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Abstract Background SARS-CoV-2, a highly contagious coronavirus, is responsible for the global pandemic of COVID-19 in 2019. Currently, it remains uncertain whether SARS-CoV-2 possesses oncogenic or oncolytic potential in influencing tumor progression. Therefore, it is important to evaluate the clinical and functional role of SARS-CoV-2 on tumor progression. Methods Here, we integrated bioinformatic analysis of COVID-19 RNA-seq data from the GEO database and performed functional studies to explore the regulatory role of SARS-CoV-2 in solid tumor progression, including lung, colon, kidney and liver cancer. Results Our results demonstrate that infection with SARS-CoV-2 is associated with a decreased expression of genes associated with cancer proliferation and metastasis in lung tissues from patients diagnosed with COVID-19. Several cancer proliferation or metastasis related genes were frequently downregulated in SARS-CoV-2 infected intestinal organoids and human colon carcinoma cells. In vivo and in vitro studies revealed that SARS-CoV-2 nucleocapsid (N) protein inhibits colon and kidney tumor growth and metastasis through the N-terminal (NTD) and the C-terminal domain (CTD). The molecular mechanism indicates that the N protein of SARS-CoV-2 interacts with YBX1, resulting in the recruitment of PKM mRNA into stress granules mediated by G3BP1. This process ultimately destabilizes PKM expression and suppresses glycolysis. Conclusion Our study reveals a new function of SARS-CoV-2 nucleocapsid protein on tumor progression.

Abstract Non‐volatile photomemory based on photomodulated luminescent materials offers unique advantages over voltage‐driven memory, including low residual crosstalk and high storage speed. However, conventional materials have thus far been volatile and insecure for data storage because of low trap depth and single‐level storage channels. Therefore, the development of a novel non‐volatile multilevel storage medium for data encryption remains a challenge. Herein, a robust, non‐volatile, multilevel optical storage medium is reported, based on a photomodulated Ba3MgSi2O8:Eu3+, which combined the merits of light‐induced valence (Eu3+ → Eu2+) and photochromic phenomena using optical stimulation effects, accompanied by larger luminescent and color contrasts (>90%). These two unique features provided dual‐level storage channels in a single host, significantly improving the data storage security. Notably, dual‐level optical signals could be written and erased simultaneously by alternating 265 and 365 nm light stimuli. Theoretical calculations indicated that robust color centers induced by intrinsic interstitial Mg and vacancy defects with suitable trap depths enable excellent reversibility and long‐term storage capability. By relying on different luminescent readout mechanisms, the encrypted dual‐level information can be accurately decrypted by separately probing the Eu2+ and Eu3+ signals, thus ensuring information security. This study proposes a novel approach for constructing multilevel information storage channels for information security.

This study aimed to investigate the impact of dietary protein levels (DPLs) on the growth performance, plasma parameters, nutritional metabolism, and the mTOR pathway in Chinese perch. Three replicates of Chinese perch (34.39 ± 0.16 g) were provided with five diets containing varying protein levels (39.99 %, 43.09 %, 46.04 %, 49.14 %, and 52.12 %) over an 8-week period. The results revealed that, as DPLs increased, the final weight (FW), daily weight gain (DWG)), specific growth rate (SGR) and protein efficiency ratio (PER) initially rose and then declined, reaching their peak at 49.14 % DPL group. The feed conversion ratio (FCR) decreased first and then increased. In addition, compared to 46.04 % DPL group, the 39.99 % DPL group significantly suppressed whole body crude protein, liver crude protein, and liver crude lipid contents. The 52.12 % DPL group significantly increased liver crude lipid content and aspartate aminotransferase (AST) activity, and increased plasma total cholesterol (TC), total triglyceride (TG) and total lipase (TL) concentrations. However, in Chinese perch fed with 46.04 % DPL, the expression of genes associated with liver amino acid catabolism (ast, gdh and ampd), lipid hydrolysis, and oxidation (hsl, lpl and cs), as well as glycolysis (pk), was significantly increased. And the expression levels of mTOR pathway-related genes (s6k and mtor) and the phosphorylation level of p-S6 were significantly elevated in the liver of fish fed with 46.04 % DPL. In summary, a low DPL (39.99 %) significantly impedes the growth performance of Chinese perch, resulting in an elevated feed conversion ratio. And a high DPL (52.12 %) can induce lipid deposition in the liver of Chinese perch, increase metabolic stress, and lead to liver damage. Additionally, piecewise regression analysis and second-degree polynomial analysis revealed that optimal protein level in Chinese perch feed is suggested to range between 46.10 % and 48.71 %. This study provides partial theoretical basis for the design of commercial practical feed formulas for Chinese perch.

The origami-based meta-structure has wide application in areas such as energy and wave transmission. Existing research has demonstrated the occurrence of supra-transmission in origami meta-structures and revealed its underlying mechanism. However, studies on how to regulate the phenomenon of supra-transmission are still very limited. In this work, we choose the meta-structure composed of stacked Miura-ori (SMO) as the subject. The SMO unit possesses two topologically distinct stable configurations, enabling the meta-structure to possess a rich variety of periodic layouts. Based on the established equivalent dynamic model of the SMO-based meta-structure, we employ numerical simulation methods and find that the supra-transmission threshold could be adjusted by tuning the periodic layout of the meta-structure. Furthermore, the probability of supra-transmission is also highly dependent on the periodic layout. Increasing the number of SMO units under the bulged-out configuration in each periodic layout decreases the likelihood of supratransmission occurring. The findings of this study yield an extensive array of foundational insights into the wave dynamics of origami structures. Furthermore, these insights translate into practical guidelines for designing origami-based meta-structure with tunable and programmable dynamic characteristics.

Photo-stimuli responsive materials show great potential in the fields of information encryption and storage due to their distinctive spatial or temporal color changes. However, the conventional single or multi-color static outputs by light stimulus difficulty meet practical requirements for high-security optical storage technologies. Here, a novel dynamic irradiation-responsive phosphor of Na2Ba2Si2O7:Eu is demonstrated, exhibiting high storage stability and convenient readout behaviors. The inherent Eu2+ luminescence can be dynamically tuned, instantly read out, and conveniently erased by controlling irradiation duration of a portable diode laser (365 nm). The modulation mechanism is unraveled by optically induced oxidation reactions of Eu2+→Eu3+ and defects as killer centers. The excellent luminescence modulation degree (ΔRt = 89.5%) and the accompanying larger color contrast enable the creation of invisible optical codes with multi-level encryption in bright or dark field. These results indicate potential applications of Na2Ba2Si2O7-based materials in information encryption and invisible optical storage, and are expected to expand more investigations on optically induced PL modulation behaviors based on mixed valences and defects.

Abstract This study combined population genetics and parentage analysis to obtain foundational data for the conservation of Magnolia kwangsiensis. M. kwangsiensis is a Class I tree species that occurs in two disjunct regions in a biodiversity hotspot in southwest China. We assessed the genetic diversity and structure of this species across its distribution range to support its conservation management. Genetic diversity and population structure of 529 individuals sampled from 14 populations were investigated using seven nuclear simple sequence repeat (nSSR) markers and three chloroplast DNA (cpDNA) fragments. Parentage analysis was used to evaluate the pollen and seed dispersal distances. The nSSR marker analysis revealed a high genetic diversity in M. kwangsiensis, with an average observed (Ho) and expected heterozygosities (He) of 0.726 and 0.687, respectively. The mean and maximum pollen and seed dispersal distances were 66.4 and 95.7 m and 535.4 and 553.8 m, respectively. Our data revealed two distinct genetic groups, consistent with the disjunct geographical distribution of the M. kwangsiensis populations. Both pollen and seed dispersal movements help maintain genetic connectivity among M. kwangsiensis populations, contributing to high levels of genetic diversity. Both genetically differentiated groups corresponding to the two disjunct regions should be recognized as separate conservation units.

Obesity, characterised by excessive fat accumulation, is a complex chronic condition that results from dysfunctional adipose tissue expansion due to prolonged calorie surplus. This leads to rapid adipocyte enlargement that exceeds the support capacity of the surrounding neurovascular network, resulting in increased hypoxia, inflammation, and insulin resistance. Intermittent fasting (IF), a dietary regimen that cycles between periods of fasting and eating, has emerged as an effective strategy to combat obesity and improve metabolic homeostasis by promoting healthy adipose tissue remodeling. However, the precise molecular and cellular mechanisms behind the metabolic improvements and remodeling of white adipose tissue (WAT) driven by IF remain elusive. This review aims to summarise and discuss the relationship between IF and adipose tissue remodeling and explore the potential mechanisms through which IF induces alterations in WAT. This includes several key structural changes, including angiogenesis and sympathetic innervation of WAT. We will also discuss the involvement of key signalling pathways, such as PI3K, SIRT, mTOR, and AMPK, which potentially play a crucial role in IF-mediated metabolic adaptations.

The flame propagation processes of MgH2 dust clouds with four different particle sizes were recorded by a high-speed camera. The dynamic flame temperature distributions of MgH2 dust clouds were reconstructed by the two-color pyrometer technique, and the chemical composition of solid combustion residues were analyzed. The experimental results showed that the average flame propagation velocities of 23 μm, 40 μm, 60 μm and 103 μm MgH2 dust clouds in the stable propagation stage were 3.7 m/s, 2.8 m/s, 2.1 m/s and 0.9 m/s, respectively. The dust clouds with smaller particle sizes had faster flame propagation velocity and stronger oscillation intensity, and their flame temperature distributions were more even and the temperature gradients were smaller. The flame structures of MgH2 dust clouds were significantly affected by the particle sinking velocity, and the combustion processes were accompanied by micro-explosion of particles. The falling velocities of 23 μm and 40 μm MgH2 particles were 2.24 cm/s and 6.71 cm/s, respectively. While the falling velocities of 60 μm and 103 μm MgH2 particles were as high as 15.07 cm/s and 44.42 cm/s, respectively, leading to a more rapid downward development and irregular shape of the flame. Furthermore, the dehydrogenation reaction had a significant effect on the combustion performance of MgH2 dust. The combustion of H2 enhanced the ignition and combustion characteristics of MgH2 dust, resulting in a much higher explosion power than the pure Mg dust. The micro-structure characteristics and combustion residues composition analysis of MgH2 dust indicated that the combustion control mechanism of MgH2 dust flame was mainly the heterogeneous reaction, which was affected by the dehydrogenation reaction.

The objective of the study was to investigate the effects of dietary carbohydrate on growth performance, feed utilization, proximate compositions, and hepatic glucolipid metabolism in Chinese perch. Triplicate groups of Chinese perch (29.51 ± 0.24 g) were fed five isonitrogenous and isolipidic diets containing graded levels of carbohydrate (2.4%, 9.7%, 16.5%, 23.9%, and 30.1%) for 8 weeks. The results based on second-order polynomial regression analysis of specific growth rate (SGR) proved that Chinese perch obtained the best growth performance at the 10.93% dietary carbohydrate level. Compared to 2.4%-carbohydrate group, 9.7%-carbohydrate group exhibited the increase in daily weight gain (DWG) and protein retention ratio (PER) and the decrease in feed conversion efficiency (FCR). Moreover, 9.7%-carbohydrate group showed the increase in the mRNA levels of pfk and cs involved in aerobic oxidation pathway, the content of liver glycogen increased significantly, and no change in glucose level. Above results suggested that a part of carbohydrates may be converted into energy for growth by aerobic oxidation pathway, or converted into glycogen for storage to maintain glucose homeostasis in Chinese perch fed with moderate-carbohydrate diet. Differently, 23.9%-carbohydrate and 30.1%-carbohydrate groups showed the decrease in DWG and PER, and the increase in FCR, compared to 2.4%-carbohydrate group. Additionally, 23.9%-carbohydrate and 30.1%-carbohydrate group presented the increase in the mRNA levels of g6pca and pc involved in gluconeogenesis, which caused the increase in plasma glucose level. However, other plasma indices related to TG-metabolite and its transport (total cholesterol, and low-density lipoprotein) did not show difference, which combined with elevated fatty acid synthesis-related gene accα mRNA level resulted in excessive liver lipid deposition. Above results indicated that unregulated gluconeogenesis and invalid outward transportation of liver TG-rich metabolites may account for the glucose intolerance of Chinese perch fed with carbohydrate-rich diet. Furthermore, compared to the results from the 4th week, the expression of gk, pfk, pc, cs, and accα genes significantly increased in the 30.1%-carbohydrate group at the 8th week. Both liver and muscle exhibited a significant elevation in crude fat content, while Daily DWG experienced a noticeable decrease. These results indicated that the glucose metabolism and growth of Chinese perch in the high-carbohydrate group are influenced by the interaction of feeding duration and carbohydrate levels. And within a certain time frame, Chinese perch can tolerate a diet rich in carbohydrates.

Corona Virus Disease 2019 (COVID-19) is a highly prevalent and potent infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Until now, the world is still endeavoring to develop new ways to diagnose and treat COVID-19. At present, the clinical prevention and treatment of COVID-19 mainly targets the spike protein on the surface of SRAS-CoV-2. However, with the continuous emergence of SARS-CoV-2 Variants of concern (VOC), targeting the spike protein therapy shows a high degree of limitation. The Nucleocapsid Protein (N protein) of SARS-CoV-2 is highly conserved in virus evolution and is involved in the key process of viral infection and assembly. It is the most expressed viral structural protein after SARS-CoV-2 infection in humans and has high immunogenicity. Therefore, N protein as the key factor of virus infection and replication in basic research and clinical application has great potential research value. This article reviews the research progress on the structure and biological function of SARS-CoV-2 N protein, the diagnosis and drug research of targeting N protein, in order to promote researchers’ further understanding of SARS-CoV-2 N protein, and lay a theoretical foundation for the possible outbreak of new and sudden coronavirus infectious diseases in the future.

Herein, this study contributes significantly to the advancement of continuum manipulators in two main aspects. First, a modularization concept and a hybrid actuation scheme to create a novel origami continuum manipulator with exceptional deformability are introduced. Second, an accurate model and framework for the forward and inverse kinematic analysis of origami manipulators are proposed. Specifically, each origami manipulator module can achieve axial extension and bending deformation by coordinated actuation of shape memory alloy (SMA) and pneumatic muscles, and the manipulator's end is equipped with a deformable gripper based on waterbomb origami and actuated by SMA. Through careful consideration of the self‐weight and torque balance, an accurate kinematic model based on the Denavit–Hartenberg method is established, which enables one to effectively predict the reachable extreme positions and spatial poses of the manipulator and solve the inverse kinematics using a genetic algorithm. Comprehensive experiments are conducted to validate the design's rationality and model's accuracy . In these tests, the rich spatial configurations are not only demonstrated that can be achieved by integrating hybrid actuators with origami modules but also the accuracy and reliability of the kinematic model are confirmed, opening up possibilities for the advancement and application of origami‐inspired robotics in various fields.

ABSTRACTThe nucleocapsid protein of SARS-CoV-2 plays significant roles in viral assembly, immune evasion, and viral stability. Due to its immunogenicity, high expression levels during COVID-19, and conservation across viral strains, it represents an attractive target for antiviral treatment. In this study, we identified and characterized a single-stranded DNA aptamer, N-Apt17, which effectively disrupts the liquid-liquid phase separation (LLPS) mediated by the N protein. To enhance the aptamer’s stability, a circular bivalent form, cb-N-Apt17, was designed and evaluated. Our findings demonstrated that cb-N-Apt17 exhibited improved stability, enhanced binding affinity, and superior inhibition of N protein LLPS; thus, it has the potential inhibition ability on viral replication. These results provide valuable evidence supporting the potential of cb-N-Apt17 as a promising candidate for the development of antiviral therapies against COVID-19.IMPORTANCEVariants of SARS-CoV-2 pose a significant challenge to currently available COVID-19 vaccines and therapies due to the rapid epitope changes observed in the viral spike protein. However, the nucleocapsid (N) protein of SARS-CoV-2, a highly conserved structural protein, offers promising potential as a target for inhibiting viral replication. The N protein forms complexes with genomic RNA, interacts with other viral structural proteins during virion assembly, and plays a critical role in evading host innate immunity by impairing interferon production during viral infection. In this investigation, we discovered a single-stranded DNA aptamer, designated as N-Apt17, exhibiting remarkable affinity and specificity for the N protein. Notably, N-Apt17 disrupts the liquid-liquid phase separation (LLPS) of the N protein. To enhance the stability and molecular recognition capabilities of N-Apt17, we designed a circular bivalent DNA aptamer termed cb-N-Apt17. In both in vivo and in vitro experiments, cb-N-Apt17 exhibited increased stability, enhanced binding affinity, and superior LLPS disrupting ability. Thus, our study provides essential proof-of-principle evidence supporting the further development of cb-N-Apt17 as a therapeutic candidate for COVID-19.

Abstract Background The effect of platelet factor 4 (PF4) on bone marrow mesenchymal stem cells (BMMSCs) and osteoporosis is poorly understood. Therefore, this study aimed to evaluate the effects of PF4‐triggered bone destruction in mice and determine the underlying mechanism. Methods First, in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry, respectively. Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S. Next, an osteoporotic mouse model was established by performing bilateral ovariectomy (OVX). Furthermore, the PF4 concentrations were obtained using enzyme‐linked immunosorbent assay. The bone microarchitecture of the femur was evaluated using microCT and histological analyses. Finally, the key regulators of osteogenesis and pathways were investigated using quantitative real‐time polymerase chain reaction and Western blotting. Results Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs. Furthermore, the levels of PF4 in the serum and bone marrow were generally increased, whereas bone microarchitecture deteriorated due to OVX. Moreover, in vivo mouse PF4 supplementation triggered bone deterioration of the femur. In addition, several key regulators of osteogenesis were downregulated, and the integrin α5‐focal adhesion kinase‐extracellular signal‐regulated kinase (ITGA5‐FAK‐ERK) pathway was inhibited due to PF4 supplementation. Conclusions PF4 may be attributed to OVX‐induced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5‐FAK‐ERK pathway.

With the rapid development of society, more and more unknown halogenated disinfection byproducts (DBPs) enter into drinking water and pose potential risks to humans. To explore the unknown halogenated DBPs in tap water, a selectively nontargeted analysis (SNTA) method was developed by conducting micro-liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (micro-LC-QTOFMS). In this method, two runs were employed: in the first run, the modes of TOFMS and precursor ion (the fragments were set as Cl35/Cl37, Br79/Br81, and I126.9) were performed, and the molecular ions or precursor ions of the halogenated organics could be obtained; in the second run, the product ion mode was conducted by setting the molecular ion screened above, and the MS/MS spectrums could be acquired to speculate concerning the structure. Two kinds of model DBPs (one kind had an aliphatic structure and the other was an aromatic compound) were used to optimize the parameters of the MS, and their MS characteristics were summarized. With this SNTA method, 15 halogenated DBPs were screened in two tap water samples and their structures were proposed. Of them, six DBPs had not been reported before and were assumed to be new DBPs. Overall, the detected halogenated DBPs were mostly acidic substances.

Abstract Efficient electricity market operations and cost-effective electricity generations are fundamental to a low-carbon energy future. The Western Electricity Coordinating Council (WECC) and Northeast Power Coordinating Council (NPCC) systems were built to provide efficient electrical grid simulation solutions for their respective U.S. regions. Data reuse for electricity economic studies remains a challenge due to the lack of credible and realistic economic data. This paper delivers a comprehensive dataset containing generator aggregations, generator costs, transmission limits, load distributions, and electricity prices for the WECC and NPCC systems based on real-world grid operation data at year 2020, including power plant geographic locations, generation profiles, regional power flow interchanges, and load distributions in both regions. The electricity price from the developed dataset is simulated based on the other items in the dataset, and we show that the variation of the simulated electricity price reasonably aligns with the real-world electricity price in both the WECC and NPCC regions. Overall, the developed dataset is of interest for various electricity market and economic studies, such as the economic dispatch and locational marginal price (LMP) analysis.

Recently, interventional ablation techniques have gained prominence in tumor treatment guidelines and complement traditional approaches, such as surgery, chemotherapy, and radiotherapy. Conventional ablation techniques, such as microwave, radiofrequency, and cryoablation, have been used; however, they have certain limitations, including the risk of damaging surrounding normal tissues and the heat sink effect caused by tumor blood flow.1 Irreversible electroporation (IRE), an ablation technology independent of thermal energy, is a promising alternative.2 Clinical studies have demonstrated IRE's efficacy in treating tumors, such as pancreatic and liver tumors.3 Recent research has shown that IRE can elicit specific anti-tumor immune responses in the body.5 IRE also plays a crucial role in eliminating residual tumor cells postoperatively and preventing tumor recurrence.

Summary: The tight coupling between electricity and gas has put the US New England region at constant risk of electricity price spikes due to a shortage of gas supplies, especially in the wake of limited natural gas supply in 2022. Here, we investigate the electricity-gas price couplings in the six states in New England from 2006 to 2022. We found that the price coupling in New England has been high and consistent in the past five years across all states, despite varying levels of gas-fired power generation. Additionally, we anticipate it will remain high even with increasing renewables by 2030. Furthermore, the price coupling exhibits an asymmetrical influence with electricity prices closely tracking gas prices, while gas prices are weakly affected by electricity price variations. Our findings also suggest that promoting electricity-gas cooperations could potentially mitigate the asymmetrical influence and electricity price spikes in New England.

Abstract Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn’t. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

Abstract Background Hybridization is generally considered an important creative evolutionary force, yet this evolutionary process is still poorly characterized in karst plants. In this study, we focus on natural hybridization in yellow Camellia species, a group of habitat specialists confined to karst/non-karst habitats in southwestern China. Results Based on population genome data obtain from double digest restriction-site associated DNA (ddRAD) sequencing, we found evidence for natural hybridization and introgression between C. micrantha and C. flavida, and specifically confirmed their hybrid population, C. “ptilosperma”. Ecophysiological results suggested that extreme hydraulic traits were fixed in C. “ptilosperma”, these being consistent with its distinct ecological niche, which lies outside its parental ranges. Conclusion The identified hybridization event is expected to have played a role in generating novel variation during, in which the hybrid population displays different phenological characteristics and novel ecophysiological traits associated with the colonization of a new niche in limestone karst.

Multienergy system (MES) operation has proven beneficial to the flexibility and efficiency of energy usage. Although efforts have been made toward the simulation and optimization of MESs, successful MES deployment is a grand challenge for market operations. The previous literature focuses on the modeling of the MES and the formulation of corresponding locational marginal prices (LMPs). A detailed analysis of LMP properties in an MES market-clearing model has not been fully developed. Although coupling analysis between different energy systems has been conducted from a system and power flow perspective, a coupling analysis with a specific indicator from a LMP perspective could provide operators with new insight into MES integration. Therefore, this paper first identifies six properties of the LMP in a unified MES market-clearing model. Then, based on the identified properties, two new types of critical load levels (CLL), Self-CLL and Cross-CLL, are defined and discussed to investigate the MES price pattern. Next, the Self-CLLs and Cross-CLLs for an MES are quantified by grey relation analysis (GRA) to deliver an MES coupling analysis from the perspective of LMP patterns. The identified properties and proposed analysis are demonstrated with a small MES case and a large one.

NLRP3 inflammasome mainly controls interleukin-1β (IL-1β) secretion, leading to cell death called pyroptosis constituting a major antiviral host defense and inflammatory diseases upon viral infection. The RAF-MEK1/2-ERK1/2 cascade and downstream c-Jun/Fos and Activator protein-1 (AP1) signaling pathway control the degree of inflammatory response. Influenza A virus (IAV) infection is known to stimulate NLRP3 inflammasome activation and inflammatory responses. Nevertheless, the detailed mechanism by which IAV induces NLRP3 inflammasome activation involved in transcription of pro-IL-1β mRNA remains elusive. In our study, we found that IAV infection promotes pro-IL-1β mRNA transcription and activates NLRP3 inflammasome. Detailed studies reveal that type I interferon (IFN-α/IFN-β) as well as U0126 (a selective inhibitor of MEK-1 and MEK-2) typically inhibit IAV-mediated NLRP3 inflammasome activation via downregulating pro-IL-1β mRNA. Moreover, knock-down of c-Jun decreases pro-IL-1β mRNA and inhibits NLRP3 inflammasome activation upon IAV infection. Overall, the findings uncover that AP-1 signaling pathway promotes NLRP3 inflammasome activation upon IAV infection, which provides a new idea for the therapy of NLRP3 inflammasome-associated inflammatory diseases.

Abstract Molecular oxygen (O2) is essential for most biological reactions in mammalian cells. When the intracellular oxygen content decreases, it is called hypoxia. The process of hypoxia is linked to several biological processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, and other stress responses. The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia. Hypoxia-inducible factors (HIFs) sense hypoxia to regulate the expressions of a series of downstream genes expression, which participate in multiple processes including cell metabolism, cell growth/death, cell proliferation, glycolysis, immune response, microbe infection, tumorigenesis, and metastasis. Importantly, hypoxia signaling also interacts with other cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) signaling, and endoplasmic reticulum (ER) stress. This paper systematically reviews the mechanisms of hypoxia signaling activation, the control of HIF signaling, and the function of HIF signaling in human health and diseases. In addition, the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted, which would provide novel strategies for the design and development of therapeutic drugs.

The immense potential of flexible energy storage materials applied in wearable electronic devices has stimulated a lot of science researches on manufacturing technology and performance optimization. Herein, an all-inorganic flexible ferroelectric film with multilayer heterostructure is prepared based on Mn doped Bi0.5Na0.5TiO3BiNi0.5Zr0.5O3 (Mn:BNT-BNZ) and Bi0.5Na0.5TiO3BiZn0.5Zr0.5O3 (BNT-BZZ) relaxor ferroelectrics. A win-win situation of breakdown strength and polarization is achieved in the Mn:BNT-BNZ/BNT-BZZ multilayer film with the stacking period N = 3, of which energy density and efficiency reach 80.4 J/cm3 and 62.0% respectively. It is proposed that the excellent energy storage performances are attributed to the synergistic effect of the electric field amplification effect, interface blocking effect and the polarization coupling effect based on the multilayer heterostructure. Moreover, the flexible ferroelectric film exhibits outstanding temperature (25–205 °C), frequency (0.5–5 kHz) stability and antifatigue property (1 × 108 cycles), and can well maintain stable performance at different tensile/compressive bending radii (10–5 mm) and even after 104 bending cycles with a fixed bending radius of 3 mm. This work opens up a promising route to the development of flexible energy storage materials.

Antibacterial peptide has been widely developed in cultivation industry as feed additives. However, its functions in reducing the detrimental impacts of soybean meal (SM) remain unknown. In this study, we prepared nano antibacterial peptide CMCS-gcIFN-20H (C-I20) with excellent sustained-release and anti-enzymolysis, and fed mandarin fish (Siniperca chuatsi) with a SM diet supplemented with different levels of C-I20 (320, 160, 80, 40, 0 mg/Kg) for 10 weeks. 160 mg/Kg C-I20 treatment significantly improved the final body weight, weight gain rate and crude protein content of mandarin fish and reduced feed conversion ratio. 160 mg/Kg C-I20-fed fish maintained appropriate goblet cells number and mucin thickness, as well as improved villus length, intestinal cross-sectional area. Based on these advantageous physiological changes, 160 mg/Kg C-I20 treatment effectively reduced multi-type tissue (liver, trunk kidney, head kidney and spleen) injury. The addition of C-I20 did not change the muscle composition and muscle amino acids composition. Interestingly, dietary 160 mg/Kg C-I20 supplementation prevented the reduction in myofiber diameter and change in muscle texture, and effectively increased polyunsaturated fatty acids (especially DHA + EPA) in muscle. In conclusion, dietary C-I20 in a reasonable concentration supplementation effectively alleviates the negative effects of SM by improving the intestinal mucosal barrier. The application of nanopeptide C-I20 is a prospectively novel strategy for promoting aquaculture development.

232Th/233U fuel cycle is an alternate candidate for future nuclear energy. Neutron-induced fission cross section of 232Th is one of the important nuclear data if using thorium as the fuel in the future. 232Th(n, f) cross sections from 1 to 300 MeV were measured at China Spallation Neutron Source (CSNS) Back-streaming neutron facility (Back-n) relative to 235U(n, f) and n-p scattering. A fast ionization chamber for fission cross section measurement (FIXM) and a proton recoil telescope (PRT) were used to perform the measurement. The neutron energy in this measurement reaches up to 300 MeV which is supposed to be the highest among the current Experimental Nuclear Reaction Data (EXFOR) library. It stands as the only experimental data in the region of 200-300 MeV in EXFOR as well. The experimental and evaluated data of 232Th(n, f) cross section above 60 MeV are scarce, the measurement data of this work will be valuable references for future evaluation in high energy. For the data below 60 MeV, most of our data are more consistent with ENDF/B-VIII.0, excepting in the region of 1-2 MeV where our data are more in favor of CENDL-3.2.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most common and lethal renal cell carcinoma (RCC) histological subtype. Ferroptosis is a newly discovered programmed cell death and serves an essential role in tumor occurrence and development. The purpose of this study is to analyze ferroptosis-related gene (FRG) expression profiles and to construct a multi-gene signature for predicting the prognosis of ccRCC patients. Methods RNA-sequencing data and clinicopathological data of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed FRGs between ccRCC and normal tissues were identified using ‘limma’ package in R. GO and KEGG enrichment analyses were conducted to elucidate the biological functions and pathways of differentially expressed FRGs. Consensus clustering was used to investigate the relationship between the expression of FRGs and clinical phenotypes. Univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis were used to screen genes related to prognosis and construct the optimal signature. Then, a nomogram was established to predict individual survival probability by combining clinical features and prognostic signature. Results A total of 19 differentially expressed FRGs were identified. Consensus clustering identified two clusters of ccRCC patients with distinguished prognostic. Functional analysis revealed that metabolism-related pathways were enriched, especially lipid metabolism. A 7-gene ferroptosis-related prognostic signature was constructed to stratify the TCGA training cohort into high- and low-risk groups where the prognosis was significantly worse in the high-risk group. The signature was identified as an independent prognostic indicator for ccRCC. These findings were validated in the testing cohort, the entire cohort, and the International Cancer Genome Consortium (ICGC) cohort. We further demonstrated that the signature-based risk score was highly associated with the ccRCC progression. Further stratified survival analysis showed that the high-risk group had a significantly lower overall survival (OS) rate than those in the low-risk group. Moreover, we constructed a nomogram that had a strong ability to forecast the OS of the ccRCC patients. Conclusions We constructed a ferroptosis-related prognostic signature, which might provide a reliable prognosis assessment tool for the clinician to guide clinical decision-making and outcomes research.

Abstract The current pandemic of COVID-19 is fueled by more infectious emergent Omicron variants. Ongoing concerns of emergent variants include possible recombinants, as genome recombination is an important evolutionary mechanism for the emergence and re-emergence of human viral pathogens. In this study, we identified diverse recombination events between two Omicron major subvariants (BA.1 and BA.2) and other variants of concern (VOCs) and variants of interest (VOIs), suggesting that co-infection and subsequent genome recombination play important roles in the ongoing evolution of SARS-CoV-2. Through scanning high-quality completed Omicron spike gene sequences, 18 core mutations of BA.1 (frequency >99%) and 27 core mutations of BA.2 (nine more than BA.1) were identified, of which 15 are specific to Omicron. BA.1 subvariants share nine common amino acid mutations (three more than BA.2) in the spike protein with most VOCs, suggesting a possible recombination origin of Omicron from these VOCs. There are three more Alpha-related mutations in BA.1 than BA.2, and BA.1 is phylogenetically closer to Alpha than other variants. Revertant mutations are found in some dominant mutations (frequency >95%) in the BA.1. Most notably, multiple characteristic amino acid mutations in the Delta spike protein have been also identified in the “Deltacron”-like Omicron Variants isolated since November 11, 2021 in South Africa, which implies the recombination events occurring between the Omicron and Delta variants. Monitoring the evolving SARS-CoV-2 genomes especially for recombination is critically important for recognition of abrupt changes to viral attributes including its epitopes which may call for vaccine modifications.

In next-generation mobile communication scenarios, more and more user terminals (UEs) and edge computing servers (ECSs) are connected to the network. To ensure the experience of edge computing services, we designed an unmanned aerial vehicle (UAV)-assisted edge computing network application scenario. In the considered scenario, the UAV acts as a relay node to forward edge computing tasks when the performance of the wireless channel between UEs and ECSs degrades. In order to minimize the average delay of edge computing tasks, we design the optimization problem of joint UE–ECS matching and UAV three-dimensional hovering position deployment. Further, we transform this mixed integer nonlinear programming into a continuous-variable decision process and design the corresponding Proximal Policy Optimization (PPO)-based joint optimization algorithm. Sufficient data pertaining to latency demonstrate that the suggested algorithm can obtain a seamless reward value when the number of training steps hits three million. This verifies the algorithm’s desirable convergence property. Furthermore, the algorithm’s efficacy has been confirmed through simulation in various environments. The experimental findings ascertain that the PPO-based co-optimization algorithm consistently attains a lower average latency rate and a minimum of 8% reduction in comparison to the baseline scenarios.

Input-output mapping for a given power system problem, such as loads versus economic dispatch (ED) results, has been demonstrated to be learnable through artificial intelligence (AI) techniques, including neural networks. However, the process of identifying and constructing a comprehensive dataset for the training of such input-output mapping remains a challenge to be solved. Conventionally, load samples are generated by a pre-defined distribution, and then ED is solved based on those load samples to form training datasets, but this paper demonstrates that such dataset generation is biased regarding load-ED mapping. The marginal unit and line congestion (i.e., marginal pattern) exhibit a unique characteristic called “step change” in which the marginal pattern changes when the load goes from one critical loading level (CLL) to another, and there is no change of marginal units within the interval of the two adjacent CLLs. Those loading intervals differ significantly in size. The randomly generated training dataset overfills intervals with large sizes and underfits intervals with small sizes, so it is biased. In this paper, three algorithms are proposed to construct a marginal pattern library to examine this bias according to different computational needs, and an enhancement algorithm is proposed to eliminate the bias in the load-ED training dataset generation. Three illustrative test cases demonstrate the proposed algorithms, and comparative studies are constructed to show the superiority of the enhanced, unbiased training dataset.

Toll-like receptors (TLRs) are essential for the protection of the host from pathogen infections by initiating the integration of contextual cues to regulate inflammation and immunity. However, without tightly controlled immune responses, the host will be subjected to detrimental outcomes. Therefore, it is important to balance the positive and negative regulations of TLRs to eliminate pathogen infection, yet avert harmful immunological consequences. This study revealed a distinct mechanism underlying the regulation of the TLR network. The expression of sex-determining region Y-box 4 (Sox4) is induced by virus infection in viral infected patients and cultured cells, which subsequently represses the TLR signaling network to facilitate viral replication at multiple levels by a distinct mechanism. Briefly, Sox4 inhibits the production of myeloid differentiation primary response gene 88 (MyD88) and most of the TLRs by binding to their promoters to attenuate gene transcription. In addition, Sox4 blocks the activities of the TLR/MyD88/IRAK4/TAK1 and TLR/TRIF/TRAF3/TBK1 pathways by repressing their key components. Moreover, Sox4 represses the activation of the nuclear factor kappa-B (NF-κB) through interacting with IKKα/α, and attenuates NF-kB and IFN regulatory factors 3/7 (IRF3/7) abundances by promoting protein degradation. All these contributed to the down-regulation of interferons (IFNs) and IFN-stimulated gene (ISG) expression, leading to facilitate the viral replications. Therefore, we reveal a distinct mechanism by which viral pathogens evade host innate immunity and discover a key regulator in host defense.

Human enterovirus 71 (EV71) is one of the major agents of the hand, foot, and mouth disease (HFMD), and occasionally causes severe neurological complications. There is clinical evidence that EV71 infection increases the exosomes in the serum of severe HFMD patients, suggesting a role of exosomes in EV71 pathogenesis. However, the relationship between exosomes and EV71 replication remains elusive. In this study, we initially found that EV71 infection elevated exosome biogenesis in the cultured cells. Among EV71 non-structural proteins, we identified EV71 3A, but not 3B, constitutively promoted exosome secretion. In detail, EV71 3A protein interacted with vacuolar protein sorting 25 (VPS25), while knock-down of VPS25 reduced EV71 3A protein- and EV71-induced exosome production. Further studies revealed VPS25 located on exosomes and its expression correlated to the exosome production. During EV71 infection, knock-down of VPS25 decreased exosome biogenesis to attenuate viral replication. Consistently, GW4869, an exosome inhibitor, exerted an obviously antiviral activity against EV71 replication companied with the decrease of exosome secretion or formation. These findings suggest the binding of EV71 3A and VPS25 benefited exosome biogenesis, thereby boosting viral replication. This study uncovers a novel mechanism underlying EV71-mediated exosomes in the regulation of viral replication, which provides potential anti-viral strategies against the EV71 infection and transmission in HFMD.

Abstract Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production. Notably, HIF-1α also broadly promotes the infection of other viruses. Collectively, during SARS-CoV-2 infection, ORF3a induces HIF-1α, which in turn aggravates viral infection and inflammatory responses. Therefore, HIF-1α plays an important role in promoting SARS-CoV-2 infection and inducing pro-inflammatory responses to COVID-19.

SARS-CoV-2 infection has been shown to drive NLRP3 inflammasome activation and thereby cytokine storm, but how it does so is unclear. Here the authors show that the viral N protein can bind to NLRP3, resulting in enhanced interaction with ASC and thereby with the NLRP3 inflammasome.

Demand response (DR) has received much attention for its ability to balance the changing power supply and demand with flexibility. DR aggregators play an important role in aggregating flexible loads that are too small to participate in electricity markets. In this work, a DR operation framework is presented to enable local management of customers to participate in electricity market. A novel optimization model is proposed for the DR aggregator with multiple objectives. On one hand, it attempts to obtain the optimal design of different DR contracts as well as the portfolio management so that the DR aggregator can maximize its profit. On the other hand, the customers' welfare should be maximized to incentivize users to enroll in DR programs which ensure the effective and flexible load control. The consumer psychology is introduced to model the consumers' behavior during contract signing. Several simulation studies are performed to demonstrate the feasibility of the proposed model. The results illustrate that the proposed model can ensure the profit of the DR aggregator whereas the customers' welfare is considered.

The SARS-CoV-2 virus and its homolog SARS-CoV penetrate human cells by binding of viral spike protein and human angiotensin converting enzyme II (ACE2). SARS-CoV causes high fever in almost all patients, while SARS-CoV-2 does not. Moreover, analysis of the clinical data revealed that the higher body temperature is a protective factor in COVID-19 patients, making us to hypothesize a temperature-dependent binding affinity of SARS-CoV-2 to human ACE2 receptor. In this study, our molecular dynamics simulation and protein surface plasmon resonance cohesively proved the SARS-CoV-2-ACE2 binding was less affinitive and stable under 40 °C (~18 nM) than the optimum temperature 37 °C (6.2 nM), while SARS-CoV-ACE2 binding was not (6.4 nM vs. 8.5 nM), which evidenced the temperature-dependent affinity and explained that higher temperature is related to better clinical outcome. The decreased infection at higher temperature was also validated by pseudovirus entry assay using Vero and Caco-2 cells. We also demonstrated the structural basis of the distinct temperature-dependence of the two coronaviruses. Furthermore, the meta-analysis revealed a milder inflammatory response happened in the early stage of COVID-19, which explained the low fever tendency of COVID-19 and indicated the co-evolution of the viral protein structure and the inflammatory response. The temperature dependence of the binding affinity also indicated that higher body temperature at early stages might be beneficial to the COVID-19 patients.

Fungi secrete numerous effectors to modulate host defense systems. Understanding the molecular mechanisms by which fungal effectors regulate plant defense is of great importance for the development of novel strategies for disease control. In this study, we identified necrosis- and ethylene-inducing protein 1 (Nep1)-like protein (NLP) effector gene, CgNLP1, which contributed to conidial germination, appressorium formation, invasive growth, and virulence of Colletotrichum gloeosporioides to the rubber tree. Transient expression of CgNLP1 in the leaves of Nicotiana benthamiana induced ethylene production in plants. Ectopic expression of CgNLP1 in Arabidopsis significantly enhanced the resistance to Botrytis cinerea and Alternaria brassicicola. An R2R3 type transcription factor HbMYB8-like of rubber tree was identified as the target of CgNLP1.HbMYB8-like, localized on the nucleus, and induced cell death in N. benthamiana. CgNLP1 disrupted nuclear accumulation of HbMYB8-like and suppressed HbMYB8-like induced cell death, which is mediated by the salicylic acid (SA) signal pathway. This study suggested a new strategy whereby C. gloeosporioides exploited the CgNLP1 effector to affect invasion and suppress a host defense regulator HbMYB8-like to facilitate infection.

Human adenoviruses (HAdVs) within species B, C, and E are responsible for highly contagious and potentially severe respiratory disease infections. The traditional method to type these pathogens was based on virus neutralization and hemagglutination assays, which are both time-consuming and difficult, particularly due to the nonavailability of reagents. Subsequent molecular typing based on the partial characterization of the hexon gene and/or the restriction enzyme analysis (REA) of the genomes is inadequate, particularly in identifying recombinants. Here, a rapid, simple, and cost-effective method for molecular typing HAdV respiratory pathogens is presented. This incorporates three pairs of universal PCR primers that target the variable regions of the three major capsid genes, i.e., hexon, penton base, and fiber genes, that span the genome. The protocol enables typing and characterization of genotypes within species B, C, and E, as well as of some genotypes within species D and F. To validate this method, we surveyed 100 children with HAdV-associated acute respiratory infections identified by direct immunofluorescence (Hong Kong; July through October, 2014). Throat swab specimens were collected and analyzed by PCR amplification and sequencing; these sequences were characterized by BLAST. HAdVs were detected in 98 out of 100 (98%) samples, distributing as follows: 74 HAdV-B3 (74%); 10 HAdV-E4 (10%); 7 HAdV-C2 (7%); 2 HAdV-C6 (2%); 1 HAdV-B7 (1%); 1 HAdV-C1 (1%); 2 co-infection (2%); and 1 novel recombinant (1%). This study is the first detailed molecular epidemiological survey of HAdVs in Hong Kong. The developed method allows for the rapid identification of HAdV respiratory pathogens, including recombinants, and bypasses the need for whole genome sequencing for real-time surveillance of circulating adenovirus strains in outbreaks and populations by clinical virologists, public health officials, and epidemiologists.

BackgroundCoronavirus disease 2019 (COVID-19) is a global pandemic. Previous studies have reported dyslipidemia in patients with COVID-19. Herein, we conducted a retrospective study and a bioinformatics analysis to evaluate the essential data of the lipid profile as well as the possible mechanism in patients with COVID-19.MethodsFirst of all, the retrospective study included three cohorts: patients with COVID-19, a healthy population, and patients with chronic obstructive pulmonary disease (COPD). For each subject, serum lipid profiles in the biochemical data were compared, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Furthermore, bioinformatics analyses were performed for exploring the biological or immunological mechanisms.ResultsIn line with the biochemical data of the three cohorts, the statistical result displayed that patients with COVID-19 were more likely to have lower levels of TC and HDL-C as compared with healthy individuals. The differential proteins associated with COVID-19 are involved in the lipid pathway and can target and regulate cytokines and immune cells. Additionally, a heatmap revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were possibly involved in lipid metabolic reprogramming. The viral proteins, such as spike (S) and non-structural protein 2 (Nsp2) of SARS-CoV-2, may be involved in metabolic reprogramming.ConclusionThe metabolic reprogramming after SARS-CoV-2 infections is probably associated with the immune and clinical phenotype of patients. Hence, metabolic reprogramming may be targeted for developing antivirals against COVID-19.

Abstract Background Treponema pallidum (T. pallidum) infection evokes significant immune responses, resulting in tissue damage. The immune mechanism underlying T. pallidum infection is still unclear, although microRNAs (miRNAs) have been shown to influence immune cell function and, consequently, the generation of antibody responses during other microbe infections. However, these mechanisms are unknown for T. pallidum. Methods In this study, we performed a comprehensive analysis of differentially expressed miRNAs in healthy individuals, untreated patients with syphilis, patients in the serofast state, and serologically cured patients. miRNAs were profiled from the peripheral blood of patients obtained at the time of serological diagnosis. Then, both the target sequence analysis of these different miRNAs and pathway analysis were performed to identify important immune and cell signaling pathways. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed for microRNA analysis. Results A total of 74 differentially regulated miRNAs were identified. Following RT-qPCR confirmation, three miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p) showed significant differences in the serofast and serologically cured states (P

ASB17, a member of the ankyrin repeat and SOCS box-containing protein (ASB) family, has been supposed to act as an E3 ubiquitin ligase. Actually, little is known about its biological function. In this study, we found that ASB17 knocking-out impaired the expression of the pro-inflammatory cytokines CCL2 and IL-6 in bone marrow-derived dendritic cells (BMDCs) stimulated by lipopolysaccharide (LPS), indicating an inflammation-promoting role of this gene. We reveal that ASB17 promotes LPS-induced nuclear factor kappa B (NF-κB) signal activation through interacting with TNF receptor-associated factor 6 (TRAF6) which is a crucial adaptor protein downstream of toll-like receptors (TLR). ASB17 via its aa177–250 segment interacts with the Zn finger domain of TRAF6. The interaction of ASB17 stabilizes TRAF6 protein through inhibiting K48-linked TRAF6 polyubiquitination. Therefore, we suggest that ASB17 facilitates LPS-induced NF-κB activation by maintaining TRAF6 protein stability. The inflammation enhancer role of ASB17 is recognized here, which provides new understanding of the activation process of inflammation and immune response.

Halobenzoquinones (HBQs) are emerging and widespread disinfection byproducts (DBPs), but their toxicological mechanisms to aquatic organisms remain elusive. Herein, we evaluated oxidative stress, cardiac toxicity, and cerebral toxicity after 2, 6-dichloro-1, 4-benzoquinone (2,6-DCBQ) exposure in zebrafish. Adult zebrafish were respectively exposed to 0.25, 0.5, and 1 μM 2,6-DCBQ for 96 h. The mortality rate of 2,6-DCBQ (1 μM) was 10%, while the LC50 value was 1.532 μM. Besides, 2,6-DCBQ exposure caused irregularity and elimination of myocardial fiber in the heart, and the pyknosis of nuclears and the agglutination of chromatin in the brain. We measured the 2,6-DCBQ-induced oxidative stresses in the heart and brain. Additionally, the glutathione (GSH) content, superoxide dismutase (SOD) activity, catalase (CAT) activity, and total antioxidant capacity (T-AOC) were significantly inhibited. To better understand the potential toxicity of 2,6-DCBQ, transcriptomic analysis was performed in the control and 1 μM group after 96 h exposure. As a result, 545 and 1228 differentially expressed genes (DEGs) were detected in the heart and brain, respectively. GO analysis revealed that these DEGs were primarily enriched in blood vessel development, vasculature development, and oxidoreductase activity in the heart; response to stimulus, nervous system development, and oxidoreductase activity in the brain. KEGG enrichment analysis indicated that the DEGs were mainly enriched in VEGF signaling pathway and vascular smooth muscle contraction pathway in the heart; neuroactive ligand-receptor interaction, and NOD-like receptor signaling pathway in the brain. These findings exposed the underlying toxicity mechanism of 2,6-DCBQ exposure on zebrafish cardiovascular and brain systems.

Objective: To compare the effectiveness, safety and survival outcome of transcatheter arterial chemoembolization (TACE) combined with high-intensity focused ultrasound (HIFU) versus surgical resection for treating single hepatocellular carcinoma (HCC) with Child-Pugh B cirrhosis. Methods: A hospital-based retrospective study with 146 patients diagnosed with single HCC with Child-Pugh B cirrhosis from July 2010 to July 2018 was conducted in a tertiary teaching hospital. A total of 49 patients underwent TACE combined with HIFU (the combined group), and 97 patients underwent surgical resection (the resection group). Of them, 22 patients undergoing TACE combined with HIFU and 45 patients undergoing surgical resection had small HCC (tumor diameter ≤3 cm). The overall survival (OS) time, progression-free survival (PFS) time and postoperative complications were compared between the two groups. Results: In the single HCC tumor cohort, there was no significant difference in OS between the two groups [hazard ratio (HR) = 0.6379; 95% confidence interval (95% CI) = 0.3737 to 1.089; P = .0995], while the resection group showed an obvious superiority to the combined group regarding PFS (HR = 0.3545; 95% CI = 0.2176-0.5775; P

Sonophotocatalysis is one of the most significant outcomes of the exploration of the interaction between piezoelectric field and charge carriers, which exhibits potential applications in dye degradation, water splitting, and sterilization. Although several heterojunction catalysts have been applied to improve the sonophotocatalytic capability, the importance of the morphology on the sonophotocatalytic capability has not been emphasized. In this study, brush-like ZnO nanorod arrays are synthesized on a stainless-steel mesh and subsequently vulcanized into ZnO/ZnS core–shell nanorod arrays to investigate the sonophotocatalytic capability of the heterojunction. The sonophotocatalytic capability increases from 25.1% to 45.4% through vulcanization. Afterward, the ZnO/ZnS nanorods are etched to ZnO/ZnS nanotubes without affecting the crystallography and distribution of the ZnS nanoparticle shell, further improving the capability to 63.3%. The improvement can be ascribed to the coupling effect of the enhanced piezoelectric field and the reduced migration distance, which suppresses the recombination of photoexcited electron–hole pairs while transforming the morphology from nanorod to nanotube, as proven by the electron spin resonance test and numerical simulations. This study explores a novel approach of morphology engineering for enhancing the sonophotocatalytic capability of heterojunction nanoarrays.

Human adenovirus infections can develop into diffuse multi-organ diseases in young children and immunocompromised patients, and severe cases can lead to death. However, there are no approved antiviral drugs available to treat adenovirus diseases. In this study, a chemiluminescence-based, high-throughput screening (HTS) assay was developed and applied to screen human adenovirus 5(HAdV5)inhibitors from 1,813 approved drug library and 556 traditional Chinese medicine-sourced small-molecule compounds. We identified three compounds with in vitro anti-HAdV5 activities in the low-micromolar range (EC50 values 0.3-4.5 μM, selectivity index values 20-300) that also showed inhibitory effects on HAdV3. Cardamomin (CDM) had good anti-HAdV5 activity in vitro. Furthermore, three dilutions of CDM (150, 75, and 37.5 mg/kg/d) administered to BALB/c mouse models inhibited HAdV5-fluc infection at 1 day post-infection by 80% (p < 0.05), 76% (p < 0.05), and 58% (p < 0.05), respectively. HE-staining of pathological tissue sections of mice infected with a wildtype adenoviral strain showed that CDM had a protective effect on tissues, especially in the liver, and greatly inhibited virus-induced necrosis of liver tissue. Thus, CDM inhibits adenovirus replication in vivo and in vitro. This study established a high-throughput screening method for anti-HAdV5 drugs and demonstrated CDM to be a candidate for HAdV5 therapy, potentially providing a new treatment for patients infected with adenoviruses.

Earthworm-like robots have received great attention due to their prominent locomotion abilities in various environments. In this research, by exploiting the extraordinary three-dimensional (3D) deformability of the Yoshimura-origami structure, the state of the art of earthworm-like robots is significantly advanced by enhancing the locomotion capability from 2D to 3D. Specifically, by introducing into the virtual creases, kinematics of the non-rigid-foldable Yoshimura-ori structure is systematically analyzed. In addition to exhibiting large axial deformation, the Yoshimura-ori structure could also bend toward different directions, which, therefore, significantly expands the reachable workspace and makes it possible for the robot to perform turning and rising motions. Based on prototypes made of PETE film, mechanical properties of the Yoshimura-ori structure are also evaluated experimentally, which provides useful guidelines for robot design. With the Yoshimura-ori structure as the skeleton of the robot, a hybrid actuation mechanism consisting of SMA springs, pneumatic balloons, and electromagnets is then proposed and embedded into the robot: the SMA springs are used to bend the origami segments for turning and rising motion, the pneumatic balloons are employed for extending and contracting the origami segments, and the electromagnets serve as anchoring devices. Learning from the earthworm’s locomotion mechanism--retrograde peristalsis wave, locomotion gaits are designed for controlling the robot. Experimental tests indicate that the robot could achieve effective rectilinear, turning, and rising locomotion, thus demonstrating the unique 3D locomotion capability.

Dengue virus (DENV) is a mosquito-borne pathogen that causes a spectrum of diseases including life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular leakage is a common clinical crisis in DHF/DSS patients and highly associated with increased endothelial permeability. The presence of vascular leakage causes hypotension, circulatory failure, and disseminated intravascular coagulation as the disease progresses of DHF/DSS patients, which can lead to the death of patients. However, the mechanisms by which DENV infection caused the vascular leakage are not fully understood. This study reveals a distinct mechanism by which DENV induces endothelial permeability and vascular leakage in human endothelial cells and mice tissues. We initially show that DENV2 promotes the matrix metalloproteinase-9 (MMP-9) expression and secretion in DHF patients' sera, peripheral blood mononuclear cells (PBMCs), and macrophages. This study further reveals that DENV non-structural protein 1 (NS1) induces MMP-9 expression through activating the nuclear factor κB (NF-κB) signaling pathway. Additionally, NS1 facilitates the MMP-9 enzymatic activity, which alters the adhesion and tight junction and vascular leakage in human endothelial cells and mouse tissues. Moreover, NS1 recruits MMP-9 to interact with β-catenin and Zona occludens protein-1/2 (ZO-1 and ZO-2) and to degrade the important adhesion and tight junction proteins, thereby inducing endothelial hyperpermeability and vascular leakage in human endothelial cells and mouse tissues. Thus, we reveal that DENV NS1 and MMP-9 cooperatively induce vascular leakage by impairing endothelial cell adhesion and tight junction, and suggest that MMP-9 may serve as a potential target for the treatment of hypovolemia in DSS/DHF patients.

A hydraulic pipe is a basic component of the aero hydraulic system, while high pressure and high speed lead to the enhancement of multiple field coupling effects, such as the structure, fluid, heat, and sound of the aero hydraulic pipe. A larger elastic deformation of the pipe and the more common unsteady flow of fluid can aggravate the vibration and noise of the hydraulic pipe system. Based on the 14-equation model of fluid-structure-interaction (FSI) vibration of aero hydraulic pipe, a model suitable for a wide Reynolds number range is proposed by comparing and analyzing various kinds of friction coupling models. This model is used for the FSI dynamic behavior analysis of aero hydraulic pipes, which improves the accuracy of FSI frequency-domain solutions under high Reynolds number conditions. Second, based on the 14-equation model of FSI vibration of aero hydraulic pipe and the transfer matrix method, the mathematical model of airframe deformation load of an aero hydraulic pipe is established, and the evolution law of the FSI dynamic behavior of the aero hydraulic pipe under different airframe deformation loads is analyzed. All the above analysis results were verified by the experimental analysis. The error of the analysis results of the FSI vibration frequency is smaller than 5% compared with the experimental results. The results show that the proposed method is feasible and effective for predicting the hydrodynamic behavior of the aero hydraulic pipes under load conditions.