolic metabolites were screened between different groups using partial least squares discriminant analysis. Twelve metabolic pathways with high correlation of differential phenolic metabolites and 23 main participating differential metabolites were identified through KEGG metabolic pathway enrichment analysis. The present study preliminarily revealed the differences of phenolic metabolites at different fermentation stages, and providing a theoretical basis for the further improving of the taste and quality of Chinese Baijiu.

Bladder cancer stands as a prevalent global malignancy, exhibiting notable sex-based variations in both incidence and prognosis. Despite substantial strides in therapeutic approaches, the formidable challenge of drug resistance persists. The genomic landscape of bladder cancer, characterized by intricate clonal heterogeneity, emerges as a pivotal determinant in fostering this resistance. Clonal evolution, encapsulating the dynamic transformations within subpopulations of tumor cells over time, is implicated in the emergence of drug-resistant traits. Within this review, we illuminate contemporary insights into the role of clonal evolution in bladder cancer, elucidating its influence as a driver in tumor initiation, disease progression, and the formidable obstacle of therapy resistance.

Abstract The authors devote a quantitative assessment on the synchronisation capability of a line‐start permanent magnet synchronous motor (LSPMSM) equipped with a hybrid rotor. The quantitative assessment is realised by determining a load criterion consisting of load torques and inertias under which the motor will just synchronise. During the process of load‐criterion determination, close attention is paid to parameters governing the motor synchronisation behaviour. Following the principle of stator‐current error minimisation, the time‐variant magnetising inductances and permanent magnet (PM) flux linkages of the analysed LSPMSM are simplified into slip‐dependent constants via the simple and robust genetic algorithm (GA). The load criterion is then obtained after the establishment of a dynamic motor model involving the simplified parameters. Prototyping tests focused on motor speed‐time responses under different mechanical loads are carried out to validate the obtained load criterion and the paper analyses.

Abstract As a type of magnetic device being able to realize contact‐free power transmission together with sufficient volumetric torque density, the field‐modulated magnetic gear (FMMG) has become a promising alternative to the mechanical gear having rigid construction yet suffering lots of issues generated by the continuous teeth friction. The conventional magnetic gears (MGs) that behave as simple copies of their mechanical counterparts and can be roughly defined as origination of the FMMG are briefly introduced at first. Subsequently, the topology and material advancements proposed to improve operational performance of the FMMG are comprehensively summarised so as to clarify its current development status. Finally, potential applications of the FMMG due to its inherent advantages are compared against the existent challenges. The review aims to provide referable guidelines for researchers working at the field of high‐performance MGs.

Sorghum is an important crop, and starch and phenolic compounds are major and important components in the sorghum grain. However, the underlying critical genetic elements contributing to the rich portfolio of nutrients in sorghum grains are largely unknown. Transcriptomic methods were employed to characterize the expression patterns at five different grain developmental stages of Hongyingzi (an important brewing sorghum), and another two grain sorghums, Jinuoliang 1 and Hongliangfeng 1, for comparison. The uniquely expressed genes were identified at each developmental stage of Hongyingzi when compared with the other two sorghum cultivars. The co-regulated genes at different developmental stages and the regulatory network were determined; the determinant genes and single-nucleotide polymorphisms located at the promoters of these genes involved in starch and phenolic compounds biosynthetic pathways were also identified. These results will provide insights into the potential regulatory network and further contribute to the clarification of the key determinant genes involved in the biosyntheses of starch and phenolic compounds. Meanwhile, some new transcripts and genes were identified at five different developmental stages of grains of the three sorghum cultivars. Our work can provide impetus for further study of the genes responsible for the biosynthesis of starch and phenolic compounds in the sorghum grain, and pave a way for functional validation of a batch of potential genes and single-nucleotide polymorphisms proposed in current work.

To investigate the changes in phenols and antioxidant capacity in fermented grains during different stages of the fermentation process (Xiasha, Zaosha, and single-round stages) of Maotai-flavored liquor, the total phenolic contents of 61 samples, collected in different stages, were analyzed via the Folin–Ciocalteu method, and the phenolic compounds were then identified by high-performance liquid chromatography (HPLC). Subsequently, the antioxidant activities were determined using the DPPH free radical scavenging rate and ABTS and FRAP antioxidant capacities. The correlations among the total phenolic contents, individual phenolics, and three antioxidant activities of the samples were analyzed. The results show that the total phenolic contents of the fermented samples did not change significantly in the Xiasha and Zaosha stages but showed an upward trend in the single-round stage. A total of 12 phenol acids were identified in the fermented grains, including 5 phenolic acids (e.g., ferulic acid and caffeic acid), 4 flavonoids (e.g., luteolin and apigenin), and 3 proanthocyanidins (e.g., apigeninidin), for which the DPPH free radical scavenging rates and ABTS and FRAP antioxidant capacities of all of the fermented grain samples ranged from 78.91 ± 4.09 to 98.57 ± 1.52%, 3.23 ± 0.72 to 13.69 ± 1.40 mM Trolox, and 5.06 ± 0.36 to 14.10 ± 0.69 mM FeSO4, respectively. The total phenolic contents of the fermented grain samples were significantly and positively correlated with the ABTS and FRAP (p ≤ 0.05), while no significant correlations were found between total phenolic content and DPPH. In general, the total phenolic content, phenolic substances, and antioxidant capacity of the fermented grains exhibited changes during the fermentation process in liquor production, and the phenolic components contributed more to the antioxidant properties of the fermented grains. The present study provides a theoretical reference for analyzing the dynamic changes and antioxidant properties of functional phenolic components in fermented grains.

Background: We aimed to identify two new prognostic subtypes and create a predictive index for prostate cancer (PCa) patients based on ferroptosis database. Methods: The nonnegative matrix factorization approach was used to identify molecular subtypes. We investigate the differences between cluster 1 and cluster 2 in terms of clinical features, functional pathways, tumour stemness, tumour heterogeneity, gene mutation and tumour immune microenvironment score after identifying the two molecular subtypes. Colony formation assay and flow cytometry assay were performed. Results: The stratification of two clusters was closely connected to BCR-free survival using the nonnegative matrix factorization method, which was validated in the other three datasets. Furthermore, multivariate Cox regression analysis revealed that this classification was an independent risk factor for patients with PCa. Ribosome, aminoacyl tRNA production, oxidative phosphorylation, and Parkinson's disease-related pathways were shown to be highly enriched in cluster 1. In comparison to cluster 2, patients in cluster 1 exhibited significantly reduced CD4+ T cells, CD8+ T cells, neutrophils, dendritic cells and tumor immune microenvironment scores. Only HHLA2 was more abundant in cluster 1. Moreover, we found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of C4-2B and DU145 cell lines. Conclusions: We discovered two new prognostic subtypes associated with immunological dysfunction in PCa patients based on ferroptosis-related genes and found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of PCa cell lines.

Dipeptides have been shown to be an important taste substance in alcoholic beverages. However, the characterization of dipeptides in Chinese liquors was poor. Here, dansylation combined with liquid chromatography – mass spectrometry was employed to analyze dipeptides in eight liquors of two flavors. Consequently, 35 dipeptides were identified from liquors and 32 of them were quantified. Dipeptide quantification showed LODs smaller than 2.5 ng/mL. The calibration curves showed concentration spans from two to three orders of magnitude with satisfactory linearity. The matrix effects in low and high concentrations were from −25.71 % to 24.19 % and −14.82 % to 20.73 %, respectively. Intra- and inter-day precision is lower than 15 % for both low and high concentrations. The dipeptide contents in sauce flavor liquors were higher than those in strong flavor liquors. Ala- and -Phe dipeptides showed their unique trends between sauce and strong flavor liquors. This study provides new clues to evaluate taste of liquors.

The water produced during the oxidative esterification reaction occupies the active sites and reduces the activity of the catalyst. In order to reduce the influence of water on the reaction system, a hydrophobic catalyst was prepared for the one-step oxidative esterification of methylacrolein (MAL) and methanol. The catalyst was synthesized by loading the active component Au onto ZnO using the deposition–precipitation method, followed by constructing the silicon shell on Au/ZnO using tetraethoxysilane (TEOS) to introduce hydrophobic groups. Trimethylchlorosilane (TMCS) was used as a hydrophobic modification reagent to prepare hydrophobic catalysts, which exhibited a water droplet contact angle of 111.2°. At a temperature of 80 °C, the hydrophobic catalyst achieved a high MMA selectivity of over 95%. The samples were characterized using XRD, N2 adsorption, ICP, SEM, TEM, UV-vis, FT-IR, XPS, and water droplet contact angle measurements. Kinetic analysis revealed an activation energy of 22.44 kJ/mol for the hydrophobic catalyst.

While the larger photosensitive area of Geiger-mode avalanche photodiodes (GmAPDs) enhances their detection range and signal collection, improving their utility in weak light detection, their practicality is limited by a long recovery time, high afterpulsing probability (AP) and excessive jitter. Utilizing a dynamic memristor as a quenching resistor, this research improves the count rate of a large-size GmAPD by 100× at an overvoltage of 2.5 V, compared with a fixed resistor-quenched GmAPD. Furthermore, at a photon pulse frequency of 1 MHz jitter time is reduced from 3.60 ns to 0.48 ns, and the afterpulsing probability is effectively mitigated from 30.88% to 8.58%.

Distiller’s grains (DGs) are solid mixtures that remain after the production of alcoholic beverages. A large amount of DGs is produced each year during the brewing process. Currently, they are mostly used as a feedstock or substrate in the feed industry. However, the lack of a comprehensive understanding of the chemical composition of DGs is a major constraint on their further development and application for high-value-added usages. Some studies were published on the bioactive constituents of DGs in several different types of journals. Data were therefore collated to provide a comprehensive overview of these natural products. DGs are rich in phenols, phytosterols, and fatty acids, in addition to general lipid and protein constituents. These compounds and their related extracts possess diverse biological activities, including antioxidant, anti-inflammatory, and anti-hyperglycaemic effects. We hope that this review will provide research incentives for the further development and utilisation of DGs to develop high-value-added products.

Polyphenols, as common components with various functional activities in plants, have become a research hotspot. However, researchers have found that the bioavailability and bioactivity of plant polyphenols is generally low because they are usually in the form of tannins, anthocyanins and glycosides. Polyphenol-rich fermented foods (PFFs) are reported to have better bioavailability and bioactivity than polyphenol-rich foods, because polyphenols are used as substrates during food fermentation and are hydrolyzed into smaller phenolic compounds (such as quercetin, kaempferol, gallic acid, ellagic acid, etc.) with higher bioactivity and bioavailability by polyphenol-associated enzymes (PAEs, e.g., tannases, esterases, phenolic acid decarboxylases and glycosidases). Biotransformation pathways of different polyphenols by PAEs secreted by different microorganisms are different. Meanwhile, polyphenols could also promote the growth of beneficial bacteria during the fermentation process while inhibiting the growth of pathogenic bacteria. Therefore, during the fermentation of PFFs, there must be an interactive relationship between polyphenols and microorganisms. The present study is an integration and analysis of the interaction mechanism between PFFs and microorganisms and is systematically elaborated. The present study will provide some new insights to explore the bioavailability and bioactivity of polyphenol-rich foods and greater exploitation of the availability of functional components (such as polyphenols) in plant-derived foods.

Liquid metal embrittlement (LME) in Zn-based coating plates during hot stamping is an abnormal phenomenon where intimate contact between liquid Zn and a steel matrix results in the penetration of liquid Zn into the matrix, causing ruptures. In order to alleviate LME phenomenon, this paper designed a series of eutectic Zn-Al-Mg coating alloys to improve the uniformity of the Zn element distribution in the coating during heat treatment and inhibit the reaction between Fe and Zn. The high temperature mechanical properties of the coated steels are determined using thermal simulation to calculate the relative reduction in fracture energy, which is used to evaluate the LME level of the different composition coatings. It is suggested that the Zn-4.5Al-3.0Mg coating shows the highest LME resistance at 920 °C. The microstructure of these Zn-Al-Mg coated steels is observed after austenitization at 850 °C~920 °C for 3 min, which shows that the uniformity of the microstructure after austenitizing is affected by the composition of the coating and the austenitizing temperature. The higher temperature benefits the homogenization of the coating and steel and inhibits LME. The findings of this study provide valuable insights for the development of ternary Zn based LME resistant coatings.

Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. Therefore, methods to comprehensively analyze all glyco-polymer classes on EVs are urgently needed. In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. The results indicate that GNA can identify EV-associated glyco-polymers that would remain undetected with conventional MS methods. Specifically, predictions based on GNA identified a GAG (hyaluronan) with varying abundance on EVs from two different melanoma cell lines. Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions.

High-capacity and structural stable cathode materials are challenges for sodium-ion batteries. Here, the authors report a layered P2-Na0.612K0.056MnO2 with large-sized K+ riveted in the Na-layers to enable 0.9 Na+ (de)insertion with a reversible phase transition of P2-P’2.

Abstract The torque‐slip characteristic curve (TSCC) applicable to quantitative assessment on the starting and synchronizing performance of a line‐start permanent magnet synchronous motor (LSPMSM) equipped with a hybrid rotor is determined herein. The TSCC determination starts with separating the hybrid‐rotor LSPMSM into an induction motor and a permanent magnet (PM) motor in which the former dominates part of the TSCC and the latter governs the rest. Then, the electromagnetic torques of the two subsidiary motors are calculated by means of a two‐dimensional (2‐D) semi‐numerical technique combining the subdomain method and the finite difference method (FDM). Finally, the TSCC of the hybrid‐rotor LSPMSM is acquired through adding the average components of the calculated electromagnetic torques of the subsidiary motors. Accuracy of the obtained TSCC is validated by results from the finite‐element analysis (FEA) and prototype test.

Synergistic strengthening is increasingly explored for developing high-performance copper matrix composite. In this work, the hybrid copper matrix composites reinforced with carbon nanotubes (CNTs) and micro- TiB2 particles（（CNTs-TiB2）/Cu composites）were prepared by electroless copper plating, powder metallurgy and hot extrusion. The arc erosion resistance of the hybrid copper matrix composites was studied in JF04C electrical contact testing system. And the synergistic effect of CNTs and TiB2 particles in different content ratios on the arc erosion resistance of composites was analyzed emphatically. The action mechanism of CNTs and TiB2 particles in arc erosion process is discussed in detail. Results show that the arc duration and arc energy of the hybrid copper matrix composites are lower than that of copper matrix composites single reinforced with CNTs or TiB2 particles. When the volume fraction of CNTs is 4.2% (The content of TiB2 particles is 1.6%), the arc erosion resistance of the hybrid copper matrix composites is optimal. In arc erosion process, CNTs can form a network structure parallel to the extrusion direction in copper matrix, and the continuous CNTs network structure can effectively disperse cathode arc, promote arc movement, increase work function of copper matrix composites, inhibit electron emission and reduce total emission current density. And the micro- TiB2 particles are helpful to improve the viscosity of molten pool, which can reduce the material mass loss and erosion pit on the surface of composites. Under the combined actions of CNTs and TiB2 particles (4.2CNTs-1.6TiB2)/Cu composite presents better arc erosion resistance stability, lower arc duration and energy.

Abstract Background Cancer cell-derived extracellular vesicles (EVs) have previously been shown to contribute to pre-metastatic niche formation. Specifically, aggressive tumors secrete pro-metastatic EVs that travel in the circulation to distant organs to modulate the microenvironment for future metastatic spread. Previous studies have focused on the interface between pro-metastatic EVs and epithelial/endothelial cells in the pre-metastatic niche. However, EV interactions with circulating components such as low-density lipoprotein (LDL) have been overlooked. Results This study demonstrates that EVs derived from brain metastases cells (Br-EVs) and corresponding regular cancer cells (Reg-EVs) display different interactions with LDL. Specifically, Br-EVs trigger LDL aggregation, and the presence of LDL accelerates Br-EV uptake by monocytes, which are key components in the brain metastatic niche. Conclusions Collectively, these data are the first to demonstrate that pro-metastatic EVs display distinct interactions with LDL, which impacts monocyte internalization of EVs.

Abstract With an exponential increase in extracellular vesicle (EV) studies in the past decade, focus has been placed on standardization of experimental design to ensure inter‐study comparisons and validity of conclusions. In the case of in vitro assays, the composition of cell culture media is important to consider for EV studies. In particular, levels of lipoproteins, which are critical components of the interstitial fluid, should be taken into consideration. Results from this study reveal that lipoprotein levels in cell culture medium impact the effects that EVs have on recipient cells. Additionally, evidence of EV binding and fusion to lipoprotein‐like structures in plasma is provided. However, it is unclear whether the impact of lipoproteins in cell culture is due to direct interactions with EVs, indirect effects, or a combination of both mechanisms. Taken together, cell culture studies performed in the absence of physiological levels of lipoproteins are unlikely to reflect interactions that occur between EVs and recipient cells in an in vivo environment.

Synergistic strengthening is increasingly explored for developing high-performance metal matrix composites. In the present work, copper matrix composites reinforced with carbon nanotubes (CNTs) and TiB2 microparticles were fabricated via electroless deposition, powder metallurgy, hot extrusion, and water quenching. The synergistic strengthening effect of the nano-and micro-reinforcements was elaborated and analyzed based on experimental investigation and theoretical calculation. (1CNT-4TiB2)/Cu composite exhibited a better combination of the tensile strength of 375 MPa with elongation of 32.4% than other composites, representing 86.3%, 71.5%, and 22.8% strength increment in comparison with pure Cu, 4TiB2/Cu composite, and 1CNT/Cu composite, respectively. The strengthening efficiency of CNTs in (1CNT-4TiB2)/Cu composite is markedly higher than that in 1CNT/Cu composite (126.7 and 82.3, respectively), confirming the synergistic strengthening effect in enhancing the mechanical properties. Quantitative analysis and experimental characterization indicated that the thermal mismatch and load transfer mechanism of CNTs were the main factors contributing to the tensile strength enhancement of the composite. The synergistic strengthening effect was attributed to that TiB2 microparticles improved the homogeneous dispersion of CNTs, promoting the proportion of thermal mismatch and load transfer mechanisms. The present work may provide a new sight into improving the synergistic strengthening effect in metal matrix composites.

In this paper, we propose a verifiable quantum cloud computation scheme based on blind quantum computation which effectively solves the privacy and verifiability problem for clients when interfacing with quantum computer in cloud computation. Different from most of present works (e.g. using brickwork state as resource state), we use cluster state with grid distributed structure to realize the universal and cryptographic calculation which is more suitable for the distributed architecture of cloud computation. Throughout the process, the random key is always held by the client that effectively promote the confidentiality. Moreover, we propose a new method to make the client Alice verifies the correctness of the results through only classical calculation. Security analysis shows that cloud server Bob can only obtain the dimension of input state and cluster state from the calculation, but cannot obtain any information of the input, the output and the algorithm. Dishonest Bob will be detected during the verification.

According to the perishable characteristics of refrigerated food and the objective of minimizing the total cost, the mathematical optimization model of cold chain logistics distribution center location problem is established by introducing such constraints as the freshness and time window. In order to solve the problems of slow convergence and easy to fall into local optimal solution in the process of the traditional wolf colony optimization, an immune wolf colony hybrid algorithm is proposed to solve the location problem of distribution center. In this hybrid algorithm, the idea of vaccination of immune algorithm is introduced into the wolf colony algorithm. By adjusting the antibody concentration and selecting immune operator, the diversity of the wolf colony algorithm is improved, and then the search space of the solution is expanded; the convergence speed and solution accuracy of the wolf colony algorithm are improved by using immune memory cells and immune vaccine. The simulation results show that the immune wolf colony algorithm can quickly converge to the global optimal solution and optimize the location model of logistics distribution center. The algorithm has good feasibility and robustness.

Background: The unfolded protein response (UPR) plays a significant role in maintaining protein hemostasis in tumor cells, which are crucial for tumor growth, invasion, and resistance to therapy. This study aimed to develop a UPR-related signature and explore its correlation with immunotherapy and chemotherapy in bladder cancer.Methods: The differentially expressed UPR-related genes were put into Lasso regression to screen out prognostic genes, which constituted the UPR signature, and were incorporated into multivariate Cox regression to generate risk scores. Subsequently, the predictive performance of this signature was estimated by receiver operating characteristic (ROC) curves. The CIBERSORTx, the maftool, and Gene set enrichment analysis (GSEA) were applied to explore infiltrated immune cells, tumor mutational burden (TMB), and enriched signaling pathways in both risk groups, respectively. Moreover, The Cancer Immunome Atlas (TCIA) and Genomics of Drug Sensitivity in Cancer (GDSC) databases were used to predict responses to chemotherapy and immunotherapy.Results: Twelve genes constituted the UPR-related signature. Patients with higher risk scores had worse overall survival (OS) in training and three validation sets. The UPR-related signature was closely correlated with clinicopathologic parameters and could serve as an independent prognostic factor. M0 macrophages showed a significantly infiltrated difference in both risk groups. TMB analysis showed that the risk score in the wild type and mutation type of FGFR3 was significantly different. GSEA indicated that the immune-, extracellular matrix-, replication and repair associated pathways belonged to the high risk group and metabolism-related signal pathways were enriched in the low risk group. Prediction of immunotherapy and chemotherapy revealed that patients in the high risk group might benefit from chemotherapy, but had a worse response to immunotherapy. Finally, we constructed a predictive model with age, stage, and UPR-related risk score, which had a robustly predictive performance and was validated in GEO datasets.Conclusion: We successfully constructed and validated a novel UPR-related signature in bladder cancer, which could robustly predict survival outcomes and closely correlate with the response to immunotherapy and chemotherapy in bladder cancer.

A novel Ag/Ag2CO3/BiVO4 plasmonic photocatalyst was successfully prepared by depositing Ag nanoparticles on the surface of Ag2CO3/BiVO4 through the photoreduction reaction. Due to the existence of this novel heterojunction photocatalyst structure, not only can it prevent the photogenerated charge recombination, but the unique properties of Ag also have a great advantage in the absorption of light. The Ag/Ag2CO3/BiVO4 photocatalyst showed good catalytic performance in the degradation of oxytetracycline hydrochloride (OTH) and removal of Cr6+, and the degradation rate of OTH reached 98.0% after 150 min of illumination. The successful preparation of Ag/Ag2CO3/BiVO4 was confirmed by a series of characterization methods, and the importance of •OH and h+ radicals in the degradation of OTH was demonstrated. In addition, the photocatalytic mechanism of Ag/Ag2CO3/BiVO4 photocatalyst was systematically studied in terms of degradation of OTH and reduction of Cr6+. This study is of great importance for the development of novel plasmonic heterojunction photocatalysts and to meet future environmental requirements.

ObjectivesThis study aimed to develop and validate a hypoxia signature for predicting survival outcomes in patients with bladder cancer.MethodsWe downloaded the RNA sequence and the clinicopathologic data of the patients with bladder cancer from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/repository?facetTab=files) and the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) databases. Hypoxia genes were retrieved from the Molecular Signatures Database (https://www.gsea-msigdb.org/gsea/msigdb/index.jsp). Differentially expressed hypoxia-related genes were screened by univariate Cox regression analysis and Lasso regression analysis. Then, the selected genes constituted the hypoxia signature and were included in multivariate Cox regression to generate the risk scores. After that, we evaluate the predictive performance of this signature by multiple receiver operating characteristic (ROC) curves. The CIBERSORT tool was applied to investigate the relationship between the hypoxia signature and the immune cell infiltration, and the maftool was used to summarize and analyze the mutational data. Gene-set enrichment analysis (GSEA) was used to investigate the related signaling pathways of differentially expressed genes in both risk groups. Furthermore, we developed a model and presented it with a nomogram to predict survival outcomes in patients with bladder cancer.ResultsEight genes (AKAP12, ALDOB, CASP6, DTNA, HS3ST1, JUN, KDELR3, and STC1) were included in the hypoxia signature. The patients with higher risk scores showed worse overall survival time than the ones with lower risk scores in the training set (TCGA) and two external validation sets (GSE13507 and GSE32548). Immune infiltration analysis showed that two types of immune cells (M0 and M1 macrophages) had a significant infiltration in the high-risk group. Tumor mutation burden (TMB) analysis showed that the risk scores between the wild types and the mutation types of TP53, MUC16, RB1, and FGFR3 were significantly different. Gene-Set Enrichment Analysis (GSEA) showed that immune or cancer-associated pathways belonged to the high-risk groups and metabolism-related signal pathways were enriched into the low-risk group. Finally, we constructed a predictive model with risk score, age, and stage and validated its performance in GEO datasets.ConclusionWe successfully constructed and validated a novel hypoxia signature in bladder cancer, which could accurately predict patients’ prognosis.

The high-capacity phosphorus- (P-) based anode materials for sodium-ion batteries (NIBs) often face poor performance retentions owing to the low conductivity and large volume expansion. It is thus essential to buffer these problems by appropriately alloying with other elements such as tin (Sn) and constructing well-designed microstructures. Herein, a series of P-/Sn-based composites have been synthesized by the facile and low-cost one-step ball milling. Pair distribution function (PDF) has been employed as a hardcore quantitative technique to elucidate their structures combined with other techniques, suggesting the formation and ratios of Sn4P3 and Sn crystalline domains embedded inside an amorphous P/carbon matrix. The composite with the largest amount of Sn4P3 in the P/C matrix can deliver the most balanced electrochemical performance, with a capacity of 422.3 mA-h g−1 for 300 cycles at a current density of 1000 mA g−1. The reaction mechanism has been elucidated by 23Na and 31P solid-state nuclear magnetic resonance (NMR) investigations. The study sheds light on the rational design and concrete identification of P-/Sn-based amorphous-dominant composite materials for NIBs.

The effects of soilless substrate-based versus soil cultivation on overall fruit quality and yield in tomato (Solanum lycopersicum) were studied using the tomato cv. Zhonghua Lvbao. Experiments for tomato soilless cultivation were carried out under greenhouse conditions. Plant growth, fruit quality and yield, and physiologic traits were observed. RNA-seq and RT-PCR, as well as metabolomic analyses were performed to examine the expressed genes and metabolites under soilless substrate cultivation. The results showed that the plant height, stem diameter, and chlorophyll contents of tomato under substrate-based cultivation were increased by 37.3%, 19.8%, and 15.3%, respectively, compared with soil cultivation system. Leaf photosynthetic and transpiration rates, stomatal conductance, and root vitality of tomato, under substrate-based cultivation, increased by 29.0%, 21.2%, 43.9%, and 84.5%, respectively, compared with soil cultivation. The yield reached 7177.5 kg/667 m2, and the relative yield increased by 10.1%, compared with soil cultivation. The contents of total soluble sugar, soluble solids, and vitamin C increased by 35.7%, 19.7%, and 18.2%, respectively, higher than those of soil cultivation in tomato fruits, while nitrate content and titratable acid decreased by 29.4% and 11.8%, respectively. Therefore, substrate-based-cultivation can increase production and improve tomato fruit quality and taste. We examined the expressed genes and metabolites to explore the molecular mechanism of plant growth and overall fruit quality improvement in substrate-based cultivation. A total of 476 differentially expressed genes were identified by transcriptomes profiling, of which 321 and 155 were significantly up- and down-regulated, respectively. The results of metabolomics analysis showed that 441 metabolites were detected, where 24 and 36 metabolites were up- and down-regulated, respectively. By combining analyses of transcriptomic and metabolic groups, genes and metabolites related to the fruit quality were mainly concentrated in the vitamin B6/ascorbic acid/aldonic acidmetabolism, and glycerophospholipid metabolic pathways. Therefore, substrate-based cultivation can elevate vitamin and soluble sugar contents and the expression of fruit flavor related genes, which lays an initial background for exploring the mechanism of substrate-based cultivation, in order to improve the quality of tomato in the future.

Abstract Background Percutaneous nephrolithotomy (PCNL) remains the standard procedure for large (≥2 cm) renal calculi; however, laparoscopic pyelolithotomy (LPL) can be used as an alternative management procedure. The aim of present study was to compare LPL and PCNL in terms of efficacy and safety for the management of large renal pelvic stones. Methods A literature search was performed in Jan 2016 using electronic databases (Cochrane Central Register of Controlled Trials, Medline, and EMBASE) to identify relevant studies for the meta-analysis. Only comparative studies investigating LPL versus PCNL were included. Effect sizes were estimated by pooled odds ratio (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). Results Five randomized and nine non-randomized studies were identified for analysis, involving a total of 901 patients. Compared with PCNL, LPL provided a significantly higher stone-free rate (OR 3.94, 95% CI 2.06–7.55, P

This paper presents an experimental study on the dynamic compressive behaviour of polypropylene (PP) fibre reinforced concrete under various strain rates using split Hopkinson pressure bar (SHPB) equipment. The effects of PP fibre content and strain rate on the dynamic compressive stress-strain relationship and failure patterns were estimated. The results indicated that the addition of PP fibre enhanced the dynamic compressive properties of concrete mixtures although it resulted in a significant reduction in workability and a slight decrease in static compressive strength. Considering the workability, static compressive strength and dynamic compressive behaviour, the optimal PP fibre content was found to be 0.9 kg/m3 as the mixture exhibited the highest increase in dynamic compressive strength of 5.6%, 40.3% in fracture energy absorption and 11.1% in total energy absorption; further, it showed the least reduction (only 5.8%) in static compressive strength among all mixtures compared to the reference mixture without fibre. For all mixtures, the dynamic compressive properties, energy absorption capacity, strain at peak stress, ultimate strain and dynamic increase factor (DIF) were significantly influenced by strain rate, i.e., strain rate effect. When the strain rate was relatively low, PP fibres were effective in controlling the cracking, and the dynamic compressive properties of PP fibre reinforced mixtures were improved accordingly.