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Recently, a new sub-branch Ⅰb of Mpox virus (MPXV) has triggered a new round of Mpox outbreak. 2024-08-14, Mpox was once again classified as a public health emergency of international concern (PHEIC) by the WHO. Early detection and diagnosis of Mpox cases is the key to interrupting the spread of Mpox in hospitals. In this article, we will review the pathogenetic features, epidemiological features, clinical features, diagnostic criteria, preventive and control measures of Mpox, with a view to providing reference for the early identification, scientific prevention and control of Mpox.

Abstract Background The emergence of new molecular targeted drugs marks a breakthrough in asthma treatment, particularly for severe cases. Yet, options for moderate-to-severe asthma treatment remain limited, highlighting the urgent need for novel therapeutic drug targets. In this study, we aimed to identify new treatment targets for asthma using the Mendelian randomization method and large-scale genome-wide association data (GWAS). Methods We utilized GWAS data from the UK Biobank (comprising 56,167 patients and 352,255 control subjects) and the FinnGen cohort (including 23,834 patients and 228,085 control subjects). Genetic instruments for 734 plasma proteins and 154 cerebrospinal fluid proteins were derived from recently published GWAS. Bidirectional Mendelian randomization analysis, Steiger filtering, colocalization, and phenotype scanning were employed for reverse causal inference detection, further substantiating the Mendelian randomization results. A protein-protein interaction network was also constructed to reveal potential associations between proteins and asthma medications. Results Under Bonferroni significance conditions, Mendelian randomization analysis revealed causal relationships between seven proteins and asthma. In plasma, we observed that an increase of one standard deviation in IL1R1[1.30 (95% CI 1.20–1.42)], IL7R[1.07 (95% CI 1.04–1.11)], ECM1[1.03 (95% CI 1.02–1.05)], and CD200R1[1.18 (95% CI 1.09–1.27)] were associated with an increased risk of asthma, while an increase in ADAM19 [0.87 (95% CI 0.82–0.92)] was found to be protective. In the brain, each 10-fold increase in IL-6 sRa [1.29 (95% CI 1.15–1.45)] was associated with an increased risk of asthma, while an increase in Layilin [0.61 (95% CI 0.51–0.73)] was found to be protective. None of the seven proteins exhibited a reverse causal relationship. Colocalization analysis indicated that ECM1 (coloc.abf-PPH4 = 0.953), IL-6 sRa (coloc.abf-PPH4 = 0.966), and layilin (coloc.abf-PPH4 = 0.975) shared the same genetic variation as in asthma. Conclusion A causal relationship exists between genetically determined protein levels of IL1R1, IL7R, ECM1, CD200R1, ADAM19, IL-6 sRa, and Layilin (LAYN) and asthma. Moreover, the identified proteins may serve as attractive drug targets for asthma, especially ECM1 and Layilin (LAYN). However, further research is required to comprehensively understand the roles of these proteins in the occurrence and progression of asthma.

Abstract Interstitial lung disease (ILD) is known to be a major complication of systemic sclerosis (SSc) and a leading cause of death in SSc patients. As the most common type of ILD, the pathogenesis of idiopathic pulmonary fibrosis (IPF) has not been fully elucidated. In this study, weighted correlation network analysis (WGCNA), protein‒protein interaction, Kaplan–Meier curve, univariate Cox analysis and machine learning methods were used on datasets from the Gene Expression Omnibus database. CCL2 was identified as a common characteristic gene of IPF and SSc. The genes associated with CCL2 expression in both diseases were enriched mainly in chemokine-related pathways and lipid metabolism-related pathways according to Gene Set Enrichment Analysis. Single-cell RNA sequencing (sc-RNAseq) revealed a significant difference in CCL2 expression in alveolar epithelial type 1/2 cells, mast cells, ciliated cells, club cells, fibroblasts, M1/M2 macrophages, monocytes and plasma cells between IPF patients and healthy donors. Statistical analyses revealed that CCL2 was negatively correlated with lung function in IPF patients and decreased after mycophenolate mofetil (MMF) treatment in SSc patients. Finally, we identified CCL2 as a common biomarker from IPF and SSc, revealing the common mechanism of these two diseases and providing clues for the study of the treatment and mechanism of these two diseases.

Age-related macular degeneration (AMD) is the first permanent cause of vision loss in developed countries, which is also a disease with high incidence and blindness rate in China. Studies have demonstrated that lipid metabolism is one of the key mechanisms of AMD. However, the precise mechanism remains unclear and medications for AMD treatments based on this mechanism have not yet been established. In this review, we critically review relevant studies to examine the associations between lipid metabolism and AMD from the perspectives of lipoproteins, lipid metabolism-related molecular, and lipid metabolism-related treatments, aiming to help understand the roles that lipid metabolism mechanisms play in the development and progression of AMD and to provide ideas for future targeted lipid metabolism therapies.

Abstract Background Small cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes. Methods The current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC. Results In combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3β/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues. Conclusions Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.

BackgroundBranched-chain amino acids (BCAAs) are widely used as sports nutrition supplements. However, their impact on the rate of force development (RFD), an indicator of explosive muscle strength, has not yet been validated. This study aimed to assess the impact of BCAA supplementation on the RFD in college basketball players during simulated games.MethodsThis study employed a randomized, controlled crossover, double-blind design. Participants received either BCAAs (0.17 g/kg combined with 0.17 g/kg isocaloric glucose) or a placebo (0.34 g/kg isocaloric glucose) orally 30 min before beginning the exercise protocol. The RFD was quantified using the isometric mid-thigh pull (IMTP) test. Additional outcome measures, including strength and jump tests, agility and sprinting tests, and physiological responses, were also assessed. A two-way repeated measures ANOVA was employed to evaluate the impact of supplements (BCAAs and placebo) on RFD and other related outcome measures.ResultsAnalysis of the 50 ms RFD demonstrated significant main effects of BCAA supplementation (p = 0.003). The BCAAs group consistently exhibited higher levels of 50 ms RFD compared to the placebo group across rounds 1 to 4. For example, in round 1, the 50 ms RFD was 3702.3 ± 1223.2 N/S in the BCAAs group versus 2931.3 ± 888.8 N/S in the placebo group (p = 0.045). Although no significant between-group differences were observed for the 100, 150, 200, and 250 ms RFD measurements, the BCAAs group consistently showed superior values across all time points. The results of other outcome indicators also suggested that supplementation with BCAAs was indeed effective.ConclusionThe results indicate that BCAA supplementation can enhance RFD in basketball players, particularly at the 50 ms RFD. Our research design provides reliable insights into the effects of BCAAs on athletic performance. Further studies of similar design with larger sample sizes are necessary to confirm and extend these findings.Clinical trial registrationChinese Clinical Trial Registry, ChiCTR2400091314 (https://www.chictr.org.cn).

ABSTRACT: Infectious laryngotracheitis (ILT) and Newcastle disease (ND) are 2 highly infectious avian respiratory diseases that have caused significant economic losses in the poultry industry worldwide. In ovo vaccination is administered during the late stage of incubation and is an attractive immunization method for poultry industry. However, most of the avian live vaccine strains that are safe for use after hatching are highly pathogenic to chicken embryos and therefore unsafe for in ovo vaccination. Previously, a recombinant Newcastle disease virus (NDV) strain, rTS-gB, expressing the gB protein of Infectious laryngotracheitis virus (ILTV), was demonstrated to be safe and immunogenic as a bivalent vaccine for hatched birds. In this study, we evaluated the safety and protective efficacy of rTS-gB as an in ovo vaccine. This vaccine strain was found to be safe for in ovo vaccination, with a hatchability and survival rate of 93.3% in chickens vaccinated in ovo with rTS-gB. In ovo vaccination with rTS-gB induced effective ILTV- and NDV-specific antibody responses in birds and conferred complete protection against virulent NDV and ILTV challenges. Furthermore, shedding of the challenged ILTV in cloacal and tracheal samples from in ovo vaccinated chickens was greatly reduced. These results indicate that the rNDV strain rTS-gB is a safe and highly immunogenic in ovo vaccine candidate against both ND and ILT.

Abstract The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy and immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC treatment remains limited, and the underlying mechanisms are still uncertain. Therefore, this study aimed to characterize the effects and mechanisms of ATO in HCC. By evaluating the susceptibilities of human and murine HCC cell lines to ATO treatment, we discovered that HCC cells exhibited a range of sensitivity to ATO treatment, highlighting their inherent heterogeneity. A gene signature comprising 265 genes was identified to distinguish ATO-sensitive from ATO-insensitive cells. According to this signature, HCC patients have also been classified and exhibited differential features of ATO response. Our results showed that ATO treatment induced reactive oxygen species (ROS) accumulation and the activation of multiple cell death modalities, including necroptosis and ferroptosis, in ATO-sensitive HCC cells. Meanwhile, elevated tumoral immunogenicity was also observed in ATO-sensitive HCC cells. Similar effects were not observed in ATO-insensitive cells. We reported that ATO treatment induced mitochondrial injury and mtDNA release into the cytoplasm in ATO-sensitive HCC tumors. This subsequently activated the cGAS-STING-IFN axis, facilitating CD8+ T cell infiltration and activation. However, we found that the IFN pathway also induced tumoral PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted the anti-tumor response of ATO in ATO-sensitive HCC tumors. In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study.

Objective: The objective of this study was to decipher chemical interactions between Danshen and Danggui using liquid chromatography–mass spectrometry (LC-MS) and explore the mechanisms of Danshen–Danggui against stroke using network pharmacology and molecular docking. Materials and Methods: First, the chemical compounds of Danshen–Danggui were profiled using ultra-high-performance liquid chromatography (HPLC)-quadrupole time-of-flight MS. Accurately characterized compounds in various proportions of Danshen–Danggui were quantified using HPLC combined with triple quadrupole electrospray tandem MS. Network pharmacology was used to uncover the essential mechanisms of action of Danshen–Danggui against stroke. Discovery Studio Software was used for the molecular docking verification of key active chemicals and stroke-related targets. Results: A total of 53 compounds were characterized, and 22 accurately identified constituents (10 phenolic acids, 8 phthalides, and 4 tanshinones) were quantified in 15 proportions of Danshen–Danggui. The quantification results showed that Danggui significantly increased the dissolution of most phenolic acids (compounds from Danshen), whereas Danshen promoted the dissolution of most phthalides (compounds from Danggui). Overall, the combination of Danshen and Danggui at a 1:1 ratio resulted in the maximum total dissolution rate. Further network pharmacology and molecular docking results indicated that Danshen–Danggui exerted anti-stroke effects mainly by regulating inflammation-related (tumor necrosis factor, hypoxia-inducible factor, and toll-like receptor) signaling pathways, which ranked among the top three pathways based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Conclusion: The chemical compounds in Danshen–Danggui could interact with each other to increase the dissolution of the most active compounds, which could provide a solid basis for uncovering the compatibility mechanisms of Danshen–Danggui and Danshen–Danggui-based formulae.

In view of the natural endowment of mercury in fossil fuels and mineral resources, as well as the mercury emission controlling and regulating in the energy and resource utilization processes, the research and development on the mercury continuous emissions monitoring system (Hg-CEMS) with proprietary intellectual property rights is the most important requirement in science and technology in China. As a critical component of the Hg-CEMS system, the flue gas pretreatment system is a core technology that limits the development and application of the Hg-CEMS technology in China. This paper presents a comprehensive review of the research progress in the four key modules of the Hg-CEMS flue gas pretreatment technology, including the dilution sampling, Hg0/Hg2+ separation, Hg2+ reduction and Hg2+ calibration gas generation. Firstly, the dilution sampling techniques are highlighted in their characteristics and principles. The working principles, structures, and design considerations of the critical parameters for both critical hole and thermal dilution injectors are summarized. Emphasis is focused on the connection of numerical simulation with the optimal design methodology for the thermal dilution injector and critical hole. Secondly, regarding the Hg0/Hg2+ separation technology, various partitioning methodologies encompassing the wet absorption separation, physical adsorption separation and chemical adsorption separation are discussed. Particular attention is given to the separation and adsorption efficiency of the advanced dry chemical adsorption techniques involving the novel selective adsorbents of KCl and CaO with their updated theoretical and experimental outcomes under practical operating conditions. Thirdly, in aspect of the Hg2+ reduction technology, a comparative analysis of wet chemical reduction, low-temperature reduction and high-temperature reduction techniques is expatiated. Particular focus is on the active components of solid-state reducing agents, the impact of temperature on the reduction of divalent mercury, and the detrimental influences of flue gas components on the re-oxidation of the reduced elemental mercury in the low-temperature reduction techniques. An in-depth investigation of the impact of filler materials, acidic gas components and acid removal techniques on the reduction of divalent mercury in the high-temperature reduction techniques is highlighted. Finally, facing the technical problems, a solid generation method of the Hg2+ calibration gas is invented and its industrial utilization feasibility is verified in chemistry and experiments. In conjunction with the current status of research and application of the Hg-CEMS technology, the research technical routs, the solutions to some problems and development prospect for the above-mentioned four key modules are put forward.

The industrialization of animal agriculture has undoubtedly contributed to the improvement of human well-being by increasing the efficiency of food animal production. At the same time, it has also drastically impacted the natural environment and human society. The One Health initiative emphasizes the interdependency of the health of ecosystems, animals, and humans. In this paper, we discuss some of the most profound consequences of animal agriculture practices from a One Health perspective. More specifically, we focus on impacts to host-microbe interactions by elaborating on how modern animal agriculture affects zoonotic infections, specifically those of bacterial origin, and the concomitant emergence of antimicrobial resistance (AMR). A key question underlying these deeply interconnected issues is how to better prevent, monitor, and manage infections in animal agriculture. To address this, we outline approaches to mitigate the impacts of agricultural bacterial zoonoses and AMR, including the development of novel treatments as well as non-drug approaches comprising integrated surveillance programs and policy and education regarding agricultural practices and antimicrobial stewardship. Finally, we touch upon additional major environmental and health factors impacted by animal agriculture within the One Health context, including animal welfare, food security, food safety, and climate change. Charting how these issues are interwoven to comprise the complex web of animal agriculture's broad impacts on One Health will allow for the development of concerted, multidisciplinary interventions which are truly necessary to tackle these issues from a One Health perspective.

Selective preparation of two-dimensional polymers (2DPs) and supramolecular polymers (2DSPs) with defined thickness is crucially important for controlling and maximizing their functions, yet it has remained as a synthetic challenge. In the past decade, several approaches have been developed to allow selective preparation of discrete monolayer 2DPs and 2DSPs. Recently, crystal exfoliation and self-assembly strategies have been employed to successfully prepare bilayer 2DP and 2DSP, which represent the first step towards the controlled "growth" of 2D polymers from the thinnest monolayers to thicker few-layers along the third dimension. This Concept review discusses the concept of accurate synthesis of 2D polymers with defined layers. Advances in this research area will pave the way to rational synthetic strategies for 2D polymers with controlled thickness.