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Traffic flow prediction is one of the challenges in the development of an Intelligent Transportation System (ITS). Accurate traffic flow prediction helps to alleviate urban traffic congestion and improve urban traffic efficiency, which is crucial for promoting the synergistic development of smart transportation and smart cities. With the development of deep learning, many deep neural networks have been proposed to address this problem. However, due to the complexity of traffic maps and external factors, such as sports events, these models cannot perform well in long-term prediction. In order to enhance the accuracy and robustness of the model on long-term time series prediction, a Graph Attention Informer (GAT-Informer) structure is proposed by combining the graph attention layer and informer layer to capture the intrinsic features and external factors in spatial-temporal correlation. The external factors are represented as sports events impact factors. The GAT-Informer model was tested on real-world data collected in London, and the experimental results showed that our model has better performance in long-term traffic flow prediction compared to other baseline models.

African swine fever (ASF) is an acute, hemorrhagic, highly contagious disease in pigs caused by African swine fever virus (ASFV). Our previous study identified that the ASFV MGF300-2R protein functions as a virulence factor and found that MGF300-2R degrades IKK β via selective autophagy. However, the E3 ubiquitin ligase responsible for IKK β ubiquitination during autophagic degradation still remains unknown. In order to solve this problem, we first pulled down 328 proteins interacting with MGF300-2R through immunoprecipitation-mass spectrometry. Next, we analyzed and confirmed the interaction between the E3 ubiquitin ligase TRIM21 and MGF300-2R and demonstrated the catalytic role of TRIM21 in IKK β ubiquitination. Finally, we indicated that the degradation of IKK β by MGF300-2R was dependent on TRIM21. In summary, our results indicate TRIM21 is the E3 ubiquitin ligase involved in the degradation of IKK β by MGF300-2R, thereby augmenting our understanding of the functions of MGF300-2R and offering insights into the rational design of live attenuated vaccines and antiviral strategies against ASF.

African swine fever (ASF) is a contagious viral disease affecting pigs and wild boars. It typically presents as a hemorrhagic fever but can also manifest in various forms, ranging from acute to asymptomatic. ASF has spread extensively globally, significantly impacting the swine industry. The complex and highly variable character of the ASFV genome makes vaccine development and disease surveillance extremely difficult. The overall trend in ASFV evolution is towards decreased virulence and increased transmissibility. Factors such as gene mutation, viral recombination, and the strain-specificity of virulence-associated genes facilitate viral variations. This review deeply discusses the influence of these factors on viral immune evasion, pathogenicity, and the ensuing complexities encountered in vaccine development, disease detection, and surveillance. The ultimate goal of this review is to thoroughly explore the genetic evolution patterns and variation mechanisms of ASFV, providing a theoretical foundation for advancement in vaccine and diagnostic technologies.

SHP2, a pivotal component downstream of both receptor and non-receptor tyrosine kinases, has been underscored in the progression of various human cancers and neurodevelopmental disorders. Allosteric inhibitors have been proposed to regulate its autoinhibition. However, oncogenic mutations, such as E76K, convert SHP2 into its open state, wherein the catalytic cleft becomes fully exposed to its ligands. This study elucidates the dynamic properties of SHP2 structures across different states, with a focus on the effects of oncogenic mutation on two known binding sites of allosteric inhibitors. Through extensive modeling and simulations, we further identified an alternative allosteric binding pocket in solution structures. Additional analysis provides insights into the dynamics and stability of the potential site. In addition, multi-tier screening was deployed to identify potential binders targeting the potential site. Our efforts to identify a new allosteric site contribute to community-wide initiatives developing therapies using multiple allosteric inhibitors to target distinct pockets on SHP2, in the hope of potentially inhibiting or slowing tumor growth associated with SHP2., Competing Interests: The authors hereby declare no conflicts of interest.

Hydrogel-based flexible electronic devices have great potential in human motion monitoring, electronic skins, and human-computer interaction applications; hence, the efficient preparation of highly sensitive hydrogel-based flexible sensors is important. In the present work, the ultrafast polymerization of a hydrogel (1-3 min) was achieved by constructing a tannic acid (TA)-Fe 3+ dynamic redox system, which endowed the hydrogel with good adhesion performance (the adhesion strength in wood was 17.646 kPa). In addition, the uniform dispersal ensured by incorporating polydopamine-decorated polypyrrole (PPy@PDA) into the hydrogel matrix significantly improved the hydrogel's stretching ability (575.082%). The as-prepared PAM/CS/PPy@PDA/TA hydrogel-based flexible sensor had a high-fidelity low detection limit (strain = 1%), high sensitivity at small strains (GF = 5.311 at strain = 0-8%), and fast response time (0.33 s) and recovery time (0.25 s), and it was reliably applied to accurate human motion monitoring and handwriting recognition. The PAM/CS/PPy@PDA/TA hydrogel opens new horizons for wearable electronic devices, electronic skins, and human-computer interaction applications.

N -aryl-substituted pyrrolidines are important moieties widely found in bioactive substances and drugs. Herein, we present a practical reductive amination of diketones with anilines for the synthesis of N -aryl-substituted pyrrolidines in good to excellent yields. In this process, the N -aryl-substituted pyrrolidines were furnished via successive reductive amination of diketones via iridium-catalyzed transfer hydrogenation. The scale-up performance, water as a solvent, simple operation, as well as derivation of drug molecules showcased the potential application in organic synthesis.

The effect of a high-fat diet (HFD) on mood is a widely debated topic, with the underlying mechanisms being poorly understood. This study explores the anxiolytic effects of a four-week HFD in C57BL/6 mice. Five-week-old mice were exposed to either an HFD (60% calories from fat) or standard chow diet (CD) for four weeks, followed by cannula implantation, virus infusion, behavioral tests, and biochemical assays. Results revealed that four weeks of an HFD induced anxiolytic-like behaviors and increased the protein levels of mature brain-derived neurotrophic factor (mBDNF) and phosphorylated tyrosine kinase receptor B (p-TrkB) in the medial prefrontal cortex (mPFC). Administration of a BDNF-neutralizing antibody to the mPFC reversed HFD-induced anxiolytic-like behaviors. Elevated BDNF levels were observed in both neurons and astrocytes in the mPFC of HFD mice. Additionally, these mice exhibited a higher number of dendritic spines in the mPFC, as well as upregulation of postsynaptic density protein 95 (PSD95). Furthermore, mRNA levels of the N6-methyladenosine (m6A) demethylase, fat mass and obesity-associated protein (FTO), and the hydrolase matrix metalloproteinase-9 (MMP9), also increased in the mPFC. These findings suggest that an HFD may induce FTO and MMP9, which could potentially regulate BDNF processing, contributing to anxiolytic-like behaviors. This study proposes potential molecular mechanisms that may underlie HFD-induced anxiolytic behaviors.

Tibetan pig is a geographically isolated pig breed that inhabits high-altitude areas of the Qinghai-Tibetan plateau. At present, there is limited research on viral diseases in Tibetan pigs. This study provides a novel metagenomic exploration of the gut virome in Tibetan pigs (altitude ≈ 3000 m) across three critical developmental stages, including lactation, nursery, and fattening. The composition of viral communities in the Tibetan pig intestine, with a dominant presence of Microviridae phages observed across all stages of development, in combination with the previous literature, suggest that it may be associated with geographical locations with high altitude. Functional annotation of viral operational taxonomic units (vOTUs) highlights that, among the constantly increasing vOTUs groups, the adaptability of viruses to environmental stressors such as salt and heat indicates an evolutionary response to high-altitude conditions. It shows that the lactation group has more abundant viral auxiliary metabolic genes (vAMGs) than the nursery and fattening groups. During the nursery and fattening stages, this leaves only DNMT1 at a high level. which may be a contributing factor in promoting gut health. The study found that viruses preferentially adopt lytic lifestyles at all three developmental stages. These findings not only elucidate the dynamic interplay between the gut virome and host development, offering novel insights into the virome ecology of Tibetan pigs and their adaptation to high-altitude environments, but also provide a theoretical basis for further studies on pig production and epidemic prevention under extreme environmental conditions.

In traditional Chinese medicine, Aurantii Fructus Immatures (AFIs) have been utilized for more than 2000 years. The proportions of different fruit parts are crucial for evaluating AFI quality in China. However, the basis for this statement's substance is unclear. Differences in quality are intimately correlated with a plant's metabolite composition. On the basis of a widely targeted metabolome, this study intended to investigate the metabolite composition and evaluate the antioxidant capacity of the peel and pulp of an AFI. Metabolites were identified and quantified by UHPLC-QqQ-MS. To assess their antioxidant ability, DPPH and ABTS assays were carried out. There were 1327 chemical compounds identified by UHPLC-QqQ-MS. After screening the differential metabolites using a multivariate statistical analysis, it was found that there were 695 significant differences in the metabolites between the peel and the pulp. Among them, it was discovered that the content of active ingredients in the peel group was higher than that in the pulp group. Furthermore, the aqueous extracts from the peel showed stronger antioxidant capacities than those from the pulp. The metabolites and antioxidant capacities were significantly different between the peel and the pulp. This study of different fruit parts might provide a guide for AFI quality assessments.

In order to solve the problem of excessive consumption of petrochemical resources and the harm of free formaldehyde release to human health, biomass raw materials, such as sucrose (S) and ammonium dihydrogen phosphate (ADP) can be chemically condensed in a simple route under acidic conditions to produce a formaldehyde free wood adhesive (S-ADP), characterized by good storage stability and water resistance, and higher wet shear strength with respect to petroleum based phenolic resin adhesive. The dry and boiling shear strength of the plywood based on S-ADP adhesive are as high as 1.05 MPa and 1.19 MPa, respectively. Moreover, is Modulus of Elasticity (MOE) is as high as 4910 MPa. Interestingly, the plywood based on the developed S-ADP adhesive exhibited good flame retardancy. After burning for 90 s, its shape remains unchanged. Meanwhile, it can be concluded from thermomechanical analysis (TMA) and thermogravimetric analysis (TGA) that the S-ADP acquired excellent modulus of elasticity (MOE) and good thermal stability. It is thus thought promisingly that the use of S-ADP adhesive as a substitute for PF resin adhesive seems feasible in the near future.

Caffeic acid O -methyltransferase ( COMT ) participates in various physiological activities in plants, such as positive responses to abiotic stresses and the signal transduction of phytohormones. In this study, 18 COMT genes were identified in the chromosome-level reference genome of mango, named MiCOMTs . A phylogenetic tree containing nine groups (I-IX) was constructed based on the amino acid sequences of the 71 COMT proteins from seven species. The phylogenetic tree indicated that the members of the MiCOMTs could be divided into four groups. Quantitative real-time PCR showed that all MiCOMT genes have particularly high expression levels during flowering. The expression levels of MiCOMTs were different under abiotic and biotic stresses, including salt and stimulated drought stresses, ABA and SA treatment, as well as Xanthomonas campestris pv. mangiferaeindicae and Colletotrichum gloeosporioides infection, respectively. Among them, the expression level of MiCOMT1 was significantly up-regulated at 6-72 h after salt and stimulated drought stresses. The results of gene function analysis via the transient overexpression of the MiCOMT1 gene in Nicotiana benthamiana showed that the MiCOMT1 gene can promote the accumulation of ABA and MeJA, and improve the salt tolerance of mango. These results are beneficial to future researchers aiming to understand the biological functions and molecular mechanisms of MiCOMT genes.

This paper presents an adaptive learning structure based on neural networks (NNs) to solve the optimal robust control problem for nonlinear continuous-time systems with unknown dynamics and disturbances. First, a system identifier is introduced to approximate the unknown system matrices and disturbances with the help of NNs and parameter estimation techniques. To obtain the optimal solution of the optimal robust control problem, a critic learning control structure is proposed to compute the approximate controller. Unlike existing identifier-critic NNs learning control methods, novel adaptive tuning laws based on Kreisselmeier's regressor extension and mixing technique are designed to estimate the unknown parameters of the two NNs under relaxed persistence of excitation conditions. Furthermore, theoretical analysis is also given to prove the significant relaxation of the proposed convergence conditions. Finally, effectiveness of the proposed learning approach is demonstrated via a simulation study.

The combination of organic and inorganic materials has been considered an effective solution for achieving ambient thermoelectric energy harvesting and has been developing rapidly. Here, PEDOT:PSS/MWCNT (PPM) composite hydrogels were synthesized using the self-assembled gelation process of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) and the interaction between PEDOT:PSS and multi-walled carbon nanotubes (MWCNTs) without the addition of any surfactant. After immersion in dimethyl sulfoxide and freeze-drying, the hydrogel is easily dispersed in water and used as a direct ink writing (DIW) 3D printing ink. At room temperature, the PPM-20 printed film with 20 wt% MWCNT solids achieved a maximum power factor of 7.37 μW m -1 K -2 and maintained stable thermoelectric properties during repeated bending cycles. On this basis, a thermoelectric generator (TEG) consisting of five legs was printed, which could be produced to generate an open circuit voltage of 6.4 mV and a maximum output power of 40.48 nW at a temperature gradient of 50 K, confirming its great potential for application in high-performance flexible organic/inorganic thermoelectric materials.

The radiation effect of materials is very important and directly related to the safety and reliability of nuclear reactors. Polymer materials, one of the indispensable materials in nuclear power equipment, must withstand the ordeal of high-energy ionizing rays. In this work, through screening different γ-ray dose irradiation conditions, we systematically and comprehensively study the changes in the structure and properties of nitrile butadiene rubber (NBR) before and after γ-ray static irradiation at a high dose rate, and master the rule and mechanism of the γ-ray static irradiation effect of these polymer materials. The mapping relationship between the macroscopic properties, microstructure, and irradiation dose of NBR is accurately characterized. With an increase in total irradiation dose, the C=C double bond reaction occurs, and the C≡N bond, C=C, and C=O participate in the hyper crosslinking reaction. The glass transition temperature (T g ) increases with the cumulative irradiation amount. With the increased total irradiation amount, the degree of rubber cross-linking increases, causing an increased crystallinity and decomposition temperature. A growing amount of gamma irradiation causes the mechanical properties of the rubber to degrade simultaneously, increasing the shore hardness while decreasing the tensile strength and ultimate elongation at break. When the cumulative amount reaches 1 MGy, the ultimate elongation at break decreases significantly. A cumulative dose of radiation resistance of 4 MGy can be achieved by the samples. This work can provide theoretical and experimental support for the long-term stability of nitrile butadiene rubber and its derivatives in nuclear radiation fields and space radiation conditions.

Ischemic stroke (IS) often leads to high rates of disability and mortality worldwide with secondary damage due to neuroinflammation. Identification of potential therapeutic targets via the novel circular RNAs (circRNAs) would advance the field and provide a better treatment option for neuroinflammation after IS. Gene Ontology Term Enrichment (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to identify differentially expressed genes/miRNAs/circRNAs in the genome-wide RNA-seq profiles of ischemic mice. Meanwhile, relevant circRNAs were screened by differential expression analysis and coexpression RNA regulation network analysis. To explore the function of circ_22232 (Specc1l), we generated circ_22232 knockdown mice and applied middle cerebral artery occlusion (MCAO) to study IS. Cytokine levels were detected by enzyme-linked immunosorbent assay. Morphological changes were observed with immunohistochemical staining and hematoxylin-eosin staining. The circ_22232/miR-847-3p/Bmp1 axis was found to be highly correlated with neutrophil-associated neuroinflammation in cerebral tissue of mice. Immunohistochemical showed a progressive increase in the proportion of neutrophils after IS. In in vivo experiments, the circ_22232 knockdown alleviated cerebral injury by reducing the activation of neutrophils and inflammatory cytokine production. This suggests that circ_22232 is associated with inflammation, which may serve as a potential therapeutic target for IS.

Ferulic acid (FA) is a bioactive compound found in traditional Chinese herbal medicine; for example, it is present in Xinjiang Ferula, but also in strong-flavor Chinese baijiu. FA has been shown to play a crucial role in treating oxidative stress, skin whitening, and eye diseases. In this study, the potential role of FA as a means of inducing apoptosis and inhibiting colon cancer induced by the transplantation of CT26 cells was investigated. The results show that FA adjuvant treatment caused an upregulation in the expression of genes related to autophagy while simultaneously suppressing the expression of inflammatory response elements and improving the bodyweight, glutamic pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST) in vivo. Furthermore, FA inhibited the proliferation of CT26 cells and induced apoptosis, specifically by activating the phosphorylation of ERK and JNK to enhance the essential proteins BCL-2 and BAX in the apoptosis pathway. These results suggest that FA could be a promising auxiliary therapeutic agent for the treatment of colon cancer. Further research is needed to better understand the mechanisms underlying the beneficial effects of FA and its synergistic effects with other compounds.

A nanofluidic system consists of a nano-porous medium and functional liquid, which demonstrates a higher energy absorption density compared to conventional systems for energy absorption. Alterations in the composition of the functional liquid can significantly impact the properties of a nanofluidic system. In this paper, the widely used zeolite ZSM-5 was chosen as the porous medium to establish a nanofluidic system. Three distinct electrolyte solutions, namely KCl aqueous solutions, NaCl aqueous solutions and MgCl 2 aqueous solutions were employed as functional liquids while pure water served as the reference condition for configuring four kinds of nanofluidic systems. Pressure-induced percolation experiments were performed on the four zeolite-based systems. The difference in the infiltration process between the electrolyte solution systems and the deionized water system has been ascertained. The effect of the ion size on the infiltration and defiltration process has been determined. The results show that the introduction of ions induces a hydration effect, resulting in a higher critical infiltration pressure of the electrolyte solution system compared to an aqueous solution system. The magnitude of cation charge directly correlates with the strength of the hydration effect and the corresponding increase in critical infiltration pressure. Upon entering the nanochannel, the liquid infiltrates primarily in the form of ions rather than a cation hydration form. The larger the ion size, the shallower the penetration depth after entering the nanopore channel and the larger the corresponding relative outflow rate. The present work will provide valuable theoretical complementary and experimental data support for nanofluidic system applications.

Tertiary lymphoid structure (TLS) represents lymphocyte clusters in non-lymphoid organs. The formation and maintenance of TLS are dependent on follicular helper T (TFH) cells. However, the role of TFH cells during renal TLS formation and the renal fibrotic process has not been comprehensively elucidated in chronic kidney disease. Here, we detected the circulating TFH cells from 57 IgAN patients and found that the frequency of TFH cells was increased in IgA nephropathy patients with renal TLS and also increased in renal tissues from the ischemic-reperfusion-injury (IRI)-induced TLS model. The inducible T-cell co-stimulator (ICOS) is one of the surface marker molecules of TFH. Remarkably, the application of an ICOS-neutralizing antibody effectively prevented the upregulation of TFH cells and expression of its canonical functional mediator IL-21, and also reduced renal TLS formation and renal fibrosis in IRI mice in vivo. In the study of this mechanism, we found that recombinant IL-21 could directly promote renal fibrosis and the expression of p65. Furthermore, BAY 11-7085, a p65 selective inhibitor, could effectively alleviate the profibrotic effect induced by IL-21 stimulation. Our results together suggested that TFH cells contribute to TLS formation and renal fibrosis by IL-21. Targeting the ICOS-signaling pathway network could reduce TFH cell infiltration and alleviate renal fibrosis.

Mangoes ( Mangifera indica L.) are an important kind of perennial fruit tree, but their biochemical testing method and transformation technology were insufficient and had not been rigorously explored. The protoplast technology is an excellent method for creating a rapid and effective tool for transient expression and transformation assays, particularly in plants that lack an Agrobacterium-mediated plant transformation system. This study optimized the conditions of the protoplast isolation and transformation system, which can provide a lot of help in the gene expression regulation study of mango. The most beneficial protoplast isolation conditions were 150 mg/mL of cellulase R-10 and 180 mg/mL of macerozyme R-10 in the digestion solution at pH 5.6 and 12 h of digestion time. The 0.16 M and 0.08 M mannitol in wash solution (WI) and suspension for counting (MMG), respectively, were optimal for the protoplast isolation yield. The isolated leaf protoplasts (~5.4 × 10 5 cells/10 mL) were transfected for 30 min mediated by 40% calcium-chloride-based polyethylene glycol (PEG)-4000-CaCl 2 , from which 84.38% of the protoplasts were transformed. About 0.08 M and 0.12 M of mannitol concentration in MMG and transfection solutions, respectively, were optimal for protoplast viability. Under the florescence signal, GFP was seen in the transformed protoplasts. This showed that the target gene was successfully induced into the protoplast and that it can be transcribed and translated. Experimental results in this paper show that our high-efficiency protoplast isolation and PEG-mediated transformation protocols can provide excellent new methods for creating a rapid and effective tool for the molecular mechanism study of mangoes.

Recent technological progress is opening up practical applications for quadruped robots. In this context, comprehensive performance demands, including speed, payload, robustness, terrain adaptability, endurance, and techno-economics, are increasing. However, design conflicts inevitably exist among these performance indicators, highlighting design challenges, especially for a heavy-duty, electrically actuated quadruped robots, which are strongly constrained by motor torque density and battery energy density. Starting from task-specific holistic system thinking, in this paper, we present a novel task-oriented approach to the design of such kind of robots, incorporating hierarchical optimization and a control-in-the-loop design, while following a structured design path that effectively exploits the strengths of both heuristic and computational designs. Guided by these philosophies, we utilize heuristic design to obtain the approximate initial form of the prototype and propose a key task-oriented actuator joint configuration, utilizing commercially available components. Subsequently, we build a step-wise analytical models considering trajectory optimization and motor heat constraints for optimization of leg length and joint match parameters to achieve a compact performance requirement envelope and minimize redundancy in the construction of task-specific components. Furthermore, we construct a holistic simulation platform with a module control algorithm for typical scenarios to evaluate subsystem results and adjust design parameters iteratively, balancing conflicts and eventually achieving a reliable design specification for detailed subsystem design. Based on these strategies, we develop a heavy-duty electric prototype achieving a maximum speed of 2 m/s in trotting gait with a load weighting over 160 kg and enduring a period of 2 h. The experiment upon the prototype verifies the efficiency of the proposed approach.

Patients with schizophrenia are afflicted by severe clinical symptoms and serious cognitive dysfunction. The aim of this study is to investigate the potential relationships between clinical symptoms and empathy and their variations between overweight and non-overweight schizophrenia patients. To address this problem, a group of 776 inpatients diagnosed with chronic schizophrenia (504 overweight patients and 272 non-overweight patients) was recruited. The Positive and Negative Syndrome Scale (PANSS) and its five-factor model were employed to assess clinical symptoms, while empathy levels were measured using the Interpersonal Reactivity Index (IRI). The overweight patients had lower education levels but higher positive symptoms than the non-overweight patients (all p < 0.05). In addition, the overweight patients performed significantly better with respect to empathy (FDR-corrected p < 0.05). Additional multiple regression analyses indicated significant associations between the total score of the IRI and PANSS negative symptoms, gender, and family history of psychiatric disorders among the overweight group; among non-overweight patients, there was a significant correlation between suicide and the total score of the IRI. This study provides evidence suggesting that chronic schizophrenia patients who are overweight may have distinct clinical characteristics, particularly with respect to their empathy, compared with non-overweight patients. Moreover, different variables are associated with empathy in different groups.

This study evaluated the protective effect of Bacillus subtilis HH2 on beagles orally challenged with enterotoxigenic Escherichia coli (ETEC). We assessed the physiological parameters and the severity of diarrhea, as well as the changes in three serum immunoglobulins (IgG, IgA, and IgM), plasma diamine oxidase (DAO), D-lactate (D-LA), and the fecal microbiome. Feeding B. subtilis HH2 significantly reduced the severity of diarrhea after the ETEC challenge ( p < 0.05) and increased serum levels of IgG, IgA, and IgM ( p < 0.01). B. subtilis HH2 administration also reduced serum levels of DAO at 48 h after the ETEC challenge ( p < 0.05), but no significant changes were observed in D-LA ( p > 0.05). Oral ETEC challenge significantly reduced the richness and diversity of gut microbiota in beagles not pre-fed with B. subtilis HH2 ( p < 0.05), while B. subtilis HH2 feeding and oral ETEC challenge significantly altered the gut microbiota structure of beagles ( p < 0.01). Moreover, 14 days of B. subtilis HH2 feeding reduced the relative abundance of Deinococcus - Thermus in feces. This study reveals that B. subtilis HH2 alleviates diarrhea caused by ETEC, enhances non-specific immunity, reduces ETEC-induced damage to the intestinal mucosa, and regulates gut microbiota composition.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by reduced social interactions, impaired communication, and stereotyped behavior. The aim of this research is to investigate the changes in serotonin (5-HT) in the medial prefrontal cortex (PFC) of autism-like offspring induced by maternal lipopolysaccharide (LPS) exposure. Pregnant Sprague-Dawley rats were intraperitoneally injected with LPS to establish an autism-like model in their offspring. Offspring prenatally exposed to LPS showed autism-like behavior. The serotonin level in the mPFC of 2-week-old offspring was noticeably increased after maternal LPS exposure. Differentially expressed genes (DEGs) were enriched in pathways related to tryptophan metabolism and the serotonin system, as shown in RNA-seq findings. Consistently, tryptophan and serotonin metabolisms were altered in 2-week-old LPS-exposed offspring. The mRNA expression levels of 5-HT catabolic enzymes were remarkably reduced or tended to decrease. Moreover, maternal LPS exposure resulted in a higher serotonin 1B receptor (5-HT 1B R) expression level in the mPFC but no difference in tryptophan hydroxylase 2 (TPH2) or serotonin reuptake transporter (SERT). The concentrations of 5-HT in serum and colon were increased in LPS-exposed offspring. Meanwhile, the expression level of tryptophan hydroxylase 1 (TPH1) in the colon was increased after maternal LPS treatment, whereas SERT was reduced. Furthermore, Golgi-Cox staining showed that neuronal dendritic length and spine density were significantly reduced in the mPFC of LPS-exposed offspring. The current study reveals that maternal LPS treatment resulted in an exaltation of the 5-HT of mPFC in ASD-like young rats, which may partly be caused by the abnormal elevation of 5-HT metabolism in its colon.

Skin interstitial fluid (ISF) has emerged as a fungible biofluid sample for blood serum and plasma for disease diagnosis and therapy. The sampling of skin ISF is highly desirable considering its easy accessibility, no damage to blood vessels, and reduced risk of infection. Particularly, skin ISF can be sampled using microneedle (MN)-based platforms in the skin tissues, which exhibit multiple advantages including minimal invasion of the skin tissues, less pain, ease of carrying, capacity for continuous monitoring, etc. In this review, we focus on the current development of microneedle-integrated transdermal sensors for collecting ISF and detecting specific disease biomarkers. Firstly, we discussed and classified microneedles according to their structural design, including solid MNs, hollow MNs, porous MNs, and coated MNs. Subsequently, we elaborate on the construction of MN-integrated sensors for metabolic analysis with highlights on the electrochemical, fluorescent, chemical chromogenic, immunodiagnostic, and molecular diagnostic MN-integrated sensors. Finally, we discuss the current challenges and future direction for developing MN-based platforms for ISF extraction and sensing applications.

GPR126/ADGRG6, a member of the adhesion G-protein-coupled receptor family, balances cell differentiation and proliferation through fine-tuning of intracellular cAMP levels, which is achieved through coupling to Gs and Gi proteins. While GPR126-mediated cAMP increase has been proven to be essential for differentiation of Schwann cells, adipocytes and osteoblasts, Gi-signaling of the receptor was found to propagate breast cancer cell proliferation. Extracellular ligands or mechanical forces can modulate GPR126 activity but require an intact encrypted agonist sequence, coined the Stachel . Even though coupling to Gi can be seen for constitutively active truncated receptor versions of GPR126 as well as with a peptide agonist derived from the Stachel sequence, all known N-terminal modulators have so far only been shown to modulate Gs coupling. Here, we identified collagen VI as the first extracellular matrix ligand of GPR126 that induces Gi signaling at the receptor, which shows that N-terminal binding partners can mediate selective G protein signaling cascades that are masked by fully active truncated receptor variants.

Tobacco mosaic virus (TMV) is a systemic virus that poses a serious threat to crops worldwide. In the present study, a series of novel 1-phenyl-4-(1,3,4-thiadiazole-5-thioether)-1 H -pyrazole-5-amine derivatives was designed and synthesized. In vivo antiviral bioassay results indicated that some of these compounds exhibited excellent protective activity against TMV. Among the compounds, E 2 (EC 50 = 203.5 μg/mL) was superior to the commercial agent ningnanmycin (EC 50 = 261.4 μg/mL). Observation of tobacco leaves infected with TMV-GFP revealed that E 2 could effectively inhibit the spread of TMV in the host. Further plant tissue morphological observation indicated that E 2 could induce the tight arrangement and alignment of the spongy mesophyll and palisade cells while causing stomatal closure to form a defensive barrier to prevent viral infection in the leaves. In addition, the chlorophyll content of tobacco leaves was significantly increased after treatment with E 2 , and the net photosynthesis ( Pn ) value was also increased, which demonstrated that the active compound could improve the photosynthetic efficiency of TMV-infected tobacco leaves by maintaining stable chlorophyll content in the leaves, thereby protecting host plants from viral infection. The results of MDA and H 2 O 2 content determination revealed that E 2 could effectively reduce the content of peroxides in the infected plants, reducing the damage to the plants caused by oxidation. This work provides an important support for the research and development of antiviral agents in crop protection.

Polypropylene film is the most important organic dielectric in capacitor technology; however, applications such as power electronic devices require more miniaturized capacitors and thinner dielectric films. The commercial biaxially oriented polypropylene film is losing the advantage of its high breakdown strength as it becomes thinner. This work carefully studies the breakdown strength of the film between 1 and 5 microns. The breakdown strength drops rapidly and hardly ensures that the capacitor reaches a volumetric energy density of 2 J/cm 3 . Differential scanning calorimetry, X-ray, and SEM analyses showed that this phenomenon has nothing to do with the crystallographic orientation and crystallinity of the film but is closely related to the non-uniform fibers and many voids produced by overstretching the film. Measures must be taken to avoid their premature breakdown due to high local electric fields. An improvement below 5 microns will maintain a high energy density and the important application of polypropylene films in capacitors. Without destroying the physical properties of commercial films, this work employs the ALD oxide coating scheme to augment the dielectric strength of a BOPP in the thickness range below 5 μm, especially its high temperature performance. Therefore, the problem of the reduction in dielectric strength and energy density caused by BOPP thinning can be alleviated.

With increasing human awareness of food safety, the replacement of highly toxic pesticides with biocompatible antimicrobials has become a trend. This study proposes a biocontrol microneedle (BMN) to expand the application of the food-grade preservative epsilon-poly-L-lysine (ε-PL) in fruit preservatives by utilizing a dissolving microneedle system. The macromolecular polymer ε-PL not only possesses broad-spectrum antimicrobial activity but also exhibits good mechanical properties. With the addition of a small amount of polyvinyl alcohol, the mechanical strength of the ε-PL-based microneedle patch could be further improved to achieve an enhanced failure force of needles at 1.6 N/needle and induce an approximately 96% insertion rate in citrus fruit pericarps. An ex vivo insertion test revealed that the microneedle tips could be effectively inserted into the citrus fruit pericarp, rapidly dissolve within 3 min, and produce inconspicuous needle holes. Moreover, the high drug loading capacity of BMN was observed to reach approximately 1890 μg/patch, which is essential for enhancing the concentration-dependent antifungal activity of ε-PL. The drug distribution study has confirmed the feasibility of mediating the local diffusion of EPL in the pericarp through BMN. Therefore, BMN has great potential to reduce the incidence of invasive fungal infections in local areas of citrus fruit pericarp.

Laboratory tests were carried out in accordance with ASTM C664-10(2020) to measure diffusion parameters in an asphalt mixture. These diffusion parameters are effective measures for use in asphalt mixtures. However, the tests could not provide detailed images of the water vapour distribution in the asphalt mixture. To solve this problem, this study provides a method for establishing a numerical model of moisture diffusion in an asphalt mixture, and gives a more detailed picture of the water vapour movement inside the asphalt mixture. Through numerical simulation results obtained under different external conditions, it was demonstrated that water molecules were mainly concentrated in medium III after 100 days of diffusion. After 1000 days of diffusion, the water molecules gradually penetrated the asphalt film in the aggregate particles. Additionally, the water vapour concentrations in the asphalt mixture varied significantly from spot to spot, and various concentration gradients were formed at different locations. These findings revealed that water vapour concentrations in an asphalt mixture vary significantly from spot to spot, forming various concentration gradients at different locations. These findings will be helpful in revealing the mechanism of water damage caused by moisture in asphalt mixtures.

Nucleocytoplasmic transport receptors play key roles in the nuclear translocation of disease resistance proteins, but the associated mechanisms remain unclear. The Arabidopsis thaliana gene SAD2 encodes an importin β-like protein. A transgenic Arabidopsis line overexpressing SAD2 (OESAD2/Col-0) showed obvious resistance to Pseudomonas syringae pv. tomato DC3000 ( Pst DC3000) compared to the wild type (Col-0), but the knockout mutant sad2-5 was susceptible. Transcriptomic analysis was then performed on Col-0, OESAD2/Col-0, and sad2-5 leaves at 0, 1, 2, and 3 days post-inoculation with Pst DC3000. A total of 1825 differentially expressed genes (DEGs) were identified as putative biotic stress defense genes regulated by SAD2, 45 of which overlapped between the SAD2 knockout and overexpression datasets. Gene Ontology (GO) analysis indicated that the DEGs were broadly involved in single-organism cellular metabolic processes and in response to stimulatory stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) biochemical pathway analysis revealed that many of the DEGs were associated with the biosynthesis of flavonoids and other specialized metabolites. Transcription factor analysis showed that a large number of ERF/AP2, MYB, and bHLH transcription factors were involved in SAD2-mediated plant disease resistance. These results provide a basis for future exploration of the molecular mechanisms associated with SAD2-mediated disease resistance and establish a set of key candidate disease resistance genes.

Electric Vehicle (EV) charging demand and charging station availability forecasting is one of the challenges in the intelligent transportation system. With accurate EV station availability prediction, suitable charging behaviors can be scheduled in advance to relieve range anxiety. Many existing deep learning methods have been proposed to address this issue; however, due to the complex road network structure and complex external factors, such as points of interest (POIs) and weather effects, many commonly used algorithms can only extract the historical usage information and do not consider the comprehensive influence of external factors. To enhance the prediction accuracy and interpretability, the Attribute-Augmented Spatiotemporal Graph Informer (AST-GIN) structure is proposed in this study by combining the Graph Convolutional Network (GCN) layer and the Informer layer to extract both the external and internal spatiotemporal dependence of relevant transportation data. The external factors are modeled as dynamic attributes by the attributeaugmented encoder for training. The AST-GIN model was tested on the data collected in Dundee City, and the experimental results showed the effectiveness of our model considering external factors' influence on various horizon settings compared with other baselines.

To systematically review the effects of Tai chi on sleep quality, depression, and anxiety in patients with insomnia. The electronic databases including PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), WanFang Data, Chinese Biomedical Literature Database (CBM), and VIP Database for Chinese Technical Periodicals (VIP) were retrieved and screened by computer. Randomized controlled trials (RCT) on patients with insomnia who practiced Tai chi were collected, and the RCT risk of bias assessment criteria was used to evaluate the methodological quality of the included studies. The combined effect size was expressed as the weighted mean difference (WMD), with a confidence interval of 95% (CI). Review Manager 5.4 and Stata16.0 were used for heterogeneity analysis and sensitivity analysis. Tai chi reduced the patients' Pittsburgh sleep quality index (PSQI) score (WMD = -1.75, 95% CI: -1.88, -1.62, p < 0.001); Hamilton depression scale (HAMD) score (WMD = -5.08, 95% CI: -5.46, -4.69, p < 0.001), Hamilton anxiety scale (HAMA) score (WMD = -2.18, 95% CI: -2.98, -1.37, p < 0.001), and self-rating anxiety scale (SAS) score (WMD = -7.01, 95% CI: -7.72, -6.29, p < 0.001). Tai chi exercise has a good preventive and ameliorating effect on insomnia, which can relieve patients' depression and anxiety, simultaneously enhancing various functions of the body. However, most of the included studies reported random assignment with some lack of specific descriptions, and the blinding of participants was difficult to achieve due to the nature of exercise, which may cause bias. Therefore, more high-quality, multi-center, and bigger-sample studies need to be included in the future to further verify the results.

Dendritic cells (DCs) play key roles in promoting wound healing after myocardial infarction (MI). Our previous studies have shown that exosomes derived from DCs (DEXs) could migrate to lymphoid tissue and improve cardiac function post-MI by activating CD4 + T cells; however, the mechanism of DEXs' migration to lymphoid tissue and the improvement of cardiac function are still unknown. In our study, we found that CCR7 expression significantly increased in MI-DEXs compared with control-DEXs; meanwhile, CCL19 and CCL21, the ligands of CCR7, significantly increased in the serum of MI-model mice. Subsequently, we overexpressed and knocked down CCR7 in MI-DEXs and found that overexpressed CCR7 enhanced the migration of MI-DEXs to the spleen; however, CCR7 knockdown attenuated MI-DEXs' migration according to near-IR fluorescence imaging. Furthermore, overexpressed CCR7 in MI-DEXs enhanced the MI-DEXs' improvement of cardiac function after MI; however, CCR7-knockdown MI-DEXs attenuated this improvement. In addition, after DEXs' migration to the spleen, MI-DEXs activated CD4 + T cells and induced the expression of IL-4 and IL-10, which were significantly increased in the MI-DEX group compared with the control group. In conclusion, CCR7 could mediate DEXs' migration to the spleen and improve cardiac function after MI, and we found that the mechanism was partly via activation of CD4 + T cells and secretion of IL-4 and IL-10. Our study presented an innovative method for improving cardiac function by enhancing the migration ability of MI-DEXs after MI, while CCR7 could be a potential candidate for MI-DEX bioengineering to enhance migration.

Chemically modified mRNA (modRNA) has proven to be a versatile tool for the treatment of various cancers and infectious diseases due to recent technological advancements. However, a safe and effective delivery system to overcome the complex extracellular and intracellular barriers is required in order to achieve higher therapeutic efficacy and broaden clinical applications. Here, we explored All-Fect and Leu-Fect C as novel transfection reagents derived from lipopolymers, which demonstrated excellent biocompatibility, efficient delivery capabilities, and a robust ability to escape the lysosomes. These properties directly increase mRNA stability by preventing mRNA degradation by nucleases and simultaneously promote efficient gene translation in vitro and in vivo. The modRNA delivered with lipopolymer vectors sustained effective transfection in mouse hearts following direct intramyocardial injection, as well as in major organs (liver and spleen) after systemic administration. No observable immune reactions or systemic toxicity were detected following the systemic administration of lipopolymer-mRNA complexes to additional solid organs. This study identified commercial reagents for the effective delivery of modRNA and may help facilitate the advancement of gene-based interventions involving the safe and effective delivery of nucleic acid drug substances.

Parenting styles are crucial in the process of forming social emotions in children. They are also vital for creating effective family policies in order to improve a child's early development. As such, it is important to acknowledge the enduring association of parenting styles across generations, as well as their impact on early child development. In this study, the question as to whether the warm and hostile parenting styles of a parent/grandparent mediate the relationships between the emotional warmth and rejection parenting styles of a grandparent/great grandparent, as well as the subsequent social-emotional development of a grandson/great grandson and/or a granddaughter/great granddaughter, was examined. Cross-sectional assessment data from 194 primary caregivers of children between 6 and 36 months were analyzed using mediation analyses. In addition, moderated mediation models were used to test heterogeneity effects. This study found evidence that the warm and hostile parenting styles of a parent/grandparent mediated the associations between the emotional warmth and rejection parenting styles of a grandparent/great grandparent, as well as the subsequent socio-emotional development of a grandchild/great grandchild. Parents/grandparents tend to use a warm parenting style when the child is a boy, thereby resulting in fewer socio-emotional problems. This study provides empirical evidence for the purposes of preventive services to improve caregivers' parenting styles in the early stages of a child's development. Researchers and family practitioners should continue to support families with intervention or therapeutic techniques in order to mitigate potential lasting consequences.

Eleven monoterpenoid indole alkaloids, including three new ones, tabercrassines A-C ( 1 - 3 ), were isolated from the seeds of Tabernaemontana crassa . Tabercrassine A ( 1 ) is an ibogan-ibogan-type bisindole alkaloid which is formed by the polymerization of two classic ibogan-type monomers through a C3 unit aliphatic chain. Their structures were established by extensive analysis of HRESIMS, NMR, and ECD spectra. Cellular assays showed that alkaloids 1 - 3 all reduce A β 42 production and inhibit phospho-tau (Thr217), a new biomarker of Alzheimer's disease [AD] associated with BACE1-, NCSTN-, GSK3β-, and CDK5-mediated pathways, suggesting these alkaloids' potential against AD.

Ten jatrophane diterpenoids were isolated from the whole plant Euphorbia peplus Linn. including seven new ones, named euphjatrophanes A-G (labeled compounds 1 , 2 , 4 - 8 ). Their structures were elucidated with a combination of spectroscopic and single-crystal X-ray crystallography, enabling the identification of compounds 3 , 9 , and 10 as the previously published euphpepluones G, K, and L, respectively. All compounds were evaluated for their bioactivity with flow cytometry in assays of autophagic flux in HM Cherry-GFP-LC3 (human microglia cells stably expressing the tandem monomeric mCherry-GFP-tagged LC3) cells. Euphpepluone K ( 9 ) significantly activated autophagic flux, an effect that was verified with confocal analysis. Moreover, cellular assays showed that euphpepluone K ( 9 ) induced autophagy and inhibited Tau pathology.

Even with the ubiquitous sensing data in intelligent transportation systems, such as the mobile sensing of vehicle trajectories, traffic estimation is still faced with the data missing problem due to the detector faults or limited number of probe vehicles as mobile sensors. Such data missing issue poses an obstacle for many further explorations, e.g., the link-based traffic status modeling. Although many studies have focused on tackling this kind of problem, existing studies mainly focus on the situation in which data are missing at random and ignore the distinction between links of missing data. In the practical scenario, traffic speed data are always missing not at random (MNAR). The distinction for recovering missing data on different links has not been studied yet. In this paper, we propose a general linear model based on probabilistic principal component analysis (PPCA) for solving MNAR traffic speed data imputation. Furthermore, we propose a metric, i.e., Pearson score (p-score), for distinguishing links and investigate how the model performs on links with different p-score values. Experimental results show that the new model outperforms the typically used PPCA model, and missing data on links with higher p-score values can be better recovered.

P3b is an event-related potential (ERP) that may be abnormal in patients with tic disorders (TD), but evidence has been inconsistent. Given the possible association between P3b and TD and the need for biomarkers for TD, the primary objective of this meta-analysis was to characterize P3b in patients with TD in comparison to healthy controls (HCs)., Methods: By searching PubMed, Embase, Web of Science, SCOPUS, Medline, and Google Scholar, we identified studies that compared P3b between TD patients and HCs. The amplitude and latency of P3b were then analyzed. Subgroup analyses were conducted to investigate the influence of different experimental factors on P3b indices., Result: Overall, 19 articles involving 388 cases and 414 controls were evaluated. There were no significant abnormalities in P3b amplitude and latency in TD patients. The P3b amplitude of the TD patients was significantly decreased during the oddball task, and the P3b amplitude of the adult TD patients was also significantly decreased., Conclusion: TD patients may have an abnormal P3b compared to HCs under specified conditions.

Clostridium perfringens beta2 (CPB2) toxin is one of the main pathogenic toxins produced by Clostridium perfringens , which causes intestinal diseases in animals and humans. The N6-methyladenosine (m6A) modification is the most common reversible modification in eukaryotic disease processes. Methyltransferase-like 3 (METTL3) regulates immunity and inflammatory responses induced by the bacterial infections in animals. However, METTL3's involvement in CPB2-treated intestinal porcine epithelial cell line-J2 (IPEC-J2) remains unclear. In the current study, we used methylated RNA immunoprecipitation-quantitative polymerase chain reaction, Western blotting and immunofluorescence assay to determine the role of METTL3 in CPB2-exposed IPEC-J2 cells. The findings revealed that m6A and METTL3 levels were increased in CPB2 treated IPEC-J2 cells. Functionally, METTL3 overexpression promoted the release of inflammatory factors, increased cytotoxicity, decreased cell viability and disrupted tight junctions between cells, while the knockdown of METTL3 reversed these results. Furthermore, METTL3 was involved in the inflammatory response of IPEC-J2 cells by activating the TLR2/NF-κB signaling pathway through regulating TLR2 m6A levels. In conclusion, METTL3 overexpression triggered the TLR2/NF-κB signaling pathway and promoted CPB2-induced inflammatory responses in IPEC-J2 cells. These findings may provide a new strategy for the prevention and treatment of diarrhea caused by Clostridium perfringens .

Liposarcoma (LPS) is a rare and heterogeneous malignancy of adipocytic origin. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes, showing similar genetic characterizations but distinct biological behaviors and clinical prognosis. Compared to WDLPS, DDLPS is more aggressive and has the potential of metastasis, as the malignant adipocytic tumor's metabolic changes may have taken place during the tumorigenesis of LPSs. Therefore, to investigate the lipid alterations between the two subtypes, high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) based untargeted lipidomic analysis was performed onto LPS tissues from 6 WDLPS and 7 DDLPS patients. The lipidomic analysis showed the upregulated phosphatidylcholines and phosphoethanolamines in DDLPS, and the upregulated triglycerides and diglycerides in WDLPS, which might be due to the uncompleted adipocytic dedifferentiation leading to such tumorigenesis. Such a finding was also confirmed by the similarity comparison of two LPS subtypes to the transcriptome of stromal vascular fraction at different differentiation stages. Transcriptomic analysis also demonstrated that metabolic pathways including the pentose phosphate pathway (PPP) were upregulated in WDLPS compared to DDLPS. Therefore, the cell line LPS853 was treated with the PPP inhibitor 6-aminonicotinamide ex vivo and the proliferation and invasion of LPS853 was significantly promoted by PPP inhibition, suggesting the potential role of PPP in the development and differentiation of LPS. In conclusion, this study described the altered lipid profiles of WDLPS and DDLPS for the first time, revealing the different differentiation stages of the two subtypes and providing a potential metabolic target for LPS treatment.

With the increasing use of underground cables, the quantity and quality of intermediate joints demanded are also increasing. The quality of the traditional crimping intermediate joint is easily affected by the actual process of the operator, which may lead to the heating of the crimping part of the wire core, affecting the insulation performance of the cable, and finally causing the joint to break. However, aluminothermic reactive technology has some problems, such as a high welding temperature and an uncontrollable reaction. In order to solve these problems, according to the brazing principle and microalloying method, the optimal content of In in Sn-1.5Cu-based solder was explored, and then the connection of the middle joint of a 10 kV cable was completed using a connecting die and electrical connection process. The contact resistance and tensile strength of the joint were tested to verify the feasibility of this method. The results show that the maximum conductivity of the solder with 3.8% and 5% In content can reach 3.236 × 10 6 S/m, and the highest wettability is 93.6%. Finally, the minimum contact resistance of the intermediate joint is 7.05 μΩ, which is 43% lower than that of the aluminothermic welded joint, and the tensile strength is close to that of the welded joint, with a maximum of 7174 N.

Apart from the well-established role of the gonadotropin-inhibitory hormone (GnIH) in the regulation of the reproductive functions, much less is known about the peripheral role of the GnIH and its receptor in the metabolic processes. On account of pig being an excellent model for studies of food intake and obesity in humans, we investigated the peripheral effects of the GnIH on food intake and energy homeostasis and revealed the underlying mechanism(s) in female piglets in vivo. Compared to the vehicle-treated group, intraperitoneally injected GnIH significantly increased the food intake and altered the meal microstructure both in the fasting and ad libitum female piglet. GnIH-triggered hyperphagia induced female piglet obesity and altered islet hormone secretion in the pancreas, accompanied with dyslipidemia and hyperglycemia. Interestingly, GnIH decreased the glucose transport capacity and glycogen synthesis, whereas it increased the gluconeogenesis in the liver, while it also induced an insulin resistance in white adipose tissue (WAT) via inhibiting the activity of AKT-GSK3-β signaling. In terms of the lipid metabolism, GnIH reduced the oxidation of fatty acids, whereas the elevated fat synthesis ability in the liver and WAT was developed though the inhibited AMPK phosphorylation. Our findings demonstrate that peripheral GnIH could trigger hyperphagia-induced obesity and an associated glycolipid metabolism disorder in female piglets, suggesting that GnIH may act as a potential therapeutic agent for metabolic syndrome, obesity and diabetes.

HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) area key component of the current HIV-1 combination drug regimens. Although they exhibit potent anti-HIV-1 activity and modest toxicity, the emergence of mutant strains limits their application in clinical. Our previous research efforts contributed to the identification of compound K-5a2, which exhibits nanomolar activity in HIV-1-infected MT-4 cells. In this study, K-5a2 was shown to have a high level of anti-HIV-1 activity against various lab-adapted strains and clinical isolate strains, being comparable to ETR. Moreover, we showed the feasibility of K-5a2 as a preclinical anti-HIV-1 candidate by establishing its synergistic or additive anti-HIV-1 activity in combination with other representative anti-HIV-1 drugs and candidates. In addition, K-5a2 exhibited no inhibitory activity to the primary CYP isoforms and favorable pharmacokinetics. Taken together, its robust anti-HIV-1 potency, synergistic or additive effects with other anti-HIV drugs, and favorable pharmacokinetic and safety profiles make K-5a2 a potent alternative drug for HIV/AIDS treatment., Competing Interests: The authors declare no conflicts of interest.

In order to evaluate and improve the deformation behavior of cement-emulsified asphalt binder (CA) in cement-emulsified asphalt mixture, this study investigated the reinforcement of small additions of fibers (2%, 4%, and 6% addition by mass of cement) on the deformation resistance of CA. A repeated creep recovery test was implemented that measures the recovery rate of creep deformation and accumulated strain. Further, an improved piecewise curve-fitting method was used to determine the parameters of Burgers model, then the creep compliances were fitted and calculated. The results show the repeated creep recovery test to be a suitable method for obtaining useful information about creep and recovery deformation of fiber-reinforced CA. The influence of fiber types and dosages on the deformation recovery ability is determined based on the creep recovery ratio and accumulated strain. The improved piecewise curve-fitting method has high accuracy. Thereafter, the reinforcement effect was analyzed through the evolution of creep compliance under loading. Therefore, this paper can provide a reference for enhancing the properties of cement-emulsified asphalt mixture by maximizing the fiber reinforcement.

The coronavirus disease 2019 (COVID-19) pandemic has posed a profound psychological impact on healthcare workers. However, the role of positive affect in moderating the effect of perceived stress on the psychological states of healthcare workers remains unknown. This study aimed to analyze the moderating effect of positive affect on the association between stress and the mental health of healthcare workers during the COVID-19 pandemic. This cross-sectional study evaluated the relationships between perceived stress (the Perceived Stress Scale), positive affect (the Positive and Negative Affect Schedule), depression (the Patient Health Questionnaire-9), and anxiety (the Generalized Anxiety Disorder 7-item Scale) during the COVID-19 pandemic in 644 Chinese healthcare workers who completed online self-reports. The results revealed a significant negative association between positive affect and psychological problems, including stress, depression, and anxiety. At the total group level, multiple regression analysis showed that positive affect alleviated the influence of perceived stress on depression, but no significant moderating effect was found for anxiety. In the subgroups divided by perceived stress, the moderating effect of positive affect on depression was only significant in healthcare workers with a high level of perceived stress. These results suggested that positive affect played a moderative role in alleviating the effect of stress on depression among healthcare workers, particularly those with a high level of stress, thus emphasizing the importance of positive affect as an intervention strategy for promoting the mental health of healthcare workers in the context of the ongoing COVID-19 pandemic.

Aspongopus chinensis Dallas is used as a traditional Chinese medicine as well as an edible insect. Although its anti-tumor effects have been observed, the anti-tumor active component(s) in the hemolymph of A. chinensis remains unknown. In this study, a combination usage of ultrafiltration, gel filtration chromatography, FPLC and RP-HPLC to separate and purify active peptides was performed based on the proliferation of the human gastric cancer SGC-7901 cell line treated with candidates. One peptide (MW = 2853.3 Da) was isolated from the hemolymph of A. chinensis. A total of 24 amino acid residues were continuously determined for the active peptide: N'-ECGYCAEKGIRCDDIHCCTGLKKK-C'. In conclusion, a peptide that can inhibit the proliferation of gastric cancer SGC-7901 cells in the hemolymph of A. chinensis was purified in this study, which is homologous to members of the spider toxin protein family. These results should facilitate further works for this peptide, such as the cloning of genes, expression in vitro by prokaryotic or eukaryotic systems, more specific tests of anti-tumor activity, and so on.

Right ventricular failure (RVF) is the most important prognostic factor for morbidity and mortality in pulmonary arterial hypertension (PAH) or pulmonary hypertension (PH) caused by left heart diseases. However, right ventricle (RV) remodeling is understudied and not targeted by specific therapies. This can be partly explained by the lack of basic knowledge of RV remodeling. Since the physiology and hemodynamic function of the RV differ from those of the left ventricle (LV), the mechanisms of LV dysfunction cannot be generalized to that of the RV, albeit a knowledge of these being helpful to understanding RV remodeling and dysfunction. Store-operated Ca 2+ entry (SOCE) has recently emerged to participate in the LV cardiomyocyte Ca 2+ homeostasis and as a critical player in Ca 2+ mishandling in a pathological context. In this paper, we highlight the current knowledge on the SOCE contribution to the LV and RV dysfunctions, as SOCE molecules are present in both compartments. he relative lack of studies on RV dysfunction indicates the necessity of further investigations, a significant challenge over the coming years.

Background: Apathy is a common non-motor symptom of Parkinson's disease (PD). The influencing factors of apathy are currently controversial. This study aimed to describe the clinical characteristics of PD-associated apathy and to analyze the associated risk factors., Methods: Two hundred patients diagnosed with PD were selected. Included patients were divided into an apathetic group and a non-apathetic group. Demographic and clinical data, motor symptoms, non-motor symptoms and medication use of the two groups were assessed., Results: The incidence of apathy was 69%. Demographic and clinical data, motor symptoms, non-motor symptoms and medications use were statistically significant., Conclusions: PD patients with more severe motor symptoms, cognitive impairment, depression, anxiety, RBD, excessive daytime sleep, fatigue, low education level, long disease course, poor quality of life and lower DA dosage are more prone to apathy. Cognitive function, quality of life, educational level, DA and LEDD are independent risk factors for apathy.