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Abstract Background Cerebral cavernous malformations (CCMs) are vascular abnormalities associated with deregulated angiogenesis. Their pathogenesis and optimal treatment remain unclear. This study aims to investigate the molecular signatures of cuproptosis, a newly identified type of cell death, associated with CCMs development. Methods Bulk RNA sequencing (RNA-seq) from 15 CCM and 6 control samples were performed with consensus clustering and clustered to two subtypes based on expression levels of cuproptosis-related genes (CRGs). Differentially expressed genes and immune infiltration between subtypes were then identified. Machine learning algorithms including the least absolute shrinkage and selection operator and random forest were employed to screen for hub genes for CCMs associated with cuproptosis. Furthermore, Pathway enrichment and correlation analysis were used to explore the functions of hub genes and their association with immune phenotypes in CCMs. An external dataset was then employed for validation. Finally, employing the Cellchat algorithm on a single-cell RNA-seq dataset, we explored potential mechanisms underlying the participation of these hub genes in cell-cell communication in CCMs. Results Our study revealed two distinct CCM subtypes with differential pattern of CRG expression and immune infiltration. Three hub genes (BTBD10, PFDN4, and CEMIP) were identified and validated, which may significantly associate with CCM pathogenesis. These genes were found to be significantly upregulated in CCM endothelial cells (ECs) and were validated through immunofluorescence and western blot analysis. Single-cell RNA-seq analysis revealed the cellular co-expression patterns of these hub genes, particularly highlighting the high expression of BTBD10 and PFDN4 in ECs. Additionally, a significant co-localization was also observed between BTBD10 and the pivotal cuproptosis gene FDX1 in Mki67+ tip cells, indicating the crucial role of cuproptosis for angiogenesis in CCMs. The study also explored the cell-cell communication between subcluster of ECs expressing these hub genes and immune cells, particularly M2 macrophages, suggesting a role for these interactions in CCM pathogenesis. Conclusion This study identifies molecular signatures linking cuproptosis to CCMs pathogenesis. Three hub genes—PFDN4, CEMIP, and BTBD10—may influence disease progression by modulating immunity. Further research is needed to understand their precise disease mechanisms and evaluate their potential as biomarkers or therapeutic targets for CCMs.

With the advancement of various aerial platforms, there is an increasing abundance of aerial images captured in various environments. However, the detection of densely packed small objects within complex backgrounds remains a challenge. To address the task of detecting multiple small objects, a multi-object detection algorithm based on distance intersection over union loss non-maximum suppression (DIOU-NMS) integrated with you only look once version 5 (YOLOv5) is proposed. Leveraging the YOLOv5s model as the foundation, the algorithm specifically addresses the detection of abundantly and densely packed targets by incorporating a dedicated small object detection layer within the network architecture, thus effectively enhancing the detection capability for small targets using an additional upsampling operation. Moreover, conventional non-maximum suppression is replaced with DIOU-based non-maximum suppression to alleviate the issue of missed detections caused by target density. Experimental results demonstrate the effectiveness of the proposed method in significantly improving the detection performance of dense small targets in complex backgrounds.

Despite the significant progress in diagnostic and therapeutic strategies, vascular diseases, such as cardiovascular diseases (CVDs) and respiratory diseases, still cannot be successfully eliminated. Vascular cells play a key role in maintaining vascular homeostasis. Notably, a variety of cells produce and secrete platelet-derived growth factors (PDGFs), which promote mitosis and induce the division, proliferation, and migration of vascular cells including vascular smooth muscle cells (SMCs), aortic SMCs, endothelial cells, and airway SMCs. Therefore, PDGF/PDGR receptor signaling pathways play vital roles in regulating the homeostasis of blood vessels and the onset and development of CVDs, such as atherosclerosis, and respiratory diseases including asthma and pulmonary arterial hypertension. Recently, accumulating evidence has demonstrated that microRNA, long-chain non-coding RNA, and circular RNA are involved in the regulation of PDGF/PDGFR signaling pathways through competitive interactions with target mRNAs, contributing to the occurrence and development of the above-mentioned diseases. These novel findings are useful for laboratory research and clinical studies. The aim of this article is to conclude the recent progresses in this field, particular the mechanisms of action of these non-coding RNAs in regulating vascular remodeling, providing potential strategies for the diagnosis, prevention, and treatment of vascular-dysfunction-related diseases, particularly CVDs and respiratory diseases.

In order to study the texture evolution and the formation of an inhomogeneous microstructure in hot-rolled plate of grain-orientated silicon steel, Fe3C (hexagonal) and ferrite phases in the subsurface layer were studied using electron backscatter diffraction. The results indicate that fiber texture (ferrite) mainly composed of {441} and (110)[001] Goss oriented grains was formed at a depth of 25% of the thickness of hot-rolled plate. Matrix grains in the subsurface layer were arbitrary separated into irregular large grains (≥40 μm) and fine grains (

The bean flower thrip Megalurothrips usitatus (Bagnall) is a severe pest on cowpeas and causes a 20–30% reduction in cowpeas in Hainan, China, with even complete crop failure in severe cases. Spinetoram is currently the most important pesticide against M. usitatus in cowpea production. In the main producing areas of cowpeas in Hainan, however, the efficacy of spinetoram against M. usitatus is not well known. In the present study, we employed the maximum dose bioassay to evaluate the efficacy of the mortality rates of adult thrips at F0 in spinetoram, freshly collected from 212 field populations of M. usitatus collected from 20 villages in the Yazhou District of Hainan. Our results showed that the mortality rates of these thrip populations exposed to spinetoram were from 3.31% to 100%. Among them, the mortality rates of 66.98% (142/212) of the populations exceeded 80%, while that of 33.96% (72/212) of the populations surpassed 90%. Only a small proportion of 0.47% (1/212) the populations exhibited a mortality rate below 10%, and 4.72% (10/212) displayed rates below 50%. Furthermore, significant differences were also observed in the mortality rates of thrips among different villages. Taken together, the maximum dosage bioassay method is a rapid and easily implemented approach providing valuable insights into the field efficacy of insecticides and offers guidance in determining the optimal dosage required in the field. Spinetoram is still effective against M. usitatus in the main producing areas of cowpeas in Hainan, but caution should be exercised in its combined use with other methods to reduce potential resistance.

Abstract Retraction: [Yuanlong Cao, Keyang Gu, Junyi Wu, Xiang Zou, Lei Tao, Xin Huang, Changgen Jiang, Anomaly detection with ensemble empirical mode decomposition and approximate entropy for quick user datagram protocol internet connection‐based distributed Blockchain systems, IET Software 2023 (https://doi.org/10.1049/sfw2.12096)]. The above article from IET Software, published online on 20 January 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the Editor‐in‐Chief, Hana Chockler, the Institution of Engineering and Technology (the IET) and John Wiley and Sons Ltd. This article was published as part of a Guest Edited special issue. Following an investigation, the IET and the journal have determined that the article was not reviewed in line with the journal’s peer review standards and there is evidence that the peer review process of the special issue underwent systematic manipulation. Accordingly, we cannot vouch for the integrity or reliability of the content. As such we have taken the decision to retract the article. The authors have been informed of the decision to retract.

Breast cancer (BC) is currently the most frequent and lethal cancer among women, and therefore, identification of novel biomarkers and potential anticancer agents for BC is crucial. Chelidonine is one of the main active ingredients of Chelidonium majus, which has been applied in Chinese medicine prescriptions to treat cancer. This paper aimed to evaluate the ability of chelidonine to trigger mitotic catastrophe in BC cells and to clarify its mechanism through the AKT/FOXO3/FOXM1 pathway. Bioinformatics analysis revealed that forkhead box O3 (FOXO3) was downregulated in different subtypes of BC. Factors such as age, stage, Scarff-Bloom-Richardson (SBR) grade, diverse BC subclasses, and triple-negative status were inversely correlated to FOXO3 levels in BC patients compared with healthy controls. Notably, patients exhibiting higher FOXO3 expression levels demonstrated better overall survival (OS) and relapse-free survival (RFS). Moreover, FOXM1 levels were negatively correlated with both OS and RFS in BC patients. These results revealed that FOXO3 might be considered a predictive biomarker for the prognosis of BC. By utilizing Gene Set Enrichment Analysis (GSEA), we delved into the main Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathways of FOXO3, and the results suggested that FOXO3 was mainly involved in cancer-related pathways and the cell cycle. Thereafter, MTT and flow cytometry (FCM) analysis indicated that chelidonine inhibited BC cell line proliferation and induced M phase arrest. It was found that chelidonine treatment induced MCF-7 cell apoptosis, significantly reduced the expression of survivin and promoted the expression of p53 and caspase-9. Further morphological observation illustrated depolymerization of the actin skeleton and shortening of actin filaments in BC cells, leading to the typical characteristics of mitotic catastrophe, such as abnormal mitosis and multinucleated cells. Western blot analysis demonstrated that chelidonine inhibited the expression of p-AKT to promote the expression of FOXO3 protein and weaken the expression levels of FOXM1 and polo-like kinase 1 (PLK1). Taken together, our present work proved that FOXO3 might be considered a potential therapeutic target for BC. Chelidonine emerges as a promising agent to treat BC by inducing M phase arrest of BC cells and hindering the AKT/FOXO3/FOXM1 axis, thereby inducing mitotic catastrophe in BC.

IntroductionAs a vital component within glacier systems, the occurrences of glacial lake disasters in high mountain regions have progressively emerged as one of the most destructive natural calamities amid the backdrop of global warming. The swift advancement of glacial lake identification techniques offers a pivotal perspective for forecasting and mitigating the perils of glacial lake outburst disasters.MethodsTo evaluate the thematic evolution, research focal points, and forthcoming directions within the glacier identification domain, a comprehensive bibliometric analysis was conducted on glacial lake identification-related literature from 1991 to 2023 in the Web of Science Core Collection database.Results1) The United States, the United Kingdom, and China stand as principal nations propelling the field's advancement. The Chinese Academy of Sciences demonstrates the highest activity in terms of article publications and international collaborations. 2) Climate change, compilation of glacial lake inventories, methodologies for risk assessment, glacial lake outburst floods, comprehensive disaster management strategies, and hydrodynamic models constitute the domain's research hotspots. It is a typical multidisciplinary field. 3) Persistently high-impact topics over an extended period include “hazard”, “Late Pleistocene”, “environmental change”, “ice sheet”, and “lake sediments”. Keywords indicating the present cutting-edge research encompass “inventory”, “glacial lake outburst flood”, “risk”, “dynamics”, “Tibetan Plateau”, “evolution”, and “high mountain Asia”.DiscussionThis paper delves into the current status and pivotal concerns of glacial lake identification techniques, methodologies, and the scale of identification research themes. Further Research should concentrate on avenues like “recognition methods grounded in machine learning and deep learning”, “multisource data fusion datasets”, “novel algorithms and technologies adaptable to scale transformation and data expansion”, as well as “enhancing spatiotemporal data resolution”. This will ultimately enable precise, prolonged, and multiscalar identification of glacial lakes. his study provides valuable guidance and reference for future research in the field of glacial lake identification.

In this paper, we propose a new digital signature primitive, called expander signature, and discuss its application in blockchain. The most promising advantage of expander signature is that a signer can generate all signatures at once using a powerful computer, and stores expander keys personally. Each time the signer wants some of his signatures to be verified, he releases the related expander key. No matter when or where, the signer can do this via a resource-limited device, for example, a personal portable terminal. We formally define the syntax and security of expander signature. Under our precisely defined security model, we give generic constructions of expander signature from both public key infrastructure-based and identity-based signature schemes. The security of our constructed expander signature schemes rigorously depends on the underlying public key signature schemes. The expander keys do not leak any information about the signer’s secret key and the size of the expander keys is constant no matter how many times the expander has been occurred. Finally, we give an application example of expander signature in blockchain.

Despite the maturity of cloud services (e.g., outsourcing of computational tasks), a number of operational challenges remain. For example, how do we ensure trust between outsourcers and workers in a zero-trust environment? While a number of blockchain-based solutions that eliminate the reliance on trusted third parties have been presented, many of these existing approaches do not achieve robust fairness and/or support compatibility with other systems. In this paper, we propose an efficient fair payment system using blockchain (EFPB), designed to achieve robust fairness and compatibility. Specifically, EFPB comprises a number of cryptographic building blocks, mainly: one-way accumulator (RSA-based construction), stealth address and symmetric encryption. We then evaluate the performance of EFPB to demonstrate that it is more efficient and low-cost than other competing schemes, as well as presenting a comparative summary of functionalities.

Abstract Background Traditional Chinese medicine (TCM) posits that Chinese medicinal materials can only be clinically used after being processed and prepared into decoction pieces. Schisandra Chinensis Fructus (derived from the dried and mature fruits of Schisandra chinensis (Turcz.) Baill.) has been used as a traditional antiasthmatic, kidney strengthening, and hepatoprotective agent for 2000 years. The results of previous research show that decoction pieces of wine-steamed Schisandra chinensis (WSC) are more effective than raw decoction pieces of Schisandra chinensis (RSC) for treating cough and asthma. Steaming with wine was demonstrated to promote the dissolution of ingredients. However, the relationship between the changes in the components of the decoction pieces of WSC and the therapeutic effect remains unclear. Methods The efficacies of decoctions of RSC and WSC were compared using allergic asthma rats. The potential bioactive components in the serum of the WSC treatment group and the changes in the chemical composition of the RSC decoction pieces before and after wine steaming were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC H-CLASS XEVO TQD) to speculate quality markers (Q-markers) related to the efficacy of WSC, which were subsequently verified based on a zebrafish inflammation model. Results Steaming RSC decoction pieces with wine was found to promote improvement of allergic asthma. Reverse tracing of 22 components detected in the serum of the high dose group of WSC (WSC-H) resulted in 12 ingredients being finally designated as potential effective components. Among these ingredients, 5 components, Schisandrin, Schisandrol B, Schisandrin A, Schisandrin B, and Gomisin D, had higher dissolution rates than RSC after steaming with wine. Validation by an inflammatory zebrafish model showed that these 5 ingredients had a dose-dependent effect and were therefore Q-markers for WSC in the treatment of allergic asthma. Conclusion In this study, changes in the components of decoction pieces of RSC and WSC and Q-markers related to WSC efficacy were identified, providing valuable information for expanding the application of WSC and establishing a specific quality standard for WSC.

We aimed to improve the detection accuracy of laser methane sensors in expansive temperature application environments. In this paper, a large-scale dataset of the measured concentration of the sensor at different temperatures is established, and a temperature compensation model based on the ISSA-BP neural network is proposed. On the data side, a large-scale dataset of 15,810 sets of laser methane sensors with different temperatures and concentrations was established, and an Improved Isolation Forest algorithm was used to clean the large-scale data and remove the outliers in the dataset. On the modeling framework, a temperature compensation model based on the ISSA-BP neural network is proposed. The quasi-reflective learning, chameleon swarm algorithm, Lévy flight, and artificial rabbits optimization are utilized to improve the initialization of the sparrow population, explorer position, anti-predator position, and position of individual sparrows in each generation, respectively, to improve the global optimization seeking ability of the standard sparrow search algorithm. The ISSA-BP temperature compensation model far outperforms the four models, SVM, RF, BP, and PSO-BP, in model evaluation metrics such as MAE, MAPE, RMSE, and R-square for both the training and test sets. The results show that the algorithm in this paper can significantly improve the detection accuracy of the laser methane sensor under the wide temperature application environment.

Abstract Soft, worm-like robots show promise in complex and constrained environments due to their robust, yet simple movement patterns. Although many such robots have been developed, they either rely on tethered power supplies and complex designs or cannot move external loads. To address these issues, we here introduce a novel, maggot-inspired, magnetically driven “mag-bot” that utilizes shape memory alloy-induced, thermoresponsive actuation and surface pattern-induced anisotropic friction to achieve locomotion inspired by fly larvae. This simple, untethered design can carry cargo that weighs up to three times its own weight with only a 17% reduction in speed over unloaded conditions thereby demonstrating, for the first time, how soft, untethered robots may be used to carry loads in controlled environments. Given their small scale and low cost, we expect that these mag-bots may be used in remote, confined spaces for small objects handling or as components in more complex designs.

The Sanmenxia Basin, located on the southeastern margin of the Shanxi rift and filled with Cretaceous-Paleogene fluvial and lacustrine sediments, is a faulted basin bounded by a series of normal strike-slip faults. This provides a valuable opportunity to investigate the early tectonic deformation in the Fenwei graben. In this study, we report an integrated rock magnetism and AMS analysis of two sections from the Sanmenxia Basin spanning an interval from the Late Cretaceous to the Eocene. The rock magnetic results demonstrate that magnetite and hematite are the main magnetic carriers of remanence, and paramagnetic minerals and hematite are major contributors to the AMS in both sections of the Sanmenxia Basin. Together with the relatively low-corrected anisotropy values, the tightly grouped minimum principal axes are almost perpendicular to the bedding plane, and the well-defined magnetic lineation is generally parallel to the bedding trend, indicating that the primary sedimentary fabrics in the Sanmenxia Basin were overprinted by the initial deformation. The NW–SE magnetic lineation denotes the NW–SE stretching during the Late Cretaceous-Eocene. The stretching process may have been controlled by the Indian-Eurasian convergence and/or the subduction of the western Pacific plate.

During the hot rolling process, inhomogeneity microstructure and variations of texture along the thickness direction of hot-rolled plate were formed through shear deformation and recrystallization. The purpose of this study is to investigate the formation and evolution of fiber texture in hot-rolled plate of grain-oriented silicon steel. The results indicate that, in the surface layer s = 1 of hot-rolled plate, a large number of equiaxed grains are formed under high shear force. Under the surface layer, as shear force gradually decreases along the thickness direction, the grain aspect ratio of recrystallized grains gradually increases along the thickness direction of hot-rolled plate, and the shape of the recrystallized grains formed in the subsurface layer and center layer becomes more irregular along the thickness direction. Under the combination of compressive force and decreasing shear force along the thickness direction, fiber texture composed of dozens of specific orientations (such as {112}, {110}, {213}, {441} and Goss orientations) is formed in the subsurface layer s = 0.5~0.9 and gradually evolves along the thickness direction. Therefore, the formation of Goss texture is a small part of fiber texture and is the result of texture evolution in the subsurface layer s = 0.5~0.9.

Summary: Background: Valproic acid (VPA) represents one of the most efficient antiseizure medications (ASMs) for both general and focal seizures, but some patients may have inadequate control by VPA monotherapy. In this study, we aimed to verify the hypothesis that excitatory dynamic rebound induced by inhibitory power may contribute to the ineffectiveness of VPA therapy and become a predictor of post-operative inadequate control of seizures. Methods: Awake craniotomy surgeries were performed in 16 patients with intro-operative high-density electrocorticogram (ECoG) recording. The relationship between seizure control and the excitatory rebound was further determined by diagnostic test and univariate analysis. Thereafter, kanic acid (KA)-induced epileptic mouse model was used to confirm that its behavior and neural activity would be controlled by VPA. Finally, a computational simulation model was established to verify the hypothesis. Findings: Inadequate control of seizures by VPA monotherapy and post-operative status epilepticus are closely related to a significant excitatory rebound after VPA injection (rebound electrodes≧5/64, p = 0.008), together with increased synchronization of the local field potential (LFP). In addition, the neural activity in the model mice showed a significant rebound on spike firing (53/77 units, 68.83%). The LFP increased the power spectral density in multiple wavebands after VPA injection in animal experiments (p

This study determined the optimum reaction conditions for synthesizing selenium-containing polysaccharides. Polysaccharide IIA (with the highest yield) from Ornithogalum caudatum Ait. (Liliaceae) (OCAPIIA) was extracted and purified. Then, three parameters were selected to optimize the synthesis of selenized OCAPIIA (Se-OCAPIIA) using the Box–Behnken design (BBD) and response surface methodology (RSM). The morphology of Se-OCAPIIA was analyzed by scanning electron microscopy (SEM). The characteristic peaks and the monosaccharide composition of Se-OCAPIIA were evaluated by Fourier-transform infrared spectroscopy and gas chromatography. A D-galactose-induced aging mouse model was established, and the in vivo antioxidant activity of Se-OCAPIIA was measured. The optimal conditions for the synthesis of Se-OCAPIIA were as follows: reaction temperature, 72.38 °C; Na2SeO3 to OCAPIIA mass ratio, 0.93 g/g; and reaction time, 8.05 h. The selenium content of Se-OCAPIIA obtained using the optimized process was 3.131 ± 0.090 mg/g, close to the maximum predicted value (3.152 mg/g). Se-OCAPIIA contained D-mannose, D-glucose, and D-galactose at a molar ratio of 1.00:0.34:0.88. SEM showed that Se-OCAPIIA was spherical and flocculated. Compared with OCAPIIA, Se-OCAPIIA exhibited two characteristic peaks at 833 and 610 cm−1 in the infrared spectrum. Se-OCAPIIA increased catalase, glutathione peroxidase, and superoxide dismutase activities and decreased MDA concentrations in the mouse liver. Moreover, Se-OCAPIIA treatment improved liver morphology, decreased the levels of IL-1β and IL-6, and increased IL-10 concentration. In conclusion, the synthesis of Se-OCAPIIA is effective, simple, and feasible. Se-OCAPIIA demonstrated high antioxidant activity in vivo and is a promising antioxidant and therapeutic agent.

Over the past few decades, drug-induced liver damage (DILI) has become a serious public health problem due to drug abuse. Among multifarious reactive oxygen species, mounting evidence attests that ClO− has been used as a potential biomarker in DILI. In this work, a new “turn-on” fluorescent probe 1 was designed and synthesized by modifying 4′-hydroxybiphenyl-4-carbonitrile (dye 2) with N, N-dimethylthiocarbamate as a response site for detecting ClO−. Probe 1 displayed a low detection limit (72 nM), fast response time (30 s), wide pH operating range (6–8), great tissue penetration, large Stokes shift (125 nm) and 291-fold fluorescence enhancement at 475 nm in the mapping of ClO−. Probe 1 could trace amounts of exogenous and endogenous ClO− with high sensitivity in MCF-7 cells and HeLa cells. Expectantly, the fluoxetine-induced liver injury model is successfully established, and probe 1 has been used for detecting the fluctuation of ClO− levels in the mouse model of fluoxetine-induced liver injury. All in all, probe 1 with its high specificity, good biological compatibility and liver tissue penetration ability is expected to assist with the early diagnosis of DILI and the clinical screening of various new drugs. We expect that probe 1 could be efficiently used as a powerful molecular tool to predict clinical DILI and explore molecular mechanisms between molecules and disease.

Research on the mixing process of gas–liquid–solid multiphase flow in a high-pressure abrasive water jet (HP-AWJ) is of great significance in improving the performance of water jet cutting. In this paper, the Euler method-VOF model, a computational fluid dynamics (CFD) simulation method, is used to solve the multiphase flow of air–water in an abrasive water jet (AWJ). The Euler–Lagrange method is further used to study the multiphase flow of abrasive particles. The method considers the shape factor of the particle, uses the Rosin–Rammler function, and defines an effective model for the particle-to-wall wear model. By solving the velocity of the continuous phase and particulate phase in the AWJ cutting head, the problem of nozzle wear caused by particles is studied. Finally, the exit velocity of the AWJ and particle wear are investigated by varying the model’s parameters. The results show that the double abrasive tube model effectively improved the problem of one-sided wear inside the nozzle, and the tangential velocity of the air affected the acceleration process of the abrasive inside the nozzle, with smaller abrasive velocity resulting in less wear on the model. Simultaneously, the effects of the abrasive inlet tube and mixing chamber size on abrasive exit velocity and nozzle wear are analyzed. The results obtained provide valuable guidance for addressing the multiphase flow mixing issues in the AWJ, improving the abrasive acceleration process and extending the nozzle’s lifetime.

Abstract Background Recent scientific research has enabled the identification of macrophages related-genes (MaRG), which play a key role in the control of the immune microenvironment in many human cancers. However, the functional role of MaRGs in human tumors is ill-defined. Herein, we aimed at bioinformatically exploring the molecular signatures of MaRGs in colorectal cancer. Methods A list of MaRGs was generated and their differential expression was analyzed across multiple datasets downloaded from the publicly available functional genomics database Gene Expression Omnibus. The weighted gene co-expression network analysis (WGCNA) was also applied to identify the partner genes of these MaRGs in colorectal cancer. Results After integration of the results from analyses of different datasets, we found that 29 differentially expressed MaRGs (DE-MaRGs) could be considered as CRC-related genes as obtained from the WGCNA analysis. These genes were functionally involved in positive regulation of DNA biosynthetic process and glutathione metabolism. Protein–protein interaction network analysis indicated that PDIA6, PSMA1, PRC1, RRM2, HSP90AB1, CDK4, MCM7, RFC4, and CCT5 were the hub MaRGs. The LASSO approach was used for validating the 29 MaRGs in TCGA-COAD and TCGA-READ data and the results showed that ten among the 29 genes could be considered as MaRGs significantly involved in CRC. The maftools analysis showed that MaRGs were mutated at varying degrees. The nomogram analysis indicated the correlation of these MaRGs with diverse clinical features of CRC patients. Conclusions Conclusively, the present disclosed a signature of MaRGs as potential key regulators involved in CRC pathogenesis and progression. These findings contribute not only to the understanding of the molecular mechanism of CRC pathogenesis but also to the development of adequate immunotherapies for CRC patients.

A biometric lock design method was proposed based on the internal features of human body, namely PBLock.It used the backscattered RF signals to collect the impedance characteristics of human fingertips through the contact between human fingers and tags.The advantage of such authentication method is that the human impedance was not easy to be stolen, and it was fully integrated with the hardware characteristics of the device (RFID tags), which greatly increased the difficulty for the attacker to copy and clone.To ensure the availability and efficiency of the system, an optimization authentication mechanism was proposed by cutting tag antenna, which effectively improved the impedance sensitivity.Moreover, the feasibility of passive drive was discussed by using the electromagnetic energy advantage of RFID system.Through a large number of experimental evaluations, the authentication accuracy of PBLock can reach 96%, and the average time cost of a single authentication is 1.4 seconds.Some attack models were presented based on practical environment.The results show that PBLock can effectively prevent counterfeiting attack, impersonation attack and replay attack, which provides an opportunity for the secure application of new biometric electronic locks.

Abstract Background The DENND1A gene is one of the most important sites associated with polycystic ovary syndrome (PCOS). We attempted to analyze the correlation between five single nucleotide polymorphisms (SNPs) in the DENND1A gene and the development of PCOS. Methods A total of 346 PCOS patients and 225 normal ovulatory women were involved in the case-control study. Clinical variables and hormones were recorded. According to the Hap Map database, five tagging SNPs (rs2479106, rs2768819, rs2670139, rs2536951 and rs2479102) in the DENND1A gene were identified. The TaqMan probe and the PCR–RFLP (restriction fragment length polymorphism) methods were used for revealing these genotypes. TaqMan Genotype Software was used to analyze the alleles of the five SNPs. Results Linkage disequilibrium and the gene frequency analysis demonstrated that the CCGGG haplotype might increase the risk of PCOS (P = 0.038, OR = 1.89, 95% CI = 1.027–3.481). Significant differences were found in genotypic and allelic distributions at the rs2536951 and rs2479102 loci between PCOS women and controls (P

Quantum computers with tens to hundreds of noisy qubits are being developed today. To be useful for real-world applications, we believe that these near-term systems cannot simply be scaled-down non-error-corrected versions of future fault-tolerant large-scale quantum computers. These near-term systems require specific architecture and design attributes to realize their full potential. To efficiently execute an algorithm, the quantum coprocessor must be designed to scale with respect to qubit number and to maximize useful computation within the qubits' decoherence bounds. In this work, we employ an application-system-qubit co-design methodology to architect a near-term quantum coprocessor. To support algorithms from the real-world application area of simulating the quantum dynamics of a material system, we design a (parameterized) arbitrary single-qubit rotation instruction and a two-qubit entangling controlled-Z instruction. We introduce dynamic gate set and paging mechanisms to implement the instructions. To evaluate the functionality and performance of these two instructions, we implement a two-qubit version of an algorithm to study a disorder-induced metal-insulator transition and run 60 random instances of it, each of which realizes one disorder configuration and contains 40 two-qubit instructions (or gates) and 104 single-qubit instructions. We observe the expected quantum dynamics of the time-evolution of this system.

Abstract Introduction Chronic cerebral hypoperfusion has been considered the etiology for sporadic Alzheimer's disease (AD). However, no valid clinical evidence exists due to the similar risk factors between cerebrovascular disease and AD. Methods We used moyamoya disease (MMD) as a model of chronic hypoperfusion and cognitive impairment, without other etiology interference. Results Based on the previous reports and preliminary findings, we hypothesized that chronic cerebral hypoperfusion could be an independent upstream crucial variable, resulting in AD, and induce pathological hallmarks such as amyloid beta peptide and hyperphosphorylated tau accumulation. Discussion Timely intervention with revascularisation would help reverse the brain damage with AD hallmarks and lead to cognitive improvement.

Soil microbial communities play an important role in nutrient cycling; however, their response under repeated long-term fertilization has attracted little attention and needs further appraisal. A 14-day incubation study compared the relative abundance, diversity, and composition of bacterial and fungal microbial communities in soils treated with long-term applications of chemical fertilizer (CF), pig manure plus chemical fertilizer (PMCF), and rice straw plus chemical fertilizer (SRCF) in a paddy field. A high-throughput sequencing approach was applied to assess the diversity and composition of microbial community. Results revealed the Shannon index of the bacterial community decreased with fertilizer addition but increased in case of fungal community. The abundance of the Actinobacteria was higher in the PMCF, while Proteobacteria were higher in the CF and SRCF treatments than those in the unamended control under alternate wetting and drying (AWD) and permanent flooding (PF). In addition, chemical fertilizer history increased the abundance of Firmicutes under AWD. Initially, Nitrospira were found higher in the unamended control than in the amended treatments, but an increase was observed with time in fertilized treatments. Among all genera, Proteobacteria were the most abundant bacterial genus. The main properties that markedly affected the bacterial communities were SOC (R2 = 0.4037, p < 0.02), available P (R2 = 0.3273, p < 0.05), and NO3− (R2 = 0.3096, p < 0.08). Soil physicochemical factors and biogenic factors explained a variation of 46.27% and 29.35%, respectively. At the same time, 4.59% was the combined effect of physicochemical and biogenic factors. Our results suggested that the physicochemical properties had a more significant impact on bacterial activities than water regime by increasing N and organic matter concentrations in the soils.

The anaerobic ammonium oxidizing bacteria (anammox) are the hidden culprit behind the excessive nitrogen loss under a favorable environment, since their detection and abundance get disturbed by several unknown factors. This study intends to find the gap between actual anammox working capacity under different water conditions and fertilizers in the laboratory. The 15N-isotopic tracer technique was used to measure anammox and denitrification rate, and anammox community structure was analyzed through high-throughput sequencing with cytochrome cd-1 nitrite reductase functional gene (an_nirS gene, initially found in Candidatus Scalindua). The experiment consisted of four treatments, i.e., (I) CK_ Control, (II) UR_Urea, (III) PM_Pig Manure, and (IV) SRF_ Slow release fertilizer, under two water conditions, i.e., (a) Continuous flooding_ CF, (b) Alternate wetting and drying_ AWD. Results showed that anammox under CF decreased over time by −40.24%, and denitrification increased up to 39.25%. However, anammox activity under AWD increased up to 10.62% with the availability of NO2–, and surprisingly accompanied by the reduction in denitrification loss (-31.97%), being the most critical factor. We found that soil nifH and AOB genes were strongly favorable for anammox activity, while we observed the presence of anammox and AOB genes co-existing at the same time in paddy soil. The high-throughput sequencing with an_nirS functional gene showed a much higher diversity of anammox genera ever reported, mostly uncultured and unidentified. We concluded that water management is more prominent than fertilizer for anammox, and the most critical factor is the duration of AWD cycle, because of short term air supply could boost anammox activity and gene abundance, and could reduce denitrifier activity as well as nirK gene abundance.

Abstract A fiber-optic Raman spectrum sensor system is used for the fast diagnosis of esophageal cancer during clinical endoscopic examination. The system contains a 785 nm exciting laser, a Raman fiber-optic probe with 7 large core fibers and a focus lens, and a highly sensitive spectrum meter. The Raman spectrum of the tissue could be obtained within 1 second by using such a system. A signal baseline removal and denoising technology is used to improve the signal quality. A novel signal feature extraction method for differentiating the normal and esophageal cancer tissues is proposed, based on the differences in half-height width (HHW) in 1200 cm‒1 to 1400 cm‒1 frequency band and the ratios of the spectral integral energy between 1600 cm‒1 − 1700 cm‒1 and 1500 cm‒1 − 1600 cm‒1 band. It shows a high specificity and effectivity for the diagnosis of esophageal cancer.

Abstract Background Polymalic acid (PMA) is a water-soluble biopolymer with many attractive properties for food and pharmaceutical applications mainly produced by the yeast-like fungus Aureobasidium pullulans. Acid hydrolysis of PMA, resulting in release of the monomer l-malic acid (MA), which is widely used in the food and chemical industry, is a competitive process for producing bio-based platform chemicals. Results In this study, the production of PMA and MA from sucrose and sugarcane molasses by A. pullulans was studied in shake flasks and bioreactors. Comparative metabolome analysis of sucrose- and glucose-based fermentation identified 81 intracellular metabolites and demonstrated that pyruvate from the glycolysis pathway may be a key metabolite affecting PMA synthesis. In silico simulation of a genome-scale metabolic model (iZX637) further verified that pyruvate carboxylase (pyc) via the reductive tricarboxylic acid cycle strengthened carbon flux for PMA synthesis. Therefore, an engineered strain, FJ-PYC, was constructed by overexpressing the pyc gene, which increased the PMA titer by 15.1% compared with that from the wild-type strain in a 5-L stirred-tank fermentor. Sugarcane molasses can be used as an economical substrate without any pretreatment or nutrient supplementation. Using fed-batch fermentation of FJ-PYC, we obtained the highest PMA titers (81.5, 94.2 g/L of MA after hydrolysis) in 140 h with a corresponding MA yield of 0.62 g/g and productivity of 0.67 g/L h. Conclusions We showed that integrated metabolome- and genome-scale model analyses were an effective approach for engineering the metabolic node for PMA synthesis, and also developed an economical and green process for PMA and MA production from renewable biomass feedstocks.

Coal mine waters often have high salinity, hardness and alkalinity. The treatment of coal mine water requires careful management of multi-stage reverse osmosis (RO) systems to achieve effective recovery of water for domestic reuse, as well as zero liquid discharge to minimise the impact to the local environment. Design of RO systems for coal mine water treatment has been limited to the use of commercial design packages provided by membrane manufacturers, which do not provide insights into the impact of operating parameters such as feedwater salinity, concentrations of sparingly soluble salts, feed pressure and their interactions with different RO modules on the fouling/scaling potential of RO membranes. This also restricts the use of novel RO products and the delivery of an optimum design based on real needs. In this work, a mathematical model was developed to simulate a standard brackish water RO pressure vessel consisting six full-size RO membrane elements, using computational fluid dynamics (CFD). The model can be used to predict the permeate flowrate, water recovery levels, as well as the spatial information of the accumulation and scaling potential of sparingly soluble salts on the membrane surface. The results obtained from the model showed good agreement with the results obtained from the commercial RO design software WAVE. The CFD model was then used to predict the scaling threshold on various positions of a full-scale RO element, at different operating conditions, using parametric simulations based on Central Composite Designs. Outputs from this work not only provide insights into the microscopic flow characteristics of multiple full-scale elements in the RO pressure vessel, but also predicts the position where scaling would occur, at different feed conditions, for any RO products.

A three-dimensional model for the simulation of concentration polarisation in a full-scale spiral wound reverse osmosis (RO) membrane element was developed. The model considered the coupled effect of complex spacer geometry, pressure drop and membrane filtration. The simulated results showed that, at a salt concentration of 10,000 mg/L and feed pressure of 10.91 bar, permeate flux decreased from 27.6 L/(m2 h) (LMH) at the module inlet to 24.1 LMH at the module outlet as a result of salt accumulation in the absence of a feed spacer. In contrast, the presence of the spacer increased pressure loss along the membranes, and its presence created vortices and enhanced fluid velocity at the boundary layer and led to a minor decrease in flux to 26.5 LMH at the outlet. This paper underpins the importance of the feed spacer’s role in mitigating concentration polarisation in full-scale spiral wound modules. The model can be used by both the industry and by academia for improved understanding and accurate presentation of mass transfer phenomena of full-scale RO modules by different commercial manufacturers that cannot be achieved by experimental characterization of the mass transfer coefficient or by CFD modelling of simplified 2D flow channels.

Understanding the distribution and transport of Uranium is important because it can lead to both chemical and radiological toxicity. This study presents the Uranium concentrations time series from 1964 to 2009 obtained from a 3 m deep snow pit at Dome Argus, East Antarctic Plateau. The data shows that Uranium concentrations vary from 0.0067 pg g-1 to 0.12 pg g-1, with a mean concentration of 0.044 pg g-1. Its mean concentration is 2-3 folds lower than at West Antarctica study sites, such as the Antarctic Peninsula (mean 0.12 pg g-1), IC-6 (Ice Core-6) (mean 0.11 pg g-1) and a suite of ice cores from the US ITASE traverse. Before the mid-1980s, the varieties of Uranium concentrations are relatively stable, with a very low mean concentration of 0.016 pg g-1and its main source is sea salt deposition, while a small number of anthropogenic sources are likely to be caused by Uranium mining operations in South Africa. A remarkable increase of Uranium concentrations has occurred since the mid-1980s (by a factor of ~ 9) compared with the amount before the mid-1980s. This increase coincides with the Uranium records at IC-6 and Antarctic Peninsula (DP-07-01) during the same period, and are mostly attributed to Uranium mining operations in Australia as a potential primary anthropogenic Uranium source. Our observations suggest that Uranium pollution in the atmosphere might have already become a global phenomenon.

The pressure control for a liquid nature gas (LNG) ship is vital for the cargo handling system which is a nonlinear, unstable, and controllable complex system accompanied by the dynamics of time delay. To improve the control effect, this article proposed a robust controller based on closed-loop gain shaping algorithm by mirror-mapping approach. In addition, the complete mechanism models for the system are established to predict the changes of temperature, pressure, and liquid inventory in the cargo tank. The heat exchanges and evaporation of liquid are also considered. By collecting the data from the LNG ship “Dapeng,” the system models are validated. At the same time, the comparative experiment is introduced to verify the reliability and effectiveness. The scheme has been compared with the 2-DOF structure control law of modified Smith predictor. The comparative experimental results show that the scheme proposed in this note has a strong disturbance rejection ability and steady-state performance. The controller designed in this note has advantages of simplified construction method, satisfactory control effect and robustness.

This paper introduces a novel control strategy into the insulation space for liquid natural gas carriers. The control strategy proposed can improve the effects of control for differential pressure and reduce the energy consumption of nitrogen. The method combines a nonlinear feedback technique with a closed-loop gain shaping algorithm (CGSA). It is designed for the pressure control system which is vital for liquid natural gas carriers (LNGCs) in marine transportation. The control error is modulated using nonlinear function. The deviation signal is replaced with a nonlinear feedback signal. Comparison experiments are conducted under different conditions to prove the effectiveness of this strategy. This paper compares three control strategies: a control strategy with nonlinear feedback based on CGSA, a control strategy without nonlinear feedback based on CGSA, and a two-degree-of-freedom (DOF) control strategy. The simulation results show that this control strategy with nonlinear feedback performs better than the other two. The average reduction of control input is about 38.8%. The effect of pressure control is satisfactory.

A novel electromagnetic scattering model is presented for studying coupling field of super-low altitude target under diverse terrestrial environments in semi-active radar system. The PO+MEC hybrid method is applied to obtain the electromagnetic scattering of target. The Physical Optics (PO) is introduced to calculate the scattering from facets of target. The Method of Equivalent Currents (MEC) is introduced to calculate the scattering from edges of target. Antenna radiation pattern of seeker is introduced to modify traditional Four Path Method (FPM) in semi-active radar system. Based on the modified FPM, the characteristics of coupling field from super-low altitude target under diverse terrestrial environments in semi-active radar system are studied. Simulation results can use for reference in the fields of remote sensing and detection for super-low altitude target.

Malic acid is a dicarboxylic acid widely used in the food industry, and is also a potential C4 platform chemical. Corncob is a low-cost renewable feedstock from agricultural industry. However, side-reaction products (furfural, 5-hydroxymethylfurfural (HMF), formic acid, and acetic acid) that severely hinder fermentation are formed during corncob pretreatment. The process for producing malic acid from a hydrolysate of corncob was investigated with a polymalic acid (PMA)-producing Aureobasidium pullulans strain. Under the optimal hydrolysate sugar concentration 110 g/L, A. pullulans was further adapted in an aerobic fibrous bed bioreactor (AFBB) by gradually increasing the sugar concentration of hydrolysate. After nine batches of fermentation, the production and productivity of malic acid reached 38.6 g/L and 0.4 g/L h, respectively, which was higher than that in the first batch (27.6 g/L and 0.29 g/L h, respectively). The adapted strain could grow under the stress of 0.5 g/L furfural, 3 g/L HMF, 2g/L acetic acid, and 0.5 g/L formic acid, whereas the wild type did not. Transcriptome analysis revealed that the differentially expressed genes were related to carbohydrate transport and metabolism, lipid transport and metabolism, signal transduction mechanism, redox metabolism, and energy production and conversion under 0.5 g/L furfural and 3 g/L HMF stress conditions. In total, 42 genes in the adapted strain were upregulated by 15-fold or more, and qRT-PCR also confirmed that the expression levels of key genes (i.e. SIR, GSS, CYS, and GSR) involved in sulfur assimilation pathway were upregulated by over 10-fold in adapted strain for cellular protection against oxidative stress.

The aggregation of high-affinity immunoglobulin E (IgE) receptors (FcεRI) on mast cells is a critical event in the initiation of an allergic reaction. Coengagement of FcεRI with immunoglobulin G (IgG) low-affinity receptor FcγRIIB/CD32 inhibits degranulation and the release of inflammatory mediators from mast cells and has therefore been proposed as a new therapeutic approach for the treatment of allergies. In this study, we investigated whether FcγRIIB, besides inhibiting degranulation, negatively regulates other signalling pathways downstream of FcεRI. For this, we determined the phosphorylation and/or expression of proteins involved in the regulation of mast-cell apoptosis. Coaggregation led to an attenuation of Akt phosphorylation but did not inhibit phosphorylation of transcription factor Foxo3a or its proapoptotic target, Bim. Similarly, FcεRI-dependent expression of the prosurvival gene A1 was not affected by coaggregation. Our data demonstrate that coengagement of FcεRI and FcγRIIB inhibits degranulation but not the signalling pathways regulating Bcl-2 family members Bim and A1.

“Smart Pavement” is an emerging infrastructure for various on-road applications in transportation and road engineering. However, existing road monitoring solutions demand a certain periodic maintenance effort due to battery life limits in the sensor systems. To this end, we present an end-to-end self-powered wireless sensor—ePave—to facilitate smart and autonomous pavements. The ePave system includes a self-power module, an ultra-low-power sensor system, a wireless transmission module and a built-in power management module. First, we performed an empirical study to characterize the piezoelectric module in order to optimize energy-harvesting efficiency. Second, we developed an integrated sensor system with the optimized energy harvester. An adaptive power knob is designated to adjust the power consumption according to energy budgeting. Finally, we intensively evaluated the ePave system in real-world applications to examine the system’s performance and explore the trade-off.