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In this work, we report a counter-intuitive activation of abnormal grain growth (AGG) in randomly-oriented fine grains (FGs) in an L-PBF Al–Mg–Sc–Zr alloy, which is unlikely from perspectives of curvature-driven grain growth, crystallographic texture or strain-induced boundary migration. The observed spontaneous AGG is understood in light of the growth instability of an arbitrary grain in an evolving particle-pinned polycrystalline aggregation. A generalized criterion for AGG is hence proposed, which efficaciously explains the observed susceptibility of FGs to AGG, the presence of multiple AGG activation sites, and the asynchrony of AGG activation.

This study systematically investigates the flow behavior of 7050 aluminum (Al) alloy produced via spray forming and subjected to a proposed pretreatment through thermal compression tests. The experimental findings reveal that the peak stress increased with decreasing deformation temperature or increasing strain rates. The parameters in the Arrhenius constitutive model were determined and verified by experimental results for spray formed (SFed) 7050 Al alloy. Hot deformation activation energy of the SFed 7050 Al alloy (147.38 kJ/mol) is notably lower than that of cast Al–Zn–Mg–Cu–Zr alloys, which is attributed to factors such as fine grains, low segregation, pores, and dispersed Al3Zr induced by pretreatment. Furthermore, processing maps have been constructed at various strains, revealing optimal stable deformation conditions at 300–450 °C/0.001–0.15s−1 and 425–450 °C/0.2–1s−1. Microstructural analysis of deformed samples highlights the critical role of dynamic recrystallization in influencing the stable and unstable areas of the alloy, which may be activated by high temperature and slow strain rate. The hot deformation mechanism of the SFed Al alloy is governed by interactions among η-Mg(Zn,Al,Cu)2 precipitates, dispersed Al3Zr particles, dislocation structures, and (sub-)grain boundaries.

Abstract Dysregulation of the transforming growth factor‐β (TGF‐β) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug‐resistant CSCs. Through a genome‐wide CRISPR activation screen utilizing stem‐like drug‐resistant properties as a readout, the TGF‐β receptor‐associated binding protein 1 (TGFBRAP1) is identified as a TGF‐β‐inducible positive feedback regulator that governs sensitivity to tyrosine kinase inhibitors (TKIs) and promotes liver cancer stemness. By interacting with and stabilizing the TGF‐β receptor type 1 (TGFBR1), TGFBRAP1 plays an important role in potentiating TGF‐β signaling. Mechanistically, TGFBRAP1 competes with E3 ubiquitin ligases Smurf1/2 for binding to TGFΒR1, leading to impaired receptor poly‐ubiquitination and proteasomal degradation. Moreover, hyperactive TGF‐β signaling in turn up‐regulates TGFBRAP1 expression in drug‐resistant CSC‐like cells, thereby constituting a previously uncharacterized feedback mechanism to amplify TGF‐β signaling. As such, TGFBRAP1 expression is correlated with TGFΒR1 levels and TGF‐β signaling activity in hepatocellular carcinoma (HCC) tissues, as well as overall survival and disease recurrence in multiple HCC cohorts. Therapeutically, blocking TGFBRAP1‐mediated stabilization of TGFBR1 by selective inhibitors alleviates Regorafenib resistance via reducing CSCs. Collectively, targeting feedback machinery of TGF‐β signaling pathway may be an actionable approach to mitigate drug resistance and liver cancer stemness.

Abstract Objective The aim of the study is to identify clinical and dosimetric factors that could predict the risk of radiation-induced hypothyroidism(RIHT) in head and neck cancer(HNC) patients following intensity-modulated radiotherapy(IMRT). Methods A total of 103 HNC patients were included in our study. General clinical characteristic and dosimetric data of all recruited patients were analyzed, respectively. The univariate and multivariate logistic regression anlalysis were successively conducted to identify optimal predictors, which aim to construct the nomogram. And the joint prediction was performed. Results The incidence of patients with HNC was 36.9% (38/103). Among the clinical factors, gender, N stage, chemotherapy, frequency of chemotherapy and surgery involving the thyroid were related to RIHT. Logistic regression analysis showed that thyroid volume, Dmean, VS45, VS50, VS60 and V30,60 were independent predictors of RIHT, which were also incorporated in the nomogram. An AUC of 0.937 (95%CI, 0.888–0.958) also was showed outstanding resolving ability of the nomogram. When the volume of the thyroid was greater than 10.6 cm3, the incidence of RIHT was 14.8%, and when the volume of the thyroid was equal to or smaller than 10.6 cm3, the incidence was 72.5%. The incidence rates of RIHT in the group with VS60≦8.4cm3 and VS60 > 8.4cm3 were 61.4% and 19.3%, respectively. Conclusions Thyroid volume and thyroid VS60 are independent predictors of RIHT in patients with HNC. Moreover, more attention should be paid to patients with thyroid volume ≤ 10.6cm3. Thyroid VS60 > 8.4cm3 may be a useful threshold for predicting the development of RIHT. The nomogram conducted by the research may become a potential and valuable tool that could individually predict the risk of RIHT for HNC patients.

The cast Al–3Li–2Cu-0.15Zr alloy is a promising material due to its high strength-to-weight ratio and stiffness. In this work, the Sn addition and heat treatment were employed to regulate its microstructure and mechanical properties. The results indicate that Sn exists in the matrix as Sn solute atoms and Sn-rich particles including Li5Sn2, Li13Sn5, Li7Sn2, and Li22Sn5. The number of these particles increases as the Sn content rises. The addition of Sn significantly enhances the grain refinement, reducing the average grain size to 50.2 μm when 0.3 wt% Sn is incorporated. During the aging process, the δ′ and δ'/β′ precipitates gradually grow and coarsen, while the T1 and θ′ precipitates nucleate and grow. Some δ′ precipitates attach to the board of θ′ to form sandwich-like phases, such as δ'/θ'/δ'. The addition of Sn promotes the nucleation of θ′ and T1 precipitates. This is achieved by leveraging the Sn-rich particles as nucleation sites and utilizing Sn solute atoms to decrease the interface energy between these precipitates and α-Al. Moreover, the addition of Sn with a high vacancy binding energy and the reduction of aging temperature can effectively decrease the diffusion rate of Li atoms and vacancies, thereby inhibiting the broadening of the δ′-PFZ. After a suitable heat treatment, the Sn-modified Al–Li alloy exhibits a microstructure characterized by fine and equiaxed grain, fine and uniform δ′ precipitates, and a narrow δ′-PFZ, contributing to excellent mechanical properties of the alloy. Significantly, the underlying mechanisms behind the aforementioned observations were discussed analytically.

Abstract Reprogrammed cellular metabolism is essential for maintaining cancer stem cells (CSCs) state. Here, we report that mitochondrial D-lactate catabolism is a necessary initiating oncogenic event during tumorigenesis of esophageal squamous cell carcinoma (ESCC). We discover that cyclin-dependent kinase 7 (CDK7) phosphorylates nuclear Yes-associated protein 1 (YAP) at S127 and S397 sites and enhances its transcription function, which promotes D-lactate dehydrogenase (LDHD) protein expression. Moreover, LDHD is enriched significantly in ESCC-CSCs rather than differentiated tumor cells and high LDHD status is connected with poor prognosis in ESCC patients. Mechanistically, the CDK7-YAP-LDHD axis helps ESCC-CSCs escape from ferroptosis induced by D-lactate and generates pyruvate to satisfy energetic demands for their elevated self-renewal potential. Hence, we conclude that esophageal CSCs adopt a D-lactate elimination and pyruvate accumulation mode dependent on CDK7-YAP-LDHD axis, which drives stemness-associated hallmarks of ESCC-CSCs. Reasonably, targeting metabolic checkpoints may serve as an effective strategy for ESCC therapy.

As an important part of the additive manufacturing technology, wire arc additive manufacture (WAAM) is outstanding with high deposition efficiency, large size of deposited parts, short periodic time, and low costs. WAAM also shows potential in in-situ composite manufacturing and gradient material preparation. Given the potential in wire arc manufacturing of double-alloy gradient structured materials, the walls were deposited using alternating feeds (depositing a layer of A wire and then depositing a layer of B wire) of high-strength-low-plasticity ZL205 and low-strength-high-plasticity 4043 welding wire. In this process, the liquid phases of the two types of wire were efficiently mixed, which showed a regular distribution of molten pool track and avoided evident defects. Generally, through such gradient structure design, high-strength low-toughness materials and high-toughness low-strength materials can be effectively combined, which achieves the regulation of mechanical properties. Specifically, the overall structural and mechanical properties can be improved by adjusting the proportion of a certain component. As an extension from the wire arc printing technology, WAAM shows extremely high application potential and industrial values. Moreover, the addition of a dissimilar alloy can decrease the formation of columnar grains during additive manufacturing. Such compositional gradient can destroy the columnar extensive growth during the deposition in WAAM.

Normal pressure hydrocephalus (NPH) is a prevalent type of hydrocephalus, including secondary normal pressure hydrocephalus (SNPH) and idiopathic normal pressure hydrocephalus (INPH). However, its clinical diagnosis and pathological mechanism are still unclear. Leucine-rich α-2 glycoprotein (LRG) is involved in various human diseases, including cancer, diabetes, cardiovascular disease, and nervous system diseases. Now the physiological mechanism of LRG is still being explored. According to the current research results on LRG, we found that the agency of LRG has much to do with the known pathological process of NPH. This review focuses on analyzing the LRG signaling pathways and the pathological mechanism of NPH. According to the collected literature evidence, we speculated that LRG probably be involved in the pathological process of NPH. Finally, based on the mechanism of LRG and NPH, we also summarized the evidence of molecular targeted therapies for future research and clinical application.

With the development of new urban power systems, the centralized-distributed hierarchical partition management architecture has gradually become a consensus. Existing hierarchical partition methods are mostly static. And if the partition results are determined, it will remain unchanged for a relatively long time. However, the new type power system experiences more frequent and larger fluctuations in power generation and load, requiring dynamic responses to the system’s real-time operation. In this case, traditional partition methods are no longer applicable, and new hierarchical partition methods for system operation need to be adopted. Therefore, this paper proposes a power balance mechanism of urban power system based on dynamic hierarchical partition method, including dynamic hierarchical partition method and corresponding decoupling power balance models. The former can continuously change the results of hierarchical partition according to the real-time state of the power system, so as to reduce the inter-regional liaison cost and improve the economy. The latter improves the independence of the region and the security of the power system through decoupling power balance. Eventually, the proposed method is validated with an modified Hawaii 37-node system.

Abstract Effective treatment for metastasis, a leading cause of cancer‐associated death, is still lacking. To seed on a distal organ, disseminated cancer cells (DCCs) must adapt to the local tissue microenvironment. However, it remains elusive how DCCs respond the pro‐metastatic niche signals. Here, systemic motif‐enrichment identified myocyte enhancer factor 2D (MEF2D) as a critical sensor of niche signals to regulate DCCs adhesion and colonization, leading to intrahepatic metastasis and recurrence of liver cancer. In this context, MEF2D transactivates Itgb1 (coding β1‐integrin) and Itgb4 (coding β4‐integrin) to execute temporally unique functions, where ITGB1 recognizes extracellular matrix for early seeding, and ITGB4 acts as a novel sensor of neutrophil extracellular traps‐DNA (NETs‐DNA) for subsequent chemotaxis and colonization. In turn, an integrin‐FAK circuit promotes a phosphorylation‐dependent USP14‐orchastrated deubiquitination switch to stabilize MEF2D via circumventing degradation by the E3‐ubiquitin‐ligase MDM2. Clinically, the USP14(pS432)‐MEF2D‐ITGB1/4 feedback loop is often hyper‐active and indicative of inferior outcomes in human malignancies, while its blockade abrogated intrahepatic metastasis of DCCs. Together, DCCs exploit a deubiquitination‐dependent switch on MEF2D to integrate niche signals in the liver mesenchyme, thereby amplifying the pro‐metastatic integrin‐FAK signaling. Disruption of this feedback loop is clinically applicable with fast‐track potential to block microenvironmental cues driving metastasis.

Membranes with fast and selective ion transport are essential for electrochemical processes. Here the authors provide mechanistic insights into the structures of metal-ion coordinated polybenzimidazole membranes and the preferential K+ transport, and their application in an alkaline zinc-iron flow battery.

This study focuses on the inversion of sub-bottom profile (SBP) data in the northern South China Sea using an empirical relationship derived from sediment acoustic data. The sub-bottom profile is primarily utilized for various marine applications, such as geological mapping and resource exploration. In this research, we present a study conducted in the northern slope canyon of the South China Sea. Firstly, we obtained the seabed reflection coefficient from sub-bottom profiles obtained by the autonomous underwater vehicle (AUV) detection system. Secondly, we utilized the acoustic empirical relationship in the northern South China Sea to establish relationship equations between the seabed reflection coefficient and the porosity, density, and average particle size of the sediment at a main frequency of 4 kHz (the AUV shallow profile main frequency). Then, using these equations, we were able to invert the physical parameters such as porosity, density, and average particle size of the seabed surface sediments. Finally, the inverted results are compared and analyzed by using the sediment samples test data. The overall deviation rate of the inverted physical parameters is within the range of ±10% when compared. The inverted results closely match the measured values, accurately reflecting the dynamic changes in the physical properties of seabed surface sediments. Notably, the average grain size is a direct indicator of the sediment particles size with smaller particles found in deeper water. The variation characteristics of sediment physical parameters align well with the variation of sediment types in the canyon, which is consistent with changes in the water depth, topography, and hydrodynamic conditions of the area. This further demonstrates the reliability of the inversion results.

Flow batteries (FBs) have emerged as a promising technology for practical energy storage, mainly due to their outstanding characteristics of ultralong lifespan, safety, and scalability. Despite these attractive features, current FB technologies remain relatively expensive and have low energy density, limiting their widespread implementation. The multi-electron transfer FB systems are one of the most promising strategies to reduce the cost and enhance energy density. In this review, we give a comprehensive overview of the progress on multi-electron reaction materials, including the inorganic halogen-based, transition metal-based, and heteropoly acid-based materials and organic molecules (viologen derivatives, quinone derivatives, and heterocyclic aromatic compound derivatives). Finally, the challenge and perspective on the exploration of multi-electron materials for high-performance FBs are also provided.

Pituitary adenoma (PA) is the third most common central nervous system tumor originating from the anterior pituitary, but its pathogenesis remains unclear. The Wnt signaling pathway is a conserved pathway involved in cell proliferation, Self-renewal of stem cells, and cell differentiation. It is related to the occurrence of various tumors, including PA. This article reviews the latest developments in Wnt pathway inhibitors and pathway-targeted drugs. It discusses the possibility of combining Wnt pathway inhibitors with immunotherapy to provide a theoretical basis for the combined treatment of PA.

Background: Esophageal cancers are primarily categorized as esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). While various (epi) genomic alterations associated with tumor development in ESCC and EAC have been documented, a comprehensive comparison of the transcriptomes in these two cancer subtypes remains lacking. Methods: We collected 551 gene expression profiles from publicly available sources, including normal, ESCC, and EAC tissues or cell lines. Subsequently, we conducted a systematic analysis to compare the transcriptomes of these samples at various levels, including gene expression, promoter activity, alternative splicing (AS), alternative polyadenylation (APA), and gene fusion. Results: Seven distinct cluster gene expression patterns were identified among the differentially expressed genes in normal, ESCC, and EAC tissues. These patterns were enriched in the PI3K-Akt signaling pathway and the activation of extracellular matrix organization and exhibited repression of epidermal development. Notably, we observed additional genes or unique expression levels enriched in these shared pathways and biological processes related to tumor development and immune activation. In addition to the differentially expressed genes, there was an enrichment of lncRNA co-expression networks and downregulation of promoter activity associated with the repression of epidermal development in both ESCC and EAC. This indicates a common feature between these two cancer subtypes. Furthermore, differential AS and APA patterns in ESCC and EAC appear to partially affect the expression of host genes associated with bacterial or viral infections in these subtypes. No gene fusions were observed between ESCC and EAC, thus highlighting the distinct molecular mechanisms underlying these two cancer subtypes. Conclusions: We conducted a comprehensive comparison of ESCC and EAC transcriptomes and uncovered shared and distinct transcriptomic signatures at multiple levels. These findings suggest that ESCC and EAC may exhibit common and unique mechanisms involved in tumorigenesis.

The effects of combined Ti and Zr addition on microstructures and mechanical properties are systematically investigated in Al–Zn–Mg–Cu alloy by microstructure characterizations and a physical-based model. The results show that combined addition of Ti and Zr can promote the precipitation of nano L12 Al3(Ti,Zr) dispersoids, while primary D022 Al3Ti and Al3(Ti,Zr) phases are formed during solidification when Ti addition is over 0.2 wt%. As compared to the 0Ti alloy, the ductility and toughness is enhanced markedly by 0.1–0.2 wt%Ti addition since the volume fraction of nano L12 Al3(Ti,Zr) dispersoids is increased. Both the strength and ductility are significantly decreased when Ti addition is more than 0.35 wt%. The strain hardening behavior and fractured morphology analyses suggest that the deterioration of mechanical properties is mainly due to the localized recrystallization and cracks caused by coarse primary phases, which cause the higher dislocation dynamic recovery rate. Combined addition of minor Ti and Zr elements may provide a simple approach to improve toughness and simultaneously reduce cost in developing high-strength Al alloys.

Abstract Background Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it’s role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. Methods In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. Results As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p

Interpretability of DNN-based object detection has been a rising concern for the research community. The first step towards this goal is a saliency map that visualizes the importance (saliency) of pixels in an image for the object detected by a specific model. Black-box based methods generate a saliency map without the need to look into the internals of a model, thus applicable to all models without the need of adaptation. In addition, they provide more reliable evaluation on the saliency of pixels than white-box methods by means of the absence of these pixels from the image. However, with current black-box methods, the absence of pixels is produced by random image masks. Despite the need of a great number of random masks for sufficient coverage, the quality of the pixel saliency is not assured to be satisfactory. In this work, we propose a more effective black-box framework with hierarchical masking. In this framework, called GSM-HM, pixel saliency is evaluated at multiple levels, with each lower level performing a refinement on the saliency information of the upper level. This hierarchical framework significantly reduces the masking efforts on less valuable pixels, thus it can produce saliency maps with higher qualities. In our experiments, the quality of a generated saliency map is evaluated with four different metrics: deletion, insertion, convergence and RAM (the ratio of average to maximum). Compared with D-RISE, a recent black-block method, GSM-HM generates more accurate saliency maps evaluated by these metrics.

Summary: Long bones are generated by mesoderm-derived skeletal progenitor/stem cells (SSCs) through endochondral ossification, a process of sequential chondrogenic and osteogenic differentiation tightly controlled by the synergy between intrinsic and microenvironment cues. Here, we report that loss of TRIM28, a transcriptional corepressor, in mesoderm-derived cells expands the SSC pool, weakens SSC osteochondrogenic potential, and endows SSCs with properties of ectoderm-derived neural crest cells (NCCs), leading to severe defects of skeletogenesis. TRIM28 preferentially enhances H3K9 trimethylation and DNA methylation on chromatin regions more accessible in NCCs; loss of this silencing upregulates neural gene expression and enhances neurogenic potential. Moreover, TRIM28 loss causes hyperexpression of GREM1, which is an extracellular signaling factor promoting SSC self-renewal and SSC neurogenic potential by activating AKT/mTORC1 signaling. Our results suggest that TRIM28-mediated chromatin silencing establishes a barrier for maintaining the SSC lineage trajectory and preventing a transition to ectodermal fate by regulating both intrinsic and microenvironment cues.

A coaxial infrared-blue hybrid laser system was adopted in the cladding of high reflectivity pure copper on an AlSi7Mg alloy substrate, and the cladding stability, molten pool size and microstructure of the cladded samples by three types of laser sources (infrared, blue and their hybrid sources) were compared. The infrared-blue hybrid laser was validated to compensate for the forming instability of a high-power infrared laser and a low-power density blue laser. In addition, the heat accumulation in the cladding process with the hybrid laser was more obvious and the cooling rate was slower (1.36 × 104 K/s), which led to a coarser microstructure (1.56∼2.42 μm). Therefore, the hybrid laser can bring about stability and a larger molten pool size in cladding pure copper on the aluminum substrate, which is closely related to the great increase in the total laser absorption rate of the high reflectivity alloy and the reduction in the fluctuation of the absorption rate.

Xylooligosaccharide (XOS) is an attractive prebiotic mainly due to its bifidogenic effect. However, commercial XOS with different compositions is often applied in the food industry at different doses without specifications. In this study, we evaluated the bifidogenic activity of XOS at different doses with either mixtures or pure fractions with different degrees of polymerization (DP), using three strains of Bifidobacterium spp., including B. breve ATCC 15700, B. bifidum ATCC 29521, and B. animalis subsp. lactis HN019. Three growth indicators showed strain-specific bifidogenic activity of XOS, and the activity was both dose- and fraction-dependent as only certain fractions stimulated significant growth. Adding 0.25% XOS (w/v) also promoted increase in total bifidobacterial population of rat fecal samples fermented in vitro. Albeit the antibacterial activity of XOS fractions can be demonstrated, significant growth inhibition can only be achieved when 4.0% XOS mixture was added in Staphylococcus aureus ATCC 6538 pure culture. In contrast, in the presence of B. lactis HN019, 1.0% XOS showed significant antibacterial activity against S. aureus ATCC 6538 in milk. In addition, RNA sequencing suggested downregulation of genes involved in S. aureus ATCC 6538 infection, pathogenesis, and quorum sensing, by XOS. In conclusion, the report urges scientific specifications on XOS chemistry for its effective application as a novel food ingredient or functional food and provides novel insights into its bifidogenic and antibacterial activities.

With the rising demand for nuclear energy, the storage/transportation of radioactive nuclear by-products are critical safety issues for humans and the environment. These by-products are closely related to various nuclear radiations. In particular, neutron radiation requires specific protection by neutron shielding materials due to its high penetrating ability to cause irradiation damage. Herein, a basic overview of neutron shielding is presented. Since gadolinium (Gd) has the largest thermal neutron capture cross-section among various neutron absorbing elements, it is an ideal neutron absorber for shielding applications. In the last two decades, there have been many newly developed Gd-containing (i.e., inorganic nonmetallic-based, polymer-based, and metallic-based) shielding materials developed to attenuate and absorb the incident neutrons. On this basis, we present a comprehensive review of the design, processing methods, microstructure characteristics, mechanical properties, and neutron shielding performance of these materials in each category. Furthermore, current challenges for the development and application of shielding materials are discussed. Finally, the potential research directions are highlighted in this rapidly developing field.

Perspective: Rechargeable aqueous zinc-ion batteries (AZIBs) have gained increasing attention owing to their low cost and high safety. Although hydrated vanadium oxides exhibit rich redox chemistry and open layer architecture, the insertion of multivalent Zn2+ during cycling inevitably leads to host collapse and severe vanadium dissolution. Accordingly, various ions and conducting polymers have been introduced into the interlayer to produce vanadium bronzes with a robust crystal structure. However, these pre-intercalated vanadium bronzes demonstrate limited improvement and still face the challenge of metal ion displacement and confusing reaction mechanisms. Herein, we report a novel molecular bronze with intercalated 3-phenylpropylamine for use as an AZIB cathode, which produces an ultrahigh interlayer of 18.0 Å. The cathode delivered an improved capacity of 420 mAh g−1 at 0.1 A g−1, an impressive rate capability of 158 mAh g−1 at 35 A g−1, and an outstanding lifespan with a capacity retention of 94% over 1200 cycles at 2A g−1. Furthermore, the reaction mechanism of H+/Zn2+ co-insertion was investigated in detail. This work proves that this strategy is universal for vanadium oxide bronzes and opens a new avenue for the fabrication of novel molecular bronzes as advanced AZIB cathodes.

Membranes with fast and selective ion transport are highly relevant for energy storage devices. Here, the authors report a layered double hydroxide membrane with high ionic selectivity and hydroxide ion conductivity for flow battery applications, and reveal the ions transport mechanism of the membrane.

Abstract Background RNA-binding proteins (RBPs) play crucial roles in various biological processes. Deep learning-based methods have been demonstrated powerful on predicting RBP sites on RNAs. However, the training of deep learning models is very time-intensive and computationally intensive. Results Here we present a deep learning-based RBPsuite, an easy-to-use webserver for predicting RBP binding sites on linear and circular RNAs. For linear RNAs, RBPsuite predicts the RBP binding scores with them using our updated iDeepS. For circular RNAs (circRNAs), RBPsuite predicts the RBP binding scores with them using our developed CRIP. RBPsuite first breaks the input RNA sequence into segments of 101 nucleotides and scores the interaction between the segments and the RBPs. RBPsuite further detects the verified motifs on the binding segments gives the binding scores distribution along the full-length sequence. Conclusions RBPsuite is an easy-to-use online webserver for predicting RBP binding sites and freely available at http://www.csbio.sjtu.edu.cn/bioinf/RBPsuite/ .

Increasing evidence has indicated that circular RNAs (circRNAs) act as competing endogenous RNAs (ceRNAs) regulatory network to regulate the expression of target genes by sponging microRNAs (miRNAs), and therefore play an essential role in many neuropsychiatric disorders, including cocaine use disorder. However, the functional roles and regulatory mechanisms of circRNAs as ceRNAs in dorsolateral prefrontal cortex (dlPFC) of patients with cocaine use disorder remain to be determined. In this study, an expression profiling for dlPFC in 19 patients with cocaine use disorder and 17 controls from Gene Expression Omnibus datasets was used for the differentially expressed circRNAs analysis and the differentially expressed mRNAs analysis. Several tools were used to predict the miRNAs targeted by the circRNAs and the miRNAs targeted mRNAs, which then overlapped with the cocaine-associated differentially expressed mRNAs to determine the functional roles of circRNAs. Functional analysis for the obtained mRNAs was performed via Gene Ontology (GO) in Metascape database. Integrated bioinformatics analysis was conducted to further characterize the circRNA–miRNA–mRNA regulatory network and identify the functions of distinct circRNAs. We found a total of 41 differentially expressed circRNAs, and 98 miRNAs were targeted by these circRNAs. The overlapped mRNAs targeted by the miRNAs and the differentially expressed mRNAs constructed a circRNA–miRNA–mRNA regulation network including 24 circRNAs, 43 miRNAs, and 82 mRNAs in the dlPFC of patients with cocaine use disorder. Functional analysis indicated the regulation network mainly participated in cell response-related, receptor signaling-related, protein modification-related and axonogenesis-related pathways, which might be involved with cocaine use disorder. Additionally, we determined four hub genes (HSP90AA1, HSPA1B, YWHAG, and RAB8A) from the protein–protein interaction network and constructed a circRNA–miRNA-hub gene subnetwork based on the four hub genes. In conclusion, our findings provide a deeper understanding of the circRNAs-related ceRNAs regulatory mechanisms in the pathogenesis of cocaine use disorder.

Based on the precipitation data from the meteorological and hydrological stations and the Quantitative Precipitation Estimation (QPE) from radars over Jiangxi between May and June in 2019, we have made a fusion test of hourly precipitation from the meteorological and hydrological stations and by radars with 1 km×1 km resolution by using the space-time multiscale analysis system (STMAS), and made an analysis and assessment of fusion test results. The results show that the precipitation detected by meteorological stations, hydrological stations and radars has a similar spatial distribution. It is found that the severe precipitation zones and the patterns of precipitation distribution are very consistent. Comparing with the precipitation observed, the different fusion test results have a consistent variation tendency, but all are the underestimating to a certain extent. Those fused precipitation from the hydrological stations have a significant improvement in underestimation. The independent verification results indicate that the test results fused precipitation from hydrological stations have an obvious improvement in the accuracy of different level of precipitation, whose correlation coefficient increases by 9.2%, and root mean square error and mean absolute error decreases by 14.3% and 12.1%, respectively. After further fusing precipitation from hydrological stations, precipitation fusion results of different height areas are significantly improved, especially in the areas of elevation greater than 800 m whose correlation coefficient increases by 8.8% and root mean square error decreases by 14.1%.

Low-cost flow batteries with high power density are promising for energy storage, but membranes with simultaneously high ion conductivity and selectivity should be developed. Here the authors report a thin-film composite membrane that breaks the trade-off between ion conductivity and selectivity.

Alkaline zinc-iron flow battery (AZIFB) is promising for stationary energy storage to achieve the extensive application of renewable energies due to its features of high safety, high power density and low cost. However, the major bottlenecks such as the occurrence of short circuit, water migration and low efficiency have limited its further applications, of which an ion-conducting membrane acts as a pivotal role in addressing these issues. The benchmark Nafion series membranes or anion-exchange membranes are confronted with their low ionic conductivity or poor stability in alkaline media. Therefore, a membrane is required to possess (1) excellent stability to avert the occurrence of short circuit resulted from the destruction of zinc dendrite and degradation of membrane caused by alkaline media, (2) low area resistance and high selectivity to achieve a high efficiency in time of the charge-discharge procedure of AZIFB. In this review, we will start from a brief introduction of AZIFB and cover the categories of membranes applied in AZIFB. And then the fundamental aspects of the membrane, including ion transport mechanism, fabrication & structure design and performance optimization will be highlighted. Finally, the challenges and prospects of the membranes for AZIFB applications will be briefly proposed and discussed.

Bromine-based flow batteries (Br-FBs) have been one of the most promising energy storage technologies with attracting advantages of low price, wide potential window, and long cycle life, such as zinc-bromine flow battery, hydrogen-bromine flow battery, and sodium polysulfide-bromine flow battery. The research and development of aqueous Br-FBs are very fast and many achievements have been realized. However, Br-FBs suffer from the sluggish kinetics of Br2/Br- redox couple and serious self-discharge caused by the diffusion of bromine, which hinder the further commercialization and industrialization of the aqueous Br-FBs. A series of mitigation strategies have been developed to figure out these challenges, especially the modifications on electrode materials. Electrode, one of the critical components in a Br-FB, provides the reactions sites for redox couples, upon which its properties exert a significant effect on the performance of Br-FBs. Up to now, extensive research has been carried out on electrode modifications to solve the aforementioned notorious issues of Br-FBs, including surface treatment and surface modification. In this review, various electrode materials and relevant modification approaches used for Br-FBs are overviewed and summarized. Moreover, the relevant mechanisms are illustrated deeply, providing comprehensive and available instruction to pursue and develop high-performance cathodes for Br-FBs with high power density and long lifespan.

Abstract The stability control of surrounding rock for a large or super‐large section chamber group is a difficult technical problem in deep mining conditions, and this stability control has become one of the most important factors restricting the safety of a large‐scale coal mine. Based on the in‐site geological conditions of a super‐large section chamber group that functions for a coal gangues separation system in the Longgu Coal Mine, we first researched the stress, deformation, and failure characteristics of the in‐site chamber group surrounding rocks by using the FLAC3D software. Simulation results showed that the maximum vertical stress, deformation, and failure range of the surrounding rock for a super‐large section chamber group are larger than those of an ordinary section chamber. In addition, the roof subsidence and the plastic zone radius at the intersection are obviously larger than that of other parts, which increase by approximately 50.8% and 44.4%, respectively. Therefore, the chamber group intersection should be taken as the key area for surrounding rock control. Then, the influences of two key parameters of the chamber group, spacing and angle, were researched in detail to help in the design of the chamber group. Results show that when the chamber spacing is 80 m, the interaction begins to occur. When the angle is 70°, the stress of the surrounding rock and roof subsidence reach the minimum. Thus, the optimum chamber group parameters are determined to be a spacing of 80 m and an angle of 70°. Finally, from the perspective of chamber group stability, the optimal chamber group parameters can better meet the normal use for the super‐large section chamber group. This research provides a reference for the design of a super‐large section chamber group under the same or similar conditions and provides a strategy for controlling the surrounding rock.

Global development has been heavily reliant on the overexploitation of natural resources since the Industrial Revolution. With the extensive use of fossil fuels, deforestation, and other forms of land-use change, anthropogenic activities have contributed to the ever-increasing concentrations of greenhouse gases (GHGs) in the atmosphere, causing global climate change. In response to the worsening global climate change, achieving carbon neutrality by 2050 is the most pressing task on the planet. To this end, it is of utmost importance and a significant challenge to reform the current production systems to reduce GHG emissions and promote the capture of CO2 from the atmosphere. Herein, we review innovative technologies that offer solutions achieving carbon (C) neutrality and sustainable development, including those for renewable energy production, food system transformation, waste valorization, C sink conservation, and C-negative manufacturing. The wealth of knowledge disseminated in this review could inspire the global community and drive the further development of innovative technologies to mitigate climate change and sustainably support human activities.

Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is involved in multiple biological functions in cell development, differentiation, and transcriptional regulation. Tet1 deficient mice display the defects of murine glucose metabolism. However, the role of TET1 in metabolic homeostasis keeps unknown. Here, our finding demonstrates that hepatic TET1 physically interacts with silent information regulator T1 (SIRT1) via its C-terminal and activates its deacetylase activity, further regulating the acetylation-dependent cellular translocalization of transcriptional factors PGC-1α and FOXO1, resulting in the activation of hepatic gluconeogenic gene expression that includes PPARGC1A, G6PC, and SLC2A4. Importantly, the hepatic gluconeogenic gene activation program induced by fasting is inhibited in Tet1 heterozygous mice livers. The adenosine 5’-monophosphate-activated protein kinase (AMPK) activators metformin or AICAR—two compounds that mimic fasting—elevate hepatic gluconeogenic gene expression dependent on in turn activation of the AMPK-TET1-SIRT1 axis. Collectively, our study identifies TET1 as a SIRT1 coactivator and demonstrates that the AMPK-TET1-SIRT1 axis represents a potential mechanism or therapeutic target for glucose metabolism or metabolic diseases.

Study Region: Panxi mining area (15061 km2, located in Sichuan, China). Study Focus: This study aims to delineate groundwater potential zones in mining areas using a new method based on the cusp catastrophe model (CCM) and principal component analysis (PCA). First, 13 indicators were selected from natural and anthropogenic dimensions, and a comprehensive analysis of the indicators was performed using PCA. Second, the results of the PCA were considered as control variables, and the CCM was used for groundwater potential evaluation modeling. Finally, the receiver operating characteristic (ROC) curve was used to validate the new method and compare it with catastrophe fuzzy membership functions (CFMFs). New Hydrological Insights for the Region: The results suggest that the area under the ROC curve of the success and prediction rate accounted for approximately 0.85 and 0.76, respectively, in the new method, which were higher than those in the CFMFs. The largest area (39 %) with groundwater potential in the study area has a “moderate” groundwater potential status, followed by an area (28 %) with a “good” status, an area (20 %) with a “poor” status, and areas (12 % and 1%) with “very good” and “very poor” statuses, respectively. The groundwater potential in the study area was unevenly distributed and changed drastically. Topography, drainage density, and land use/land cover had the highest contribution in the modeling process.

BACKGROUND Targeted arterial infusion of verapamil combined with chemotherapy (TVCC) is an effective clinical interventional therapy for esophageal squamous cell carcinoma (ESCC), but multidrug resistance (MDR) remains the major cause of relapse or poor prognosis, and the underlying molecular mechanisms of MDR, temporal intratumoral heterogeneity, and clonal evolutionary processes of resistance have not been determined.METHODS To elucidate the roles of genetic and epigenetic alterations in the evolution of acquired resistance during therapies, we performed whole-exome sequencing on 16 serial specimens from 7 patients with ESCC at every cycle of therapeutic intervention from 3 groups, complete response, partial response, and progressive disease, and we performed whole-genome bisulfite sequencing for 3 of these 7 patients, 1 patient from each group.RESULTS Patients with progressive disease exhibited a substantially higher genomic and epigenomic temporal heterogeneity. Subclonal expansions driven by the beneficial new mutations were observed during combined therapies, which explained the emergence of MDR. Notably, SLC7A8 was identified as a potentially novel MDR gene, and functional assays demonstrated that mutant SLC7A8 promoted the resistance phenotypes of ESCC cell lines. Promoter methylation dynamics during treatments revealed 8 drug resistance protein-coding genes characterized by hypomethylation in promoter regions. Intriguingly, promoter hypomethylation of SLC8A3 and mutant SLC7A8 were enriched in an identical pathway, protein digestion and absorption, indicating a potentially novel MDR mechanism during treatments.CONCLUSION Our integrated multiomics investigations revealed the dynamics of temporal genetic and epigenetic inter- and intratumoral heterogeneity, clonal evolutionary processes, and epigenomic changes, providing potential MDR therapeutic targets in treatment-resistant patients with ESCC during combined therapies.FUNDING National Natural Science Foundation of China, Science Foundation of Peking University Cancer Hospital, CAMS Innovation Fund for Medical Sciences, Major Program of Shenzhen Bay Laboratory, Guangdong Basic and Applied Basic Research Foundation, and the third round of public welfare development and reform pilot projects of Beijing Municipal Medical Research Institutes.

Aluminum alloys fabricated by spray forming (SF) technology are commonly followed by hot-working without heat treatments. A new approach that is a pretreatment before hot-working is proposed in the present work. The results show that the microstructural stability of materials processed by this new approach is improved evidently, which is related to the pinning effect on dislocations and grain boundaries by Al3Zr particles induced during pretreatment. The strength of SF Al alloy processed by this treatment can be enhanced significantly. Owing to the combined effect of grain refinement strengthening, dislocation strengthening and precipitation strengthening, the yield strength and ultimate tensile strength can be enhanced by 171 MPa and 143 MPa, respectively. Based on experimental characterizations and a physical-based model, the underlying mechanisms regarding on enhancement of mechanical properties is mainly related to the induced Al3Zr particles and the optimized precipitates by the pretreatment.

In this study, the dependence of Er addition (0-0.49 wt %) on the microstructural evolution and related tensile strength at high temperature (HT) were investigated for the eutectic Al-Si piston alloys. The results showed there were intermetallic compounds of -Al3CuNi, -Al7Cu4Ni, Al4Cu2Mg8Si7, β-AlFeSi and Al3(Er, Cu, Fe) (Ni, Si) 2 identified at T5 states. Herein, the added Er element has led to the formation of the star-like and the irregular-shaped Al3(Er, Cu, Fe) (Ni, Si) 2 phase. The phase was stable which showed little change in both size and composition experienced solid solution at HT during the T6 treatment. For the HT strengths (350 oC), the T5 state alloys have higher UTSs than those at T6 state, both of which were reduced gradually with the increasing Er contents. The variation of HT strengths caused by the Er addition was explained by the microstructral evolution, namely Al3(Er, Cu, Fe) (Ni, Si)2 phase formation

Recently, the acoustic emission (AE) technique has been widely applied in the field of geotechnical engineering. One of the main applications of this technique is to locate damage sources, which is known as the AE source location technique. In this research, the 3D AE source location technique based on the time difference of arrival is verified by conducting pencil lead break (PLB) tests on a cylindrical metal specimen. From the results of this study, the existing method is proven to have the least error in terms of distance from the coordinate origin, but with some errors along x, y, and z axes. When the PLB sources originate in the middle part of the specimen, the calculated result has a higher accuracy, as compared to other positions. It seems that the calculated AE sources tend to be concentrated on the central part with some errors. Moreover, outside noises induced by a hammer hit have virtually no effect on this AE source location technique.

This paper proposes an effective image encryption algorithm based on the transformational prospective synchronization of a fractional-order hyperchaotic system. Compared with other chaos-based algorithms, fractional orders and synchronization precision are added as secret keys. It is shown that fractional-order, in comparison with its integer counterpart, has bigger complexity and larger key-space. Numerical simulation test results and security analyses demonstrate good performance of the proposed algorithm by encrypting the color image, gray medical image, and binary image. Furthermore, it is found that the synchronization precision accounted for in the decryption process has a significant effect on the decryption resolution.

The elimination of filarial diseases such as onchocerciasis and lymphatic filariasis is hampered by the lack of a macrofilaricidal-adult worm killing-drug. In the present study, we tested the in vivo efficacy of AN11251, a boron-pleuromutilin that targets endosymbiotic Wolbachia bacteria from filarial nematodes and compared its efficacy to doxycycline and rifampicin. Doxycycline and rifampicin were previously shown to deplete Wolbachia endosymbionts leading to a permanent sterilization of the female adult filariae and adult worm death in human clinical studies. Twice-daily oral treatment of Litomosoides sigmodontis-infected mice with 200 mg/kg AN11251 for 10 days achieved a Wolbachia depletion > 99.9% in the adult worms, exceeding the Wolbachia reduction by 10-day treatments with bioequivalent human doses of doxycycline and a similar reduction as high-dose rifampicin (35 mg/kg). Wolbachia reductions of > 99% were also accomplished by 14 days of oral AN11251 at a lower twice-daily dose (50 mg/kg) or once-per-day 200 mg/kg AN11251 treatments. The combinations tested of AN11251 with doxycycline had no clear beneficial impact on Wolbachia depletion, achieving a > 97% Wolbachia reduction with 7 days of treatment. These results indicate that AN11251 is superior to doxycycline and comparable to high-dose rifampicin in the L. sigmodontis mouse model, allowing treatment regimens as short as 10-14 days. Therefore, AN11251 represents a promising pre-clinical candidate that was identified in the L. sigmodontis model, and could be further evaluated and developed as potential clinical candidate for human lymphatic filariasis and onchocerciasis.

Synthetic materials tend to excel in either stiffness or extensibility, whereas a combination of the two is necessary to exceed the performance of natural biomaterials. Here the authors present a bioinspired polymer consisting of cyclic β-peptide rings that is capable of transitioning between rigid and unfolded conformations on demand.

Dendrite accumulation is a hindrance for alkaline zinc-based flow batteries. Here the authors design a negatively charged nanoporous membrane that mitigates zinc dendrite growth by repulsion of zincate anions, leading to a zinc-based flow battery with high power density and cycling stability.

The development of novel catalysts with both high catalytic activity and low cost toward the hydrolysis of ammonia borane is an important subject in the field of hydrogen energy. In this communications, NixCu1−xO microstructures with different morphology have been synthesized and their catalytic activities in AB hydrolysis is studied. It's found that bracelet-like nanoplatelets were obtained at x = 0.4 and exhibit highest catalytic performance with turnover frequency of 33.43 molhydrogen min−1molcat-1, which much higher than those of most of CuNi-based catalysts in the literature. Pronounced synergistic effects between CuO and NiO in AB hydrolysis also have been observed. Due to the superior catalytic performance and cheapness, the prepared bracelet-like nanoplatelets Ni0.4Cu0.6O catalysts can be a strong catalyst candidate in AB hydrolysis.

Summary: Alkaline zinc-iron flow battery is a promising technology for electrochemical energy storage. In this study, we present a high-performance alkaline zinc-iron flow battery in combination with a self-made, low-cost membrane with high mechanical stability and a 3D porous carbon felt electrode. The membrane could provide high hydroxyl ion conductivity while resisting zinc dendrites well owing to its high mechanical stability. The 3D porous carbon felt could serve as a guidance for the zinc stripping/plating, which can effectively suppress zinc dendrite/accumulation as well. Thus this battery demonstrates a coulombic efficiency of 99.5% and an energy efficiency of 82.8% at 160 mA cm−2, which is the highest value among recently reported flow battery systems. The battery can stably run for more than 500 cycles, showing very good stability. Most importantly, the practicability of this battery is confirmed by assembling a kilowatt cell stack with capital cost under $90/kWh. : Electrochemistry; Stationary Power; Energy Materials Subject Areas: Electrochemistry, Stationary Power, Energy Materials

Abstract Background Our study was designed to improve the accuracy of determining whether pulmonary nodules are benign or malignant. Methods We evaluated the clinical and imaging features and serum markers: neuron specific enolase (NSE), carcino-embryonic antigen (CEA), cytokeratin fragment antigen 21–1 (CYFRA 21–1), miRNA-21-5p, and miR-574-5pof in 39 patients with pathology information. Factors that differed significantly between those with benign versus malignant pulmonary nodules were used to establish a prediction model for identifying malignant nodules. Results The studied nodules were 51.3% malignant and 48.7% benign. Age, smoking status, nodule diameter, history of emphysema, vascular sign, burr sign, CYFRA21-1, CEA, miRNA-21-5p, and miRNA-574-5p differed significantly between the benign and malignant nodule groups. Serum levels of CYRFA21-1 and CEA could be used to distinguish between malignant and benign nodules with a positive predictive value (PPV) of 80.0%, a negative predictive value (NPV) of 84.2%, and an area under the receiver operating characteristics curve (AUC) of 0.863. Using the serum levels of miRNA-21-5p and miRNA-574-5p, the PPV was 55%, the NPV was 84.2%, and the AUC was 0.797. When all four serum markers were combined, the PPV was 80%, the NPV was 89.5%, and the AUC was 0.921. We established a prediction model for malignant nodules, including clinical features, imaging features, and serum markers. In cross-validation, the ratio of discriminant conformance was 95%. Conclusions Serum levels of miRNA-21-5p and miRNA-574-5p are significantly higher in patients with malignant nodules than in patients with benign nodules and are potential serum biomarkers. Our prediction model could improve malignant nodule diagnosis.

An intrusion behavior recognition method based on deep learning is proposed in this paper in order to improve the recognition accuracy of raster perimeter intrusion behavior. The Mach–Zehnder fiber optic interferometer was used to collect the external vibration signal sensing unit, capture the external vibration signal, use the cross-correlation characteristic method to obtain the minimum frame length of the fiber vibration signal, and preprocess the intrusion signal according to the signal strength. The intrusion signals were superimposed and several sections of signals were intercepted by fixed window length; the spectrum information is obtained by Fourier transform of the intercepted stationary signals. The convolution neural network was introduced into the pattern recognition of the intrusion signals in the optical fiber perimeter defense zone, and the different characteristics of the intrusion signals were extracted, so as to realize the accurate identification of different intrusion signals. Experimental results showed that this method was highly sensitive to intrusion events, could effectively reduce the false alarm rate of intrusion signals, and could improve the accuracy and efficiency of intrusion signal recognition.

Oesophageal schwannomas is a rare tumour and most commonly found incidentally or from diagnostic workup of dysphagia or dyspnoea. Most oesophageal schwannomas are benign and more frequently occurs in female than in the male. To date,

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