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AbstractContext The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use.Objective The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases.Methods We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence.Results Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment.Conclusions Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.

Abstract Introduction The treatment options for moderate to severe psoriasis (msPsO) in China have been greatly increased with the approvals of biologics. However, the unmet needs and treatment preferences of systemic treatments for msPsO in China remain unclarified. Methods Fifty dermatologists and 300 patients with msPsO (41% with severe psoriasis) were surveyed for effectiveness, safety, treatment convenience, and treatment preferences (using a choice-based conjoint questionnaire). Descriptive statistics and conjoint simulation analyses were employed to summarize survey information and assess treatment preferences. Results Both patients and dermatologists reported shorter treatment duration for oral drugs (2.7–6.2 months) than that for biologics (9.5–17.0 months). The most frequently reported treatment discontinuation reasons by the surveyed patients and dermatologists were unsatisfactory effectiveness (average 84.5%) for oral drugs and loss of efficacy over time (average 68.5%) for biologics. Commonly reported treatment inconveniences included regular lab tests for traditional oral drugs (average 71.5%) and administration assistance for biologics (average 58.0%). Injection site reactions (average 51.5%) and needle fear (average 35.5%) were frequently reported for biologics among the surveyed patients and dermatologists. Once-daily oral treatment was preferred over biweekly subcutaneous injection treatment when the two had comparable attributes (average in patients 87.1% vs. 12.9%; average in dermatologists 93.4% vs. 6.6%). Conclusions Unmet needs of systemic treatments remain for msPsO in China. Once-daily oral treatment is preferred over biweekly subcutaneous injections to treat msPsO when other treatment attributes are comparable.

Background While extensive research has provided a wealth of information on psoriasis in general, there remains a critical gap in understanding the unique characteristics of psoriasis in special body areas, such as the scalp, nails, palms, and genitals.Objective To investigate the characterization and treatment of psoriasis patients in special body areas.Methods The study was a retrospective analysis of patients with psoriasis enrolled in the Psoriasis Standardized Diagnosis and Treatment Center Project between January 2020 and September 2021.Results The study encompassed 346 patients, 81% of them had psoriasis in at least two special body areas, with the nails as the most common area. Patients with genital psoriasis reported higher Dermatology Life Quality Index (DLQI) scores. A higher propensity for scalp and palmoplantar psoriasis was noted in patients with genital psoriasis. The proportion of patients treated with biologics rose, as the number of specific areas involved increased.Conclusions Patients with genital psoriasis are more likely to have scalp and palmoplantar psoriasis. This study highlights the significant escalation in the proportion of biologics when the involvement of special body areas was ≥2.

IntroductionAfrican swine fever (ASF) is a lethal and highly contagious transboundary animal disease with the potential for rapid international spread. In the absence of a widely available and definitively proven vaccine, rapid and early detection is critical for ASF control. The quick and user-friendly lateral flow assay (LFA) can easily be performed by following simple instructions and is ideal for on-site use. This study describes the development and validation of two LFAs for the rapid detection of ASF virus (ASFV) in pig serum.MethodsThe highly immunogenic antigens (p30 and p72) of ASFV Georgia 2007/1 (genotype II) were expressed in plants (Nicotiana benthamiana) and were used to immunize BALB/c mice to generate specific monoclonal antibodies (mAbs) against the p30 and p72 proteins. mAbs with the strongest binding ability to each protein were used to develop p30_LFA and p72_LFA for detecting the respective ASFV antigens. The assays were first evaluated using a spike-in test by adding the purified p30 or p72 protein to a serum sample from a healthy donor pig. Further validation of the tests was carried out using serum samples derived from experimentally infected domestic pigs, field domestic pigs, and feral pigs, and the results were compared with those of ASFV real-time PCR.Resultsp30_LFA and p72_LFA showed no cross-reaction with common swine viruses and delivered visual results in 15 min. When testing with serially diluted proteins in swine serum samples, analytical sensitivity reached 10 ng/test for p30_LFA and 20 ng/test for p72_LFA. Using real-time PCR as a reference, both assays demonstrated high sensitivity (84.21% for p30_LFA and 100% for p72_LFA) with experimentally ASFV-infected pig sera. Specificity was 100% for both LFAs using a panel of PBS-inoculated domestic pig sera. Excellent specificity was also shown for field domestic pig sera (100% for p30_LFA and 93% for p72_LFA) and feral pig sera (100% for both LFAs).ConclusionThe results obtained in this study suggest that p30_LFA and p72_LFA hold promise as rapid, sensitive, user-friendly, and field-deployable tools for ASF control, particularly in settings with limited laboratory resources.

Abstract Background Atherosclerosis (AS) is a critical pathological event during the progression of cardiovascular diseases. It exhibits fibrofatty lesions on the arterial wall and lacks effective treatment. N6-methyladenosine (m6A) is the most common modification of eukaryotic RNA and plays an important role in regulating the development and progression of cardiovascular diseases. However, the role of m6A modification in AS remains largely unknown. Therefore, in this study, we explored the transcriptome distribution of m6A modification in AS and its potential mechanism. Methods Methylation Quantification Kit was used to detect the global m6A levels in the aorta of AS mice. Western blot was used to analyze the protein level of methyltransferases. Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were used to obtain the first transcriptome range analysis of the m6A methylene map in the aorta of AS mice, followed by bioinformatics analysis. qRT-PCR and MeRIP-qRT-PCR were used to measure the mRNA and m6A levels in target genes. Results The global m6A and protein levels of methyltransferase METTL3 were significantly increased in the aorta of AS mice. However, the protein level of demethylase ALKBH5 was significantly decreased. Through MeRIP-seq, we obtained m6A methylation maps in AS and control mice. In total, 26,918 m6A peaks associated with 13,744 genes were detected in AS group, whereas 26,157 m6A peaks associated with 13,283 genes were detected in the control group. Peaks mainly appeared in the coding sequence (CDS) regions close to the stop codon with the RRACH motif. Moreover, functional enrichment analysis demonstrated that m6A-containing genes were significantly enriched in AS-relevant pathways. Interestingly, a negative correlation between m6A methylation abundance and gene expression level was found through the integrated analysis of MeRIP-seq and RNA-seq data. Among the m6A-modified genes, a hypo-methylated but up-regulated (hypo-up) gene Fabp5 may be a potential biomarker of AS. Conclusions Our study provides transcriptome-wide m6A methylation for the first time to determine the association between m6A modification and AS progression. Our study lays a foundation for further exploring the pathogenesis of AS and provides a new direction for the treatment of AS.

BackgroundPsoriasis is an immune-mediated disorder influenced by environmental factors on a genetic basis. Despite advancements, challenges persist, including the diminishing efficacy of biologics and small-molecule targeted agents, alongside managing recurrence and psoriasis-related comorbidities. Unraveling the underlying pathogenesis and identifying valuable biomarkers remain pivotal for diagnosing and treating psoriasis.MethodsWe employed a series of bioinformatics (including single-cell sequencing data analysis and machine learning techniques) and statistical methods to integrate and analyze multi-level data. We observed the cellular changes in psoriatic skin tissues, screened the key genes Fatty acid binding protein 5 (FABP5) and The killer cell lectin-like receptor B1 (KLRB1), evaluated the efficacy of six widely prescribed drugs on psoriasis treatment in modulating the dendritic cell-associated pathway, and assessed their overall efficacy. Finally, RT-qPCR, immunohistochemistry, and immunofluorescence assays were used to validate.ResultsThe regulatory influence of dendritic cells (DCs) on T cells through the CD70/CD27 signaling pathway may emerge as a significant facet of the inflammatory response in psoriasis. Notably, FABP5 and KLRB1 exhibited up-regulation and co-localization in psoriatic skin tissues and M5-induced HaCaT cells, serving as potential biomarkers influencing psoriasis development.ConclusionOur study analyzed the impact of DC-T cell crosstalk in psoriasis, elucidated the characterization of two biomarkers, FABP5 and KLRB1, in psoriasis, and highlighted the promise and value of tofacitinib in psoriasis therapy targeting DCs.

African swine fever (ASF) is a highly contagious and severe hemorrhagic transboundary swine viral disease with up to a 100% mortality rate, which leads to a tremendous socio-economic loss worldwide. The lack of safe and efficacious ASF vaccines is the greatest challenge in the prevention and control of ASF. In this study, we generated a safe and effective live-attenuated virus (LAV) vaccine candidate VNUA-ASFV-LAVL3 by serially passaging a virulent genotype II strain (VNUA-ASFV-L2) in an immortalized porcine alveolar macrophage cell line (3D4/21, 50 passages). VNUA-ASFV-LAVL3 lost its hemadsorption ability but maintained comparable growth kinetics in 3D4/21 cells to that of the parental strain. Notably, it exhibited significant attenuation of virulence in pigs across different doses (103, 104, and 105 TCID50). All vaccinated pigs remained healthy with no clinical signs of African swine fever virus (ASFV) infection throughout the 28-day observation period of immunization. VNUA-ASFV-LAVL3 was efficiently cleared from the blood at 14–17 days post-infection, even at the highest dose (105 TCID50). Importantly, the attenuation observed in vivo did not compromise the ability of VNUA-ASFV-LAVL3 to induce protective immunity. Vaccination with VNUA-ASFV-LAVL3 elicited robust humoral and cellular immune responses in pigs, achieving 100% protection against a lethal wild-type ASFV (genotype II) challenge at all tested doses (103, 104, and 105 TCID50). Furthermore, a single vaccination (104 TCID50) provided protection for up to 2 months. These findings suggest that VNUA-ASFV-LAVL3 can be utilized as a promising safe and efficacious LAV candidate against the contemporary pandemic genotype II ASFV.

The Maillard reaction system of glucose and glycine was applied to study the formations of furfural compounds. The effects of glucose/glycine molar concentration ratio, initial pH, heating temperature and time on the formations of 5-hydroxymethylfurfural (HMF), 2-furfural (F) and 5-methyl-2-furfural (MF) were evaluated. The kinetic equations of HMF, F and MF were established and their apparent activation energies were also predicted. The results showed that: Glucose/glycine molar concentration ratio had great influence on the formations of furfural compounds. The formation of HMF continued to increase with the increase of ratio, and the formations of F and MF reached the maximum when the ratio was 1:1. The acidic pH conditions could promote the formation of HMF, while the neutral and alkaline pH conditions were conducive to the formation of F. The total amount of furfural compounds decreased rapidly with the increase of pH. The amounts of HMF, F, and MF in the glucose-glycine reaction system increased with the increase of heating temperature and time. The formations of HMF and F in glucose and glycine model followed first-order kinetics model at lower temperatures (HMF: 70~110 ℃; F: 70 ℃), while their formations were in accordance with zero-order kinetics model at higher temperatures (HMF: 130 ℃; F: 90~130 ℃). The formation of MF followed zero-order kinetics model at 90~130 ℃. The results would provide guidance on the production and control of HMF, F, and MF in the food thermal processing industry.

ABSTRACTOasis cities are deeply affected by human activities in arid and semi-arid regions. Vegetation is an important repository in the carbon cycle of oasis urban ecosystems. The continuous expansion of urban has a disproportionate impact on the carbon sequestration capacity of vegetation. Till now, studies have been conducted to quantify the impact of urbanization on vegetation carbon sequestration capacity, the mechanism of such impact remains unclear and lacks systematic investigations, especially in oasis urban. Understanding the impact mechanism greatly benefits the sustainable development of oasis urban and regional carbon neutrality. To fill this knowledge gap, we design a theoretical framework to analyze the impact of urbanization on vegetation carbon sequestration capacity by isolating the direct and indirect impacts in Urumqi, China. Some results based on Landsat images indicated that the Impervious Surface Areas (ISAs) expanded by 436.98 km2 during 2000 – 2019. The Net Primary Productivity (NPP) calculated using the Vegetation Photosynthesis Model (VPM) was directly caused by the loss of 51.45 Gg C (1 Gg = 109 g). Another important finding proved that the direct carbon loss caused by urbanization did not change the upward trend of the total carbon sequestration capacity of vegetation, but only slowed down this upward trend by 20.86%. Our results provide new insights into urban vegetation carbon sinks and contribute to a better understanding of the uncertainty of urbanization toward carbon neutrality. This study will provide scientific data support and suggestions for the sustainable development of oasis cities and the regional carbon budget.

The dynamics of Gross Primary Productivity (GPP) is key to understand the global carbon cycle. Multiple GPP products are currently available based on remote sensing, Light Use Efficiency model (LUE) or diagnostic biophysical model. However, little knowledge is available on the spatial patterns of the uncertainty of different GPP products and their potential drivers over the Central Asia (CA), a fragile environment for accurate GPP estimation. This study investigates the sensitivity of the 8-day, monthly and yearly GPP uncertainties based on the three-cornered hat (TCH) method and Shapley additive explanation (SHAP) model in terms of vegetation, energy, water, climate and terrain factors in the dryland ecosystem during the 2003–2015 period. Ten GPP products were examined, including one product (FLUXCOM) from machine learning (ML), six products (EC-LUE, FluxSat, LUEopt, MODIS, MuSyQ and VPM) based on the (LUE), two products (GOSIF and NIRv) from satellite-based direct proxies (Proxies) and one product (PML) from the diagnostic biophysical model. The results indicate that the spatial distribution of the ten GPP products in CA showed similar patterns at different time scales, but with values varied at different products and time scales. According to the eddy covariance (EC) observations and the TCH-based uncertainties, the FLUXCOM product showed smaller relative uncertainties than other products. The attribution analysis denotes that the sources of uncertainty of the GPP varied for each product, and thus the improvement strategies for different products should be implemented separately The FLUXCOM should adapt the vegetation- related module to the dryland environment of CA. The LUE model should optimize the LUE parameters for the dryland ecosystem and incorporate the water related variables in the model. The Proxies model should incorporate the water and energy variables (such as soil moisture and radiation) as input data to improve their performance in CA. The diagnostic model should consider the elevation variable as input data, which may improve the performance of the PML in CA. Our results do not only provide an important basis for the selection of GPP products in the study of the carbon cycle in CA, but also offer a new insight into the GPP model development and improvement for the dryland ecosystem.

Objective To compare the specificity, sensitivity, variability and consistency among three different diagnostic criteria for atopic dermatitis (AD) in subjects with and without AD. Methods We retrospectively analyzed patients with AD initially diagnosed according to the Hanifin Rajka criteria at our clinic between September 2020 and October 2021. Demographic characteristics, clinical manifestations and the results of laboratory tests were used to analyze the sensitivity and specificity of Williams criteria, Zhang's criteria/Chinese criteria and Chinese diagnostic criteria for childhood AD. Patients with other dermatological diseases visiting our clinic during the same period were used as controls. The sensitivity and specificity of the three diagnostic criteria were compared using McNemar's test, while Kappa values were used to determine the consistency of the diagnostic criteria. Results One hundred and ten patients with AD and 91 patients without AD were included in this analysis. The highest sensitivity and lowest specificity were Chinese diagnostic criteria for childhood AD (83.6%, 59.3%). Both Zhang's criteria/Chinese criteria and Williams criterion displayed the highest specificity (90.1% for both). Both positive and negative predictive values (90.2%, 75.2%) were higher for Zhang's criteria/Chinese criteria than the others. The Williams criteria exhibited the highest false negative rate (29.1%), while the highest false positive rate was found for the Chinese diagnostic criteria for AD in children (40.7%). The Zhang's criteria/Chinese criteria displayed the highest Youden index and Kappa coefficient, with a Kappa coefficient of 0.645 (95% CI: 0.541-0.748, P

Abstract Background Chemotherapy is the main treatment strategy for patients with advanced HER2-negative gastric cancer (GC); yet, many patients do not respond well to treatment. This study evaluated the sensitivity of a mini patient-derived xenograft (MiniPDX) animal model in patients with HER2-negative intermediate-advanced GC. Methods In this single-arm, open-label clinical study, we consecutively recruited patients with HER2-negative advanced or recurrent GC from September 2018 to July 2021. Tumor tissues were subjected to MiniPDX drug sensitivity tests for screening individualized anti-tumor drugs; appropriate drug types or combinations were selected based on drug screening results. The primary endpoints were progression-free survival (PFS) and safety, and the secondary endpoints were overall survival (OS) and objective response rate (ORR). Results A total of 17 patients were screened, and 14 eligible patients were included.The median follow-up time was 9 (2–34) months. The median PFS time was 14.1 (2–34) months, the median OS time was 16.9 (2–34) months, ORR was 42.9% (6/14), and DCR was 92.9% (13/14). The most common treatment-related adverse events (TRAE) were fatigue (14 (100%)), anorexia (13 (93%)) and insomnia (12 (86%)), and the most common grade 3 or worse TRAE was fatigue (6 (43%)), and anorexia (6 (43%)). The occurrence rate of myelosuppression, nausea and vomiting, abnormal liver enzymes, and other grade 3–4 chemotherapy adverse reactions were relatively low, and no grade 5 treatment-related adverse events occurred. Conclusion Screening HER2-negative medium-advanced GC/GJC chemotherapy regimens and targeted drugs based on MiniPDX animal models showed good tumor activity and safety.

Abstract Background P. aeruginosa, a highly virulent Gram-negative bacterium, can cause severe nosocomial infections, and it has developed resistance against most antibiotics. New therapeutic strategies are urgently needed to treat such bacterial infection and reduce its toxicity caused by endotoxin (lipopolysaccharide, LPS). Neutrophils have been proven to be able to target inflammation site and neutrophil membrane receptors such as Toll-like receptor-4 (TLR4) and CD14, and exhibit specific affinity to LPS. However, antibacterial delivery system based on the unique properties of neutrophils has not been reported. Methods A neutrophil-inspired antibacterial delivery system for targeted photothermal treatment, stimuli-responsive antibiotic release and endotoxin neutralization is reported in this study. Specifically, the photothermal reagent indocyanine green (ICG) and antibiotic rifampicin (RIF) are co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP-ICG/RIF), followed by coating with neutrophil membrane to obtain antibacterial delivery system (NM-NP-ICG/RIF). The inflammation targeting properties, synergistic antibacterial activity of photothermal therapy and antibiotic treatment, and endotoxin neutralization have been studied in vitro. A P. aeruginosa-induced murine skin abscess infection model has been used to evaluate the therapeutic efficacy of the NM-NP-ICG/RIF. Results Once irradiated by near-infrared lasers, the heat generated by NP-ICG/RIF triggers the release of RIF and ICG, resulting in a synergistic chemo-photothermal antibacterial effect against P. aeruginosa (~ 99.99% killing efficiency in 5 min). After coating with neutrophil-like cell membrane vesicles (NMVs), the nanoparticles (NM-NP-ICG/RIF) specifically bind to inflammatory vascular endothelial cells in infectious site, endowing the nanoparticles with an infection microenvironment targeting function to enhance retention time. Importantly, it is discovered for the first time that NMVs-coated nanoparticles are able to neutralize endotoxins. The P. aeruginosa murine skin abscess infection model further demonstrates the in vivo therapeutic efficacy of NM-NP-ICG/RIF. Conclusion The neutrophil-inspired antibacterial delivery system (NM-NP-ICG/RIF) is capable of targeting infection microenvironment, neutralizing endotoxin, and eradicating bacteria through a synergistic effect of photothermal therapy and antibiotic treatment. This drug delivery system made from FDA-approved compounds provides a promising approach to fighting against hard-to-treat bacterial infections.

Conforming to the current replace–reduce–refine 3Rs’ guidelines in animal experiments, a series of explorative efforts have been made to set up operable biomedical imaging-guided platforms for qualitative and quantitative evaluations on pharmacological effects of tumor vascular-disrupting agents (VDAs), based on the chick embryos (CEs) with its chorioallantoic membrane (CAM), in this overview. The techniques and platforms have been hierarchically elaborated, from macroscopic to microscopic and from overall to specific aspects. A protocol of LED lamplight associated with a new deep-learning algorithm was consolidated to screen out weak CEs by using the CAM vasculature imaging. 3D magnetic resonance imaging (MRI) and laser speckle contrast imaging (LSCI) to monitor the evolution of CE and vascular changes in CAM are introduced. A LSCI–CAM platform for studying the effects of VDAs on normal and cancerous vasculature of CAM and possible molecular mechanisms has been demonstrated. Finally, practical challenges and future perspectives are highlighted. The aim of this article is to help peers in biomedical research to familiarize with the CAM platform and to optimize imaging protocols for the evaluation of vasoactive pharmaceuticals, especially anticancer vascular targeted therapy.

Psoriasis is a complex, chronic autoimmune disorder predominantly affecting the skin. Accumulating evidence underscores the critical role of localized cellular inflammation in the development and persistence of psoriatic skin lesions, involving cell types such as keratinocytes, mesenchymal cells, and Schwann cells. However, the underlying mechanisms remain largely unexplored. Long non-coding RNAs (lncRNAs), known to regulate gene expression across various cellular processes, have been particularly implicated in immune regulation. We utilized our neural-network learning pipeline to integrate 106,675 cells from healthy human skin and 79,887 cells from psoriatic human skin. This formed the most extensive cell transcriptomic atlas of human psoriatic skin to date. The robustness of our reclassified cell-types, representing full-layer zonation in human skin, was affirmed through neural-network learning-based cross-validation. We then developed a publicly available website to present this integrated dataset. We carried out analysis for differentially expressed lncRNAs, co-regulated gene patterns, and GO-bioprocess enrichment, enabling us to pinpoint lncRNAs that modulate localized cellular inflammation in psoriasis at the single-cell level. Subsequent experimental validation with skin cell lines and primary cells from psoriatic skin confirmed these lncRNAs’ functional role in localized cellular inflammation. Our study provides a comprehensive cell transcriptomic atlas of full-layer human skin in both healthy and psoriatic conditions, unveiling a new regulatory mechanism that governs localized cellular inflammation in psoriasis and highlights the therapeutic potential of lncRNAs in this disease’s management.

Food safety has increasingly become a human health issue that concerns all countries in the world. Some substances in food that can pose a significant threat to human health include, but are not limited to, pesticides, biotoxins, antibiotics, pathogenic bacteria, food quality indicators, heavy metals, and illegal additives. The traditional methods of food contaminant detection have practical limitations or analytical defects, restricting their on-site application. Hydrogels with the merits of a large surface area, highly porous structure, good shape-adaptability, excellent biocompatibility, and mechanical stability have been widely studied in the field of food safety sensing. The classification, response mechanism, and recent application of hydrogel-based biosensors in food safety are reviewed in this paper. Furthermore, the challenges and future trends of hydrogel biosensors are also discussed.

The 2023 International African Swine Fever Workshop (IASFW) took place in Beijing, China, on 18–20 September 2023. It was jointly organized by the U.S.-China Center for Animal Health (USCCAH) at Kansas State University (KSU) and the Chinese Veterinary Drug Association (CVDA) and sponsored by the United States Department of Agriculture Foreign Agricultural Service (USDA-FAS), Harbin Veterinary Research Institute, and Zoetis Inc. The objective of this workshop was to provide a platform for ASF researchers around the world to unite and share their knowledge and expertise on ASF control and prevention. A total of 24 outstanding ASF research scientists and experts from 10 countries attended this meeting. The workshop included presentations on current ASF research, opportunities for scientific collaboration, and discussions of lessons and experiences learned from China/Asia, Africa, and Europe. This article summarizes the meeting highlights and presents some critical issues that need to be addressed for ASF control and prevention in the future.

Against the background of the current high level of development of off-campus tutoring institutions and the implementation of the "Double Reduction" policy of education, the establishment of a scientific evaluation index system for of the management behavioral norms is a powerful guarantee for the supervision of off-campus tutoring behavioral norms. The construction of the evaluation index system is mainly based on the content of policy supervision of off-campus tutoring. The existing supervision tools use the system model construction and index weight calculation method of the analytic hierarchy process (AHP) for reference. An evaluation system of operations behavioral norms for off-campus tutoring institutions is constructed, which consists of four dimensions: "operations foundation, organizational construction, operations process, and operations results". The evaluation system of behavioral norms for off-campus tutoring institutions includes "4 first-level indicators, 11 second-level indicators and 34 third-level indicators". It implements a scientific dynamic evaluation and monitoring of the degree of behavioral norms for off-campus tutoring. Therefore, it provides a decision-making basis for promoting off-campus tutoring institutions to improve and standardize operations and promote the effective achievement of the "Double Reduction" goal.

Abstract Aerogel fibers garner tremendous scientific interest due to their unique properties such as ultrahigh porosity, large specific surface area, and ultralow thermal conductivity, enabling diverse potential applications in textile, environment, energy conversion and storage, and high‐tech areas. Here, the fabrication methodologies to construct the aerogel fibers starting from nanoscale building blocks are overviewed, and the spinning thermodynamics and spinning kinetics associated with each technology are revealed. The huge pool of material choices that can be assembled into aerogel fibers is discussed. Furthermore, the fascinating properties of aerogel fibers, including mechanical, thermal, sorptive, optical, and fire‐retardant properties are elaborated on. Next, the nano‐confining functionalization strategy for aerogel fibers is particularly highlighted, touching upon the driving force for liquid encapsulation, solid–liquid interface adhesion, and interfacial stability. In addition, emerging applications in thermal management, smart wearable fabrics, water harvest, shielding, heat transfer devices, artificial muscles, and information storage, are discussed. Last, the existing challenges in the development of aerogel fibers are pointed out and light is shed on the opportunities in this burgeoning field.

African swine fever (ASF) is a lethal and highly contagious transboundary animal disease with the potential for rapid international spread. Currently, there is no ASF vaccine commercially available. All infected animals must be isolated and culled immediately upon the confirmation of the presence of the virus. Studies leading to the rational development of protective ASF vaccines are urgently needed. Here, we generated a safe and efficacious live-attenuated vaccine (LAV) VNUA-ASFV-LAVL2 by serially passaging a field isolate (VNUA-ASFV-05L1, genotype II) in porcine alveolar macrophages (PAMs, 65 passages) and an immortalized porcine alveolar macrophage cell line (3D4/21, 55 passages). VNUA-ASFV-LAVL2 can efficiently replicate in both PAMs and 3D4/21 cells. It provides 100% protection, even with the low dose of 102 HAD50, to the vaccinated pigs against the challenge of contemporary pandemic ASFV field isolate. Pigs vaccinated with this LAV in a dose range of 102 to 105 HAD50 remained clinically healthy during both the 28-day observation period of immunization and the 28-day observation period of challenge. VNUA-ASFV-LAVL2 was eliminated from blood by 28 days post-inoculation (DPI), and from feces or oral fluids by 17 DPI. Although the vaccine strain in serum remained a safe and attenuated phenotype after five passages in swine, a reversion-to-virulence study using blood or tissue homogenates at peak viremia will be conducted in the future. ASFV-specific IgG antibodies and significant cellular immunity were detected in vaccinated pigs before the ASFV challenge. These results indicate that the VNUA-ASFV-LAVL2 strain is a safe and efficacious LAV against the genotype II ASFV strain responsible for current ASF outbreaks in Asia.

In real life, there will be a lot of uncertainty problems, one of which is due to the vagueness of the concept of things, that is, it is difficult to determine whether an object conforms to this concept. This situation widely exists in some states, phenomena, parameters and interrelationships between things. For such uncertain events with heavy subjective influencing factors and incomplete data, it is suitable to use fuzzy methods to deal with them. In present our work, we firstly introduce the notion of D-number cognitive maps (DCMs), which are intelligent framework models based on D-number theory and cognitive maps. Compared with Evidential Cognitive Maps (ECMs) and Fuzzy Cognitive Maps (FCMs), DCMs can fuse multiple sources of information with uncertainty and construct a cognitive map model with incomplete and conflicting information. To better solve the problem of knowledge combination, D-number fuzzy cognitive maps (DFCMs) are also constructed based on D-number theory and fuzzy cognitive maps. In many practical applications, the establishment of fuzzy cognitive maps is usually completed by using a simple arithmetic average method for multiple experts to obtain comprehensive fuzzy cognitive maps. This simple processing method may lead to the loss of some important information so that the synthesized results do not reflect reality. To overcome this challenge, we synthesize the knowledge of multiple experts by using D-number theory and the characteristics of the representation of expert knowledge in FCMs. It is based on expert knowledge, and the synthesized reliability distribution function is used as the basis of final weight synthesis.

Immunotherapy is a revolutionary and promising approach to cancer treatment. However, traditional cancer immunotherapy often has the disadvantages of limited immune response rate, poor targeting, and low treatment index due to systemic administration. Hydrogels are drug carriers with many advantages. They can be loaded and transported with immunotherapeutic agents, chemical anticancer drugs, radiopharmaceuticals, photothermal agents, photosensitizers, and other therapeutic agents to achieve controlled release of drugs, extend the retention time of drugs, and thus successfully trigger anti-tumor effects and maintain long-term therapeutic effects after administration. This paper reviews recent advances in injectable hydrogel-based cancer immunotherapy, including immunotherapy alone, immunotherapy with combination chemotherapy, radiotherapy, phototherapy, and DNA hydrogel-based immunotherapy. Finally, we review the potential and limitations of injectable hydrogels in cancer immunotherapy.

Gastric cancer (GC) is a malignant cancer that reduces life expectancy worldwide. Although treatment strategies have improved, patients with GC still have poor prognoses. Hence, it is necessary to understand the molecular mechanisms of GC and to find new therapeutic targets. Mitochondrial dynamics and mitochondrial dysfunction are associated with cancer cell growth and progression. Numerous studies have reported that non-coding RNAs (ncRNAs) can participate in the occurrence and development of GC by regulating mitochondrial dynamics. Elucidating the crosstalk between ncRNAs and mitochondria would be helpful in preventing and treating GC. Herein, we review and summarize the functions of oncogenes and tumor suppressors in suppressing ncRNAs and regulating mitochondrial dynamics in GC tumor growth, proliferation, invasion and metastasis. This review provides new insights into the pathogenesis of and intervention for GC.

A metal-free and efficient visible-light induced cascade cyclization of alkyne-tethered cyclohexadienones with selenosulfonates for the synthesis of 3-sulfonyl-5-selanyl-4a,5-dihydro-2H-chromen-6(8aH)-one in good to excellent yields has been developed, in which three new stereocenters are formed and both sulfone and selenyl groups are simultaneously introduced.

Breast cancer has become the most commonly diagnosed cancer, surpassing lung cancer, with 2.26 million new breast cancers worldwide in 2020. Hence, there is an urgent need to develop effective molecularly targeted therapeutic drugs to treat breast cancer. In this paper, we designed, synthesized and screened a novel thiophene-triazine derivative, XS-2, as a potent dual PI3K/mTOR inhibitor for the treatment of breast cancer. Also, XS-2 was found to be potentially effective against triple-negative breast cancer (TNBC) in vitro during the investigation. We evaluated the in vitro inhibitory effect of XS-2 on 10 cancer cell lines by MTT and 6 kinases to investigated its in vivo antitumor activity in MCF-7 xenograft tumor-bearing BALB/c nude mice. In addition, the in vitro/in vivo toxicity to mice was also assessed by hemolytic toxicity, H&E staining and blood biochemical analysis. In order to investigate the antitumor mechanism of XS-2, a series of experiments were carried out in vitro/in vivo animal model and molecular biological levels such as the cell cycle and the apoptosis assay, real-time PCR, western blot, docking and molecular simulations analysis, etc. What’s more, wound healing assay, Transwell and Western Blot were applied to explore the ability of XS-2 to inhibit the cell invasion and migration. The results showed that XS-2 exhibited strong antitumor activity both in vitro and in vivo. The inhibitory activities of XS-2 on ten cancer cell lines were ranging from 1.07 ± 0.11 to 0.002 ± 0.001 μM, which were 1565 times better than that of the lead compound GDC-0941, inhibitory activities against PI3Kα and mTOR kinases were 291.0 and 60.8 nM, respectively. Notably, XS-2 not only showed significant in vivo antitumor activity and low toxicity, with the tumor inhibition rate of 57.0 %, but also exhibited strong inhibitory in the expression of related proteins of PI3K pathway in tumor tissues. In addition, XS-2 significantly inhibited breast cancer MCF-7 and MDA-MB-231 cells in a concentration- and time-dependent manner, and inhibited the migration and invasion ability of MDA-MB-231 and MCF-7 cells. More than that, XS-2 could inhibit the increase of the expression levels of N-cadherin and vimentin upregulated by EGF and reversed the E-cadherin expression down regulated by EGF, resulting in inhibiting EMT in MCF-7 and MDA-MB-231 cells. The results showed that XS-2 was expected to be successfully developed as a high-efficiency and low-toxicity breast cancer therapeutic drug with the potential to inhibit the invasion and migration of TNBC. This provides a new research idea for the treatment of TNBC, which is of great significance.

We used mouse CRC cell line (MC38) to establish a heterotopic mouse model, and applied [89Zr]-labeled PD-L1 antibody KN035 for PET imaging. Attenuated Salmonella typhimurium 3261 was used as an anti-tumor vaccine, and the combined anti-tumor immunotherapy with bivalent genetic vaccine and anti-PD1 antibody Nivolumab was conducted. MicroPET was performed to observe the changes of tumor tissues and expression of PD-L1. We found that the recombinant double-gene plasmids were stably expressed in COS7 cells. Study results showed the combined immunotherapy improved the effectiveness over genetic vaccine alone. This study supports that combination of genetic vaccines and anti-immunocheckpoint immunotherapy can inhibit MC38 tumor growth.

Currently, conventional neoadjuvant therapy or postoperative adjuvant therapy, such as chemotherapy and radiation therapy, can only bring limited survival benefits to gastric cancer (GC). Median survival after palliative chemotherapy is also low, at about 8–10 months. Immunotargeting is a new option for the treatment of GC, but has not been widely replicated. The highly immunosuppressed tumor microenvironment (TME) discounts the efficacy of immunotherapy for GC. Therefore, new strategies are needed to enhance the immune response of the TME. This paper reviewed the relationship between microorganisms and GC, potential links between microorganisms and immunotherapy and research of microorganisms combined immunotherapy.

Bi12O15Cl6/g-C3N4 binary type Ⅱ heterojunction photocatalyst was prepared by wet impregnation method. The crystal structure, morphology, and optical absorption of the samples were characterized by XRD, SEM, and UV-vis diffuse reflectance spectroscopy. With tetracycline as the target pollutant, the effects of doping ratio, dosage, and initial solution concentration on the photocatalytic degradation of Bi12O15Cl6/g-C3N4 were investigated under visible light. The results show that the removal rate of tetracycline is 96.43% in visible light irradiation for 150 min when the doping ratio is 50%, the dosage is 1.6 g/L, and the initial concentration of the solution is 10 mg/L. Finally, through the free radical capture experiment, it was proved that the free radicals playing the main role in the process of photocatalysis are h+ and ·O2-.

Abstract Psoriasis is the most common skin disease in adults. Current experimental and clinical evidences suggested the infiltrating immune cells could target local skin cells and thus induce psoriatic phenotype. However, recent studies indicated the existence of a potential feedback signaling loop from local resident skin cells to infiltrating immune cells. Here, we deconstructed the full-thickness human skins of both healthy donors and patients with psoriasis vulgaris at single cell transcriptional level, and further built a neural-network classifier to evaluate the evolutional conservation of skin cell types between mouse and human. Last, we systematically evaluated the intrinsic and intercellular molecular alterations of each cell type between healthy and psoriatic skin. Cross-checking with psoriasis susceptibility gene loci, cell-type based differential expression, and ligand-receptor communication revealed that the resident psoriatic skin cells including mesenchymal and epidermis cell types, which specifically harbored the target genes of psoriasis susceptibility loci, intensively evoked the expression of major histocompatibility complex (MHC) genes, upregulated interferon (INF), tumor necrosis factor (TNF) signalling and increased cytokine gene expression for primarily aiming the neighboring dendritic cells in psoriasis. The comprehensive exploration and pathological observation of psoriasis patient biopsies proposed an uncovered immunoregulatory axis from skin local resident cells to immune cells, thus provided a novel insight for psoriasis treatment. In addition, we published a user-friendly website to exhibit the transcriptional change of each cell type between healthy and psoriatic human skin.

Neutralizing antibodies (nAbs) can be used before or after infection to prevent or treat viral diseases. However, there are few efficacious nAbs against classical swine fever virus (CSFV) that have been produced, especially the porcine-originated nAbs. In this study, we generated three porcine monoclonal antibodies (mAbs) with in vitro neutralizing activity against CSFV, aiming to facilitate the development of passive antibody vaccines or antiviral drugs against CSFV that offer the advantages of stability and low immunogenicity. Pigs were immunized with the C-strain E2 (CE2) subunit vaccine, KNB-E2. At 42 days post vaccination (DPV), CE2-specific single B cells were isolated via fluorescent-activated cell sorting (FACS) baited by Alexa Fluor™ 647-labeled CE2 (positive), goat anti-porcine IgG (H + L)-FITC antibody (positive), PE mouse anti-pig CD3ε (negative) and PE mouse anti-pig CD8a (negative). The full coding region of IgG heavy (H) chains and light (L) chains was amplified by reverse transcription-polymerase chain reaction (RT-PCR). Overall, we obtained 3 IgG H chains, 9 kappa L chains and 36 lambda L chains, which include three paired chains (two H + κ and one H + λ). CE2-specific mAbs were successfully expressed in 293T cells with the three paired chains. The mAbs exhibit potent neutralizing activity against CSFVs. They can protect ST cells from infections in vitro with potent IC50 values from 14.43 µg/mL to 25.98 µg/mL for the CSFV C-strain, and 27.66 µg/mL to 42.61 µg/mL for the CSFV Alfort strain. This study is the first report to describe the amplification of whole-porcine IgG genes from single B cells of KNB-E2-vaccinated pig. The method is versatile, sensitive, and reliable. The generated natural porcine nAbs can be used to develop long-acting and low-immunogenicity passive antibody vaccine or anti-CSFV agents for CSF control and prevention.

Soil moisture (SM) is a key parameter of the hydrological process, which affects exchanges of water and heat at the land/atmosphere interface. The “trapezoid” (or “triangle”) method has been widely applied to SM monitoring based on the pixel distribution within the thermal and optical remote sensing observations. However, the trapezoid method is a linear empirical model highly related to the retrieval accuracy of the surface temperature. In the article, the moderate-resolution imaging spectroradiometer (MODIS) data were applied to retrieve SM through an improved method over the Tibetan Plateau. The improved method is integrated with the “trapezoid” model and multiple learning techniques, Random Forest (RF) and Extreme Gradient Boosting (XGBoost). Meanwhile, RF and XGBoost were both trained with SM target data (the scale of SM and soil temperature) derived from the Tibetan Plateau observations, and the input variables were derived from MODIS observations. Compared with the SM measured, the results showed the root mean square error, the mean absolute error, and the correlation coefficient of the ensemble retrievals were 0.046-0.081 m3m-3, 0.030-0.065 m3m-3, and 0.60-0.87, respectively, which is better than that of the separate model. The ideas to implement the combination of traditional inversion algorithms and machine learning methods are helpful for researches in remote sensing fields.

Abstract Due to the complexity, aggressiveness, and heterogeneity of malignant melanoma, it is difficult to eradicate the whole tumor through conventional treatment. Herein, a strategy of metabolic engineering labeled anaerobic oncolytic bacteria (Clostridium butyricum) is demonstrated to achieve the ablation of melanoma. In this system, the metabolic substrate of C. butyricum d‐alanine (d‐Ala) is first conjugated with a photosensitizer (TPApy) showing aggregation‐induced emission (AIE). The yielded metabolic substrate of d‐Ala‐TPAPy can be metabolically incorporated into bacterial peptidoglycan to form engineered C. Butyricum. Once the engineered C. butyricum is injected into melanoma, the bacteria can only proliferate in an anaerobic zone, stimulate the tumor immune microenvironment, and ablate the tumor hypoxia region. Following that, the relatively rich oxygen content in the peripheral area can induce the death of C. butyricum. The photosensitizer (PS) on the bacteria can subsequently exert a photodynamic effect in the oxygen‐rich region and further remove the melanoma residue under light irradiation. Prominent in vivo melanoma ablation results revealed that the engineering oncolytic bacteria can provide a promising regime for solid tumor eradication.

In this study, we designed and synthesized a series of novel [1,2,4]triazolo [4,3-a]pyrazine derivatives, and evaluated them for their inhibitory activities toward c-Met/VEGFR-2 kinases and antiproliferative activities against tested three cell lines in vitro. Most of the compounds showed satisfactory activity compared with lead compound foretinib. Among them, the most promising compound 17l exhibited excellent antiproliferative activities against A549, MCF-7, and Hela cancer cell lines with IC50 values of 0.98 ± 0.08, 1.05 ± 0.17, and 1.28 ± 0.25 µM, respectively, as well as excellent kinase inhibitory activities (c-Met IC50 = 26.00 nM and VEGFR-2 IC50 = 2.6 µM). Moreover, compound 17l inhibited the growth of A549 cells in G0/G1 phase in a dose-dependent manner, and induced the late apoptosis of A549 cells. Its intervention on intracellular c-Met signaling of A549 was verified by the result of Western blot. Fluorescence quantitative PCR showed that compound 17l inhibited the growth of A549 cells by inhibiting the expression of c-Met and VEGFR-2, and its hemolytic toxicity was low. Molecular docking and molecular dynamics simulation indicated that compound 17l could bind to c-Met and VEGFR-2 protein, which was similar to that of foretinib.

Background: For anaphylaxis, a life-threatening allergic reaction, the incidence rate was presented to have increased from the beginning of the 21st century. Underdiagnosis and undertreatment of anaphylaxis are public health concerns.Objective: This guideline aimed to provide high-quality and evidence-based recommendations for the emergency management of anaphylaxis.Method: The panel of health professionals from fifteen medical areas selected twenty-five clinical questions and formulated the recommendations with the supervision of four methodologists. We collected evidence by conducting systematic literature retrieval and using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.Results: This guideline made twenty-five recommendations that covered the diagnosis, preparation, emergency treatment, and post-emergency management of anaphylaxis. We recommended the use of a set of adapted diagnostic criteria from the American National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network (NIAID/FAAN), and developed a severity grading system that classified anaphylaxis into four grades. We recommended epinephrine as the first-line treatment, with specific doses and routes of administration for different severity of anaphylaxis or different conditions. Proper dosage is critical in the administration of epinephrine, and the monitor is important in the IV administration. Though there was only very low or low-quality evidence supported the use of glucocorticoids and H1 antagonists, we still weakly recommended them as second-line medications. We could not make a well-directed recommendation regarding premedication for preventing anaphylaxis since it is difficult to weigh the concerns and potential effects.Conclusion: For the emergency management of anaphylaxis we conclude that:• NIAID/FAAN diagnostic criteria and the four-tier grading system should be used for the diagnosis• Prompt and proper administration of epinephrine is critical.

The Jinghe County of the Ebinur Lake Basin was chosen as the study area. Based on Landsat TM / OLI images obtained in 2007 and 2017, this paper attempts to use CLUE-S model to predict LUCC under three different scenarios (Natural Development scenario, Farmland Protection scenario, Water Resources Protection scenarios) in 2027. Landscape indices and ecological risk index were calculated and spatially interpolated for the whole region, and the results of ecological risk could be divided into five different zones: extremely low, low, moderate, high and extremely high. They were carried out for assessing the spatial–temporal changes in ecological risk for each landscape pattern. The results show that: (1) Among the three scenarios designed in this paper, the spatial distribution of LUCC in the Water Resource Protection scenario has the most obvious changes, followed by the Farmland Protection scenario and the Natural Development scenario becomes the third. In the water resources protection scenario, the scale of the desert decreases, but the forest and grass part increases, which is conducive to ecological improvement. (2) the distribution area of high ecological risk areas was the largest of three different scenarios, especially the farmland protection scenario. The area of low-risk level is the largest under the water conservation scenario. The ecological risk of LUCC under the water resources protection scenario is lower, which is better for ecological environment. (3) Water bodies mainly concentrate upon low ecological risk degree, accounting for approximately 62.8%, 82.2%, and 73.1% of low ecological risk; Farmland mainly lies in the low-risk areas, accounting for 59.1%, 63.5% and 68.8% of the lower ecological risk levels; In 2027, the unused land and other land types are the main land types of the higher ecological risk areas under three different scenarios, whose proportions are 67.40%, 68.24% and 65.90%, respectively.

Herein, Zn3In2S6 photocatalyst with (110) exposed facet was prepared by low temperature solvothermal method. On this basis, a highly efficient binary Zn3In2S6/g-C3N4 was obtained by low temperature solvothermal method and applied to the degradation of tetracycline (TC). The samples of the preparation were characterized by X-ray diffraction, scanning electron microscope, transmission electron microscope, UV–vis diffuse reflection spectroscopy, and photoluminescence spectroscopy. Furthermore, the degradation performance of photocatalysts on TC was investigated under different experimental conditions. Finally, the mechanism of Zn3In2S6/g-C3N4 composite material degrading TC is discussed. The results show that Zn3In2S6 and Zn3In2S6/g-C3N4 photocatalysts with excellent performance could be successfully prepared at lower temperature. The Zn3In2S6/g-C3N4 heterojunction photocatalyst could significantly improve the photocatalytic activity compared with g-C3N4. After 150 min of illumination, the efficiency of 80%Zn3In2S6/g-C3N4 to degrade TC was 1.35 times that of g-C3N4. The improvement of photocatalytic activity was due to the formation of Zn3In2S6/g-C3N4 heterojunction, which promoted the transfer of photogenerated electron–holes. The cycle experiment test confirmed that Zn3In2S6/g-C3N4 composite material had excellent stability. The free radical capture experiment showed that ·O2− was the primary active material. This study provides a new strategy for the preparation of photocatalysts with excellent performance at low temperature.

Heterocyclic compounds with excellent nonlinear optical (NLO) properties are highly significant and have many potentials uses in various fields such as nuclear science, optoelectronics etc. Herein, an organic dye JK-201 was used theoretically to design a series of novel D-π-A based NLO molecules (DTA1-DTA12). This novel series of NLO molecules was quantum chemically designed by structural tailoring at the 1st π-spacer and acceptors unit of the JK-201 molecule. To explore the effect of spacers and acceptors on the electronic, photophysical, and NLO properties of DTA1-DTA12, density functional theory (DFT) investigations were performed for different simulation analyses. UV–Vis spectra revealed that all these novel compounds exhibited broader absorption spectra with the largest shift and a narrowed bandgap (1.84–2.07 eV) compared to the parent molecule (JK-201). Among all the designed compounds, the largest redshift was examined in DTA11 (538.99 nm). Furthermore, with the help of frontier molecular orbital (FMO) study, charge transfer processes between the orbitals and chemical reactivity of designed molecules were explained. Moreover, the Energy gap (ELUMO-EHOMO) was also used to express global reactivity parameters (GRPs). These GRP findings evaluated that all molecules (DTA1-DTA12) had higher global softness (σ = 13.15–14.77 a.u) and lower hardness (η = 0.034–0.038 a.u) values, which indicated that these compounds were more reactive. Nevertheless, significantly higher NLO behavior was examined in all compounds. Overall, compound DTA5 showed a larger value of the linear polarizability (= 2868.08 a.u.), while compound DTA12 displayed a larger hyperpolarizability (βtotal = 268494.71 a.u) value. This present work presented that by controlling the type of π-spacer and acceptor units, metal-free NLO materials can be designed, which can be valuable for hi-tech NLO applications.

Although humans constitute an exceptionally cooperative species that is able to collaborate on large scales for common benefits, cooperation remains a longstanding puzzle in biological and social science. Moreover, cooperation is not always related to resource allocation and gains but is often related to losses. Revealing the neurological mechanisms and brain regions related to cooperation is important for reinforcing cooperation-related gains and losses. Recent neuroscience studies have found that the decision-making process of cooperation is involved in the function of the ventromedial prefrontal cortex (VMPFC). In the present study, we aimed to investigate the causal role of the VMPFC in cooperative behavior concerning gains and losses through the application of transcranial direct current stimulation (tDCS). We integrated cooperation-related gains and losses into a unified paradigm. Based on the paradigm, we researched cooperation behaviors regarding gains in standard public good games and introduced public bad games to investigate cooperative behavior regarding losses. Our study revealed that the VMPFC plays different roles concerning gains and losses in situations requiring cooperation. Anodal stimulation over the VMPFC decreased cooperative behavior in public bad games, whereas stimulation over the VMPFC did not change cooperative behavior in public good games. Moreover, participants’ beliefs about others’ cooperation were changed in public bad games but not in public good games. Finally, participants’ cooperative attitudes were not influenced in the public good or public bad games under the three stimulation conditions.

MicroRNA (miRNA) is an important regulator for gene expression. Recent studies showed that some heterogenous miRNAs derived from both parasite and plant can regulate expression of mammalian gene in a cross-species or even a cross-kingdom manner. Here, we identified a Schistosoma japonicum miRNA (designated as sja-miR-61) that is present in the hepatocyte of mice infected with the parasite. The sja-miR-61 mimics significantly inhibited the migration of both mouse and human hepatoma cells in vitro. In a xenograft animal model, significant reductions of the tumor volume and weight were observed in mice inoculated with hepatoma cells transfected with sja-miR-61 mimics compared to the controls. We found that the in vivo inhibition of tumor growth was through its anti-angiogenesis activity. Mechanically, we identified the phosphoglycerate mutase 1 (PGAM1) gene as a target of sja-miR-61 and found that the sja-miR-61-mediated suppression of cell migration and anti-angiogenesis by cross-species down-regulation of PGAM1 expression. These data indicated that sja-miR-61 is a tumor suppressor miRNA that may have therapeutic potential for human cancers.

Against the background of economic globalization, the strategies for constructing college students' entrepreneurial value judgment are explored, providing college graduates with more employment options and thereby keeping up with the trend of the times. The documentary analysis and questionnaire survey methods are adopted to investigate contemporary college students' entrepreneurial value judgments, and the investigation results are organized. According to documentary materials, the discovered problems are analyzed to put forward strategies for constructing college students' entrepreneurial value judgments based on educational psychology. Results show that only 14.1% of college graduates choose to start a business; 48.7% do not understand or recognize the entrepreneurial values; 14.8% believe teaching activities on constructing entrepreneurial value judgments are insufficient, and the entrepreneurial atmosphere is lacking. Regarding the above investigation results, strategies for constructing college students' entrepreneurial value judgments are proposed, involving the construction environment, construction system, construction method, and construction mechanism. Hence, considering contemporary college students' entrepreneurial values, the proposed strategies for constructing college students' entrepreneurial judgments are suitable and valuable, providing a practical reference for enriching and perfecting the college innovation and entrepreneurship education systems.

Kojic acid is an important secondary metabolite of industrial importance produced by Aspergillus oryzae. The kojic acid gene cluster plays an essential role in kojic acid production, and harbors kojA, kojR and kojT. The deletion of kojT, encoding a major facilitator superfamily (MFS) transporter, did not completely abolish kojic acid production, implying that other transporters are required for the transport of kojic acid. The aim of this study is to look for the transporters involved in kojic acid production. Here, Aokap4 encoding a novel MFS transporter was identified, which was adjacent to kojT in the kojic acid gene cluster. The deletion of Aokap4 contributed to the hyphal growth, conidial production and biomass of A. oryzae. Moreover, Aokap4 is required for heat- and cell-wall-stress tolerance but not oxidative and osmotic stress. The disruption of Aokap4 impaired kojic acid production with the reduced expression of kojA, kojR and kojT. Furthermore, when kojT was deleted in the Aokap4-disrupted strain, the yield of kojic acid declined to the same level as that of the kojT-deletion mutant, whereas the production of kojic acid was recovered when kojT was overexpressed in the Aokap4 knockout strain, suggesting that kojT acts downstream of Aokap4. AoKap4 was the second identified MSF transporter involved in kojic acid production after kojT was found a decade ago. This study contributes to a better understanding of the biological roles of the MFS transporter and lays a foundation for future studies on kojic acid synthesis in A. oryzae.

Classical swine fever can be controlled effectively by vaccination with C-strain vaccine. In this study, we developed a novel competitive enzyme-linked immunosorbent assay (cELISA) based on a C-strain Erns specific monoclonal antibody (mAb 1504), aiming to serologically measure immune responses to C-strain vaccine in pigs, and finally to make the C-strain become a DIVA-compatible vaccine. The cELISA system was established based on the strategy that mAb 1504 will compete with the C-strain induced antibodies in the pig serum to bind the C-strain Erns protein. The cELISA was optimized and was further evaluated by testing different categories of pig sera. It can efficiently differentiate C-strain immunized from wild-type CSFV-infected pigs and lacks cross-reaction with other common swine viruses and viruses in genus Pestivirus such as Bovine viral diarrhea virus (BVDV). The C-strain antibody can be tested in pigs 7–14 days post vaccination with this cELISA. The sensitivity and specificity of the established cELISA were 100% (95% confidence interval: 95.60 to 100%) and 100% (95% confidence interval: 98.30 to 100%), respectively. This novel cELISA is a reliable tool for specifically measuring and differentiating immune responses to C-strain vaccine in pigs. By combining with the wild-type CSFV-specific infection tests, it can make the C-strain have DIVA capability.

Revenge is common in our daily lives, and people feel good when engaging in revenge behavior. However, revenge behavior is a complex process and remains somewhat of a puzzle of human behavior. Neuroimaging studies have revealed that revenge behaviors are associated with activation of a neural network containing the anterior cingulate cortex, ventral striatum, inferior frontal gyrus, and dorsolateral prefrontal cortex (DLPFC). Recent brain stimulation research using transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation has shown a causal relationship between brain regions and revenge behaviors, but the findings have been mixed. In the present study, we aimed to study whether stimulation in the DLPFC can change participants’ revenge behavior in conditions where participants’ wealth was taken away in different ways. We adapted the moonlighting game and designed a new paradigm. Our study revealed that revenge behavior increased following activation in the right DLPFC, suggesting that the right DLPFC plays an important role in overriding self-interest and retaliation. In addition, our results revealed that the right DLPFC is crucial in revenge behavior related to the motivation of invasion.

Myocardial ischemia (MI) is one of the most common cardiovascular diseases with high incidence and mortality. Huang-Lian-Jie-Du-Tang (HLJDT) is a classic traditional Chinese prescription to clear “heat” and “poison”. In this study, we used a deliberate strategy integrating the methods of network pharmacology, pharmacodynamics, and metabonomics to investigate the molecular mechanism and potential targets of HLJDT in the treatment of MI. Firstly, by a network pharmacology approach, a global view of the potential compound-target-pathway network based on network pharmacology was constructed to provide a preliminary understanding of bioactive compounds and related targets of HLJDT for elucidating its molecular mechanisms in MI. Subsequently, in vivo efficacy of HLJDT was validated in a rat model. Meanwhile, the corresponding metabonomic profiles were used to explore differentially induced metabolic markers thus providing the metabolic mechanism of HLJDT in treating MI. The results demonstrated the myocardial protection effect of HLJDT on ischemia by a multicomponent-multitarget mode. This study highlights the reliability and effectiveness of a network pharmacology-based approach that identifies and validates the complex of natural compounds in HLJDT for illustrating the mechanism for the treatment of MI.

Antisocial behavior and prosocial behavior in the condition of inequality have long been observed in daily life. Understanding the neurological mechanisms and brain regions associated with antisocial and prosocial behavior and the development of new interventions are important for reducing violence and inequality. Fortunately, neurocognitive research and brain imaging research have found a correlation between antisocial or prosocial behavior and the prefrontal cortex. Recent brain stimulation research adopting transcranial direct current stimulation or transcranial magnetic stimulation has shown a causal relationship between brain regions and behaviors, but the findings are mixed. In the present study, we aimed to study whether stimulation of the DLPFC can change participants’ antisocial and prosocial behavior in the condition of inequality. We integrated antisocial and prosocial behavior in a unified paradigm. Based on this paradigm, we discussed costly and cost-free antisocial and prosocial behavior. In addition, we also measured participants’ disadvantageous and advantageous inequality aversion. The current study revealed an asymmetric effect of bilateral stimulation over the DLPFC on costly antisocial behavior, while such an effect of antisocial behavior without cost and prosocial behavior with and without cost were not observed. Moreover, costly antisocial behavior exhibited by men increased after receiving right anodal/left cathodal stimulation and decreased after receiving right cathodal anodal/left anodal stimulation compared with the behavior observed under sham stimulation. However, subjects’ inequality aversion was not influenced by tDCS.

Psoriasis is a chronic inflammatory skin disease that affects approximately 125 million people worldwide. It has significant impacts on both physical and emotional health-related quality of life comparable to other major illnesses. Accurately prediction of psoriasis using biomarkers from routine laboratory tests has important practical values. Our goal is to derive a powerful predictive model for psoriasis disease based on only routine hospital tests. We collected a data set including 466 psoriasis patients and 520 healthy controls with 81 variables from only laboratory routine tests, such as age, total cholesterol, HDL cholesterol, blood pressure, albumin, and platelet distribution width. In this study, Boruta feature selection method was applied to select the most relevant features, with which a Random Forest model was constructed. The model was tested with 30 repetitions of 10-fold cross-validation. Our classification model yielded an average accuracy of 86.9%. 26 notable features were selected by Boruta, among which 15 features are confirmed from previous studies, and the rest are worth further investigations. The experimental results demonstrate that the machine learning approach has good potential in predictive modeling for the psoriasis disease given the information only from routine hospital tests.

Social conformity has been evaluated in many different contexts, ranging from an emotional contagion in psychology, to speculative episodes in economics, to mass protests concerning politics. Previous neuroscience studies suggest that the ventromedial prefrontal cortex (vmPFC) participates in social conformity, especially when it comes to the value integration process, but the specific mechanism of vmPFC is still unclear. In this study, we aimed to identify a direct link between the vmPFC and conformity tendencies by means of transcranial direct current stimulation (tDCS). Conformity tendencies are measured by the probability that participants change their decisions when they observe the majority responses. In our experiment, subjects could make two decisions in each trial, once without social information and once with social information, which allowed us to directly observe the conformity tendency of subjects in different conditions. We found that cathodal stimulation of the vmPFC significantly increased conformity tendency and decreased response time when the initial decision of participants differs from the majority opinion. Based on the experimental results, our study suggests that the vmPFC mainly inhibits and regulates the informational conformity behavior. These findings complement investigations of the neural mechanism of conformity and the role of the vmPFC in the neural circuit behind conformity behavior.

The concentration of 5-hydroxymethyl-2-furfural (HMF) is an important quality-related index in milk and milk products. Fast, cost-effective and environmentally friendly determination of HMF is of great significance in milk products control. In this study, a three-dimensional (3D) graphene-like surface (3DGrls) was successfully prepared within 5 min by an electrochemical amperometric pretreatment on a pencil graphite electrode (PGE). The fast-obtained 3D graphene-like surface increased the electrode surface area and enhanced the electron transfer capability without the addition of any harmful chemicals. The morphology and chemical composition of the obtained electrode were characterized by scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and electrochemical impedance spectroscopy (EIS). The results found that the electrochemical response to HMF at the prepared 3DGrls/PGE was 34 times higher than that at PGE. The modified electrode showed a good linear response to HMF in a concentration range of 0.35~116 μM with a low limit of detection (LOD) of 0.099 μM. The integrated electrode also exhibited excellent stability and wonderful antifouling property. Furthermore, the 3DGrls/PGE was successfully applied for the determination of HMF in three processed cheese samples with satisfactory results.

Apoptosis is an evolutionarily conserved suicide process. It plays critical roles in the development and homeostasis of cardiac tissues. However, excessively stimulated apoptotic activity induced by a myriad of deleterious stimuli can result in too much cardiomyocyte death. The regenerative potential of the adult cardiomyocytes is limited. The cardiomyocyte loss cannot be compensated by efficient cell proliferation. It inevitably leads to various heart diseases. Therefore, the inhibition of cardiomyocyte apoptosis is an important therapeutic strategy for heart diseases. Chinese materia medica (CMM) has more than 2000 years of history and provides effective adjuvant therapeutic strategies for heart disease at the clinical level. The mechanisms underlying the beneficial effects of CMM on heart diseases have been a major focus of recent research. Interestingly, it has been demonstrated that CMM can up-regulate the levels of anti-apoptotic proteins and down-regulate the levels of pro-apoptotic proteins to inhibit apoptotic activity, thereby suppressing cardiomyocyte apoptosis in response to harmful stimuli. The inhibitory effects of CMM on apoptotic activity are mediated by the transduction of intracellular signaling. In this review, we summarize and discuss current findings on the roles and mechanisms of CMM in cardiomyocyte apoptosis.