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IL-2 regulates the immune response by interacting with different IL-2 receptor (IL-2R) subunits. High dose of IL-2 binds to IL-2Rβγ c heterodimer, which induce various side effects while activating immune function. Disrupting IL-2 and IL-2R interactions can block IL-2 mediated immune response. Here, we used a computational approach to de novo design mini-binder proteins against IL-2R β chain (IL-2Rβ) to block IL-2 signaling. The hydrophobic region where IL-2 binds to IL-2Rβ was selected and the promising binding mode was broadly explored. Three mini-binders with amino acid numbers ranging from 55 to 65 were obtained and binder 1 showed the best effects in inhibiting CTLL-2 cells proliferation and STAT5 phosphorylation. Molecular dynamics simulation showed that the binding of binder 1 to IL-2Rβ was stable; the free energy of binder1/IL-2Rβ complex was lower, indicating that the affinity of binder 1 to IL-2Rβ was higher than that of IL-2. Free energy decomposition suggested that the ARG35 and ARG131 of IL-2Rβ might be the key to improve the affinity of binder. Our efforts provided new insights in developing of IL-2R blocker, offering a potential strategy for ameliorating the side effects of IL-2 treatment., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

With the rapid development of the internet of things (IoT) era, IoT devices may face limitations in battery capacity and computational capability. Simultaneous wireless information and power transfer (SWIPT) and mobile edge computing (MEC) have emerged as promising technologies to address these challenges. Due to wireless channel fading and susceptibility to obstacles, this paper introduces intelligent reflecting surfaces (IRS) to enhance the spectral and energy efficiency of wireless networks. We propose a system model for IRS-assisted uplink offloading computation, downlink offloading computation results, and simultaneous energy transfer. Considering constraints such as IRS phase shifts, latency, energy harvesting, and offloading transmit power, we jointly optimize the CPU frequency of IoT devices, offloading transmit power, local computation workload, power splitting (PS) ratio, and IRS phase shifts. This establishes a multi-variate coupled nonlinear problem aimed at minimizing IoT devices energy consumption. We design an effective alternating optimization (AO) iterative algorithm based on block coordinate descent, and utilize closed-form solutions, Dinkelbach-based Lagrange dual method, and semidefinite relaxation (SDR) method to minimize IoT devices energy consumption. Simulation results demonstrate that the proposed scheme achieves lower energy consumption compared to other resource allocation strategies.

The mutual interactions of endoplasmic reticulum (ER) resident proteins in the ER maintain its functions, prompting the protein folding, modification, and transportation. Here, a new method, named YST-PPI (YESS-based Split fast TEV protease system for Protein-Protein Interaction) was developed, targeting the characterization of protein interactions in ER. YST-PPI method integrated the YESS system, split-TEV technology, and endoplasmic reticulum retention signal peptide (ERS) to provide an effective strategy for studying ER in situ PPIs in a fast and quantitative manner. The interactions among 15 ER-resident proteins, most being identified molecular chaperones, of S. cerevisiae were explored using the YST-PPI system, and their interaction network map was constructed, in which more than 74 interacting resident protein pairs were identified. Our studies also showed that Lhs1p plays a critical role in regulating the interactions of most of the ER-resident proteins, except the Sil1p, indicating its potential role in controlling the ER molecular chaperones. Moreover, the mutual interaction revealed by our studies further confirmed that the ER-resident proteins perform their functions in a cooperative way and a multimer complex might be formed during the process., (© 2024 Wiley‐VCH GmbH.)

The switch machine, an essential element of railway infrastructure, is crucial in maintaining the safety of railway operations. Traditional methods for fault diagnosis are constrained by their dependence on extensive labeled datasets. Semi-supervised learning (SSL), although a promising solution to the scarcity of samples, faces challenges such as the imbalance of pseudo-labels and inadequate data representation. In response, this paper presents the Semi-Supervised Adaptive Matrix Machine (SAMM) model, designed for the fault diagnosis of switch machine. SAMM amalgamates semi-supervised learning with adaptive technologies, leveraging adaptive low-rank regularizer to discern the fundamental links between the rows and columns of matrix data and applying adaptive penalty items to correct imbalances across sample categories. This model methodically enlarges its labeled dataset using probabilistic outputs and semi-supervised, automatically adjusting parameters to accommodate diverse data distributions and structural nuances. The SAMM model's optimization process employs the alternating direction method of multipliers (ADMM) to identify solutions efficiently. Experimental evidence from a dataset containing current signals from switch machines indicates that SAMM outperforms existing baseline models, demonstrating its exceptional status diagnostic capabilities in situations where labeled samples are scarce. Consequently, SAMM offers an innovative and effective approach to semi-supervised classification tasks involving matrix data.

Solar-driven steam evaporation technology, known for its low energy consumption and environmental friendliness, has emerged as a promising approach for seawater desalination, wastewater purification, etc. However, creating a low-cost solar evaporation system that simultaneously achieves rapid water transport, efficient light absorption, and salt tolerance remains challenging. Here, a dual-layer evaporator based on reed roots has been developed after a simple H 2 O 2 delignification treatment and flame treatment, which exhibited enhanced water transport performance and photothermal properties. As excepted, delignification treatment enhanced the capillary water transport ability of reed roots, which is conducive to promoting the dilution of salt in the evaporator and preventing salt deposition. The evaporator demonstrates an impressive steam generation efficiency of 83.5 % and a remarkable water evaporation rate of 1.407 kg m -2  h -1 under 1 sun, thanks to its well-designed structure and optimized performance. Moreover, the evaporator exhibited excellent practical performance for outdoor applications and demonstrates a remarkable capacity for sewage purification, effectively treating heavy metal ion wastewater as well as dye wastewater. As a result, the objective of our research is to explore opportunities for the implementation of deployable, cost-effective, low-carbon-footprint solar water purification systems, particularly for some impoverished regions, to ensure the provision of high-quality water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Safety-critical systems, such as the railway signal system, are subject to potentially high costs from failures, including loss of life and property damage. The use of new technology, including communication-based train control (CBTC) systems with software and computers, has changed the types of accidents that occur. Software-related issues and dysfunctional interactions between system components controlled by the software are increasingly the cause of incidents. Developing a "safe" safety-critical system requires accurate and complete safety requirements, which are the foundation of system development. Traditional hazard analysis techniques are insufficient for identifying the causes of accidents in modern railway signaling systems. Systems-Theoretic Process Analysis (STPA) is a powerful new hazard analysis method designed to address these limitations. Building upon this foundation, a hierarchical approach to safety requirement development has been further developed. This approach combines STPA analysis with a hierarchical modeling approach to establish traceability links from safety requirements to specific architectures, refine and allocate system-level safety requirements to relevant subsystems, and abstract safety requirements at higher hierarchical levels to enable easy changes to lower-level implementations. This paper employs the aforementioned methodology within the context of the CBTC system, thereby enhancing risk management and hazard analysis, enabling early insights, and facilitating the generation of safety requirements of CBTC System., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zuxi Chen reports financial support was provided by Fujian Province Department of Science and Technology. Xiaoyong Wang reports financial support was provided by Shanghai Province Department of Science and Technology. Meng Mei reports financial support was provided by 10.13039/501100002855Ministry of Science and Technology of the People's Republic of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Human rhinovirus 3C protease (HRV 3CP) has a high specificity against the substrate of LEVLFQ↓G at P1' site, which plays an important role in biotechnology and academia as a fusion tag removal tool. However, a non-ignorable limitation is that an extra residue of Gly would remain at the N terminus of the recombinant target protein after cleavage with HRV 3CP, thus potentially causing protein mis-functionality or immunogenicity. Here, we developed a combinatorial strategy by integrating structure-guided library design and high-throughput screening of eYESS approach for HRV 3CP engineering to expand its P1' specificity. Finally, a C3 variant was obtained, exhibiting a broad substrate P1' specificity to recognize 20 different amino acids with the highest activity against LEVLFQ↓M (k cat /K M  = 3.72 ± 0.04 mM -1 ∙s -1 ). Further biochemical and NGS-mediated substrate profiling analysis showed that C3 variant still kept its substrate stringency at P1 site and good residue tolerance at P2' site, but with an expanded P1' specificity. Structural simulation of C3 indicated a reconstructed S1' binding pocket as well as new interactions with the substrates. Overall, our studies here prompt not only the practical applications and understanding of substrate recognition mechanisms of HRV 3CP, also provide new tools for other enzyme engineering., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The Staphylococcus aureus clumping factor A (ClfA) is a fibrinogen (Fg) binding protein that plays an important role in the clumping of S. aureus in blood plasma. The current anti-infective approaches targeting ClfA are mainly based on monoclonal antibodies but showed less impressive efficacy for clinical applications. Nanobodies offer advantages in enhanced tissue penetration and a propensity to bind small epitopes. However, there is no report on generating specific nanobodies for ClfA. Here, we constructed a synthetic nanobody library based on yeast surface display to isolate nanobodies against the Fg binding domain ClfA 221 - 550 . We firstly obtained a primary nanobody directed to ClfA 221 - 550 , and then employed error-prone mutagenesis to enhance its binding affinity. Finally, 18 variants were isolated with high affinities (EC50, 1.1 ± 0.1 nM to 4.8 ± 0.3 nM), in which CNb1 presented the highest inhibition efficiency in the adhesion of S. aureus to fibrinogen. Moreover, structural simulation analysis indicated that the epitope for CNb1 partially overlapped with the binding sites for fibrinogen, thus inhibiting ClfA binding to Fg. Overall, these results indicated that the specific nanobodies generated here could prevent the adhesion of S. aureus to fibrinogen, suggesting their potential capacities in the control of S. aureus infections., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Staphylococcus enterotoxin B (SEB) interacts with MHC-II molecules to overactivate immune cells and thereby to produce excessive pro-inflammatory cytokines. Disrupting the interactions between SEB and MHC-II helps eliminate the lethal threat posed by SEB. In this study, a de novo computational approach was used to design protein binders targeting SEB. The MHC-II binding domain of SEB was selected as the target, and the possible promising binding mode was broadly explored. The obtained original binder was folded into triple-helix bundles and contained 56 amino acids with molecular weight 5.9 kDa. The interface of SEB and the binder was highly hydrophobic. ProteinMPNN optimization further enlarged the hydrophobic region of the binder and improved the stability of the binder-SEB complex. In vitro study demonstrated that the optimized binder significantly inhibited the inflammatory response induced by SEB. Overall, our research demonstrated the applicability of this approach in de novo designing protein binders against SEB, and thereby providing potential therapeutics for SEB induced diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Multiple testing has been a prominent topic in statistical research. Despite extensive work in this area, controlling false discoveries remains a challenging task, especially when the test statistics exhibit dependence. Various methods have been proposed to estimate the false discovery proportion (FDP) under arbitrary dependencies among the test statistics. One key approach is to transform arbitrary dependence into weak dependence and subsequently establish the strong consistency of FDP and false discovery rate under weak dependence. As a result, FDPs converge to the same asymptotic limit within the framework of weak dependence. However, we have observed that the asymptotic variance of FDP can be significantly influenced by the dependence structure of the test statistics, even when they exhibit only weak dependence. Quantifying this variability is of great practical importance, as it serves as an indicator of the quality of FDP estimation from the data. To the best of our knowledge, there is limited research on this aspect in the literature. In this paper, we aim to fill in this gap by quantifying the variation of FDP, assuming that the test statistics exhibit weak dependence and follow normal distributions. We begin by deriving the asymptotic expansion of the FDP and subsequently investigate how the asymptotic variance of the FDP is influenced by different dependence structures. Based on the insights gained from this study, we recommend that in multiple testing procedures utilizing FDP, reporting both the mean and variance estimates of FDP can provide a more comprehensive assessment of the study's outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Biometric Society.)

Staphylococcus enterotoxin B (SEB) is one of the primary virulence factors of Staphylococcus aureus but there is still a lack of targeted drugs. SEB activates immune cells via interacting with MHC-II on antigen-presenting cells, leading to the production of large amounts of pro-inflammatory cytokines. Blocking the interaction between SEB and MHC-II can avert the overactivation of immune cells. Nanobodies are the smallest functional antibodies that can bind stably to antigens. In this study, an ideal approach to obtain specific nanobodies without immunizing camelids was introduced. We constructed a library containing up to 5 × 10 8 nanobodies, and then screened those targeting SEB by using yeast surface display (YSD) technique and fluorescence-activated cell sorting (FACS). A total of 8 nanobodies with divergent complementarity-determining regions (CDRs) sequences were identified and one candidate Nb8 with high affinity to SEB was isolated. In vitro study demonstrated that Nb8 significantly inhibited SEB-induced inflammatory response. Molecular docking simulation indicated that the unique CDR3 sequence contributed to the binding of Nb8 to the MHC-II binding domain of SEB and accordingly cut off the connection between SEB and MHC-II. Our efforts contributed to the development of specific nanobodies for eliminating the threats of SEB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Excessive phosphate and tetracycline (TC) contaminants pose a serious risk to human health and the ecological environment. As such exploring the simultaneous adsorption of phosphate and TC is garnering increasing attention. In this study, an efficient lanthanum ferrate magnetic biochar (FLBC) was synthesised from crab shells using an ultrasound-assisted sol-gel method to study its performance and mechanisms for phosphate and TC adsorption in aqueous solutions in mono/bis systems. According to the Langmuir model, the developed exhibited a maximum adsorption capacity of 65.62 mg/g for phosphate and 234.1 mg/g for TC (pH:7.0 ± 0.1, and 25 °C). Further, it exhibited high resistance to interference and pH suitability. In practical swine wastewater applications, whereby the concentrations of phosphate and TC are 37 and 19.97 mg/L, respectively, the proposed material demonstrated excellent performance. In addition, electrostatic adsorption, chemical precipitation and ligand exchange were noted to be the main mechanisms for phosphate adsorption by FLBC, whereas hydrogen bonding and π-π interaction were the main adsorption mechanisms for TC adsorption. Therefore, this study successfully prepared a novel and efficient adsorbent for phosphate and TC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This article presents a novel parallel path detection algorithm for identifying suspicious fraudulent accounts in large-scale banking transaction graphs. The proposed algorithm is based on a three-step approach that involves constructing a directed graph, shrinking strongly connected components, and using a parallel depth-first search algorithm to mark potentially fraudulent accounts. The algorithm is designed to fully exploit CPU resources and handle large-scale graphs with exponential growth. The performance of the algorithm is evaluated on various datasets and compared with serial time baselines. The results demonstrate that our approach achieves high performance and scalability on multi-core processors, making it a promising solution for detecting suspicious accounts and preventing money laundering schemes in the banking industry. Overall, our work contributes to the ongoing efforts to combat financial fraud and promote financial stability in the banking sector., Competing Interests: The authors declare that they have no competing interests., (© 2023 Chen et al.)

It is generally thought that under basal conditions, neurons produce ATP mainly through mitochondrial oxidative phosphorylation (OXPHOS), and glycolytic activity only predominates when neurons are activated and need to meet higher energy demands. However, it remains unknown whether there are differences in glucose metabolism between neuronal somata and axon terminals. Here, we demonstrated that neuronal somata perform higher levels of aerobic glycolysis and lower levels of OXPHOS than terminals, both during basal and activated states. We found that the glycolytic enzyme pyruvate kinase 2 (PKM2) is localized predominantly in the somata rather than in the terminals. Deletion of Pkm2 in mice results in a switch from aerobic glycolysis to OXPHOS in neuronal somata, leading to oxidative damage and progressive loss of dopaminergic neurons. Our findings update the conventional view that neurons uniformly use OXPHOS under basal conditions and highlight the important role of somatic aerobic glycolysis in maintaining antioxidant capacity., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Anaerobic digestion has become a global practice for valorizing food waste, but the recycling of the digestate (FWD) remains challenging. This study aimed to address this issue by utilizing FWD as a low-cost feedstock for Ca-rich biochar production. The results demonstrated that biochar pyrolyzed at 900 °C exhibited impressive As(V) adsorption performance without any modifications. Kinetic analysis suggested As(V) was chemisorbed onto CDBC9, while isotherm data conformed well to Langmuir model, indicating monolayer adsorption with a maximum capacity of 76.764 mg/g. Further analysis using response surface methodology revealed that pH value and adsorbent dosage were significant influencing factors, and density functional theory (DFT) calculation visualized the formation of ionic bonds between HAsO 4 2- and CaO(110) and Ca(OH) 2 (101) surfaces. This work demonstrated the potential of using FWD for producing Ca-rich biochar, providing an effective solution for As(V) removal and highlighting the importance of waste material utilization in sustainable environmental remediation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Sphingolipids, as members of the large lipid family, are important components of plasma membrane. Sphingolipids participate in biological signal transduction to regulate various important physiological processes such as cell growth, apoptosis, senescence, and differentiation. Numerous studies have demonstrated that sphingolipids are strongly associated with glucose metabolism and insulin resistance. Insulin resistance, including peripheral insulin resistance and brain insulin resistance, is closely related to the occurrence and development of many metabolic diseases. In addition to metabolic diseases, like type 2 diabetes, brain insulin resistance is also involved in the progression of neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the specific mechanism of sphingolipids in brain insulin resistance has not been systematically summarized. This article reviews the involvement of sphingolipids in brain insulin resistance, highlighting the role and molecular biological mechanism of sphingolipid metabolism in cognitive dysfunctions and neuropathological abnormalities of the brain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mei, Liu, Mei, Zhao and Li.)

Social media is a real-time social sensor to sense and collect diverse information, which can be combined with sentiment analysis to help IoT sensors provide user-demanded favorable data in smart systems. In the case of insufficient data labels, cross-domain sentiment analysis aims to transfer knowledge from the source domain with rich labels to the target domain that lacks labels. Most domain adaptation sentiment analysis methods achieve transfer learning by reducing the domain differences between the source and target domains, but little attention is paid to the negative transfer problem caused by invalid source domains. To address these problems, this paper proposes a cross-domain sentiment analysis method based on feature projection and multi-source attention (FPMA), which not only alleviates the effect of negative transfer through a multi-source selection strategy but also improves the classification performance in terms of feature representation. Specifically, two feature extractors and a domain discriminator are employed to extract shared and private features through adversarial training. The extracted features are optimized by orthogonal projection to help train the classification in multi-source domains. Finally, each text in the target domain is fed into the trained module. The sentiment tendency is predicted in the weighted form of the attention mechanism based on the classification results from the multi-source domains. The experimental results on two commonly used datasets showed that FPMA outperformed baseline models.

Although incineration is a recommended disposal strategy for dyeing sludge (DS), sulfurous gases problem is severe. Wood sawdust (WS) and rice husk (RH) are eco-friendly and CO 2 -neutral additives to relieve sulfur emission from DS incineration. However, the interaction between organic sulfur and biomass is uninterpreted. This study explores the effect of WS and RH on the combustion behavior and sulfur evolution from organic sulfur model compound combustion via thermogravimetry (TG) with mass spectrometry (MS). Results indicated that the sulfone and mercaptan combustion activities in DS were more drastic than in other forms. WS and RH additives generally deteriorated the combustibility and burnout performance of model compounds. The combustion of mercaptan and sulfone in DS contributed to most gaseous sulfur pollutants, where CH 3 SH and SO 2 were the predominant forms. WS and RH minimized the sulfur release from mercaptan and sulfone incineration, whose in-situ retention ratios reached 20.14 % and 40.57 %. The retention mechanism to sulfur could be divided into: (1) Diffusion stage: the closed structure of biomass residue restrained sulfurous gases from escaping. (2) Chemical reaction stage: multiple sulfation occurred and inhibited sulfur release. Ca/K sulfate and compound sulfates were predisposed and thermostable sulfur-fixing products for the mercaptan-WS and sulfone-RH co-combustion systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Human cytomegalovirus (HCMV) is a leading cause of congenital birth defects. Though the underlying mechanisms remain poorly characterized, mouse models of congenital CMV infection have demonstrated that the neuronal migration process is damaged. In this study, we evaluated the effects of HCMV infection on connexin 43 (Cx43), a crucial adhesion molecule mediating neuronal migration. We show in multiple cellular models that HCMV infection downregulated Cx43 posttranslationally. Further analysis identified the immediate early protein IE1 as the viral protein responsible for the reduction of Cx43. IE1 was found to bind the Cx43 C terminus and promote Cx43 degradation through the ubiquitin-proteasome pathway. Deletion of the Cx43-binding site in IE1 rendered it incapable of inducing Cx43 degradation. We validated the IE1-induced loss of Cx43 in vivo by introducing IE1 into the fetal mouse brain. Noteworthily, ectopic IE1 expression induced cortical atrophy and neuronal migration defects. Several lines of evidence suggest that these damages result from decreased Cx43, and restoration of Cx43 levels partially rescued IE1-induced interruption of neuronal migration. Taken together, the results of our investigation reveal a novel mechanism of HCMV-induced neural maldevelopment and identify a potential intervention target. IMPORTANCE Congenital CMV (cCMV) infection causes neurological sequelae in newborns. Recent studies of cCMV pathogenesis in animal models reveal ventriculomegaly and cortical atrophy associated with impaired neural progenitor cell (NPC) proliferation and migration. In this study, we investigated the mechanisms underlying these NPC abnormalities. We show that Cx43, a critical adhesion molecule mediating NPC migration, is downregulated by HCMV infection in vitro and HCMV-IE1 in vivo . We provide evidence that IE1 interacts with the C terminus of Cx43 to promote its ubiquitination and consequent degradation through the proteasome. Moreover, we demonstrate that introducing IE1 into mouse fetal brains led to neuronal migration defects, which was associated with Cx43 reduction. Deletion of the Cx43-binding region in IE1 or ectopic expression of Cx43 rescued the IE1-induced migration defects in vivo . Our study provides insight into how cCMV infection impairs neuronal migration and reveals a target for therapeutic interventions., Competing Interests: The authors declare no conflict of interest.

Congenital human cytomegalovirus (HCMV) infection causes severe damage to the fetal brain, and the underlying mechanisms remain elusive. Cytokine signaling is delicately controlled in the fetal central nervous system to ensure proper development. Here we show that suppressor of cytokine signaling 3 (SOCS3), a negative feedback regulator of the IL-6 cytokine family signaling, was upregulated during HCMV infection in primary neural progenitor cells (NPCs) with a biphasic expression pattern. From viral protein screening, pUL97 emerged as the viral factor responsible for prolonged SOCS3 upregulation. Further, by proteomic analysis of the pUL97-interacting host proteins, regulatory factor X 7 (RFX7) was identified as the transcription factor responsible for the regulation. Depletion of either pUL97 or RFX7 prevented the HCMV-induced SOCS3 upregulation in NPCs. With a promoter-luciferase activity assay, we demonstrated that the pUL97 kinase activity and RFX7 were required for SOCS3 upregulation. Moreover, the RFX7 phosphorylation level was increased by either UL97-expressing or HCMV-infection in NPCs, suggesting that pUL97 induces RFX7 phosphorylation to drive SOCS3 transcription. We further revealed that elevated SOCS3 expression impaired NPC proliferation and migration in vitro and caused NPCs migration defects in vivo. Taken together, these findings uncover a novel regulatory mechanism of sustained SOCS3 expression in HCMV-infected NPCs, which perturbs IL-6 cytokine family signaling, leads to NPCs proliferation and migration defects, and consequently affects fetal brain development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Epilepsy is a neurological disease and approximately 30% of patients have failed to respond to current anti-epilepsy drugs. The neuroinflammation mechanism has raised increasing concerns and been regarded as the novel treatment strategy in epilepsy, but the target molecules require further research. Pyruvate kinase isoform 2 (PKM2) is well studied in peripheral inflammation, but its role in epilepsy neuroinflammation remains unclear. We knocked down microglia PKM2 in the hippocampus using a stereotaxic adeno-associated virus (AAV) microinjection and established a pilocarpine-induced status epilepticus (PISE) model. Racine score was used to evaluate the seizure grade. Next, we used WB, Multiplex tyramide signal amplification (TSA) staining and other methods to determine neuroinflammation and the complement component 3 (C3)-C3aR interaction in primary microglia. Results showed that microglia PKM2 knockdown reduced epilepsy grade and rescued neuron loss. Mechanistically, PKM2 knockdown inhibited microglia activation and inflammation factor secretion through suppressing p65 expression and phosphorylation. The reduced microglia C1q, TNF-α, and IL-1α were responsible for the decreased astrocyte C3 expression and the following neuron damage caused by the C3-C3aR interaction. Our data suggest that microglia PKM2 inhibition ameliorates neuroinflammation and neuron loss through C3-C3aR interaction in epilepsy, which provides an attractive target for the intervention of damaged neuron-glia crosstalk in epilepsy.

In this work, natural biopolymer stemming from lignocellulosic peanut hull biomass was used as a green and low-cost adsorbent to eliminate anionic Congo red (CR) and Cr(VI) ions from aqueous sample. In order to enhance the removal performance, the lignocellulosic biopolymer was subjected to amino-modification by the graft copolymerization of (3-acrylamidopropyl) trimethylammonium chloride and N, N'-methylenebisacrylamide. The property of the prepared amino-functionalized biopolymer (AFB) was examined through FTIR, TG, SEM, particle size analysis, zeta potential determination and XPS. The adsorption efficacy of AFB for CR and Cr(VI) was tested at different pH, contact time and initial concentration. The kinetic, isotherm and thermodynamics investigations revealed that the uptakes of CR and Cr(VI) were the combination processes of chemical and physical interactions, and both endothermic in nature. The AFB exhibited good reusability without significant loss in adsorption capacity after five consecutive cycles. Mechanistic analysis indicated that the quaternary ammonium groups in AFB contributed a lot to the binding of anionic compounds through electrostatic attraction. In addition, n-π and hydrogen bonding while reduction and coordination were also responsible for the removal of CR and Cr(VI), respectively. The present study provides a favorable strategy for the removal of anionic contaminates in water by using green and sustainable lignocellulosic wastes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Zymomonas mobilis is a promising microorganism for industrial bioethanol production. However, ethanol produced during fermentation is toxic to Z. mobilis and affects its growth and bioethanol production. Although several reports demonstrated that the RNA-binding protein Hfq in Z. mobilis contributes to the tolerance against multiple lignocellulosic hydrolysate inhibitors, the role of Hfq on ethanol tolerance has not been investigated. In this study, hfq in Z. mobilis was either deleted or overexpressed and their effects on cell growth and ethanol tolerance were examined. Our results demonstrated that hfq overexpression improved ethanol tolerance of Z. mobilis, which is probably due to energy saving by downregulating flagellar biosynthesis and heat stress response proteins, as well as reducing the reactive oxygen species induced by ethanol stress via upregulating the sulfate assimilation and cysteine biosynthesis. To explore proteins potentially interacted with Hfq, the TEV protease mediated Yeast Endoplasmic Reticulum Sequestration Screening system (YESS) was established in Z. mobilis . YESS results suggested that Hfq may modulate the cytoplasmic heat shock response by interacting with the heat shock proteins DnaK and DnaJ to deal with the ethanol inhibition. This study thus not only revealed the underlying mechanism of enhanced ethanol tolerance by hfq overexpression, but also provided an alternative approach to investigate protein-protein interactions in Z. mobilis ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tang, Wang, Yang, Zhang, Wu, Yang, Mei, He, Wang and Yang.)

The resource utilization of sewage sludge can solve its disposal issue essentially. Meanwhile the removal of diclofenac (DCF) in wastewater is an emerging environmental problem. In this study, a novel strategy of sludge utilizing via hydrothermal - peroxydisulfate (PDS) dewatering coupled pyrolysis process was proposed. The obtained sludge-derived biochar (HSC) could be as candidate to activate PDS to degrade DCF. Results indicated that exceed 90% of DCF was eliminated within 30 min in HSC-PDS/DCF ternary system under the optimized condition (0.6 mmol/L PDS and 0.5 mg/L HSC, without temperature and pH pre-adjusting). The inner mechanism of HSC-PDS/DCF system was revealed as follows: (1) Major: CO in quinones and ketone structure in HSC accelerated the degradation of DCF via non-radical pathway (electron transfer and 1 O 2 ). (2) Minor: Graphitic N structure accelerated the electron transfer and O 2 •- originated from defective sites involved into the redox. Several by-products were identified and two tentative degradation pathways of DCF (eg. dechlorination and C-N cleavage) were proposed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

During the long coevolution of human cytomegalovirus (HCMV) and humans, the host has formed a defense system of multiple layers to eradicate the invader, and the virus has developed various strategies to evade host surveillance programs. The intrinsic immunity primarily orchestrated by promyelocytic leukemia (PML) nuclear bodies (PML-NBs) represents the first line of defense against HCMV infection. Here, we demonstrate that microrchidia family CW-type zinc finger 3 (MORC3), a PML-NBs component, is a restriction factor targeting HCMV infection. We show that depletion of MORC3 through knockdown by RNA interference or knockout by CRISPR-Cas9 augmented immediate-early protein 1 (IE1) gene expression and subsequent viral replication, and overexpressing MORC3 inhibited HCMV replication by suppressing IE1 gene expression. To relief the restriction, HCMV induces transient reduction of MORC3 protein level via the ubiquitin-proteasome pathway during the immediate-early to early stage. However, MORC3 transcription is upregulated, and the protein level recovers in the late stages. Further analyses with temporal-controlled MORC3 expression and the major immediate-early promoter (MIEP)-based reporters show that MORC3 suppresses MIEP activity and consequent IE1 expression with the assistance of PML. Taken together, our data reveal that HCMV enforces temporary loss of MORC3 to evade its repression against the initiation of immediate-early gene expression., (© 2022 Wiley Periodicals LLC.)

In this study, the effects of the catalysis of heavy metals on the pyrolysis of waste polyester textiles (WPTs) and the adsorption behaviors of the pyrolysis products of WPTs for Cr(VI) were explored. TG-DTG analysis indicated that the metal ions catalyzed the pyrolysis process by reducing the temperature of the decomposition of WPTs. The surface morphology and pore structure of the carbons were analyzed using SEM and BET. The results demonstrated that Zn-AC possessed the largest specific surface area of 847.87 m 2 /g. The abundant acidic functional groups on the surface of the activated carbons were proved to be involved in the Cr(VI) adsorption process via FTIR analysis. Cr(VI) adsorption experiments indicated that the adsorption process was more favorable at low pH conditions, and the maximum adsorption capacities of Zn-AC, Fe-AC, and Cu-AC for Cr(VI) were 199.07, 136.25, and 84.47 mg/g, respectively. The FTIR and XPS analyses of the carbons after Cr(VI) adsorption, combined with the adsorption kinetics and isotherm simulations, demonstrated that the adsorption mechanism includes pore filling, an electrostatic effect, a reduction reaction, and complexation. This study showed that metal salts catalyze the pyrolysis processes of WPTs, and the activated carbons derived from waste polyester textiles are promising adsorbents for Cr(VI) removal.

Phenotypic evaluation and molecular biotechnology are both important in the identification and utilization of crop germplasm resources. In this study, the phenotypic variation and genetic diversity of 149 main potato cultivars in China were investigated with 12 phenotypic traits and 24 SSR markers. The coefficient of variation of 12 phenotypic traits ranged from 12.11% to 156.93%. The results of SSR markers exhibited a relatively high level of genetic variation ( Na =5.458 ± 1.499, Ne =3.300 ± 1.087, I =1.397 ± 0.298, Ho =0.797 ± 0.178, He = 0.660 ± 0.117, and PIC =0.702 ± 0.087). Population structure and phylogenetic tree analysis divided the varieties into three subgroups. The results indicated that ninety percent of the molecular variance was attributed to within-group differences, and the remaining 10% was attributed to variation among groups. Consistent with previous report, alleles of the STI032 marker were significantly associated with tuber starch content and growth period traits in the population. The results of this study could facilitate the utilization of potato germplasm resources, molecular genetic breeding and improvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Mei, Jin, Xu, Duan, Bian, Li, Wang and Jin.)

Microplastics (MPs), as emerging contaminant detected in dyeing sludge (DS), inevitably affected the subsequent treatment and disposal of DS. However, the effect of MPs on the predominant disposal path (incineration) of DS remains far from explicit. This study used thermogravimetry-mass spectrometry (TG-MS) method to explore the effect of representative MPs, polyethylene terephthalate (PET) and polyvinyl chloride (PVC), on combustion characteristics, gas evolution and kinetics on DS combustion. Results showed that PET inhibited the whole combustion of DS by physical barrier. Relatively, PVC delayed the combustion of light volatile but promoted heavy volatile and char reaction due to HCl catalyst. Generally, MPs deteriorated the combustibility, burnout performance and combustion stability of DS. MPs aggravated HCl and gaseous N emissions. Noticeably, the interactions between DS and PVC accelerated the emissions of gaseous pollutants, especially under high dose condition. DAEM and FWO models could well describe the combustion kinetic of DS containing MPs. MPs led to an increase in activation energy of DS, namely, it deteriorated the combustion efficiency of DS. The combustion mechanisms could be divided into two stages: (1) diffusion (D 3 ) stage: melted MPs blocked the gas channels, (2) chemical reaction (F 3 ): the residual chars were thermally stable., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A promoter plays a crucial role in controlling the expression of the target gene in cells, thus being one of the key biological parts for synthetic biology practices. Although significant efforts have been made to identify and characterize promoters with different strengths in various microorganisms, the compatibility of promoters within different hosts still lacks investigation. In this study, we chose the native P gap promoter of Zymomonas mobilis to investigate nucleotide sequences within promoter regions affecting promoter compatibility between Escherichia coli and Z. mobilis . P gap is one of the strongest promotors in Z. mobilis that has many excellent characteristics to be developed as microbial cell factories. Using EGFP as a reporter, a Z. mobilis -derived P gap mutant library was constructed and sorted in E. coli , with candidate promoters exhibiting high fluorescence intensity collected. A total of 53 variants were finally selected and sequenced by Sanger sequencing. The sequencing results grouped these variants into 12 different P gap variant types, among which seven types presented higher promoter strength than native P gap in E. coli . The next-generation sequencing technique was then employed to identify key mutations within the P gap promoter region that affect the promoter compatibility. Finally, six important sites were identified and confirmed to help increase P gap strength in E. coli while keeping similar strength of native P gap in Z. mobilis . Compared to native P gap , synthetic promoters combining these sites had enhanced strength; especially, P gap -6M combining all six sites exhibited 20-fold greater strength than native P gap in E. coli . This study thus not only determined six important sites affecting promoter compatibility but also confirmed a series of P gap promoter variants with strong promoter activity in both E. coli and Z. mobilis . In addition, a strategy was established in this study to investigate and determine nucleotide sequences in promoter regions affecting promoter compatibility, which can be applied in other microorganisms to help reveal universal factors affecting promoter compatibility and design promoters with desired strengths among different microbial cell factories.

Autism spectrum disorder (ASD), a highly hereditary and heterogeneous neurodevelopmental disorder, is influenced by genetic and environmental factors. Tuberous sclerosis complex (TSC) is a common syndrome associated with ASD. Cytomegalovirus (CMV) infection is an environmental risk factor for ASD. The similarities in pathological and mechanistic pathways of TSC and CMV intrigued us to investigate whether CMV and TSC interacted in ASD's occurrence. We detected CMV IgG seroprevalence of 308 TSC patients from our prospective cohort (September 2011 to March 2021) and 93 healthy children by magnetic particle indirect chemiluminescence immunoassay. A total of 206 TSC patients enrolled were divided into ASD and non-ASD groups, and the relationship between ASD and CMV seroprevalence was analyzed. Nested PCR and Western blot were used to detect CMV DNAs and proteins in cortical malformations of seven TSC patients with and without ASD. No difference was found in CMV seroprevalence between TSC patients and healthy children (74.0% versus 72.0%, P  = 0.704). Univariate analysis showed the seroprevalence in TSC patients with ASD was higher than that in TSC patients without ASD (89.2% versus 75.1%, P  = 0.063), and multifactorial analysis showed that CMV seroprevalence was a risk factor for ASD in TSC patients (OR = 3.976, 95% CI = 1.093 to 14.454). Moreover, CMV was more likely to be detected in the cortical malformations in TSC patients with ASD but not in those without ASD. The findings demonstrated that CMV may increase the susceptibility of TSC to ASD. IMPORTANCE CMV is an environmental risk factor for ASD, but its role in syndromic autism with known genetic etiology has been rarely studied. The pathogenesis of ASD is related to the interaction between environmental and genetic factors. This study demonstrated that CMV can contribute to the occurrence of ASD related to TSC, a common genetic syndrome associated with ASD. Our findings provided support for the theory of gene-environment interaction (G × E) in pathogenesis of ASD and a new perspective for the prevention and therapy for TSC related ASD.

Natural biomass materials are endowed with good potential for pollutant remediation due to low cost, environment friendliness and easy accessibility. In this work, an efficient biomass-based adsorbent named g-PS was fabricated by free radical graft copolymerization of peanut shell with methacrylic acid and N,N'-methylenebis(acrylamide). The structural and morphological properties of g-PS were characterized and analyzed. The effectiveness of g-PS as adsorbent to remove cationic dye and heavy metal pollutants (i.e. methylene blue (MB), basic red 46 (BR) and Cd(II)) from water was evaluated. The batch adsorption tests indicated that g-PS showed rapid removal rates for MB, BR and Cd(II), with the adsorption equilibriums achieved within 30 min. The adsorption processes of three compounds were more suitable to be described by Langmuir and pseudo-second-order models. The maximum adsorption capacities were 538.34 mg/g for MB, 687.52 mg/g for BR and 62.01 mg/g for Cd(II) at 298 K. The coadsorption experiments in the mixed system indicated that g-PS was still effective for simultaneous removal of both BR and Cd(II). Additionally, g-PS exhibited satisfactory removal performance even after seven repeated uses. The as-prepared g-PS can be used as a promising adsorbent candidate to dispose wastewater containing cationic dyes and heavy metals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pyrolysis is a potential recovery method for waste printed circuit boards (WPCBs), but the organic brominated products are toxic and hazardous. Iron has been used as a catalyst for debromination from pyrolysis oil, but the effects of in-situ iron on WPCBs pyrolysis is still not well understood. Herein, the pyrolysis mechanism for laminates of PCBs in the absence and presence of iron was studied via analyzing pyrolysis characteristics, kinetics, and products. According to the thermogravimetry experiments, pyrolysis of all samples could be divided into four stages, and iron accelerated the pyrolysis reaction by decreasing the activation energy as calculated using the Starink method. Volatiles released during the heating process were continuously determined by TG-FTIR-MS, and products generated at different pyrolysis temperatures were collected and characterized. The obtained results exhibited that iron promoted the generation of gaseous products and facilitated the conversion of organic bromides to inorganic bromides. Therefore, retaining iron was beneficial to energy saving and environmental protection for WPCBs pyrolysis. In addition, the decomposition mechanisms of brominated epoxy resin with and without iron were proposed. This work would contribute to the improvement and application of WPCBs pyrolysis technology., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Thiamphenicol (TAP) is an amphenicol antibiotic, which has a broad-spectrum inhibitory effect on both gram-positive and gram-negative bacteria. Since it is widely used in animals and aquaculture, its residues in environment may bring potential risk for human health and ecosystems. While TAP can be removed through conventional physical or chemical methods, its bioremediation using microorganisms is less studied. Here, we report the removal of TAP by a bacterial strain, Aeromonas hydrophila HS01, which can remove more than 90.0% of TAP in a living cell-dependent manner. Our results indicated that its removal efficiency can be greatly affected by the growth condition. Proteomics studies revealed a number of differentially expressed proteins of HS01 in the presence of TAP, which may play critical roles in the transportation and degradation of TAP. All these results indicate bacterial strain A. hydrophila HS01 is a new microbial resource for efficiently removing TAP, and may shed new insights in developing bioremediation approaches for TAP pollution., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neurodevelopmental disorders. However, the neuropathogenesis remains largely elusive due to a lack of informative animal models. In this study, we developed a congenital murine CMV (cMCMV) infection mouse model with high survival rate and long survival period that allowed long-term follow-up study of neurodevelopmental disorders. This model involves in utero intracranial injection and mimics many reported clinical manifestations of cCMV infection in infants, including growth restriction, hearing loss, and impaired cognitive and learning-memory abilities. We observed that abnormalities in MRI/CT neuroimaging were consistent with brain hemorrhage and loss of brain parenchyma, which was confirmed by pathological analysis. Neuropathological findings included ventriculomegaly and cortical atrophy associated with impaired proliferation and migration of neural progenitor cells in the developing brain at both embryonic and postnatal stages. Robust inflammatory responses during infection were shown by elevated inflammatory cytokine levels, leukocyte infiltration, and activation of microglia and astrocytes in the brain. Pathological analyses and CT neuroimaging revealed brain calcifications induced by cMCMV infection and cell death via pyroptosis. Furthermore, antiviral treatment with ganciclovir significantly improved neurological functions and mitigated brain damage as shown by CT neuroimaging. These results demonstrate that this model is suitable for investigation of mechanisms of infection-induced brain damage and long-term studies of neurodevelopmental disorders, including the development of interventions to limit CNS damage associated with cCMV infection.

Circular RNA (circRNA) is a non-coding molecule produced through alternative splicing of one or more exons of a gene in the presence of an RNA-induced silencing complex (RISC). Its formation depends on complementary intron sequences on both sides of the circularized sequence. CircRNA functions as a sponge for miRNA, playing the role of the transcriptional regulator or potential biomarker. It has an impact on fetal growth and on synaptic facilitation in the brain. In this review, we illustrate biogenesis mechanisms, characteristics, and functions of cirRNAs. We also summarize methods using sequence feature and RNA next-generation sequencing data for circRNA prediction. Finally, we discuss the state of the research on circRNA in diseases, which will bring new contributions to future disease treatments., (© 2021 Bentham Science Publishers.)

Characterizing protein-protein interactions (PPIs) is an effective method to help explore protein function. Here, through integrating a newly identified split human Rhinovirus 3 C (HRV 3 C) protease, super-folder GFP (sfGFP), and ClpXP-SsrA protein degradation machinery, we developed a fluorescence-assisted single-cell methodology (split protease-E. coli ClpXP (SPEC)) to explore protein-protein interactions for both eukaryotic and prokaryotic species in E. coli cells. We firstly identified a highly efficient split HRV 3 C protease with high re-assembly ability and then incorporated it into the SPEC method. The SPEC method could convert the cellular protein-protein interaction to quantitative fluorescence signals through a split HRV 3 C protease-mediated proteolytic reaction with high efficiency and broad temperature adaptability. Using SPEC method, we explored the interactions among effectors of representative type I-E and I-F CRISPR/Cas complexes, which combining with subsequent studies of Cas3 mutations conferred further understanding of the functions and structures of CRISPR/Cas complexes.

For improving the utilization efficiency of pesticides, we developed a novel pesticide delivery particle (YINCP@EC) with a core-shell structure based on yeast biochar, imidacloprid (IMI), ammonium bicarbonate (NH 4 HCO 3 ), calcium alginate (CA), and ethyl cellulose (EC). Therein, yeast biochar, IMI and NH 4 HCO 3 were absorbed in the network-structured of CA to obtain YINCP through hydrogen bonds. The resulting composite was granulated using an ion gelation technique and then coated with EC to form YINCP@EC. In this platform, yeast biochar serving as a photothermal agent can efficiently convert sunlight energy into thermal energy, thereby triggering NH 4 HCO 3 decomposition into CO 2 and NH 3 that can break through the EC coating and facilitate IMI release. In addition, the influence of yeast biochar content, pH, and coexisting ions was systematically studied to evaluate the release behavior of IMI from YINCP@EC. Moreover, the hydrophobic EC shell endowed YINCP@EC with high stability in aqueous solution for at least 60 days. Consequently, this novel composite with simple preparation, low cost and remarkable photothermal-responsive properties has a huge application potential in agriculture., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To develop a new DNA assembly method based on FnCas12a and T5 exonuclease., Results: We developed a method named as FnCas12a and T5 exonuclease (CT5) cloning system. FnCas12a performs site-directed cleavage to the target DNA fragments, and T5 exonuclease generates 20-30 nt single-stranded region at each end of the DNA fragments for homologous recombination-mediated DNA assembly. CT5 was applied to multi-fragment assembly and DNA cloning of large vectors (> 10 kb). The efficiencies were approximately 91.4% and 97%, respectively. In addition, CT5 cloning is also utilized for the "walking" of DNA elements, which enables subtle modification of the relative distances of DNA elements in plasmids., Conclusions: The CT5 method was a precise and exquisite DNA operating system and provided an ideal platform for the study of gene functions, genetic engineering and synthetic biology.

This innovative study makes use of a thermal hydrolysis process (THP) and the conditioner sodium persulfate (SPS) to improve the dewaterability of sewage sludge. The best-operating conditions were optimized using response surface methodology (RSM): 100 mg/g of dry solids (DS) of SPS, 101 min of reaction time of THP, and a temperature of 200 °C. Distribution of extracellular polymeric substances (EPS), zeta potential, bound water, and solid characters were analyzed to reveal the mechanisms involved in the dewatering process. These results indicate that the sewage sludge after treatment (SPS combined with THP) had a superior dewaterability. The specific resistance to filtration (SRF) under the best conditions was 0.51 × 10 11  m/kg, decreasing by 91.65% compared to the raw sludge (RS) (6.11 × 10 11  m/kg). This mechanism could be explained as follows: (1) Aromaticity and hydrophobicity of sludge cake after SPS + THP treatment was increased; (2) sludge flocs were re-flocculated by charge neutralization, giving rise to a loose and porous structure; (3) the structure of extracellular polymeric substances and cells was destroyed, and the bound water was released. Overall, the conditioning by combination of SPS and THP is an effective mean to improve sewage sludge dewaterability. Graphical abstract.

Co-combustion of dyeing sludge (DS) and rice husk (RH) is a promising energy-from-waste method. The aim of this work was to investigate and quantify the effect of RH additive on combustion performance, gas evolution (especially gaseous pollutants) and kinetics during DS combustion by thermogravimetry-mass spectrometry method. Results revealed that the introduction of RH improved the combustibility, burnout performance and combustion stability of DS. Optimal RH addition (10% RH) reduced the emission of gaseous pollutants (NH 3 , NO 2 , COS, SO 2 and CS 2 ). The interaction between DS and RH inhibited the devolatilization reaction and emission of gaseous sulfur substances, and it also restrained NO 2 emission under optimal RH additive amount. A four-interval kinetic model (D 1  → F 3  → D 1  → F 3 ) was established to describe the co-combustion process (R 2  greater than 0.9999). RH addition, especially at high doses, led to an increase in activation energy relative to DS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The Boolean Satisfiability problem (SAT) is a prototypical NP-complete problem, which has been widely studied due to its significant importance in both theory and applications. Stochastic local search (SLS) algorithms are among the most efficient approximate methods available for solving certain types of SAT instances. The quantitative configuration checking (QCC) heuristic is an effective approach for improving SLS algorithms on solving the SAT problem, resulting in an efficient SLS solver for SAT named Swqcc. In this paper, we focus on combining the QCC heuristic with an aspiration mechanism, and then design a new heuristic called QCCA. On the top of Swqcc, we utilize the QCCA heuristic to develop a new SLS solver dubbed AspiSAT. Through extensive experiments, the results illustrate that, on random 3-SAT instances, the performance of AspiSAT is much better than that of Swqcc and Sparrow, which is an influential and efficient SLS solver for SAT. In addition, we further enhance the original clause weighting schemes employed in Swqcc and AspiSAT, and thus obtain two new SLS solvers called Ptwqcc and AspiPT, respectively. The eperimental results present that both Ptwqcc and AspiPT outperform Swqcc and AspiSAT on random 5-SAT instances, indicating that both QCC and QCCA heuristics are able to cooperate effectively with different clause weighting schemes., Competing Interests: The authors have declared that no competing interests exist.

The anaerobic digestion of food waste, can result in large amounts of solid waste digestate, often without methods of disposal. In this study, a biochar was prepared from food waste digestate (FWD) by pyrolysis, and its potential to activate peroxymonosulfate (PMS) for the removal of pollutants from a simulated textile wastewater was evaluated. The results showed that the addition of biochar (0.5 g/L) and PMS (1 mM) to wastewater could remove >99% of a representative azo dye pollutant (reactive brilliant red X-3B, 1 g/L) within 10 min. The efficiency of this removal process was attributed to the catalytic sites in the biochar (graphitic carbon and nitrogen, pyridinium nitrogen and CO structures) which could activate PMS to produce reactive oxygen species ( 1 O 2 , O 2 - , OH and SO 4 - ). The results obtained in this study confirmed the activation potential of the biochar derived from FWD on PMS, providing an alternative utilization strategy for anaerobic FWD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Solid digestate generated in the anaerobic digestion of food wastes was evaluated as a potential feedstock for biochar preparation by pyrolysis in this study. To understand the pyrolysis mechanism, thermogravimetric experiments were firstly implemented at different heating rates, then apparent activation energy during pyrolysis was calculated by using the Starink isoconversional method, ranging from 144.64 kJ/mol to 293.36 kJ/mol with the conversion increasing in the region from 0.10 to 0.90. The evolutions of released volatiles were accurately and continuously analyzed by TG-FTIR-MS. Results show that dehydration and CO 2 emission were the main reasons for mass loss, and light hydrocarbons were released in step II of the pyrolysis process. Elemental compositions and surface properties of the biochars obtained at different pyrolysis temperatures were characterized by EA, XRF and BET. The obtained results provide an alternative strategy for disposing waste generated in anaerobic digestion of food waste., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Human lysozyme (hLYZ), known for its bacteriolytic activity, is widely applied in the food and pharmaceutical industries as an antimicrobial agent. However, its extensive application was limited by its low large-scale production efficiency. In this study, a combinational method of integrating codon optimization, multiple gene copies, and ER molecular chaperone co-expression was developed to improve the heterologous production of hLYZ in Pichia pastoris GS115. Our results showed that increasing the copy number of the optimized hLYZ gene in P. pastoris could enhance its secretory production level up to 1.57-fold. The recombinant opt-hLYZ-6C strain that contains six copies of opt-hLYZ gene exhibited the highest mRNA transcription levels, giving the highest production of 0.22 ± 0.02 mg/mL of hLYZ in the medium supernatant with a bacteriolytic activity of 14,680 ± 300 U/mL against Micrococcus lysodeikticus in the shaking flask experiment. Moreover, co-overexpression of ER retention molecular chaperones, such as Pdi1 or Ero1, in the recombinant opt-hLYZ-6C strain both presented positive effects on the secretory production of hLYZ. Our further characterization indicated that tandem co-expression of Ero1 and Pdi1 together presented an added-up effect. The secretory production of hLYZ in the medium supernatant reached 0.34 ± 0.02 mg/mL of the recombinant opt-hLYZ-6C-EP strain in the shaking flask experiment, with a bacteriolytic activity of 21,200 ± 400 U/mL. Compared to the recombinant opt-hLYZ-1C strain, these final improvements were calculated as 2.43-fold and 2.30-fold on secretory protein levels and antibacterial activity, respectively. Finally, the recombinant opt-hLYZ-6C-EP strain was applied for high-density cultivation in 5 L of fermenter, in which the secretory yield of hLYZ reached 2.34 ± 0.02 mg/mL in the medium supernatant, with a bacteriolytic activity of 1.76 ± 0.02 × 10 5 U/mL against M. lysodeikticus . All these numbers presented the highest heterologous production levels of hLYZ in microbial systems., (Copyright © 2020 He, Wu, Mei, Ning, Li, Ma, Zhang and Yi.)

Oxidative stress is a major pathogenic mechanism in Parkinson's disease (PD). As an important cellular antioxidant, glutathione (GSH) balances the production and incorporation of free radicals to protect neurons from oxidative damage. GSH level is decreased in the brains of PD patients. Hence, clarifying the molecular mechanism of GSH deficiency may help deepen our knowledge of PD pathogenesis. Here we report that the astrocytic dopamine D2 receptor (DRD2) regulates GSH synthesis via PKM2-mediated Nrf2 transactivation. In addition we find that pyridoxine can dimerize PKM2 to promote GSH biosynthesis. Further experiments show that pyridoxine supplementation increases the resistance of nigral dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in wild-type mice as well as in astrocytic Drd2 conditional knockout mice. We conclude that dimerizing PKM2 may be a potential target for PD treatment.

Human rhinovirus 3C protease (HRV 3C-P) is a high-value commercial cysteine protease that could specifically recognize the short peptide sequence of LEVLFQ↓GP. In here, a strategy based on our previous Yeast Endoplasmic Reticulum Sequestration Screening (YESS) approach was developed in Saccharomyces cerevisiae , a model microorganism, to fully characterize the substrate specificity of a typical human virus protease, HRV 3C-P, in a quantitative and fast manner. Our results demonstrated that HRV 3C-P had very high specificity at P1 and P1' positions, only recognizing Gln/Glu at the P1 position and Gly/Ala/Cys/Ser at the P1' position, respectively. Comparably, it exhibited efficient recognition of most residues at the P2' position, except Trp. Further biochemical characterization through site mutagenesis, enzyme structural modeling, and comparison with other 3C proteases indicated that the S1 pocket of HRV 3C-P was constituted by neutral and basic amino acids, in which His160 and Thr141 specifically interacted with Gln or Glu residues at the substrate P1 position. Additionally, the stringent S1' pocket determined its unique property of only accommodating residues without or with short side chains. Based on our characterization, LEVLFQ↓GM was identified as a more favorable substrate than the original LEVLFQ↓GP at high temperature, which might be caused by the conversion of random coils to β-turns in HRV 3C-P along with the temperature increase. Our studies prompted a further understanding of the substrate specificity and recognition mechanism of HRV 3C-P. Besides, the YESS-PSSC combined with the enzyme modeling strategy in this study provides a general strategy for deciphering the substrate specificities of proteases.

For the first time, a convenient, online couplable, sensitive and environmentally friendly sample pretreatment method, namely, magnetism-reinforced in-tube solid phase microextraction (MR/IT-SPME) was proposed to effectively enrich heavy metal ions (HMIs). Monolithic capillary microextraction column embedded modified Fe 3 O 4 magnetic nanoparticles (MCEN) was conveniently synthesized and employed as the microextraction column of MR/IT-SPME. Subsequently, the MCEN was put into a magnetic coil which was utilized to exert variable magnetic field during extraction procedure. Three HMIs, including Cu(II), Co(II) and Hg(II), were selected as studied ions and reacted with chelating agent sodium diethyldithiocarbamatetrihydrate to form metallic coordination compounds. The complexes were infused to the MCEN to perform the MR/IT-SPME extraction and then online determined by high-performance liquid chromatography equipped with diode array detection (HPLC-DAD). A series of key parameters affecting the extraction performance were investigated in detail. Results revealed that the exertion of magnetic field in adsorption and desorption steps favored the adsorption and release of the coordination compounds, with the extraction efficiencies enhanced from 47-65% to 67-89%. Finally, the developed online MR/IT-SPME-HPLC-DAD approach was successfully applied to determine studied HMIs in environmental water and seafood samples. The confirmatory experiments further evidenced the reliability and feasibility of the introduced approach for the analysis of trace HMIs in complex samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Emerging evidence has demonstrated that the integrity and the function of blood-brain barrier (BBB) are gradually impaired in the processes of aging and nervous system disorders, including neurodegenerative diseases (e.g. Parkinson's disease, PD). The leakage of BBB contributes to the infiltration of peripheral immune cells and harmful mediators into brain parenchyma, even the drugs that can not cross BBB under physiological conditions. Therefore, PD has been regarded as not only a neurodegenerative disease, but also a systemic disorder. In the present study, we demonstrate for the first time that Dexrazoxane (Dex), a drug clinically used to reduce doxorubicin-induced cardiotoxicity in chemotherapy, can enter into midbrain and striatum through broken BBB in 6-hydroxydopamine (6-OHDA)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent models of PD. Unexpectedly, Dex (1.5, 5, 15 mg/kg, i.p.) administration for 3-week significantly ameliorates apomorphine-induced contralateral rotation behavior in 6-OHDA-treated rats and Dex (10 mg/kg, i.p.) treatment for 5-week improves MPTP-induced mouse motor dysfunctions. We find that Dex administration protects dopaminergic neurons against neurotoxin-induced degeneration in SNc, accompanied by the attenuated glial cell activation. Further study indicates that suppression of oxidative stress and endoplasmic reticulum stress, as well as the inhibition of systemic inflammation in both peripheral tissues and brain, contribute to the neuroprotective effects of Dex in PD models. Our study implies that Dex may serve as an effective neuroprotectant to treat neurodegeneration and has potential clinical value in term of PD therapeutics., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

For antibody discovery and engineering, yeast surface display (YSD) of antigen-binding fragments (Fabs) and coupled fluorescence activated cell sorting (FACS) provide intact paratopic conformations and quantitative analysis at the monoclonal level, and thus holding great promises for numerous applications. Using anti-TNFα mAbs Infliximab, Adalimumab, and its variants as model Fabs, this study systematically characterized complementary approaches for the optimization of Fab YSD. Results suggested that by using divergent promoter GAL1-GAL10 and endoplasmic reticulum (ER) signal peptides for co-expression of light chain and heavy chain-Aga2 fusion, assembled Fabs were functionally displayed on yeast cell surface with sigmoidal binding responses toward TNFα. Co-expression of a Hsp70 family molecular chaperone Kar2p and/or protein-disulfide isomerase (Pdi1p) significantly improved efficiency of functional display (defined as the ratio of cells displaying functional Fab over cells displaying assembled Fab). Moreover, fusing ER retention sequences (ERSs) with light chain also enhanced Fab display quality at the expense of display quantity, and the degree of improvements was correlated with the strength of ERSs and was more significant for Infliximab than Adalimumab. The feasibility of affinity maturation was further demonstrated by isolating a high affinity Fab clone from 1:10 3 or 1:10 5 spiked libraries., (Copyright © 2019 Mei, Li, Wang, Lee, Iverson, Zhang, Ge and Yi.)