Search

Abstract Background Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients. Methods This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients. Results RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71–22.92) versus 9.59 (6.57–13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P 0.7. Conclusion Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.

Abstract Background Since its discovery, severe fever with thrombocytopenia syndrome (SFTS) has been characterized by rapid progression and poor prognosis, and no specific treatment is available. The aim of this study was to investigate the early warning indicators of mortality in SFTS patients. Methods This is a retrospective cross-sectional study. The study subjects were patients who were admitted to the hospital with a confirmed diagnosis of SFTS from January 2023 to October 2023, and their clinical symptoms and signs at the time of admission, as well as the laboratory indexes of the first blood collection after admission were collected, grouped according to the prognosis, and statistically analyzed. Results A total of 141 patients were collected, of which 27 patients died and 114 patients were in the survival group. Through statistical analysis, patients with combined hemorrhagic manifestations, disturbance of consciousness, lymphopenia, elevated lipase, and prolonged thrombin time on admission were independent risk factors for patients’ death. By plotting the working characteristic curve of the subjects, as well as calculating the area under the curve, the results showed that the AUC of lymphopenia count was 0.670, 95% CI (0.563–0.776), P = 0.006; the AUC of elevated serum lipase index was 0.789, 95% CI (0.699–0.878), p

Understanding how the bacteriomes in tuberculous lesions can be influenced by the susceptibility of Mycobacterium tuberculosis (MTB) can provide valuable information for preventing and treating drug resistant tuberculosis (DR-TB). High-throughput 16S rRNA sequencing was employed to analyze the bacteriome in pulmonary TB lesions from 14 patients with DR-TB and 47 patients with drug sensitive tuberculosis (DS-TB), along with 18 normal lung tissues (NT) from 18 lung cancer patients serving as the bacterial baseline. The phylogenetic investigation of communities by reconstruction of unobserved states2 (PICRUSt2) algorithm was utilized to predict bacterial metabolic functions. The major phyla of pulmonary bacteriomes included Proteobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Fusobacteria. Alpha diversity indices, including ACE, Chao1, Shannon and OTU observed, all demonstrated different bacterial communities of DS-TB samples from that of NT samples; while only Shannon indicated difference between DR-TB and NT samples. The analysis of similarity (ANOSIM) showed significantly different bacterial communities within TB lesions compared to NT samples (R = 0.418, p = 0.001). However, difference was not observed between DR-TB and DS-TB samples (ANOSIM, R = 0.069, p = 0.173). The bacterial profiles within each DR-TB individual appeared unique, with no obvious clusters corresponding to drug-resistant phenotypes. Nevertheless, indicator genera identified in DR-TB and DS-TB lesions demonstrated distinctive micro-ecological environments. Most COG functions were enriched in TB lesions, and the most significant one was [J] translation, ribosomal structure and biogenesis. The distinct enrichment patterns of bacterial enzymes in DR-TB and DS-TB lesions suggest that pulmonary bacterial activities can be modulated by the susceptibility of MTB bacilli. This study provides fresh perspectives and strategies for the precise diagnosis and assessment of drug resistance tuberculosis.

Abstract Mechanically robust hydrogel fibers have demonstrated great potential in energy dissipation and shock‐absorbing applications. However, developing such materials that are recyclable, energy‐efficient, and environmentally friendly remains an enormous challenge. Herein, inspired by spider silk, a continuous and scalable method is introduced for spinning a polyacrylamide hydrogel microfiber with a hierarchical sheath‐core structure under ambient conditions. Applying pre‐stretch and twist in the as‐spun hydrogel microfibers results in a tensile strength of 525 MPa, a toughness of 385 MJ m−3, and a damping capacity of 99%, which is attributed to the reinforcement of hydrogen‐bond nanoclusters within the microfiber matrix. Moreover, it maintains both structural and mechanical stability for several days, and can be directly dissolved in water, providing a sustainable spinning dope for re‐spinning into new microfibers. This work provides a new strategy for the spinning of robust and recyclable hydrogel‐based fibrous materials.

Background Wearable technology is used in healthcare to monitor the health of individuals. This study presents an updated systematic literature review of the use of wearable technology in promoting child and adolescent health, accompanied by recommendations for future research. Methods This review focuses on studies involving children and adolescents aged between 2 and 18 years, regardless of their health condition or disabilities. Studies that were published from 2016 to 2024, and which met the inclusion criteria, were extracted from four academic databases (i.e. PubMed, Cochrane, Embase, and Web of Science) using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol. Data on intervention purposes, interventions deployed, intervention duration, measurements, and the main outcomes of the studies were collected. Results A total of 53 studies involving 14,852 participants were reviewed. They focused on various aspects, including the ownership and use of wearable devices ( n = 3), the feasibility ( n = 22), effectiveness ( n = 4), and adherence ( n = 2) of intervention strategies, or a combination of multiple aspects ( n = 22). Among the interventions deployed, Fitbit was the most frequently used, featuring in 26 studies, followed by ActiGraph ( n = 11). In intervention studies, the majority of studies focused on pre-morbidity prevention ( n = 26) and the treatment of illnesses ( n = 20), with limited attention given to postoperative monitoring ( n = 4). Conclusions The use of wearable technology by children and adolescents has proven to be both feasible and effective for health promotion. This systematic review summarizes existing research by exploring the use of wearable technology in promoting health across diverse youth populations, including healthy and unhealthy individuals. It examines health promotion at various stages of the disease continuum, including pre-disease prevention, in-disease treatment, and postoperative monitoring. Additionally, the review provides directions for future research.

Understanding customer sentiment through product reviews is important for businesses aiming to enhance their products and services. Traditional sentiment analysis often struggles to detect the wide range of emotional nuances, particularly those expressed through emojis, in online reviews. To address this challenge, our paper introduces a novel technique called Emoji-Enhanced BERT (EEBERT) based, on the BERT architecture. The Sentiment Adjustment Factor (SAF), created for emoji tokenization with the embeddings layer, is applied to analyze sentiment and emotion within review text content. Sentiments classification is evaluated using three different methods: (1) evaluating the full review text; (2) analyzing the text with emojis; and (3) integrating star ratings and total votes in EEBERT. These methods were fine-tuned using a labeled Amazon product reviews dataset. The approach utilizes a well-vetted dataset comprising approximately 10 million customer reviews from four different categories. This dataset is condensed to 26,818 reviews to only consider emoji contained reviews, covering 3,275 distinct emojis. A systematic approach to classifying reviews and an innovative technique for assessing the emotional semantics of emojis are developed. The proposed model achieves an accuracy of 97.00%, further applies continuous testing via 5-fold cross-validation, achieving an average accuracy of 99.21%, which supports the reliability of the EEBERT model.

As the behavior analysis of human body is more and more used in the fields of intelligent monitoring and motion analysis, it is of great significance to conduct research.The current two-dimensional regression network algorithm models in human motion recognition and estimation do not consider the interrelationships between human joint points, resulting in missing connections between joint points and low accuracy of feature maps. Therefore, this study proposes an improved two-dimensional regression network algorithm model based on local constraints and relational networks, and verifies its effectiveness. The experimental results show that, considering only local constraints, the proportion of the head in the correct key points of the improved algorithm in the wrist joint score is 84.72%, while the comparison algorithm is 84.55%, an increase of 1.17%. The maximum value is 88.7% when the number of regression network modules is 8. In practical applications, the actual label results of indoor and outdoor environments are basically consistent with those of the detected image, but there are errors under indoor occlusion conditions. Considering both local constraints and relational networks, the improved algorithm has variant standard scores of 98.8%, 95.3%, 93.3%, 89.4%, 95.1%, 96.2%, and 94.2% for the correct percentage of 7 joint points, respectively, which are higher than the comparison algorithm. Overall, the proposed two-dimensional regression network algorithm based on local constraints and relationship networks has practicality and effectiveness, which can be effectively applied in practical human motion recognition.

Obesity presents a significant global health challenge, increasing the susceptibility to chronic conditions such as diabetes, cardiovascular disease, and hypertension. Within the context of obesity, lipid metabolism, adipose tissue formation, and inflammation are intricately linked to endoplasmic reticulum stress (ERS). ERS modulates metabolism, insulin signaling, inflammation, as well as cell proliferation and death through the unfolded protein response (UPR) pathway. Serving as a crucial nexus, ERS bridges the functionality of adipose tissue and the inflammatory response. In this review, we comprehensively elucidate the mechanisms by which ERS impacts adipose tissue function and inflammation in obesity, aiming to offer insights into targeting ERS for ameliorating metabolic dysregulation in obesity-associated chronic diseases such as hyperlipidemia, hypertension, fatty liver, and type 2 diabetes.

Abstract Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. Ferroptosis, a new form of cell death, plays a crucial role in the pathogenesis of DN. Renal tubular injury triggered by ferroptosis might be essential in this process. Numerous studies demonstrate that the vitamin D receptor (VDR) exerts beneficial effects by suppressing ferroptosis. However, the underlying mechanism has not been fully elucidated. Thus, they verified the nephroprotective effect of VDR activation and explored the mechanism by which VDR activation suppressed ferroptosis in db/db mice and high glucose‐cultured proximal tubular epithelial cells (PTECs). Paricalcitol (PAR) is a VDR agonist that can mitigate kidney injury and prevent renal dysfunction. PAR treatment could inhibit ferroptosis of PTECs through decreasing iron content, increasing glutathione (GSH) levels, reducing malondialdehyde (MDA) generation, decreasing the expression of positive ferroptosis mediator transferrin receptor 1 (TFR‐1), and enhancing the expression of negative ferroptosis mediators including ferritin heavy chain (FTH‐1), glutathione peroxidase 4 (GPX4), and cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11). Mechanistically, VDR activation upregulated the NFE2‐related factor 2/heme oxygenase‐1 (Nrf2/HO‐1) signaling pathway to suppress ferroptosis in PTECs. These findings suggested that VDR activation inhibited ferroptosis of PTECs in DN via modulating the Nrf2/HO‐1 signaling pathway.

Recently, image generation technology has demonstrated surprising effects. However, precisely recognizing the emotion in sound to accurately express it on the face of a designated person is a huge challenge. To address this challenge, a new framework, Sound to Expression (S2E), which can use the emotion in sound to guide facial expression image generation, is proposed. A speech dataset for emotion recognition is constructed. S2E can edit facial expressions with different emotions in sounds for different people. S2E consists of Continuous Wavelet Transform (CWT), YOLOv3, ChatGPT-3, and facial expression diffusion editing model (FEDEM). CWT is utilized to extract emotional features from different sounds. YOLOv3 is employed to identify the emotion categories. The emotion category and a specific person's name are input into ChatGPT-3 to randomly generate a description of the person and emotion. The description is input into FEDEM to generate a facial expression image. To generate more accurate images and address emotional semantic deviation, a new facial detail emotional preservation loss is proposed. The experimental results show that S2E can accurately recognize the emotion in the voice and use this emotion to guide the editing of the facial expression for the specified person to generate more accurate images.

Plants of the Meliaceae family have long attracted researchers’ interest due to their various insecticidal activities, with triterpenes being the main active ingredients. In this paper, we discuss 93 triterpenoids with insecticidal activity from 37 insecticidal plant species of 15 genera (Munronia, Neobeguea, Pseudocedrela, Nymania, Quivisia, Ruagea, Dysoxylum, Soymida, Lansium, Sandoricum, Walsura, Trichilia, Swietenia, Turraea, and Xylocarpus) in the family Meliaceae. Among these genera, Trichilia deserves further research, with twelve species possessing insecticidal activity. The 93 insecticidal molecules included 27 ring-seco limonoids (comprising 1 ring A-seco group chemical, 1 ring B-seco group chemical, 5 ring D-seco group chemicals, 14 rings A,B-seco group chemicals, 5 rings B,D-seco group chemicals, and 1 rings A,B,D-seco group chemical), 22 ring-intact limonoids (comprising 5 cedrelone-class chemicals, 6 trichilin-class chemicals, 7 havanensin-class chemicals, 2 azadirone-class chemicals, 1 vilasinin-class chemical, and 1 other chemical), 33 2,30-linkage chemicals (comprising 25 mexicanolide-class chemicals and 8 phragmalin-class chemicals), 3 1,n-linkage-group chemicals, 3 onoceranoid-type triterpenoids, 2 apotirucallane-type terpenoids, 2 kokosanolide-type tetranortriterpenoids, and 1 cycloartane triterpene. In particular, 59 molecules showed antifeedant activity, 30 molecules exhibited poisonous effects, and 9 molecules possessed growth regulatory activity. Particularly, khayasin, beddomei lactone, 3β,24,25-trihydroxycycloartane, humilinolides A–E and methyl-2-hydroxy-3β-isobutyroxy-1-oxomeliac-8(30)-enate showed excellent insecticidal activities, which were comparable to that of azadirachtin and thus deserved more attention. Moreover, it was noteworthy that various chemicals (such as 12α-diacetoxywalsuranolide, 11β,12α-diacetoxycedrelone, 1α,7α,12α-triacetoxy-4α-carbomethoxy-11β-hydroxy-14β,15β-epoxyhavanensin, and 11-epi-21-hydroxytoonacilide, etc.) from Turraea showed excellent insecticidal activity. Specially, the insecticidal activity of khayasin from Neobeguea against the coconut leaf beetle were similar to that of rotenone. Therefore, it was a promising candidate insecticide for the control of the coconut leaf beetle.

ObjectiveAnalyzing the epidemiological characteristics of influenza cases among children aged 0–17 years in Guangzhou from 2019 to 2022. Assessing the relationships between multiple meteorological factors and influenza, improving the early warning systems for influenza, and providing a scientific basis for influenza prevention and control measures.MethodsThe influenza data were obtained from the Chinese Center for Disease Control and Prevention. Meteorological data were provided by Guangdong Meteorological Service. Spearman correlation analysis was conducted to examine the relevance between meteorological factors and the number of influenza cases. Distributed lag non-linear models (DLNM) were used to explore the effects of meteorological factors on influenza incidence.ResultsThe relationship between mean temperature, rainfall, sunshine hours, and influenza cases presented a wavy pattern. The correlation between relative humidity and influenza cases was illustrated by a U-shaped curve. When the temperature dropped below 13°C, Relative risk (RR) increased sharply with decreasing temperature, peaking at 5.7°C with an RR of 83.78 (95% CI: 25.52, 275.09). The RR was increased when the relative humidity was below 66% or above 79%, and the highest RR was 7.50 (95% CI: 22.92, 19.25) at 99%. The RR was increased exponentially when the rainfall exceeded 1,625 mm, reaching a maximum value of 2566.29 (95% CI: 21.85, 3558574.07) at the highest rainfall levels. Both low and high sunshine hours were associated with reduced incidence of influenza, and the lowest RR was 0.20 (95% CI: 20.08, 0.49) at 9.4 h. No significant difference of the meteorological factors on influenza was observed between males and females. The impacts of cumulative extreme low temperature and low relative humidity on influenza among children aged 0–3 presented protective effects and the 0–3 years group had the lowest RRs of cumulative extreme high relative humidity and rainfall. The highest RRs of cumulative extreme effect of all meteorological factors (expect sunshine hours) were observed in the 7–12 years group.ConclusionTemperature, relative humidity, rainfall, and sunshine hours can be used as important predictors of influenza in children to improve the early warning system of influenza. Extreme weather reduces the risk of influenza in the age group of 0–3 years, but significantly increases the risk for those aged 7–12 years.

Peptides present an alternative modality to immunoglobulin domains or small molecules for developing therapeutics to either agonize or antagonize cellular pathways associated with diseases. However, peptides often suffer from poor chemical and physical stability, limiting their therapeutic potential. Disulfide-constrained peptides (DCP) are naturally occurring and possess numerous desirable properties, such as high stability, that qualify them as drug-like scaffolds for peptide therapeutics. DCPs contain loop regions protruding from the core of the molecule that are amenable to peptide engineering via direct evolution by use of phage display technology. In this study, we have established a robust platform for the discovery of peptide therapeutics using various DCPs as scaffolds. We created diverse libraries comprising seven different DCP scaffolds, resulting in an overall diversity of 2 x 1011. The effectiveness of this platform for functional hit discovery has been extensively evaluated, demonstrating a hit rate comparable to that of synthetic antibody libraries. By utilizing chemically synthesized and in vitro folded peptides derived from selections of phage displayed DCP libraries, we have successfully generated functional inhibitors targeting the HtrA1 protease. Through affinity maturation strategies, we have transformed initially weak binders against Notch2 with micromolar Kd values to high-affinity ligands in the nanomolar range. This process highlights a viable hit-to-lead progression. Overall, our platform holds significant potential to greatly enhance the discovery of peptide therapeutics.

From June 7th to 11th, 2023, eight cases of Mpox were identified in Guangzhou, China. This is the first report of multiple local sporadic cases after the imported case in Chongqing, China. Epidemiological investigation revealed that these cases had no history of international travel and no connections with each other. Haplotype network and phylogenetic analyses indicated that the possible origin is likely from Japan, although the direct origin may remain uncertain due to limited genomic sequences and sampling bias in GISAID. The three Guangzhou sequences have accumulated several novel mutations, suggesting the local transmission of Mpox may have been ongoing for some time. Based on the daily cases during the early stage of Mpox outbreak in four other countries, the number of possible infected cases in Guangzhou is inferred to be more than 300, suggesting that swift and efficient control measures must be implemented to mitigate the risk of a potential epidemic.

Abstract Semantic action recognition aims to classify actions based on the associated semantics, which can be applied in video captioning and human‐machine interaction. In this paper the problem is addressed by jointly learning multiple pose lexicons based on multiple body parts. Specifically, multiple visual pose models are learnt, and one visual pose model is associated with one body part, which characterises the likelihood of an observed video frame being generated from hidden visual poses. Moreover, multiple pose lexicon models are simultaneously learnt along with visual pose models. One pose lexicon model is associated with one body part that establishes a probabilistic mapping between the hidden visual poses and semantic poses parsed from textual instructions. To capture the temporal relations among body parts, a transition model is also learnt to measure the probability of the alignment transitioned from one position to another position. The body part‐based pose lexicon learning provides a novel method of cross‐modality semantic correlation, which can be applied in other spatial and temporal data. Action classification is finally formulated as the problem of finding the maximum posterior probability that a given multiple sequences of visual frames follow multiple sequences of semantic poses, subject to the most likely visual pose sequences and alignment sequences. Experiments were conducted on five action datasets to validate the effectiveness of the proposed method.

The microstructure evolution and strengthening mechanism of materials after shot peening have always been the focus of research. In this paper, a novel coupled constitutive model was proposed to predict the depth of fine-grain of the 2060-T8 aluminum-lithium (Al–Li) alloy after shot peening. Besides, combining the numerical and experimental methods, the influences of shot size on yield stress, dislocation density, and crystal orientation of Al–Li alloy were systematically studied to reveal the strengthening mechanism. The results show that larger shot sizes can significantly improve the depth of the dislocation density layer and the fine-grain layer of 2060 Al–Li alloy. The depth of the refinement layer increases from 50 μm to 80 μm when the shot size grows from 0.3 mm to 0.6 mm. It is found the depth of the grain refinement layer in the experiment is consistent with the depth where is a sudden change of grain size in the simulation. Additionally, electron backscatter diffraction (EBSD) shows that many sub-grains are produced in the material due to high dislocation density, and the proportion of low-angle grain boundaries (LAGB) increases significantly, from 48.3% to more than 98.4%. The crystal orientation in the grain has changed obviously and Goss texture {100} obtained in the deformation band. In contrast, with the increase in shot size, the proportion of the Schmid factor with a high-level trend increases. However, the hardening effect of the material is much greater than the softening effect which results in higher yield stress and microhardness of the top surface.

Abstract Background To achieve different central preset force levels requires various fine-tuning efforts and may elicit different uptight responses. The mandibular lever system has a distinct regularity in the fine-tuning function of the upper limbs. The purpose of the present study was to detect whether the uptight responses elicited from motivating clenching differ from those induced by motivating forearm raising at different force levels. Methods Twenty-five healthy females were enrolled in this study. The target was low, medium, and maximum force levels with or without visual feedback and/or maintenance effort. Surface electromyographic (SEMG) activity was recorded from the bilateral anterior temporalis and masseter or left biceps brachii muscle (BicL), and the T-Scan III System synchronously recorded the sensitive force values. The uptight responses and task difficulties were recorded for occlusal and left forearm lifting tasks using a unique visual analogue scale. Results The highest uptight response value was achieved at a low clenching force level with visual feedback requiring no maintenance effort but at a maximum forearm-raising force level with visual feedback and maintenance effort. The SEMG activities of both jaw-closing muscles and BicL were associated with the central preset force level (P

Dendritic cells (DCs), the most efficient antigen-presenting cells (APCs), bridge the innate and adaptive immune systems. As such, the turn-over of DCs is critical during autoimmune responses, and the dysregulation of DC apoptosis could cause severe immune destruction in the host. For example, reduction of immunogenic DCs by increased apoptosis could lead to immune tolerance to pathogen infection that might allow exposure of nuclear autoantigens, whereas reduced apoptosis could result in long-term lymphocyte activation to break the immune tolerance for the development of autoimmune disease. Thus, keeping a balance between survival and apoptosis of DCs is crucial to maintain immune homeostasis. In this review, we summarize the recent development on the factors inducing DC apoptosis and their underlying mechanisms to provide insights into the immunopathogenesis of some autoimmune diseases, which could lead to effective therapeutic interventions in the clinics.

We collected nighttime behavioral data by observing a group of white-headed langurs (Trachypithecus leucocephalus), comprising 16 individuals in a limestone forest in Guangxi Chongzuo National Nature Reserve, China, from October 2016 to August 2017. We recorded various aspects of the langurs’ nighttime behavior, including the duration of entering/leaving sleeping sites, the duration of remaining in sleeping sites, the duration and frequency of movement, and the number and size of sleeping clusters in sleeping sites. The primary aim was to investigate thermoregulation strategy in these primates at night. By applying thermoregulation hypotheses, we aimed to elucidate the underlying factors driving seasonal changes in white-headed langurs’ nighttime behavior. All individuals spent 7.53 ± 1.16 min on entering sleeping sites, and spent 9.70 ± 3.05 min on leaving sleeping sites, which could be a response to predation risk. Movement throughout the night was observed in most individuals. Sleeping clusters were formed by white-headed langurs during the night, with larger clusters sizes occurring in the cold season (4.68 ± 0.69) compared with the hot season (3.59 ± 0.77). Additionally, langurs prolonged their stay in sleeping sites during the cold season (12.36 ± 0.63 h) compared with the hot season (11.20 ± 0.63 h), potentially as a thermoregulation strategy to combat low temperature. Our findings indicate that temperature, rainfall, day length and food availability influence the nighttime behavior of white-headed langurs, highlighting the importance of ecological variables in determining primate nocturnal behavioral responses. The observed changes in white-headed langurs’ nighttime behavior strongly support their inclination toward behavioral strategies that minimize thermoregulation costs in limestone forests.

Abstract Background Long non‐coding RNAs (lncRNAs) have critical functions within esophageal squamous cell carcinoma (ESCC). However, the function and mechanism underlying ESCC‐associated lncRNA‐1 (ESCCAL‐1) in ESCC tumorigenesis have not been well clarified. Methods ESCCAL‐1, miR‐590 and LRP6 were quantified using qRT‐PCR. Cell viability, migration and invasion abilities were measured using CCK‐8 assay and transwell assays. The protein pression was determined with western blot assay. The xenograft model assays were used to examine the impact of ESCCAL‐1 on tumorigenic effect in vivo. Direct relationships among ESCCAL‐1, miR‐590 and LRP6 were confirmed using dual‐luciferase reporter assays. Results The present work discovered the ESCCAL‐1 up‐regulation within ESCC. Furthermore, ESCCAL‐1 was found to interact with miR‐590 and consequently restrict its expression. Functionally, knocking down ESCCAL‐1 or over‐expressing miR‐590 hindered ESCC cell growth, invasion, and migration in vitro. Moreover, inhibition of miR‐590 could reverse the effect of knockdown of ESCCAL‐1 on cells. Importantly, it was confirmed that LRP6 was miR‐590’s downstream target and LRP6 over‐expression also partly abolished the role of miR‐590 overexpression in ESCC cells. Conclusion We have uncovered a novel regulatory network comprising aberrant interaction of ESCCAL‐1/miR‐590/LRP6 participated in ESCC progression.

Cellular senescence and associated secretory phenotype (SASP) are thought to contribute to aging and tissue dysfunction, though it is unclear how SASP impacts regeneration. Here the authors show that SASP factors impair regeneration, and that Ptk7 is a key secreted protein mediating that dysregulation.

Aim This study aims to explore the expression and role of CD72 in B lymphocytes in immune thrombocytopenic purpura (ITP).Methods The expression level of CD72 in B lymphocytes was detected by flow cytometry in 18 ITP patients and 19 controls of healthy donor or iron-deficiency anemia patients. B cell proliferation was determined by 5-bromo-2′-deoxyuridine incorporation (BrdU) in the culture of 17 ITP patients’ and 11 controls’ peripheral mononuclear cells (PMNCs). The secretion levels of antibodies against human platelet antigens (HPA), as well as B cell proliferation-related cytokine interleukin 1(IL-1) and macrophage migration inhibitory factor (MIF) in culture supernatants were measured by ELISA.Results CD72 was significantly increased in B cells of newly diagnosed or persistent ITP compared with ITP in remission. B cell proliferation in culture with CD72 antibody addition was significantly decreased both in ITP patients and in controls compared with isotype antibody addition. CD72 antibody did not significantly alter HPA antibody level in ITP patients. CD72 antibody increased IL-1 and MIF levels in ITP patients’ cell culture supernatant but not in controls.Conclusion CD72 expression elevation accompanies the active status of ITP. In vitro addition of CD72 antibody has a negative impact on B cell proliferation. The function of CD72 in B cell proliferation in ITP may be related to IL-1 and MIF secretion.

BackgroundIn patients with invasive fungal infection (IFI), the steady-state serum trough concentration (Cmin) of voriconazole (VCZ) is highly variable and can lead to treatment failure (Cmin < 0.5 mg/L) and toxicity (Cmin ≥ 5.0 mg/L). However, It remains challenging to determine the ideal maintenance dose to achieve the desired Cmin level quickly.AimsThis randomized, prospective observational single-center study aimed to identify factors affecting VCZ-Cmin and maintenance dose and create an algorithmic model to predict the necessary maintenance dose. MeThe study enrolled 306 adult IFI patients, split into two groups: non-gene-directed (A) (where CYP2C19 phenotype is not involved in determining VCZ dose) and gene-directed (B) (where CYP2C19 phenotype is involved in determining VCZ dose).ResultsResults indicated that CYP2C19 genetic polymorphisms might significantly impact VCZ loading and maintenance dose selection. CYP2C19 phenotype, C-reaction protein (CRP), and average daily dose/body weight were significant influencers on VCZ-Cmin, while CYP2C19 phenotype, CRP, and body weight significantly impacted VCZ maintenance dose. A feasible predictive formula for VCZ stable maintenance dose was derived from the regression equation as a maintenance dose (mg) =282.774-0.735×age (year)+2.946×body weight(Kg)-19.402×CYP2C19 phenotype (UM/RM/NM:0, IM:1, PM:2)-0.316×CRP (mg/L) (p < 0.001).DiscussionDiThis formula may serve as a valuable supplement to the Clinical Pharmacogenetics Implementation Consortium (CPIC®) guideline for CYP2C19 and VCZ therapy, especially for IFI patients with highly variable inflammatory cytokines during VCZ therapy.

Toxoplasma gondii is the causative agent of toxoplasmosis, a zoonotic disease that poses a threat to human health and a considerable loss to livestock farming. At present, clinical therapeutic drugs mainly target T. gondii tachyzoites and fail to eradicate bradyzoites. Developing a safe and effective vaccine against toxoplasmosis is urgent and important. Breast cancer has become a major public health problem and the therapeutic method needs to be further explored. Many similarities exist between the immune responses caused by T. gondii infection and the immunotherapy for cancers. T. gondii dense granule organelles secrete immunogenic dense granule proteins (GRAs). GRA5 is localized to the parasitophorous vacuole membrane in the tachyzoite stage and the cyst wall in the bradyzoite stage. We found that T. gondii ME49 gra5 knockout strain (ME49Δgra5) was avirulent and failed to form cysts but stimulated antibodies, inflammatory cytokines, and leukocytes infiltration in mice. We next investigated the protective efficacy of ME49Δgra5 vaccination against T. gondii infection and tumor development. All the immunized mice survived the challenge infection of either wild-type RH, ME49, VEG tachyzoites, or ME49 cysts. Moreover, ME49Δgra5 tachyzoite inoculation in situ attenuated the growth of murine breast tumor (4T1) in mice and prevented 4T1’s lung metastasis. ME49Δgra5 inoculation upregulated the levels of Th1 cytokines and tumor-infiltrating T cells in the tumor microenvironment and triggered anti-tumor responses by increasing the number of natural killer, B, and T cells, macrophages, and dendritic cells in the spleen. Collectively, these results suggested that ME49Δgra5 was a potent live attenuated vaccine against T. gondii infection and breast cancer.

Aims/hypothesisThrough a comprehensive analysis of the clinical randomized controlled trials of traditional Chinese medicine (TCM) combined with conventional western medicine (CWM) in treating type 2 diabetes(T2DM) in the past ten years, the clinical efficacy and safety of different TCMs combined with CWM were explored. This study aimed to provide specific suggestions for clinical guidance on treating T2DM.MethodsA literature search was conducted in CNKI, WanFang, VIP, CBM, PubMed, Embase, and Web of Science. The search time was limited from 2010 to the present time. The literature type was a controlled clinical trial study of TCM combined with CWM intervention in treating T2DM. The outcome indices of the efficacy evaluation included fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), adverse reactions, and clinical efficacy. Stata 15 and RevMan 5.4 software were used to conduct a network meta-analysis and a traditional meta-analysis.ResultsThe results showed that shenqi jiangtang granule combined with sulfonylurea, shenqi jiangtang granules combined with metformin and jinlida granules combined with insulin had significant effects on reductions in FBG, 2hPG and clinical efficacy compared with western medicines alone, which included fasting blood glucose [MD=-2.17, 95%CI=(-2.50, -1.85)], blood sugar at 2 hours after a meal [MD=-1.94, 95%CI=(-2.23, -1.65)], and clinical curative effect [OR= 1.73, 95%CI=(0.59, 2.87)].ConclusionsTCM combined with CWM has a very significant effect on treating T2DM compared with CWM alone. According to the network meta-analysis, the best intervention measures of different TCMs for different outcome indicators were obtained.Systematic review registrationidentifier 42022350372.

Introduction: Psoriasis is an inflammatory autoimmune skin disease that is hard to cure and prone to relapse. Currently available global immunosuppressive agents for psoriasis may cause severe side effects, thus it is crucial to identify new therapeutic reagents and druggable signaling pathways for psoriasis.Methods: To check the effects of SOCE inhibitors on psoriasis, we used animal models, biochemical approaches, together with various imaging techniques, including calcium, confocal and FRET imaging.Results and discussion: Store operated calcium (Ca2+) entry (SOCE), mediated by STIM1 and Orai1, is crucial for the function of keratinocytes and immune cells, the two major players in psoriasis. Here we showed that a natural compound celastrol is a novel SOCE inhibitor, and it ameliorated the skin lesion and reduced PASI scores in imiquimod-induced psoriasis-like mice. Celastrol dose- and time-dependently inhibited SOCE in HEK cells and HaCaT cells, a keratinocyte cell line. Mechanistically, celastrol inhibited SOCE via its actions both on STIM1 and Orai1. It inhibited Ca2+ entry through constitutively-active Orai1 mutants independent of STIM1. Rather than blocking the conformational switch and oligomerization of STIM1 during SOCE activation, celastrol diminished the transition from oligomerized STIM1 into aggregates, thus locking STIM1 in a partially active state. As a result, it abolished the functional coupling between STIM1 and Orai1, diminishing SOCE signals. Overall, our findings identified a new SOCE inhibitor celastrol that suppresses psoriasis, suggesting that SOCE pathway may serve as a new druggable target for treating psoriasis.

Kip-related proteins (KRPs), as inhibitory proteins of cyclin-dependent kinases, are involved in the growth and development of plants by regulating the activity of the CYC-CDK complex to control cell cycle progression. The KRP gene family has been identified in several plants, and several KRP proteins from Arabidopsis thaliana have been functionally characterized. However, there is little research on KRP genes in soybean, which is an economically important crop. In this study, we identified nine GmKRP genes in the Glycine max genome using HMM modeling and BLASTP searches. Protein subcellular localization and conserved motif analysis showed soybean KRP proteins located in the nucleus, and the C-terminal protein sequence was highly conserved. By investigating the expression patterns in various tissues, we found that all GmKRPs exhibited transcript abundance, while several showed tissue-specific expression patterns. By analyzing the promoter region, we found that light, low temperature, an anaerobic environment, and hormones-related cis-elements were abundant. In addition, we performed a co-expression analysis of the GmKRP gene family, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) set enrichment analysis. The co-expressing genes were mainly involved in RNA synthesis and modification and energy metabolism. Furthermore, the GmKRP2a gene, a member of the soybean KRP family, was cloned for further functional analysis. GmKRP2a is located in the nucleus and participates in root development by regulating cell cycle progression. RNA-seq results indicated that GmKRP2a is involved in cell cycle regulation through ribosome regulation, cell expansion, hormone response, stress response, and plant pathogen response pathways. To our knowledge, this is the first study to identify and characterize the KRP gene family in soybean.

Chimeric antigen receptor T-cell (CAR-T) therapy has been approved for relapsed/refractory B-cell lymphomas and greatly improves disease outcomes. The impressive success has inspired the application of this approach to other types of tumors. The relapsed/refractory T-cell malignancies are characteristic of high heterogeneity and poor prognoses. The efficacy of current treatments for this group of diseases is limited. CAR-T therapy is a promising solution to ameliorate the current therapeutic situation. One of the major challenges is that normal T-cells typically share mutual antigens with malignant cells, which causes fratricide and serious T-cell aplasia. Moreover, T-cells collected for CAR transduction could be contaminated by malignant T-cells. The selection of suitable target antigens is of vital importance to mitigate fratricide and T-cell aplasia. Using nanobody-derived or naturally selected CAR-T is the latest method to overcome fratricide. Allogeneic CAR-T products and CAR-NK-cells are expected to avoid tumor contamination. Herein, we review the advances in promising target antigens, the current results of CAR-T therapy clinical trials in T-cell malignancies, the obstacles of CAR-T therapy in T-cell malignancies, and the solutions to these issues.

Identifying subgroups of T-cell acute lymphoblastic leukemia (T-ALL) with poor survival will significantly influence patient treatment options and improve patient survival expectations. Current efforts to predict T-ALL survival expectations in multiple patient cohorts are lacking. A deep learning (DL)-based model was developed to determine the prognostic staging of T-ALL patients. We used transcriptome sequencing data from TARGET to build a DL-based survival model using 265 T-ALL patients. We found that patients could be divided into two subgroups (K0 and K1) with significant difference (P< 0.0001) in survival rate. The more malignant subgroup was significantly associated with some tumor-related signaling pathways, such as PI3K-Akt, cGMP-PKG and TGF-beta signaling pathway. DL-based model showed good performance in a cohort of patients from our clinical center (P = 0.0248). T-ALL patients survival was successfully predicted using a DL-based model, and we hope to apply it to clinical practice in the future.

The gaseous molecule carbon monoxide (CO) can freely pass through the cell membrane and participate in signal transduction in the cell to regulate physiological activities in plants. Here, we report that CO has a positive regulatory role in stomatal development. Exogenous CO donor CORM-2 [Tricarbonyldichlororuthenium (II) dimer] treatment resulted in an increase of stomatal index (SI) on the abaxial epidermis of cotyledons in wild-type, which can be reversed by the addition of the CO biosynthesis inhibitor ZnPPIX [Protoporphyrin IX zinc (II)]. Consistent with this result, mutation of the CO biosynthesis gene HY1 resulted in a decrease of SI in hy1-100 plants, while overexpression of HY1 led to an increase of SI. Further investigation revealed that CO acts upstream of SPCH and YDA in the stomatal development pathway, since the loss of function mutants spch-1 and yda-2 were insensitive to CORM-2. The expression of EPF2 was inhibited by CORM-2 treatment in wild type and is lower in hy1 than in wild-type plants. In contrast, the expression of STOMAGEN was promoted by CORM-2 treatment and is higher in HY1-overexpression lines. Loss of function mutants of both epf2 and stomagen are insensitive to CORM-2 treatment. These results indicated that CO positively regulates stomatal initiation and distribution by modulating the expression of EPF2 and STOMAGEN.

Abstract Background To examine the effects of physical and mental health factors and family functioning on the self‐perception of ageing in elderly people. Methods A random cluster sampling method was used to select elderly people aged over 60 from three communities in Handan City. Subjects were evaluated via face‐to‐face interviews using the Chinese version of the Ageing Perception Questionnaire, the Family Function Scale, the SF‐36 Short‐Form Health Survey, and a self‐compiled general questionnaire. A single factor and stepwise multiple regression analysis were evaluated using SPSS 17.0 software. Results Among the 1815 elderly people surveyed, the total negative dimension score was 91.67 ± 16.58 with an index of 73.34%, which is higher than the positive dimension score (6.01 ± 0.52, 60.10%). Elderly people with varying degrees of family dysfunction accounted for 11.63%, and the score for self‐perceived ageing in elderly participants with good family function was 95.74 ± 12.63. The proportions with poor physical and mental health factors were 45.40% and 28.10%, respectively, and the scores for ageing self‐perception in elderly participants with good or moderate mental health were 89.11 ± 12.65 and 86.22 ± 12.58, respectively. A stepwise multiple regression analysis showed that age, presence of a spouse, and family function were positive protective factors for ageing self‐perception, while physical health factors were risk factors for the positive dimension of self‐perceived ageing. Age and family function were risk factors for the negative dimension of ageing self‐perception, while physical and mental health factors were protective factors for the negative dimension of self‐perceived ageing. Conclusions Younger elderly and elderly people with good family function have positive self‐perceptions of ageing, while elderly participants with poor physical and mental health have a negative perception of ageing.

Abstract Background To investigate the trends and correlation between antibacterial consumption and carbapenem resistance in Gram-negative bacteria from 2012 to 2019 in a tertiary-care teaching hospital in southern China. Methods This retrospective study included data from hospital-wide inpatients collected between January 2012 and December 2019. Data on antibacterial consumption were expressed as defined daily doses (DDDs)/1000 patient-days. Antibacterials were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. The trends in antimicrobial usage and resistance were analyzed by linear regression, while Pearson correlation analysis was used for assessing correlations. Results An increasing trend in the annual consumption of tetracyclines, β-lactam/β-lactamase inhibitor (BL/BLI) combinations, and carbapenems was observed (P

Protein S-acylation, also known as palmitoylation, is an important lipid post-translational modification of proteins in eukaryotes. S-acylation plays critical roles in a variety of protein functions involved in plant development and responses to abiotic and biotic stresses. The status of S-acylation on proteins is dynamic and reversible, which is catalyzed by protein S-acyltransferases (PATs) and reversed by acyl protein thioesterases. The cycle of S-acylation and de-S-acylation provides a molecular mechanism for membrane-associated proteins to undergo cycling and trafficking between different cell compartments and thus works as a switch to initiate or terminate particular signaling transductions on the membrane surface. In plants, thousands of proteins have been identified to be S-acylated through proteomics. Many S-acylated proteins and quite a few PAT-substrate pairs have been functionally characterized. A recently characterized acyl protein thioesterases family, ABAPT family proteins in Arabidopsis, has provided new insights into the de-S-acylation process. However, our understanding of the regulatory mechanisms controlling the S-acylation and de-S-acylation process is surprisingly incomplete. In this review, we discuss how protein S-acylation level is regulated with the focus on catalyzing enzymes in plants. We also propose the challenges and potential developments for the understanding of the regulatory mechanisms controlling protein S-acylation in plants.

One of the most important growth factors in cannabis cultivation is light which plays a big role in its successful growth. However, understanding that how light controls the industrial hemp growth and development is poor and needs advanced research. Therefore, a pot study was conducted to investigate the effects of different colors of light, that is, white light (WL), blue light (BL), red light (RL), and 50% red with 50% blue mix light (RBL) on morphology, gaseous exchange and antioxidant capacity of industrial hemp. Compared with WL, BL significantly increase hemp growth in terms of shoot fresh biomass (15.1%), shoot dry biomass (27.0%), number of leaves per plant (13.7%), stem diameter (10.2%), root length (6.8%) and chlorophyll content (7.4%). In addition, BL promoted net photosynthesis, stomatal conductance, and transpiration, while reduces the lipid peroxidation and superoxide dismutase and peroxidase activities. However, RL and RBL significantly reduced the plant biomass, gas exchange parameters with enhanced antioxidant enzymes activities. Thus, blue light is useful for large-scale sustainable production of industrial hemp.

Abstract Deregulated store‐operated calcium entry (SOCE) mediated by aberrant STIM1‐ORAI1 signaling is closely implicated in cancer initiation and progression. Here the authors report the identification of an alternatively spliced variant of STIM1, designated STIM1β, that harbors an extra exon to encode 31 additional amino acids in the cytoplasmic domain. STIM1β, highly conserved in mammals, is aberrantly upregulated in glioma tissues to perturb Ca2+ signaling. At the molecular level, the 31‐residue insertion destabilizes STIM1β by perturbing its cytosolic inhibitory domain and accelerating its activation kinetics to efficiently engage and gate ORAI calcium channels. Functionally, STIM1β depletion affects SOCE in glioblastoma cells, suppresses tumor cell proliferation and growth both in vitro and in vivo. Collectively, their study establishes a splicing variant‐specific tumor‐promoting role of STIM1β that can be potentially targeted for glioblastoma intervention.

Abstract Background Toxoplasma gondii is an opportunistic protozoan infecting almost one-third of the world’s population. Toxoplasma gondii rhoptry protein 18 (TgROP18) is a key virulence factor determining the parasite’s acute virulence and is secreted into host cells during infection. We previously identified the interaction of TgROP18 and host cell immune-related receptor protein IL20RB, and observed the activation of STAT3 in human keratinocytes (HaCaT) cells infected by the rop16 knockout RH strain, though TgROP16 is regarded as being responsible for host STAT3 activation during T. gondii invasion. Therefore, we hypothesize TgROP18 can activate host STAT3 through binding to IL20RB. Methods CRISPR-CAS9 technology was used to generate the ROP16 and ROP18 double knockout RH strain, RH-∆rop16∆rop18. SDS-PAGE and western blot were used to detect STAT3 activation in different HaCaT cells with high endogenous IL20RB expression treated with T. gondii tachyzoites infection, recombinant ROP18, or IL-20. FRET and co-immunoprecipitation (Co-IP) was used to detect the protein-protein interaction. Results We observed that TgROP18 was involved in a synergic activation of the host JAK/STAT3 pathway together with TgROP16 in human HaCaT cells infected with T. gondii or treated with recombinant TgROP18 protein, stimulating host proinflammatory immune responses such as expression of TNF-α. The effect of recombinant ROP18 on STAT3 phosphorylation was presented in a dose-dependent manner. Additionally, TgROP18 was identified to target IL20RB on its extracellular domain. When we treated different cell lines with the recombinant ROP18, STAT3 phosphorylation could only be observed in the cells with endogenous IL20RB expression, such as HaCaT cells. Conclusions These findings indicate that TgROP18-IL20RB interaction upon T. gondii invasion was involved in STAT3 activation, which is associated with host cell defense.

Abstract Background Lung adenocarcinoma (LAC) is composed of lepidic, papillary, mucinous, micropapillary and solid components in its parenchyma. Complex responses to therapeutics result from intratumoral heterogeneity. However, it remains confused that what components in a mixed LAC tumor are responsible to the heterogeneous EGFR mutation and PD-L1 expression. Methods We investigated EGFR status via laser microdissection to capture spatially separated cancer cell subpopulations and digital droplet PCR to determine the abundance of EGFR sensitizing mutation and naïve T790M. Whilst, PD-L1 expression level via tumor proportion score (TPS) was evaluated by Ventana immunohistochemistry using SP263 antibody. PD-L1 expression levels were tiered in =50% groups. Results EGFR mutation harbored in 154 (59%) of 261 LAC patients and more frequently occurred in papillary, lepidic and micropapillary constituents. Higher levels of PD-L1 were found in LACs at stage III and IV (68.3%) versus those at stage I and II (31.7%) (P = 0.04). Solid predominant LACs (41.3%) expressed PD-L1 with TPS > =50%, versus mucinous and lepidic LACs (P =50% were associated with patients’ progression-free survival and longer in the =50%, respectively (P > 0.05). Conclusion Intratumoral genetic heterogeneity of LACs was demonstrated associated with histological patterns. Heterogeneous PD-L1 expression in higher level usually occurred in solid component both in EGFR mutated and EGFR wild-typed LACs. EGFR mutated LACs heterogeneously had sensitizing and resistant mutation and was accompanied with PD-L1 expression, but discordant among histological constituents. Immune checkpoint inhibitor combined with third generation EGFR tyrosine kinase inhibitor should be more effective to these LACs.

ABSTRACTInfluenza B virus (IBV) is one of the most important human respiratory viruses: it causes approximately one-third of the global influenza-related disease burden each year. However, compared with the several pathogenicity-related molecular markers that have been identified for influenza A virus (IAV), little is known about potential IBV pathogenicity-related markers. Here, although the IBV strain B/Anhui-Tunxi/1528/2014 (AH1528/14) exhibited a more efficient replication ability in vitro and higher pathogenicity in vivo compared with IBV strain B/Anhui-Baohe/127/2015 (AH127/15), only three amino acids differences (HAA390E, NAN342D and PB1V212I) were observed among their full genomes. The contributions of each amino acid difference to the virus pathogenicity were further investigated. Compared with the wild type IBV virus rAH127, the recombinant virus harbouring a single substitution of HAA390E had a similar phenotype, whereas the recombinant virus harbouring PB1V212I replicated to a moderately higher titre in both MDCK cells and in mice. Notably, the virus harbouring NAN342D showed significantly better growth properties in MDCK cells and higher fatality rates in mice. In addition, the presence of NAN342D dramatically enhanced the viral neuraminidase activity. In conclusion, our study identified a novel IBV molecular marker, NAN342D, that could significantly increase the virulence of IBV in mice.

With the rapid development of communication technologies, the Internet use has become the main channel for citizens to obtain information and knowledge. It has been widely established that Internet use can have a significant impact on citizens’ expectations, perceptions, and behaviors. Government trust is the reasonable expectation of citizens on in the administrative activities of the government and its administrators, which should rightly be influenced by the behavior of citizens’ Internet use. However, limited studies have investigated the relationship between Internet use and citizens’ trust in the government. Therefore, in this study, the effect of Internet use on trust in the government was investigated using data from the 2017 Chinese Social Survey. The baseline regression results revealed that Internet use reduces trust in the government. This phenomenon was persistently observed after several robustness tests. A heterogeneity analysis revealed that Internet use negatively influenced citizens from Eastern and Western China, lower age groups, and agricultural households. Social amplification of the risk and the theory of rational choice revealed that a sense of security partially mediates the relationship between Internet use and citizens’ trust in the government. Internet use reduces citizens’ sense of security and subsequently decreases trust in the government. Our findings revealed establishing a network information supervision and public opinion guidance mechanism. At the same time, consider the role of social security services in resolving social risks. These initiatives are essential to ensure citizens’ trust in their government.

Tetranychus urticae Koch (T. urticae) is one of the most tremendous herbivores due to its polyphagous characteristics, and is resistant to most acaricides. In this study, enzyme-linked immunosorbent assay (ELISA), transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) were carried out to analyze the mechanisms of T. urticae metabolic resistance to cyflumetofen and bifenthrin on cowpea. The enzyme activity of UDP-glucuronosyltransferases (UGTs) and carboxylesterases (CarEs) in the cyflumetofen-resistant (R_cfm) strain significantly decreased, while that of cytochrome P450 monooxygenases (P450s) significantly increased. Meanwhile, the activities of glutathione-S-transferases (GSTs), CarEs and P450s in the bifenthrin-resistant (R_bft) strain were significantly higher than those in the susceptible strain (Lab_SS). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses, in the R_cfm mite strain, two carboxyl/cholinesterase (CCE) genes and two P450 genes were upregulated and one gene was downregulated, namely CYP392E7; in the R_bft mite strain, eleven CCE, nine UGT, two P450, four GST and three ABC genes were upregulated, while four CCE and three P450 genes were downregulated. Additionally, 94 differentially expressed genes (DEGs) were common to the two resistant groups. Specifically, TuCCE46 and TuCCE70 were upregulated in both resistant groups. Furthermore, the qRT-PCR validation data were consistent with those from the transcriptome sequencing analysis. Specifically, TuCCE46 (3.37-fold) was significantly upregulated in the R_cfm strain, while in the R_bft strain, TeturUGT22 (5.29-fold), teturUGT58p (1.74-fold), CYP392A11 (2.89-fold) and TuGSTd15 (5.12-fold) were significantly upregulated and TuCCE01 (0.13-fold) and CYP392A2p (0.07-fold) were significantly downregulated. Our study indicates that TuCCE46 might play the most important role in resistance to cyflumetofen, and TuCCE01, teturUGT58p, teturUGT22, CYP392A11, TuGSTd15, TuGSTm09 and TuABCG-13 were prominent in the resistance to bifenthrin. These findings provide further insight into the critical genes involved in the metabolic resistance of T. urticae to cyflumetofen and bifenthrin.

Since the advent of the Internet has changed how risk information develops and disseminates, citizens’ risk perception alters correspondingly. Although extant studies have explored the impacts of Internet use on citizens, only a few have focused on citizens’ perception of social safety exclusively. This study examined the effect of Internet use and Internet use frequency on citizens’ perception of social safety with 2017 China Social Survey data. It found that Internet use and Internet use frequency have a significant negative impact on citizens’ social safety perception. Compared to non-users, the probability of perceiving society as very safe decreases significantly by 2.3% for Internet users. Subsequently, this study avoided the endogeneity issues by employing the Bioprobit and CMP methods, and the robustness check adopted propensity score matching methods. In general, it supported results in benchmark regression. The heterogeneity analysis indicated that Internet use had a higher negative impact on citizens in the western region, rural household registration, and middle-aged groups. It suggests that the establishment of a comprehensive mechanism to regulate online information involving governments, Internet industrial organizations, and Internet users may improve governance effectiveness. In addition, education targeting Internet literacy is required to enable a more rational citizen participation on the Internet.

Polymer-based composite films with multiple properties, such as low dielectric loss tangent, high dielectric constant, and low cost are promising materials in the area of electronics and electric industries. In this study, flexible dielectric films were fabricated via an electric field-assisted method. Polyaniline (PANI) was modified by polyvinylpyrrolidone (PVP) to form a core–shell structure to serve as functional particles and silicone rubber polydimethylsiloxane (PDMS) served as the matrix. The dielectric constant of the composites prepared under electric fields was improved by the micro-structures formed by external electric fields. With the addition of 2.5 wt% PVP@PANI, the dielectric constant could be significantly enhanced, up to 23; the dielectric loss tangent is only 1, which is lower than that of the aligned PANI samples. This new processing technology provides important insights for aligning fillers in polymer matrix to form composites with enhanced dielectric properties.

Toxoplasma gondii is an intracellular pathogen that exerts its virulence through inhibiting host’s innate immune responses, which is mainly related to the type II interferon (IFN-γ) response. IFN-γ inducible tripartite motif 21 (TRIM21), an E3 ligase, plays an important role in anti-infection responses against the intracellular pathogens including bacteria, virus, and parasite. We found that T. gondii virulence factor ROP18 of the type I RH strain (TgROP18I) interacted with human TRIM21, and promoted the latter’s phosphorylation, which subsequently accelerated TRIM21 degradation through lysosomal pathway. Furthermore, TRIM21 protein level was found to be upregulated during RH and CEP strains of T. gondii infection. TRIM21 knocking down reduced the ubiquitin labeling on the parasitophorous vacuole membrane (PVM) [which led to parasitophorous vacuole (PV) acidification and death of CEP tachyzoites], and relieved the inhibition of CEP proliferation induced by IFN-γ in human foreskin fibroblast (HFF) cells which was consistent with the result of TRIM21 overexpression. On the other hand, TRIM21 overexpression enhanced the inhibition of CEP proliferation, and inhibited the binding of IκB-α with p65 to activate the IFN-γ-inducible NF-κB pathway, which might be resulted by TRIM21-IκB-α interaction. In brief, our research identified that in human cells, IFN-γ-inducible TRIM21 functioned in the innate immune responses against type III T. gondii infection; however, TgROP18I promoted TRIM21 phosphorylation, leading to TRIM21 degradation for immune escape in type I strain infection.

ABSTRACTIt has recently been proposed that the Eurasian avian-like H1N1 (EA H1N1) swine influenza virus (SIV) is one of the most likely zoonotic viruses to cause the next influenza pandemic. Two main genotypes EA H1N1 viruses have been recognized to be infected humans in China. Our study finds that one of the genotypes JS1-like viruses are avirulent in mice. However, the other are HuN-like viruses and are virulent in mice. The molecular mechanism underlying this difference shows that the NP gene determines the virulence of the EA H1N1 viruses in mice. In addition, a single substitution, Q357K, in the NP protein of the EA H1N1 viruses alters the virulence phenotype. This substitution is a typical human signature marker, which is prevalent in human viruses but rarely detected in avian influenza viruses. The NP-Q357K substitution is readily to be occurred when avian influenza viruses circulate in pigs, and may facilitate their infection of humans and allow viruses also carrying NP-357K to circulate in humans. Our study demonstrates that the substitution Q357K in the NP protein plays a key role in the virulence phenotype of EA H1N1 SIVs, and provides important information for evaluating the pandemic risk of field influenza strains.

The insulin receptor (IR) is a transmembrane protein that is activated by ligands in insulin signaling pathways. The IR has been considered as a novel therapeutic target for clinical intervention, considering the overexpression of its protein and A-isoform in multiple cancers, Alzheimer’s disease, and Type 2 diabetes mellitus in humans. Meanwhile, it may also serve as a potential target in pest management due to its multiple physiological influences in insects. In this review, we provide an overview of the structural and molecular biology of the IR, functions of IRs in humans and insects, physiological and nonpeptide small molecule modulators of the IR, and the regulating mechanisms of the IR. Xenobiotic compounds and the corresponding insecticidal chemicals functioning on the IR are also discussed. This review is expected to provide useful information for a better understanding of human IR-related diseases, as well as to facilitate the development of novel small-molecule activators and inhibitors of the IR for use as medicines or pesticides.

Plant-originated triterpenes are important insecticidal molecules. Research on the insecticidal activity of molecules from Meliaceae plants has always been a hotspot due to the molecules from this family showing a variety of insecticidal activities with diverse mechanisms of action. In this paper, we discussed 116 triterpenoid molecules with insecticidal activity from 22 plant species of five genera (Cipadessa, Entandrophragma, Guarea, Khaya, and Melia) in Meliaceae. In these genera, the insecticidal activities of plants from Entandrophragma and Melia have attracted substantial research attention in recent years. Specifically, the insecticidal activities of plants from Melia have been systemically studied for several decades. In total, the 116 insecticidal chemicals consisted of 34 ring-intact limonoids, 31 ring-seco limonoids, 48 rearranged limonoids, and 3 tetracyclic triterpenes. Furthermore, the 34 ring-intact limonoids included 29 trichilin-class chemicals, 3 azadirone-class chemicals, and 1 cedrelone-class and 1 havanensin-class limonoid. The 31 ring-seco limonoids consisted of 16 C-seco group chemicals, 8 B,D-seco group chemicals, 4 A,B-seco group chemicals, and 3 D-seco group chemicals. Furthermore, among the 48 rearranged limonoids, 46 were 2,30-linkage group chemicals and 2 were 10,11-linkage group chemicals. Specifically, the 46 chemicals belonging to the 2,30-linkage group could be subdivided into 24 mexicanolide-class chemicals and 22 phragmalin-class chemicals. Additionally, the three tetracyclic triterpenes were three protolimonoids. To sum up, 80 chemicals isolated from 19 plant species exhibited antifeedant activity toward 14 insect species; 18 chemicals isolated from 17 plant species exhibited poisonous activity toward 10 insect species; 16 chemicals isolated from 11 plant species possessed growth-regulatory activity toward 8 insect species. In particular, toosendanin was the most effective antifeedant and insect growth-regulatory agent. The antifeedant activity of toosendanin was significant. Owing to its high effect, toosendanin has been commercially applied. Three other molecules, 1,3-dicinnamoyl-11-hydroxymeliacarpin, 1-cinnamoyl-3-methacryl-11-hydroxymeliacarpin, and 1-cinnamoyl-3-acetyl-11-hydroxymeliacarpin, isolated from Meliaazedarach, exhibited a highly poisonous effect on Spodoptera littoralis; thus, they deserve further attention.

Tumor vaccines aim to expand tumor-specific T cells and reactivate existing tumor-specific T cells that are in a dormant or unresponsive state. As such, there is growing interest in improving the durable anti-tumor activity of tumor vaccines. Failure of vaccine-activated T cells to protect against tumors is thought to be the result of the immune escape mechanisms of tumor cells and the intricate immunosuppressive tumor microenvironment. In this review, we discuss how tumor cells and the tumor microenvironment influence the effects of tumor infiltrating lymphocytes and summarize how to improve the efficacy of tumor vaccines by improving the design of current tumor vaccines and combining tumor vaccines with other therapies, such as metabolic therapy, immune checkpoint blockade immunotherapy and epigenetic therapy.

The acute inflammatory lung injury is an important cause of death due to influenza A virus (IAV) infection. Insulin-like growth factor 1 (IGF1) played an important role in the regulation of inflammation in the immune system. To investigate the role of IGF1 in IAV-mediated acute inflammatory lung injury, the expression of IGF1 and inflammatory cytokines was tested after IAV A/Puerto Rico/8/1934 (H1N1; abbreviated as PR8) infection in A549 cells. Then, a BALB/c mouse model of PR8 infection was established. On days 3, 5, 7, and 9 post-infection, the mice lung tissue was collected to detect the expression changes in IGF1 mRNA and protein. The mice were divided into four groups: (1) PBS (abbreviation of phosphate buffered saline); (2) PR8 + PBS; (3) PR8 + IGF1; and (4) PR8 + PPP (abbreviation of picropodophyllin, the IGF1 receptor inhibitor). The body weight and survival rate of the mice were monitored daily, and the clinical symptoms of the mice were recorded. On day 5 post-infection, the mice were sacrificed to obtain the serum and lung tissues. The expression of inflammatory cytokines in the serum was detected by enzyme linked immunosorbent assay; lung injury was observed by hematoxylin-eosin staining; the viral proliferation in the lung was detected by real-time quantitative PCR; and the protein expression of the main molecules in the phosphatidylinositol-3-kinases/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways was detected by Western blot. It was found that IGF1 expression is upregulated in A549 cells and BALB/c mice infected with PR8, whereas IGF1 regulated the expression of inflammatory cytokines induced by PR8 infection. Overexpression of IGF1 aggravated the IAV-mediated inflammatory response, whereas the inhibition of IGF1 receptor reduced such inflammatory response. The phosphorylation of IGF1 receptor triggered the PI3K/AKT and MAPK signaling pathways to induce an inflammatory response after IAV infection. Therefore, IGF1 plays an important immune function in IAV-mediated acute inflammatory lung injury. IGF1 may provide a therapeutic target for humans in response to an influenza outbreak, and inhibition of IGF1 or IGF1 receptor may represent a novel approach to influenza treatment.

Abstract The problem in this paper is motivated by physical problems concerned with the case when a class of continuous and equimeasurable densities of a string is given then how to find minimal frequencies among these given densities, that is, what kind of densities minimize the frequencies. By taking Dirichlet eigenvalues into account, given a certain weight function ω, we will show the minimizer of the mth eigenvalue is the m-degree continuous symmetrical decreasing rearrangement of ω. The main result of this paper can be viewed as complementary to Schwarz’s work (Schwarz in J. Math. Mech. 10:401–422, 1961).