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The Mg–8Li dual phase alloy was deformed by multi-directional compression with different passes. Microstructure evolution of deformed Mg–8Li alloy was analyzed by electron backscatter diffraction. X-ray diffraction profile was used to calculate the dislocation density in α-Mg and β-Li phase to reveal the quantitively change trend under different compression passes. The mechanical properties were assessed through tensile and compressive tests. The Mg–8Li alloy exhibited optimal mechanical properties when compressed with 12 passes (sample 12MDC), with a compression yield strength of 183.1 MPa and a tensile yield strength of 124.2 MPa. The improved mechanical properties in sample 12MDC were attributed to an increase in {10 1‾ 2} twin and {101‾ 3}-{101‾ 2} double twin boundaries, along with the presence of sub-grain boundaries and a reduced grain size in the α-Mg phase. Additionally, the inconsistent results between microhardness and dislocation density calculation manifests the uneven distribution of dislocations in β-Li phase. Broken α-Mg phase brings more phase interface to relieve the strain in β-Li phase, which results to a decreased dislocation density in sample 12MDC (1.19 × 1011/m2). Results show that weaken tension-compression yield asymmetry and more even distribution of dislocation in both phases could be achieved when the compression passes increases to 12.

The orientation (including the c axis orientation and crystal direction parallel to rolling direction) evolution of grown recrystallization grains during annealing at 250 °C for 45–180 min in Mg–Zn-Gd alloy was characterized by quasi-in-situ electron backscatter diffraction method. An unusual grain orientation rotation during the process of static recrystallization grain growth, rather than common plastic deformation or recrystallization nucleation process, was observed. Due to the higher storage energy, the growth size in the early stage of annealing (1.41 μm) is larger than that in the late stage of annealing (0.73 μm) for most (∼76%) grains, and corresponding average c-axis rotation angles are 3.65° and 1.39°, respectively, indicating that the larger the increase in grain size, the greater the changing degree in grain orientation. It is speculated that the orientation rotation during grain growth process is mediated by the interaction between dislocations and grain boundaries. The results reported in the current paper can provide a new insight into the study on the relationship between preferential grain growth and non-basal texture formation in rare earth contained Mg alloys.

Abstract Flexible pressure sensors can convert mechanical stimuli to electrical signals to interact with the surroundings, mimicking the functionality of the human skins. Piezocapacitive pressure sensors, a class of most widely used devices for artificial skins, however, often suffer from slow response-relaxation speed (tens of milliseconds) and thus fail to detect dynamic stimuli or high-frequency vibrations. Here, we show that the contact-separation behavior of the electrode-dielectric interface is an energy dissipation process that substantially determines the response-relaxation time of the sensors. We thus reduce the response and relaxation time to ~0.04 ms using a bonded microstructured interface that effectively diminishes interfacial friction and energy dissipation. The high response-relaxation speed allows the sensor to detect vibrations over 10 kHz, which enables not only dynamic force detection, but also acoustic applications. This sensor also shows negligible hysteresis to precisely track dynamic stimuli. Our work opens a path that can substantially promote the response-relaxation speed of piezocapacitive pressure sensors into submillisecond range and extend their applications in acoustic range.

The study utilizes a multi-directional compression (MDC) process on a basal-textured ZK60 alloy with the aim of inducing extensive twinning, which is followed by an aging treatment on the pre-deformed sample. The mechanical response and corrosion behavior of the deformed and aged samples are systematically investigated. The MDC process effectively generates numerous {10 1‾ 2} twins with increased compression passes, resulting in the enhanced grain refinement. The interplay between twins and numerous dislocations formed during pre-deformation plays a crucial role in altering both the distribution and morphology of the second phase precipitated during aging. During the aging process, the alloy exhibits a higher concentration of dense rod-like β′ phase and disk-like β″ phase. Remarkably, the compressive yield strength and ultimate strength of aged ZK60 alloy along the rolling direction are significantly improved without obvious compromise of ductility by pre-compression. Notably, the yield strength of the sample after 12-passes compression and aging (APD-12) is approximately 45 % higher than that of the sample without pre-compression (APD-0). Furthermore, the corrosion resistance of ZK60 alloy displays notable improvement upon pre-compression treatment. Specifically, the hydrogen evolution in the APD-12 sample is halved compared to the APD-0 sample. Electrochemical assessments were conducted on both pre-compressed and non-pre-compressed samples, revealing their distinct behaviors. Furthermore, an in-depth exploration has also been undertaken into the underlying mechanisms contributing to the enhancement of mechanical properties and corrosion resistance resulting from the pre-compression.

Histopathology image analysis plays a crucial role in cancer diagnosis. However, training a clinically applicable segmentation algorithm requires pathologists to engage in labor‐intensive labeling. In contrast, weakly supervised learning methods, which only require coarse‐grained labels at the image level, can significantly reduce the labeling efforts. Unfortunately, while these methods perform reasonably well in slide‐level prediction, their ability to locate cancerous regions, which is essential for many clinical applications, remains unsatisfactory. Previously, CAMEL is proposed, which achieves comparable results to those of fully supervised baselines in pixel‐level segmentation. However, CAMEL requires 1280 × 1280 image‐level binary annotations for positive WSIs. Here, CAMEL2 is presented, by introducing a threshold of the cancerous ratio for positive bags, it allows one to better utilize the information, consequently enabling us to scale up the image‐level setting from 1280 × 1280 to 5120 × 5120 while maintaining accuracy. The results with various datasets demonstrate that CAMEL2, with the help of 5120 × 5120 image‐level binary annotations, which are easy to annotate, achieves comparable performance to that of a fully supervised baseline in both instance‐ and slide‐level classifications.

Abstract Early diagnosis and intervention of Alzheimer’s disease (AD) are particularly important to delay the pathological progression. Although fluorescent probes have been widely employed for investigating and diagnosing AD, their biological applications are significantly restricted due to the low penetration ability of the blood–brain barrier (BBB) in vivo. In this study, we reported the first Golgi-targeted two-photon (TP) fluorescent probe, DCM-DH, for detecting viscosity in the Golgi apparatus. The probe was rationally designed to exhibit superior analytical performance including high sensitivity, specific Golgi-targeting, efficient BBB penetration ability, and deep tissue penetration (247 μm) in the brains of AD model mice. Using the probe, we demonstrated that the fluorescence intensity in the human liver cancer cell (HepG2 cells) was higher than that of human normal liver cell (LO2 cells), and the brain viscosity of AD model mice increased significantly. We anticipate that this competent tool could be easily extended to other AD biomarkers for fundamental research on this detrimental disease.

In this work, the dynamic, quasi-static response and twinning behavior of bimodal textured Mg–3Al–1Zn alloy is comparatively investigated at room temperature. The relationship between yield stress and bimodal texture is quantified and characterized as an increase of the yield stress with the increasing of the percentage of ⊥ED (extrusion direction) component; the ultimate strength under high strain rate (103 s−1) was quite higher than that under quasi-static condition (10−3 s−1); but, the yield stress was just the reverse. The competition between twin nucleation and growth is significantly affected by a coupled effect of strain rate and texture. Twin nucleation shows positive strain rate sensitivity and is largely enhanced by dynamic deformation. However, the twin growth tendency is bimodal texture and strain rate dependent: it is favorable under quasi-static condition for samples with more soft orientations, while for samples with more hard orientations, dynamic deformation promotes twin growth. It is also found that a higher strain rate can stimulate the activation of more twin variant types in bimodal textured magnesium alloys.

Soil degradation threatens agricultural productivity and food supply, leading to hunger issues in some developing regions. To address this challenge, we developed a low-cost, highly efficient, and long-term stable soil improvement method. We chose polyvinyl alcohol (PVA), a commercially available polymer that is safe and non-degradable, to serve as a soil adhesive. We mixed PVA solution into the soil and applied a drying treatment to enhance the bonding between PVA and the soil, achieving highly water-stable soil. This PVA-stabilized soil exhibits low bulk density, high porosity, and high permeability, making it an ideal substrate for planting. In a germination test, the PVA-stabilized soil revealed a higher germination rate and growth rate compared to those of the non-treated soil. We believe this simple and efficient soil improvement method can restore degraded soil and contribute to sustainable agriculture.

In this work, pre-strain annealing strengthening (PSAS) effect was investigated in an extruded Mg-1.0Gd-1.5 Zn (wt.%) alloy with respect to different grain sizes. The evolution of microstructures was provided by scanning electron microscopy (SEM), electron backscattered diffraction (EBSD), transmission electron microscopy (TEM) and high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) under the initial state, pre-compression, intermediate annealing and re-compression conditions. The obtained results showed a grain size-dependent PSAS effect in the alloy. The sample with larger grain sizes corresponded to a higher strengthening effect, which mainly resulted from a more remarkable hindrance for the growth of existing twins and a larger proportion of activation for the nucleation of new twins. This was closely associated with the increase of back stress and friction stress for twin boundary motion impeded by the larger restraint of dislocations, the higher stress field surrounding solutes and the more Zn segregation. In addition to twinning behavior, Guinier Preston (G.P.) zones on basal 〈a〉 dislocations were found after intermediate annealing and provided an extra strengthening by inhibiting the motions of gilding pre-existing dislocations and newly formed ones, but it was independent on the grain size.

Filtering capacitors are essential to smooth high voltage alternating current lines but are typically limited to hundreds of volts. Here, the authors demonstrate an aqueous hybrid electrochemical capacitor that can exhibit an operating voltage of 1,000 V when assembled into a device of 670 units.

Ellagic acid, known for its various biological activities, is widely used. Ellagic acid from pomegranate peels is safe for consumption, while that from gallnuts is only suitable for external use. However, there is currently no effective method to confirm the source of ellagic acid. Therefore, this study establishes an analysis method using ultra-high-performance liquid chromatography–electrospray ionization–high-resolution mass spectrometry (UHPLC-ESI-HR-MS) to identify the components of crude ellagic acid extracts from pomegranate peels and gallnuts. The analysis revealed that there was a mix of components in the crude extracts, such as ellagic acid, palmitic acid, oleic acid, stearic acid, and 9(10)-EpODE. Furthermore, it could be observed that ellagic acid extracted from gallnuts contained toxic substances such as anacardic acid and ginkgolic acid (15:1). These components could be used to effectively distinguish the origin of ellagic acid from pomegranate peels or gallnuts. Additionally, a rapid quantitative analysis method using UHPLC-ESI-MS with multiple reaction monitoring (MRM) mode was developed for the quality control of ellagic acid products, by quantifying anacardic acid and ginkgolic acid (15:1). It was found that one of three ellagic acid health care products contained ginkgolic acid (C15:1) and anacardic acid at more than 1 ppm.

Carbon nanotubes (CNTs) and graphene have commonly been applied as the sensitive layer of strain sensors. However, the buckling deformation of CNTs and the crack generation of graphene usually leads to an unsatisfactory strain sensing performance. In this work, we developed a universal strategy to prepare welded CNT–graphene hybrids with tunable compositions and a tunable bonding strength between components by the in situ reduction of CNT–graphene oxide (GO) hybrid by thermal annealing. The stiffness of the hybrid film could be tailored by both initial CNT/GO dosage and annealing temperature, through which its electromechanical behaviors could also be defined. The strain sensor based on the CNT–graphene hybrid could be applied to collect epidermal bio-signals by both capturing the faint skin deformation from wrist pulse and recording the large deformations from joint bending, which has great potential in health monitoring, motion sensing and human–machine interfacing.

As 5G networks become more complex and heterogeneous, the difficulty of network operation and maintenance forces mobile operators to find new strategies to stay competitive. However, most existing network fault diagnosis methods rely on manual testing and time stacking, which suffer from long optimization cycles and high resource consumption. Therefore, we herein propose a knowledge- and data-fusion-based fault diagnosis algorithm for 5G cellular networks from the perspective of big data and artificial intelligence. The algorithm uses a generative adversarial network (GAN) to expand the data set collected from real network scenarios to balance the number of samples under different network fault categories. In the process of fault diagnosis, a naive Bayesian model (NBM) combined with domain expert knowledge is firstly used to pre-diagnose the expanded data set and generate a topological association graph between the data with solid engineering significance and interpretability. Then, as the pre-diagnostic prior knowledge, the topological association graph is fed into the graph convolutional neural network (GCN) model simultaneously with the training data set for model training. We use a data set collected by Minimization of Drive Tests under real network scenarios in Lu’an City, Anhui Province, in August 2019. The simulation results demonstrate that the algorithm outperforms other traditional models in fault detection and diagnosis tasks, achieving an accuracy of 90.56% and a macro F1 score of 88.41%.

Abstract Background Cisplatin, the alkylating agent of platinum(II) (Pt(II)), is the most common antitumor drug in clinic; however, it has many side effects, therefore it is higly desired to develop low toxicity platinum(IV) (Pt(IV)) drugs. Multi-omics analysis, as a powerful tool, has been frequently employed for the mechanism study of a certain therapy at the molecular level, which might be helpful for elucidating the mechanism of platinum drugs and facilitating their clinical application. Methods Strating form cisplatin, a hydrophobic Pt(IV) prodrug (CisPt(IV)) with two hydrophobic aliphatic chains was synthesized, and further encapsulated with a drug carrier, human serum albumin (HSA), to form nanoparticles, namely AbPlatin(IV). The anticancer effect of AbPlatin(IV) was investigated in vitro and in vivo. Moreover, transcriptomics, metabolomics and lipidomics were performed to explore the mechanism of AbPlatin(IV). Results Compared with cisplatin, Abplatin(IV) exhibited better tumor-targeting effect and greater tumor inhibition rate. Lipidomics study showed that Abplatin(IV) might induce the changes of BEL-7404 cell membrane, and cause the disorder of glycerophospholipids and sphingolipids. In addition, transcriptomics and metabolomics study showed that Abplatin(IV) significantly disturbed the purine metabolism pathway. Conclusions This research highlighted the development of Abplatin(IV) and the use of multi-omics for the mechanism elucidation of prodrug, which is the key to the clinical translation of prodrug. Graphical Abstract

The rapid progress of interdisciplinary researches from materials science, biotechnologies, biomedical engineering, and medicine, have resulted in the emerging of bioinspired skins for various fantasticating applications. Bioinspired skin is highly promising in the application of rehabilitation medicine owing to their advantages, including personalization, excellent biocompatibility, multi-functionality, easy maintainability and wearability, and mass production. Therefore, this review presents the recent progress of bioinspired skin towards next-generation rehabilitation medicine. The classification is first briefly introduced. Then, various applications of bioinspired skins in the field of rehabilitation medicine at home and abroad are discussed in detail. Last, we provide the challenges we are facing now, and propose the next research directions.

The kidney plays a central role in maintaining the fluid and electrolyte homeostasis in the body. Bicarbonate transporters NBCn1, NBCn2, and AE2 are expressed at the basolateral membrane of the medullary thick ascending limb (mTAL). In a previous study, NBCn1, NBCn2, and AE2 are proposed to play as a regulatory pathway to decrease NaCl reabsorption in the mTAL under high salt condition. When heterologously expressed, the activity of these transporters could be stimulated by the InsP3R binding protein released with inositol 1,4,5-trisphosphate (IRBIT), L-IRBIT (collectively the IRBITs), or protein phosphatase PP1. In the present study, we characterized by immunofluorescence the expression and localization of the IRBITs, and PP1 in rat kidney. Our data showed that the IRBITs were predominantly expressed from the mTAL through the distal renal tubules. PP1 was predominantly expressed in the TAL, but is also present in high abundance from the distal convoluted tubule through the medullary collecting duct. Western blotting analyses showed that the abundances of NBCn1, NBCn2, and AE2 as well as the IRBITs and PP1 were greatly upregulated in rat kidney by dietary sodium. Co-immunoprecipitation study provided the evidence for protein interaction between NBCn1 and L-IRBIT in rat kidney. Taken together, our data suggest that the IRBITs and PP1 play an important role in sodium handling in the kidney. We propose that the IRBITs and PP1 stimulates NBCn1, NBCn2, and AE2 in the basolateral mTAL to inhibit sodium reabsorption under high sodium condition. Our study provides important insights into understanding the molecular mechanism for the regulation of sodium homeostasis in the body.

Lead (Pb) contamination of planting soils is increasingly serious, leading to harmful effects on soil microflora and food safety. Exopolysaccharides (EPSs) are carbohydrate polymers produced and secreted by microorganisms, which are efficient biosorbent materials and has been widely used in wastewater treatment to remove heavy metals. However, the effects and underlying mechanism of EPS-producing marine bacteria on soil metal immobilization, plant growth and health remain unclear. The potential of Pseudoalteromonas agarivorans Hao 2018, a high EPS-producing marine bacterium, to produce EPS in soil filtrate, immobilize Pb, and inhibit its uptake by pakchoi (Brassica chinensis L.) was studied in this work. The effects of strain Hao 2018 on the biomass, quality, and rhizospheric soil bacterial community of pakchoi in Pb-contaminated soil were further investigated. The results showed that Hao 2018 reduced the Pb concentration in soil filtrate (16%–75%), and its EPS production increased in the presence of Pb2+. When compared to the control, Hao 2018 remarkably enhanced pakchoi biomass (10.3%–14.3%), decreased Pb content in edible tissues (14.5%–39.2%) and roots (41.3%–41.9%), and reduced the available Pb content (34.8%–38.1%) in the Pb-contaminated soil. Inoculation with Hao 2018 raised the pH of the soil, the activity of several enzymes (alkaline phosphatase, urease, and dehydrogenase), the nitrogen content (NH4+-N and NO3−-N), and the pakchoi quality (Vc and soluble protein content), while also raising the relative abundance of bacteria that promote plant growth and immobilize metals, such as Streptomyces and Sphingomonas. In conclusion, Hao 2018 reduced the available Pb in soil and pakchoi Pb absorption by increasing the pH and activity of multiple enzymes and regulating microbiome composition in rhizospheric soil.

E-skins often have poor interfaces that lead to unstable performances. Here, authors report e-skins with a quasi-homogeneous composition and bonded micro-structured interfaces, through which both the sensitivity and stability of the devices are improved.

Abstract Background Epidemiological studies have confirmed that abnormal circadian rhythms are associated with tumorigenesis in breast cancer. However, few studies have investigated the pathological roles of rhythm genes in breast cancer progression. In this study, we aimed to evaluate the aberrant expression of 32 rhythm genes in breast cancer and detect the pathological roles and molecular mechanisms of the altered rhythm gene in regulating the progression of triple negative breast cancer (TNBC). Methods The aberrant expression of rhythm genes in breast cancer was screened by searching the GEPIA database and validated by using qRT-PCR and immunohistochemistry staining. Bioinformatics analysis combined with luciferase reporter experiment and chromatinimmunopercitation (ChIP) were used to investigate the molecular mechanism about aberrant expression of identified rhythm gene in breast cancer. The pathological roles of identified rhythm gene in TNBC progression was evaluated by colony formation assay, wound healing experiment, transwell assay, subcutaneous tumor formation and the mouse tail vein injection model through gain-of-function and loss-of-function strategies respectively. mRNA array, bioinformatics analysis, luciferase reporter experiment, ChIP and immunoflurescence assay were employed to investigate the key molecules and signaling pathways by which the identified rhythm gene regulating TNBC progression. Results We identified that nuclear factor interleukin 3 regulated (NFIL3) expression is significantly altered in TNBC compared with both normal breast tissues and other subtypes of breast cancer. We found that NFIL3 inhibits its own transcription, and thus, downregulated NFIL3 mRNA indicates high expression of NFIL3 protein in breast cancer. We demonstrated that NFIL3 promotes the proliferation and metastasis of TNBC cells in vitro and in vivo, and higher expression of NFIL3 is associated with poor prognosis of patients with TNBC. We further demonstrated that NFIL3 enhances the activity of NF-κB signaling. Mechanistically, we revealed that NFIL3 directly suppresses the transcription of NFKBIA, which blocks the activation of NF-κB and inhibits the progression of TNBC cells in vitro and in vivo. Moreover, we showed that enhancing NF-κB activity by repressing NFKBIA largely mimics the oncogenic effect of NFIL3 in TNBC, and anti-inflammatory strategies targeting NF-κB activity block the oncogenic roles of NFIL3 in TNBC. Conclusion NFIL3 promotes the progression of TNBC by suppressing NFKBIA transcription and then enhancing NF-κB signaling-mediated cancer-associated inflammation. This study may provide a new target for TNBC prevention and therapy. Graphical Abstract

Abstract Background Increasing evidence suggests that aberrant methylation is involved in 5-fluorouracil (5-FU) resistance in gastric cancer (GC). Our previous work has identified that Methyl-CpG binding protein 2 (MeCP2) promotes GC progression by binding to the methylation sites of promoter regions of specific genes to affect the downstream signaling pathways. However, the function and molecular mechanisms of MeCP2 in GC 5-FU resistance remain unclear. Methods We detected the expression of MeCP2 in 5-FU-resistant GC cells and examined cell behaviors when MeCP2 was silenced. The molecular mechanisms were explored through chromatin immunoprecipitation (ChIP)-qRT-PCR, luciferase reporter assay, clinical tissue samples analysis, and in vivo tumorigenicity assay. Results MeCP2 was up-regulated in 5-FU-resistant GC cells. Knockdown of MeCP2 enhanced the sensitivity of the cells to 5-FU. Moreover, MeCP2 promoted NOX4 transcription in the cells by binding to the promoter of NOX4. Silencing NOX4 rescued the inductive effect of MeCP2 overexpression on 5-FU sensitivity of GC cells and reduced the expression of NOX4 and PKM2 in MeCP2 overexpressed 5-FU-resistant GC cells. In addition, our in vivo experiments demonstrated that MeCP2 knockdown enhanced 5-FU sensitivity in tumors. Conclusion MeCP2 confers 5-FU resistance in GC cells via upregulating the NOX4/PKM2 pathway, which may lead to a promising therapeutic strategy for GC.

Homeobox D3 (HOXD3), a member of the homeobox family, was described to regulate tumorigenesis, invasion, metastasis, and angiogenesis in various tumor types. However, the molecular mechanisms regulating HOXD3 during hepatocellular carcinoma (HCC) migration, invasion, and angiogenesis remain elusive. In this study, we demonstrated that HOXD3 expression is enhanced by the binding of methyl‐CpG‐binding protein 2 (MeCP2), a methyl‐CpG binding protein, together with CREB1to the hypermethylated promoter of HOXD3. Inhibition of HOXD3 eliminated the tumorigenic effects of MeCP2 on HCC cells. Furthermore, HOXD3 directly targeted the promoter region of heparin‐binding epidermal growth factor (HB‐EGF) via the EGFR‐ERK1/2 cell signaling pathway and promoted invasion, metastasis, and angiogenesis of HCC in vitro and in vivo. Additionally, elevated expression of MeCP2, CREB1, and HB‐EGF in HCC correlated with a poor survival rate. Our findings reveal the function of the MeCP2/HOXD3/HB‐EGF regulatory axis in HCC, rendering it an attractive candidate for the development of targeted therapeutics and as a potential biomarker in patients with HCC.

Abstract Background UBTF is an HMGB-box DNA binding protein and a necessary Pol I/Pol II basal transcription factor. It has been found that UBTF involves in carcinogenesis and progression of a few cancers. Nevertheless, the the biological function and potential molecular mechanism of UBTF in melanoma are still not clear and need to be clarified. Methods UBTF and GIT1 expressions in melanoma specimens and cell lines were examined by quantitative real-time PCR (qRT-PCR) and Western blot. MTT and colony formation assays were used to investigate the effects of UBTF and GIT1 on melanoma cell proliferation. Cell cycle and apoptosis assays were detected by flow cytometry. Tumor formation assay was used to analyze the effect of UBTF on melanoma growth. Bioinformatics predicting, chromatin immunoprecipitation (ChIP)-qRT-PCR and reporter gene assay were fulfilled for verifing GIT1 as UBTF targeting gene. Results Here we reported that UBTF mRNA and protein expressions were upregulated in primary melanoma specimens and cell lines. UBTF overexpression facilitated melanoma cell proliferation and cell cycle progression and restrained. Silencing UBTF suppressed cell multiplication, cell cycle progression and tumor growth, and promoted apoptosis. UBTF expression was positively related with GIT1 expression in human melanoma tissues. It was verified that UBTF promoted GIT1 transcription in melanoma cells through binding to the promoter region of GIT1. Furthermore, GIT1 overexpression promoted melanoma cell growth and suppressed apoptosis. Knockdown of GIT1 inhibited cell multiplication and induced apoptosis. Overexpression of GIT1 eliminated the effects of silencing UBTF on melanoma cells. Importantly, UBTF activated MEK1/2-ERK1/2 signalling pathways by upregulating GIT1 expression. Conclusions Our study demonstrates that UBTF promotes melanoma cell proliferation and cell cycle progression by promoting GIT1 transcription, thereby activating MEK1/2-ERK1/2 signalling pathways. The findings indicate that UBTF plays a crucial function in melanoma and may be a potential therapeutic target for the treatment of this disease.

Introduction: Gastric cancer (GC) is one of the most common malignant tumors worldwide. Single-cell sequencing technology can achieve an accurate and unbiased assessment of cell heterogeneity. Therefore, it is necessary to explore the molecular characteristics of GC-related malignant cells at a single-cell resolution. Methods: Single-cell RNA sequencing GC profiles were collected from the Gene Expression Omnibus database. Moreover, feature gene sets of metabolic pathways and hypoxia signals were collected from the Molecular Signatures Database. The marker genes of specific cell types were collected from the published literature and CellMarker database. The R package InferCNV was used to calculate the copy-number variations of cells and to identify real cancer cells. The weighted relative pathway activity algorithm was used to evaluate the differences in metabolic activity between cell types. Results: Our study found that cancer epithelial cells exhibited individual differences in molecular features and showed metabolic heterogeneity. Oxidative phosphorylation and glycolytic pathway activity were the major contributors to the metabolic heterogeneity of cancer epithelial cells. Furthermore, we used the hypoxia signaling pathway to indirectly evaluate the oxygen content of cells and found that hypoxia contributed to the heterogeneity of cancer epithelial cells. Finally, functional identification of genes co-expressed with HIF1A showed that the reprogramming of the oxidative stress response contributed to the tumor malignant progression. Conclusions: This study described hypoxia-induced metabolic reprogramming of GC at a single-cell level, partially addressing the lack of insight into the heterogeneity of cancer cell metabolism when using traditional sequencing technology.

It continues to be a challenge to design innovative NiCoP composite anode materials to further improve rate capacity. In this work, bimetallic flower-like NiCoP encapsulated in an N-doped carbon shell (designated as NiCoP@NC) as a high-rate capable anode material for lithium-ion batteries (LIBs) was successfully designed and synthesized. The novel structure design combines the advantages of flower-like NiCoP (core) and N-doped carbon (shell). Flower-like NiCoP offers numerous interface and redox reaction sites for improving lithium storage, while the N-doped carbon shell effectively buffers volume expansion and enhances electrical conductivity. The synergistic effect between NiCoP and the N-doped carbon shell proposes a marvelous high-rate capacity (320 mA h/g even at 5 A/g) and a good cycle life with high reversible capacity (369.8 mA h/g for 700 cycles at 3 A/g with 81% retention). An investigation of kinetics performance shows that the introduction of the N-doped carbon shell enhances the charge transfer, and the pseudocapacitive behavior dominates the rapid Li+ storage of the NiCoP@NC electrode.

Neutrophil extracellular traps (NETs) are produced in large quantities at the site of inflammation, and they locally capture and eliminate various pathogens. Thus, NETs quickly control the infection of pathogens in the body and play vital roles in immunity and antibacterial effects. However, evidence is accumulating that NET formation can exacerbate pancreatic tissue damage during acute pancreatitis (AP). In this review, we describe the research progress on NETs in AP and discuss the possibility of NETs as potential therapeutic targets. In addition, since the current detection and visualization methods of NET formation are not uniform and the selection of markers is still controversial, a synopsis of these issues is provided in this review.

Pancreatic adenocarcinoma (PAAD) is a malignant cancer with high incidence and mortality. Glycometabolic rearrangements (aerobic glycolysis) is a hallmark of PAAD and contributes to tumorigenesis and progression through numerous mechanisms. This study aimed to identify a novel glycolysis-related lncRNA-miRNA-mRNA ceRNA signature in PAAD and explore its potential molecular function. We first calculated the glycolysis score for each PAAD patient by the ssGSEA algorithm and found that patients with higher hallmark glycolysis scores had poorer prognosis. Subsequently, we obtained a novel glycolysis-related LINC02432/hsa-miR-98–5p/HK2 axis from the TCGA and GEO databases using comprehensive bioinformatics analysis and developed a nomogram to predict overall survival. Furthermore, functional characterization analysis revealed that LINC02432/hsa-miR-98–5p/HK2 axis risk score was negatively correlated with ferroptosis. The tumor immune infiltration analysis suggested positive correlations between ceRNA risk score and infiltrated M0 macrophage levels in PAAD. Correlation analysis found that ceRNA risk scores were positively correlated with four chemokines (CXCL3, CXCL5, CXCL8 and CCL20) and one immune checkpoint gene (SIGLEC15). Meanwhile, tumor mutation burden (TMB), an indicator for predicting response to immunotherapy, was positively correlated with ceRNA risk score. Finally, the drug sensitivity analysis showed that the high-risk score patients might be more sensitive to EGFR, MEK and ERK inhibitors than low-risk score patients. In conclusion, our study suggested that LINC02432/hsa-miR-98–5p/HK2 axis may serve as a novel diagnostic, prognostic, and therapeutic target in PAAD treatment.

Abstract Breast cancer is one of the most common malignant tumors in women. It is a heterogeneous disease related to genetic and environmental factors. Presently, the treatment of breast cancer still faces challenges due to recurrence and metastasis. The emergence of single-cell RNA sequencing (scRNA-seq) technology has brought new strategies to deeply understand the biological behaviors of breast cancer. By analyzing cell phenotypes and transcriptome differences at the single-cell level, scRNA-seq reveals the heterogeneity, dynamic growth and differentiation process of cells. This review summarizes the application of scRNA-seq technology in breast cancer research, such as in studies on cell heterogeneity, cancer cell metastasis, drug resistance, and prognosis. scRNA-seq technology is of great significance to deeply analyze the mechanism of breast cancer occurrence and development, identify new therapeutic targets and develop new therapeutic approaches for breast cancer.

The multiaxial deformation behavior of magnesium alloys is an important factor in understanding the service performance of structures. In the present research, the deformation mechanism of a Mg AZ31 sheet under biaxial tension with various stress ratios (σRD:σ45) along the rolling direction (RD) and the diagonal direction (45° direction) between the normal direction (ND) and transverse direction (TD) was systematically studied for the first time using cruciform specimens. The impacts of the stress ratio, σRD:σ45, on the mechanical response, twinning behavior, texture and slip behavior were investigated. The results showed that the contribution of twinning to plastic deformation was limited and governed by the Schmid law. The activation of twinning induced a twin texture component with c-axes largely parallel to the 45° between ND and TD. The deformation induced by biaxial tension was accommodated mainly by prismatic and basal slips under the stress ratio of σRD:σ45=4:1, and the fraction of grains favoring basal slip increased with lower stress ratio along the RD. The characteristics of flow stress can be effectively explained by the relative activities of twinning and slip with stress ratio.

Wrinkling is a well-known phenomenon observed at various length scales for diverse materials. Despite a variety of research studies focusing on investigating wrinkling mechanisms and utilizing them to create surface patterns recently, wrinkling also brings about the loss of specific functional properties that were initially endowed to the thin films. For instance, wrinkling may result in the degradation of electrical and optical properties of the film; and the wrinkled films are easily delaminated. Therefore, it is still meaningful to find ways for the suppression of wrinkling on the thin film, although the relevant works are far less than those that utilize the surface instability to achieve certain structures. In this review, the approaches to restrain the emergence of wrinkles will be introduced. Following the introduction part, numerical analysis for wrinkle generation will be first discussed, by which the key parameters determining wrinkle initiation and morphology will be provided. Then, wrinkle suppression strategies by tailoring these parameters will be introduced in the following sections. This review aims to provide useful guidance for future research on alleviating surface fluctuations and achieving desired device functionality.

Silver nanowire (AgNW) films have been widely used as flexible transparent electrodes due to the high electrical conductance and high transmittance in the visible range. The infrared (IR) properties of AgNW films, however, are seldom discussed. Here, we show that ultrathin AgNWs present high transmittance in the visible range (∼95%) and high reflectance (60–70%) in the IR range of 8–14 μm. Such a significant difference makes AgNW films invisible to naked eyes but visible under an IR camera, being an ideal selection for anti-counterfeit technologies, while no excitation is required. We have demonstrated that AgNW films can be spray-coated on either flat or microstructured surfaces with high conformability and high scratch-resistance, and thus these anti-counterfeiting materials can be applied to a variety of applications. The AgNW-based anti-counterfeiting may be helpful for combating counterfeiting crimes in the fields of medicines, artwork, banknotes, brand luxuries, industrial parts, and so on. Keywords: Silver nanowires, Anti-counterfeiting, Infrared light, Excitation-free, Conformability

Grain growth can modify the texture orientation and the fraction of different texture component. The thermal stability of two texture component in an extruded magnesium AZ31 alloy was investigated. Three types samples with different texture distribution were prepared. The results show that normal grain growth takes place in the magnesium AZ31 alloy during annealing at 300 °C and 450 °C. But the grain growth does not lead to the strengthening of either texture component. Both the ⊥ED texture and //ED texture components show good thermal stability, without influence of the texture volume fraction. The two different texture component possess comparable boundary migration ability, so grains of the two texture component consume indifferently the other grains, or are equally consumed during annealing. Keywords: Mg alloy, Texture, Thermal stability, Grain growth annealing, Twinning

RNA polymerase II subunit A (POLR2A) is the largest subunit encoding RNA polymerase II and closely related to cancer progression. However, the biological role and underlying molecular mechanism of POLR2A in gastric cancer (GC) are still unclear. Our study demonstrated that POLR2A was highly expressed in GC tissue and promoted the proliferation of GC in vitro and in vivo. We also found that POLR2A participated in the transcriptional regulation of cyclins and cyclin-dependent kinases (CDKs) at each stage and promoted their expression, indicated POLR2A’s overall promotion of cell cycle progression. Moreover, POLR2A inhibited GC cell apoptosis and promoted GC cell migration. Our results indicate that POLR2A play an oncogene role in GC, which may be an important factor involved in the occurrence and development of GC.

Colon cancer is a complex, heterogeneous disease. The Colorectal Cancer Subtyping Consortium reported a novel classification system for colon cancer in 2015 to better understand its heterogeneity. This molecular classification system divided colon cancer into four distinct consensus molecular subtypes (CMS 1, 2, 3, and 4). However, the characteristics of different colon cancer molecular subtypes have not been fully elucidated. This study comprehensively analyzed the molecular characteristics of varying colon cancer subtypes using multiple databases and algorithms, including The Cancer Genome Atlas (TCGA) database, DriverDBv3 database, CIBERSORT, and MCP-counter algorithms. We analyzed the alterations in the subtype-specific genes of different colon cancer subtypes, such as the RNA levels and DNA alterations, and showed that specific subtype-specific genes significantly affected prognosis. We also explored the changes in colon cancer driver genes and representative genes of 10 signaling pathways in different subtypes. We identified genes that were altered in specific subtypes. We further detected the infiltration of 22 immune cell types in four colon cancer subtypes and the infiltration level of primary immune cells among these subtypes. Additionally, we explored changes in immune checkpoint genes (ICGs) and immunotherapy responses among different colon cancer subtypes. This study may provide clues for the molecular mechanism of tumorigenesis and progression in colon cancer. It also offers potential biomarkers and targets for the clinical diagnosis and treatment of different colon cancer subtypes.

Breast cancer is a heterogeneous malignant disease with different prognoses and has been divided into four molecular subtypes. It is believed that molecular events occurring in breast stem/progenitor cells contribute to the carcinogenesis and development of different breast cancer subtypes. However, these subtype-specific molecular characteristics are largely unknown. In this study, we employed 1217 breast cancer samples from The Cancer Genome Atlas (TCGA) database for a multiomics analysis of the molecular characteristics of different breast cancer subtypes based on PAM50 algorithms. We detected the expression changes of subtype-specific genes and revealed that the expression of particular subtype-specific genes significantly affected prognosis. We also investigated the mutations and copy number variations (CNVs) of breast cancer driver genes and the representative genes of ten signaling pathways in different subtypes and revealed several subtype-specifically altered genes. Moreover, we detected the infiltration of various immune cells in different subtypes of breast cancer and showed that the infiltration levels of major immune cell types are different among these subtypes. Additionally, we investigated the factors affecting the immune infiltration level and the immune cytolytic activity in different breast cancer subtypes, namely, the mutation burden, genome instability and cancer-associated fibroblast (CAF) infiltration. This study may shed light on the molecular events contributing to carcinogenesis and development and provide potential markers and targets for the clinical diagnosis and treatment of different breast cancer subtypes.

The hypoxic microenvironment is beneficial to the metastasis but not to the proliferation of cancer cells. However, the mechanisms regarding to hypoxia differentially regulating cancer metastasis and proliferation are largely unknown. In this study, we revealed that hypoxia induced the expression of LIN28A at mRNA level but segregated LIN28A mRNAs in the P-bodies and thus inhibits the production of LIN28A protein. This unexpected finding suggests that there may be non-coding role for LIN28A mRNA in the progression of colon cancer. We further showed that the non-coding LIN28A mRNA promotes the metastasis but not proliferation of colon cancer cells in vitro and in vivo. Mechanistically, we revealed that methionyl aminopeptidase 2 (METAP2) is one of the up-regulated metastasis regulators upon over-expression of non-coding LIN28A identified by mass spectrum, and confirmed that it is non-coding LIN28A mRNA instead of LIN28A protein promotes the expression of METAP2. Moreover, we demonstrated that knockdown of DICER abolished the promotional effects of non-coding LIN28A on the metastasis and METAP2 expression. Conclusively, we showed that hypoxia induces the production of LIN28A mRNAs but segregated them into the P-bodies together with miRNAs targeting both LIN28A and METAP2, and then promotes the metastasis by positively regulating the expression of METAP2. This study uncovered a distinctive role of hypoxia in manipulating the metastasis and proliferation by differently regulating the expression of LIN28A at mRNA and protein level.

Piezoelectric catalysis (piezocatalysis) is a physical/chemical process that utilizes piezoelectric potential for accelerating chemical reactions, in which ubiquitous mechanical energies in nature are used for various catalysis applications, e.g., treating organic water pollutants. Despite the high efficiency achieved by piezocatalytic powders, the particles used tend to diffuse in water systems and are hard to be separated, thus causing secondary pollution. Herein, a free‐standing piezocatalytic foam is designed and fabricated, which is composed of BaTiO3 nanoparticles embedded in the PVDF scaffold. The as‐prepared PVDF–BaTiO3 composite foam demonstrates outstanding piezocatalytic efficiency in removing aqueous organics among state‐of‐the‐art integral piezocatalytic platforms, which lie in the synergy of piezoelectric materials and abundant interconnected pores within the foam. Significantly, PVDF–BaTiO3 foam is further applied for purifying natural water samples, by which the permanganate index of the water sample reduces by nearly 30% after 2 h of treatment. In addition, as a monolithic platform, PVDF–BaTiO3 foam is easy to be collected, with high reuse stability and applicability for treating various pollutants, resulting in dominant advantages over powder‐based systems for practical high‐flux wastewater treatment. Herein, a piezocatalytic platform is provided for the effective degradation of organic pollutants in water, with minimal environmental side effects.

Background/Aims: MicroRNAs (miRNAs) have been well studied in human carcinogenesis and cancer progression. Our previous study showed the down-regulation of miR-338-3p expression in human gastric cancer (GC). However, the reasons of this dysregulation remain largely unclear. Methods: Bisulfite sequence analysis was performed to explore the methylation status of the promoter region of miR-338-3p. Cell wound-healing and transwell assays were performed to examine the capacity of cell migration and cell interaction. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-338-3p. Western blotting, RNA interference, and immunofluorescence (IF) were used to evaluate the expression of MMPs and the location of N-cadherin to determine the mechanism underlying miR-338-3p-induced anti-tumor effects. Results: miR-338-3p was epigenetically silenced, and this loss of expression was significantly correlated with the Borrmann Stage in GC. Restoring miR-338-3p expression in BGC-823 cells inhibited cell migration and invasion. Moreover, Ras-related protein (Rab-14) and Hedgehog acyltransferase (Hhat) were identified as direct targets of miR-338-3p. Both enforced expression of miR-338-3p and small interfering RNA induced Rab14-mediated accumulation of N-cadherin in the cell -cell junctions or Hhat-associated matrix metalloproteinase (MMP) degradation, which may underline the metastasis defects caused by loss of miR-338-3p in GC. Conclusion: These data indicate that miR-338-3p functions as a tumor suppressor in GC, and that the hypermethylation status of its CpG island might be a novel potential strategy for treating GC.

Abstract Pd/C was found to be an efficient and convenient metal catalyst for intramolecular C–H arylation reactions in the synthesis of phenanthridinones and dibenzo-α-pyrones. A variety of phenanthridinones and dibenzo-α-pyrones were synthesized under the highly active catalytic system of Pd/C-KOAc-DMA in moderate to excellent yields. The high catalytic activity, high recyclability, low costs, and ease of removal of Pd/C, combined with its commercial availability, render this protocol attractive for both synthetic and industrial applications.

Methyl-CpG binding protein 2 (MeCP2) has recently been characterized as an oncogene frequently amplified in several types of cancer. However, its precise role in gastric cancer (GC) and the molecular mechanism of MeCP2 regulation are still largely unknown. Here we report that MeCP2 is highly expressed in primary GC tissues and the expression level is correlated with the clinicopathologic features of GC. In our experiments, knockdown of MeCP2 inhibited tumor growth. Molecular mechanism of MeCP2 regulation was investigated using an integrated approach with combination of microarray analysis and chromatin immunoprecipitation sequencing (ChIP-Seq). The results suggest that MeCP2 binds to the methylated CpG islands of FOXF1 and MYOD1 promoters and inhibits their expression at the transcription level. Furthermore, we show that MeCP2 promotes GC cell proliferation via FOXF1-mediated Wnt5a/β-Catenin signaling pathway and suppresses apoptosis through MYOD1-mediated Caspase-3 signaling pathway. Due to its high expression level in GC and its critical function in driving GC progression, MeCP2 represents a promising therapeutic target for GC treatment.

Aberrant expression of microRNAs correlates with the development and progression of human cancers by targeting downstream proteins. MiR-1202 is downregulated in ovarian cancer and clear cell papillary renal cell carcinoma; however, its role in glioma remains unknown. The purpose of this study was to determine the expression and the role of miR-1202 and to elucidate its regulatory mechanism in glioma. We used quantitative real-time polymerase chain reaction to measure miR-1202 expression in both glioma tissues and cell lines. The findings showed that the miR-1202 expression decreased dramatically in clinical glioma tissues and cell lines, and miR-1202 expression was inversely correlated with the expression of Rab1A. Using bioinformatics and luciferase reporter assays, we identified Rab1A as a novel and direct target of miR-1202. In vitro, overexpression of miR-1202 inhibited glioma cell proliferation and induced endoplasmic reticulum stress and apoptosis through targeting Rab1A, whereas suppression of miR-1202 promoted cell proliferation and inhibited endoplasmic reticulum stress and apoptosis. Similarly, silencing Rab1A with small interfering RNA also suppressed glioma cell growth and induced endoplasmic reticulum stress and apoptosis. Taken together, our data indicate that miR-1202 suppresses proliferation and induces endoplasmic reticulum stress and apoptosis through targeting and inhibiting Rab1A in glioma cells. These results suggest miR-1202 as a potential therapeutic target for the treatment of glioma patients.

Rab14 is a member of RAS oncogene family, and its dysfunction has been reported to be involved in various types of human cancer. However, its expression and function were still unclear in gastric cancer. The aim of this study was to investigate the function and mechanism of Rab14 in gastric cancer cell lines. Quantitative real-time PCR (qRT-PCR) was performed in 17 gastric adenocarcinoma tissues and 4 cell lines to detect the expression of Rab14. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT), colony formation and flow cytometry assays were employed to determine the proliferative ability, cell cycle transition and apoptosis in vitro in BGC-823 or SGC-7901 cells. Western blot was performed to investigate the pathways and mechanism of Rab14 regulation. In this study, we show that Rab14 presents a significant up-regulated expression among the paired tissue samples and cell lines in gastric cancer. When we overexpressed Rab14 in SGC-7901 cells or silenced Rab14 in BGC-823 cells, we found that Rab14 could modify cell growth, cell cycle or apoptosis, which accompanied with an obvious regulation of CCND1, CDK2 and BAX involving in AKT signaling pathway. In conclusion, this study provides a new evidence on that Rab14 functions as a novel tumor oncogene and could be a potential therapeutic target in gastric cancer.

OBJECTIVE: To investigate discriminating protein patterns and serum biomarkers between clear cell renal cell carcinoma (ccRCC) patients and healthy controls, as well as between paired pre- and post-operative ccRCC patients. METHODS: We used magnetic bead-based separation followed by matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) to identify patients with ccRCC. A total of 162 serum samples were analyzed in this study, among which there were 58 serum samples from ccRCC patients, 40 from additional paired pre- and post-operative ccRCC patients (n = 20), and 64 from healthy volunteers as healthy controls. ClinProTools software identified several distinct markers between ccRCC patients and healthy controls, as well as between pre- and post-operative patients. RESULTS: Patients with ccRCC could be identified with a mean sensitivity of 88.38% and a mean specificity of 91.67%. Of 67 m/z peaks that differed among the ccRCC, healthy controls, pre- and post-operative ccRCC patients, 24 were significantly different (P