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Purpose: Evidence demonstrates that many school children fail to master fundamental movement skills (FMS). Little is known about the teaching and learning of FMS in Hong Kong. This study aimed to capture voices from both teachers and students to better understand the current FMS practices in primary physical education Methods: Semistructured interviews with physical education teachers and focus groups with students were conducted. Thematic analysis of teacher transcriptions was performed. Student focus groups were analyzed using a framework approach, guided by TARGET (i.e., Task, Autonomy, Recognition, Grouping, Evaluation, and Time). Results: Several "teacher" level themes were developed: Self-efficacy (mis)judgment, limited pedagogical content knowledge, ineffective instructional and assessment strategies, insufficient teacher training, and deprioritization of skill development in physical education. Students perceived the need for a more student-centered approach to the teaching of FMS. Conclusions: Results highlighted the need for a different approach to initial and continuous teacher education in FMS. Further investigation into the most effective forms of teacher education is necessary, in order to improve the teaching and learning of FMS in schools. [ABSTRACT FROM AUTHOR]

A new design of spallation target has been installed and operated at the first target station of the ISIS Neutron and Muon Source (ISIS TS-1), as part of the recently completed "TS-1 Project". Detailed Finite Element Analysis (FEA) simulations were used to guide the design process and predict target performance. Since the TS-1 Project target began operation in November 2022, operating data has been collected and used to validate the target simulation approach. Measured temperatures of 9 out of 10 target plates showed good agreement with FEA simulations of both steady-state and transient behaviour. However, the front target plate temperature was elevated compared to predictions. Because the installed target was now too radioactive to permit hands-on inspection, FEA simulations became an indispensable tool to understand the possible causes and safety implications of this anomalous behaviour. The anomalous elevated temperature appears to be highly localised; a combination of simulations and experiments indicates the mostly likely cause is poor thermal contact between the thermocouple and the bulk of the target plate. In all other respects the target is operating as predicted, and is running reliably at up to 120 kW. [ABSTRACT FROM AUTHOR]

In May 2016, the World Health Assembly endorsed the Global Health Sector Strategy (GHSS) on viral hepatitis 2016–2021, calling for the elimination of viral hepatitis as a public health threat by 2030. Using the 2015 data as the baseline, the main targets are to reduce annual new infections and deaths by 90% and 65%, respectively, and to increase the diagnosis rate and the treatment rate of eligible people to 90% and 80%, respectively. However, the definitions and calculations of the above targets are not standardized, and there are inconsistencies between different literatures, affecting the accuracy and consistency of the results. The targets mainly focus on chronic HBV and HCV infections. According to the relevant literatures, it is speculated that the base number for new cases of chronic HBV and HCV infections in 2015 should be 3.5 to 5.15 million, rather than 6 to 10 million, with new HBV and HCV infections being 1.7 to 3.4 million and 1.75 million, respectively. From the perspectives of intuition, simplicity, and habit, the diagnosis rate and treatment rate are suitable for being expressed as "rate", but annual new infections (rate) and deaths (rate) should be expressed as "number" or "case". The method of calculating the treatment rate also needs to be unified. Different countries/regions have different treatment indications, and different authors have different understandings, which affects the comparability of treatment rates. [ABSTRACT FROM AUTHOR]

Metabolic-associated fatty liver disease (MAFLD), also known as non-alcoholic fatty liver disease (NAFLD), is a worldwide liver disease without definitive or widely used therapeutic drugs in clinical practice. In this study, we confirm that 6-gingerol (6-G), an active ingredient of ginger (Zingiber officinale Roscoe) in traditional Chinese medicine (TCM), can alleviate fructose-induced hepatic steatosis. It was found that 6-G significantly decreased hyperlipidemia caused by high-fructose diets (HFD) in rats, and reversed the increase in hepatic de novo lipogenesis (DNL) and triglyceride (TG) levels induced by HFD, both in vivo and in vitro. Mechanistically, chemical proteomics and cellular thermal shift assay (CETSA)–proteomics approaches revealed that stearoyl-CoA desaturase (SCD) is a direct binding target of 6-G, which was confirmed by further CETSA assay and molecular docking. Meanwhile, it was found that 6-G could not alter SCD expression (in either mRNA or protein levels), but inhibited SCD activity (decreasing the desaturation levels of fatty acids) in HFD-fed rats. Furthermore, SCD deficiency mimicked the ability of 6-G to reduce lipid accumulation in HF-induced HepG2 cells, and impaired the improvement in hepatic steatosis brought about by 6-G treatment in HFD supplemented with oleic acid diet-induced SCD1 knockout mice. Taken together, our present study demonstrated that 6-G inhibits DNL by targeting SCD to alleviate fructose diet-induced hepatic steatosis. [ABSTRACT FROM AUTHOR]

Skeletal muscle mass plays a pivotal role in metabolic function, but conditions such as bed rest or injury often render resistance training impractical. The beta2‐adrenergic receptor has been highlighted as a potential target to promote muscle hypertrophy and treat atrophic conditions. Here, we investigate the proteomic changes associated with beta2‐adrenergic‐mediated muscle hypertrophy, using resistance training as a hypertrophic comparator. We utilize MS‐based proteomics to map skeletal muscle proteome remodeling in response to beta2‐adrenergic stimulation or resistance training as well as cell model validation. We report that beta2‐adrenergic stimulation mimics multiple features of resistance training in proteome‐wide remodeling, comprising systematic upregulation of ribosomal subunits and concomitant downregulation of mitochondrial proteins. Approximately 20% of proteins were regulated in both conditions, comprising proteins involved in steroid metabolism (AKR1C1, AKR1C2, AKRC1C3), protein‐folding (SERPINB1), and extracellular matrix organization (COL1A1, COL1A2). Among overall most significantly upregulated proteins were kelch‐like family members (KLHL) 40 and 41. In follow‐up experiments, we identify KLHL41 as having novel implications for beta2‐adrenergic‐mediated muscle hypertrophy. Treating C2C12 cells with beta2‐agonist for 96 h increased myotube diameter by 48% (p < 0.001). This anabolic effect was abolished by prior knockdown of KLHL41. Using siRNA, KLHL41 abundance was decreased by 60%, and the anabolic response to beta2‐agonist was diminished (+ 15%, i.e., greater in the presence of KLHL41, knock‐down × treatment: p = 0.004). In conclusion, protein‐wide remodeling induced by beta2‐adrenergic stimulation mimics multiple features of resistance training, and thus the beta2‐adrenergic receptor may be a target with therapeutic potential in the treatment of muscle wasting conditions without imposing mechanical load. [ABSTRACT FROM AUTHOR]

This article examines the use of automated insulin delivery (AID) devices in children and adolescents with type 1 diabetes (T1D). The study analyzes data from 613 participants and finds that time spent in the target glucose range (TITR) varied among different subgroups. The study suggests that TITR could be a useful metric for assessing glycaemic outcomes in AID users. The results show that higher TITR levels are associated with better glycaemic control, and the study emphasizes the importance of using the automatic mode and selecting the appropriate insulin-to-carbohydrate ratio (ICR) for each meal. However, the study acknowledges limitations in the inclusion of different AID algorithms and the lack of raw glucose data. Overall, the findings suggest that TITR can provide valuable information in evaluating glucose profiles in individuals using AID systems. [Extracted from the article]

This paper proposes a new large loop antenna with a reduced magnetic field for a near field communication (NFC) target used in a metallic environment. It also defines a fairly clear method for controlling and, more specifically, reducing the magnetic field associated with loop antennas. This antenna consists of a circular winding, inside which we insert a square winding arranged in the shape of a diamond. The particular structure of this antenna shows that it is possible to dissociate the increase in the induced magnetic field, linked to its large size, from the increase in the number of windings. This is made possible by the application of the physical principle of overlapping magnetic fields, which results in partially destructive interference. [ABSTRACT FROM AUTHOR]

Background: Natural products have a long history in drug discovery. Lycorine is an alkaloid derived from Amaryllidaceae plants, demonstrating significant pharmacological potential. Lycorine and its hydrochloride salt, lycorine hydrochloride, have shown outstanding anticancer effects both in vitro and in vivo. Purpose: This review aims to comprehensively summarize recent research advancements regarding the anticancer potential of lycorine and lycorine hydrochloride. It intends to elucidate current research limitations, optimization strategies, and future research directions to guide clinical translation. Methods: Various databases, e.g., Web of Science, PubMed, and Chinese National Knowledge Infrastructure, are systematically searched for relevant articles using keywords such as lycorine, cancer, pharmacokinetics, and toxicity. The retrieved literature is then categorized and summarized to provide an overview of the research advancements in the anticancer potential of lycorine and lycorine hydrochloride. Results: Lycorine and lycorine hydrochloride demonstrate significant anticancer activities against various types of cancer both in vitro and in vivo, employing diverse mechanisms such as inducing cell cycle arrest, triggering cellular senescence, regulating programmed cell death, inhibiting angiogenesis, suppressing metastasis, and modulating immune system. Furthermore, pharmacokinetic profiles and toxicity data are summarized. Additionally, this review discusses the druggability, limitations, optimization strategies, and target identification of lycorine, offering insights for future preclinical studies. Conclusion: The anticancer effects and safety profile of lycorine and lycorine hydrochloride suggest promising potential for clinical applications. Further research on their in-depth mechanisms and optimization strategies targeting their limitations will enhance the understanding and druggability of lycorine and lycorine hydrochloride. [ABSTRACT FROM AUTHOR]

AbstractLayered ceramic/metal plates are investigated for ballistic impact against projectiles with different nose shapes. Explicit finite element method is used to model the target and projectile. This study examines the effect of nose shapes on the ballistic performance of target. This includes replacing the metallic layer with a ceramic plate of the same thickness to identify the best ceramic-to-target plate ratio for maximum BLV. Ballistic performance is compared between two different configurations having equal total thickness of ceramic and metallic layer. Increased ceramic layer thickness upto certain thickness-ratio may significantly improve the target plate’s ballistic resistance for all bullet types. [ABSTRACT FROM AUTHOR]

Objective: Advances in nanotechnology make it possible to specifically target therapies to cancer cells and neoplasms, guide the surgical resection of tumors, and optimize the effectiveness of radiological treatments. This research article provides a concise synthesis of current knowledge in the field of galenic pharmacy focused on targeted drug delivery in oncology. This research article synthesizes current knowledge in galenic pharmacy, focusing on targeted drug delivery in oncology and reviewing recent advancements in nanopharmaceuticals for cancer treatment. Data source: The data for this review are derived from a comprehensive analysis of the most cited scientific literature (Pubmed). Recent studies, clinical trials, and technological breakthroughs related to nanopharmaceuticals have been rigorously examined. This diverse source ensures a comprehensive representation of the latest developments in the field. Summary of data: The results highlight the emergence of nanopharmaceuticals as a promising approach to cancer treatment. The most common in oncology remain liposomes, nanopolymers, and nanocrystals. From a galenic point of view, these three forms offer a wide range of improvements compared to conventional forms such as improvement in solubility as well as stability. The same observation is in the clinic where treatment response rates are significantly improved. The most advantageous form will depend on the specific characteristics of each patient and each type of cancer. The precise design of nanocarriers allows for targeted drug delivery, enhancing therapeutic efficacy while reducing side effects. Concrete examples of clinical applications are presented, illustrating the practical potential of these advancements. Conclusion: In conclusion, this review provides a holistic overview of recent developments in galenic pharmacy for targeted drug delivery in oncology. The stability of nanocarriers is a crucial challenge because it conditions the effectiveness and safety of the drugs transported. Environmental and biological variations encountered in the body can compromise this stability, jeopardizing the therapeutic effectiveness and safety of treatments. Likewise, personalized approaches are essential to address interindividual variations in treatment response, as well as patients' pharmacogenomic profiles, in order to optimize therapeutic effectiveness and minimize adverse effects. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) triggers a severe systemic inflammatory reaction in mammals, with the dimerization of TLR4/MD-2 upon LPS stimulation serving as the pivotal mechanism in the transmission of inflammatory signals. Ginsenoside Rh2 (G-Rh2), one of the active constituents of red ginseng, exerts potent anti-inflammatory activity. However, whether G-Rh2 can block the TLR4 dimerization to exert anti-inflammatory effects remains unclear. Here, we first investigated the non-cytotoxic concentration of G-Rh2 on RAW 264.7 cells, and detected the releases of pro-inflammatory cytokines in LPS-treated RAW 264.7 cells, and then uncovered the mechanisms involved in the anti-inflammatory activity of G-Rh2 through flow cytometry, fluorescent membrane localization, Western blotting, co-immunoprecipitation (Co-IP), molecular docking and surface plasmon resonance (SPR) analysis in LPS-stimulated macrophages. Our results show that G-Rh2 stimulation markedly inhibited the secretion of LPS-induced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Additionally, G-Rh2 blocked the binding of LPS with the membrane of RAW 264.7 cells through direct interaction with TLR4 and MD-2 proteins, leading to the disruption of the dimerization of TLR4 and MD-2, followed by suppression of the TLR4/NF-κB signaling pathway. Our results suggest that G-Rh2 acts as a new inhibitor of TLR4 dimerization and may serve as a promising therapeutic agent against inflammation. [ABSTRACT FROM AUTHOR]

IBS is a prevalent clinical condition affecting bowel function. There is a restricted comprehension of its pathogenesis, an absence of particular diagnostic tools, and an insufficiency of efficient pharmacological remedies. MiRNAs are a highly conserved class of non-coding small molecule RNAs, with a length of 20–24 nucleotides. Research has shown the presence of a number of differentially expressed miRNAs in the colonic tissue and peripheral blood of IBS patients. Meanwhile, miRNAs have a critical role in gene expression and the pathology of IBS as they act as significant mediators of post-transcriptional gene silencing. The investigation of miRNA molecular regulatory networks proves useful in examining the convoluted pathogenesis of IBS. This paper presents a review of recent literature on miRNAs associated with IBS, explains how miRNAs contribute to the development of IBS, and assesses the potential usefulness of miRNA analysis for diagnosing and treating IBS. [ABSTRACT FROM AUTHOR]

Abstract Background Natural products have a long history in drug discovery. Lycorine is an alkaloid derived from Amaryllidaceae plants, demonstrating significant pharmacological potential. Lycorine and its hydrochloride salt, lycorine hydrochloride, have shown outstanding anticancer effects both in vitro and in vivo. Purpose This review aims to comprehensively summarize recent research advancements regarding the anticancer potential of lycorine and lycorine hydrochloride. It intends to elucidate current research limitations, optimization strategies, and future research directions to guide clinical translation. Methods Various databases, e.g., Web of Science, PubMed, and Chinese National Knowledge Infrastructure, are systematically searched for relevant articles using keywords such as lycorine, cancer, pharmacokinetics, and toxicity. The retrieved literature is then categorized and summarized to provide an overview of the research advancements in the anticancer potential of lycorine and lycorine hydrochloride. Results Lycorine and lycorine hydrochloride demonstrate significant anticancer activities against various types of cancer both in vitro and in vivo, employing diverse mechanisms such as inducing cell cycle arrest, triggering cellular senescence, regulating programmed cell death, inhibiting angiogenesis, suppressing metastasis, and modulating immune system. Furthermore, pharmacokinetic profiles and toxicity data are summarized. Additionally, this review discusses the druggability, limitations, optimization strategies, and target identification of lycorine, offering insights for future preclinical studies. Conclusion The anticancer effects and safety profile of lycorine and lycorine hydrochloride suggest promising potential for clinical applications. Further research on their in-depth mechanisms and optimization strategies targeting their limitations will enhance the understanding and druggability of lycorine and lycorine hydrochloride. Graphical Abstract

The paper focuses on identifying the number of Overlapping Associates (O) and Overlapping Associate Strength (OSG), as well as on demonstrating the possibilities of using these indices in the analysis of a speech action. The associative fields bogatyj and bednyj presented in the Russian Associative Dictionary and rich and poor indicated in the associative norms of the University of South Florida are used as research material. It has been established that bogatyj – bednyj and rich – poor are the most frequent cue – target pairs. The power of predication in different pairs can vary significantly. The overlapping associates, which may be different in number, represent semantic features that form the similarity basis for the meanings of the studied words. It has been proved that the level of similarity largely depends not on the number of overlapping associates, but rather on the strength of their overlap. The data obtained indicate that the psychological meaning of the words bogatyj and bednyj in the Russian thesaurus is closer than rich and poor in the American one. It is also found that the index of Overlapping Associate Strength for the associate money is higher than for the associate dengi. This emphasizes its relevance for the Americans.

Abstract Purpose Bladder cancer (BLCA) is a prevalent malignancy. Dysregulated propionate metabolism, a key cancer factor, suggests a potential target for treating metastatic cancer. However, a complete understanding of the link between propionate metabolism-related genes (PMRGs) and bladder cancer is lacking. Methods From the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we gathered BLCA patient data, which was classified into distinct subgroups using non-negative matrix factorization (NMF). Survival and pathway analyses were conducted between these clusters. The PMRGs model, created through univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses, was assessed for prognostic significance using Kaplan–Meier and receiver operating characteristic (ROC) curves. A comprehensive evaluation included clinical, tumor microenvironment (TME), drug sensitivity, and immunotherapy analyses. Finally, the expression of HSD17B1 essential genes was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR), with further validation through Transwell, wound healing, colony-formation, and EDU assays. Results We discovered two distinct subcategories (CA and CB) within BLCA using NMF analysis, with CA demonstrating significantly better overall survival compared to CB. Additionally, six PMRGs emerged as critical factors associated with propionate metabolism and prognosis. Kaplan–Meier analysis revealed that high-risk PMRGs were correlated with a poorer prognosis in BLCA patients. Moreover, significant differences were observed between the two groups in terms of infiltrated immune cells, immune checkpoint expression, TME scores, and drug sensitivity. Notably, we found that suppressing HSD17B1 gene expression inhibited the invasion of bladder cancer cells. Conclusion Our study proposes molecular subtypes and a PMRG-based score as promising prognostic indicators in BLCA. Additionally, cellular experiments underscore the pivotal role of HSD17B1 in bladder cancer metastasis and invasion, suggesting its potential as a novel therapeutic target.

Abstract Background Male breast cancer (MaBC) has limited data on genomic alterations. We aimed to comprehensively describe and compare MaBC’s genomics with female breast cancer’s (FBC) across subtypes. Methods Using genomic data from Foundation Medicine, we categorized 253 MaBC into estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 210), ER-positive/HER2-positive (n = 22) and triple-negative (n = 20). One ER-negative/HER2-positive case was excluded due to n-of-1. The genomics of the final MaBC cohort (n = 252) were compared to a FBC cohort (n = 2708) stratified by molecular subtype, with adjusted p-values. In the overall MaBC and FBC cohorts, we compared mutational prevalence in cancer susceptibility genes (CSG) (ATM/BRCA1/BRCA2/CHEK2/PALB2). Results Comparing ER-positive/HER2-negative cases, MaBc had increased alterations in GATA3 (26.2% vs. 15.9%, p = 0.005), BRCA2 (13.8% vs. 5.3%, p

Macrophages play a pivotal role as host cells for Leishmania parasites, displaying a notable functional adaptability ranging from the proinflammatory, leishmanicidal M1 phenotype to the anti-inflammatory, parasite-permissive M2 phenotype. While macrophages can potentially eradicate amastigotes through appropriate activation, Leishmania employs diverse strategies to thwart this activation and redirect macrophages toward an M2 phenotype, facilitating its survival and replication. Additionally, a competition for iron between the two entities exits, as iron is vital for both and is also implicated in macrophage defensive oxidative mechanisms and modulation of their phenotype. This review explores the intricate interplay between macrophages, Leishmania, and iron. We focus the attention on the potential of iron oxide nanoparticles (IONPs) as a sort of immunotherapy to treat some leishmaniasis forms by reprogramming Leishmania-permissive M2 macrophages into antimicrobial M1 macrophages. Through the specific targeting of iron in macrophages, the use of IONPs emerges as a promising strategy to finely tune the parasite-host interaction, endowing macrophages with an augmented antimicrobial arsenal capable of efficiently eliminating these intrusive microbes. [ABSTRACT FROM AUTHOR]

Given the complexity of teaching, continuing teacher professional development (CPD) is essential for maintaining and enhancing teaching effectiveness, and bridging the gap between ever-evolving theory and practice. Technological advancements have opened new opportunities for digital tools to support CPD. However, the successful integration of such digital tools into practice poses challenges. It requires adherence to CPD prerequisites and acknowledgment of the complexity of the professional development process. This study explored the applicability of the developed digital PE teacher professional development TARGET-tool in a secondary school PE context. We examined the perceived usability of this tool and gained insights into the process of teachers' professional development as a result of using the tool. Ten PE teachers from different schools implemented the TARGET-tool within their PE context for a period of 4 to 6 weeks. Individual semi-structured interviews and the System Usability Scale provided insights into the perceived usability and the process of teacher professional development. The TARGET-tool demonstrated its potential as an effective tool for supporting teachers' professional development. Future tool improvements were identified to further optimize the perceived usability, such as simplifying complex features, providing additional support and resources, and improving (data) presentations. Using the Interconnected Model of Professional Growth as a theoretical basis, it was demonstrated how the use of the TARGET-tool engages teachers as active and reflective participants in their professional development and induces changes within the external domain, the domain of practice, the domain of consequences, and the personal domain. [ABSTRACT FROM AUTHOR]

The genome of tomato spotted wilt virus (TSWV) can encode various proteins, including RdRp, NSm, NSs, Gc, Gn, and N. Existing research primarily focuses on plant (tomato and chili pepper) resistance to TSWV mediated by resistance genes (Sw-5b and Tsw). Furthermore, the inhibitory effects of agents on the TSWV N proteins have been investigated. TSWV proteins have the potential to be used as molecular targets for pharmaceutical agents, however, the mechanism of action between TSWV proteins and pharmaceutical agents has not been systematically and comprehensively reported. This study presents a detailed analysis of the three-dimensional structures of resolved TSWV proteins and predicts the structures of four unresolved TSWV proteins using AlphaFold2 modeling. It also summarizes the advancement and application of TSWV resistance genes and TSWV inhibitors in plant protection. The potential molecular mechanisms of ningnanmycin, moroxydine, and ribavirin on TSWV proteins were analyzed, along with their possible sites of action. The aim is to establish a theoretical foundation for subsequent comprehensive excavation and exploration of novel agents with anti-TSWV properties. [ABSTRACT FROM AUTHOR]

Mitochondrial damage has a particular impact on the immune system and tumor microenvironment, which can trigger cell stress, an inflammatory response, and disrupt immune cell function, thus all of which can accelerate the progression of the tumor. Therefore, it is of essence to comprehend how the immune system function and the tumor microenvironment interact with mitochondrial dysfunction for cancer treatment. Preserving the integrity of mitochondria or regulating the function of immune cells, such as macrophages, may enhance the efficacy of cancer therapy. Future research should concentrate on the interactions among mitochondria, the immune system, and the tumor microenvironment to identify new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: Fusarium oxysporum is a significant soil-borne fungal pathogen that affects over 100 plant species, including crucial crops like tomatoes, bananas, cotton, cucumbers, and watermelons, leading to wilting, yellowing, growth inhibition, and ultimately plant death. The root rot disease of A. macrocephala, caused by F. oxysporum, is one of the most serious diseases in continuous cropping, which seriously affects its sustainable development. Methods: In this study, we explored the interaction between A. macrocephala and F. oxysporum through integrated small RNA (sRNA) and degradome sequencing to uncover the microRNA (miRNA)-mediated defense mechanisms. Results: We identified colonization of F. oxysporum in A. macrocephala roots on day 6. Nine sRNA samples were sequenced to examine the dynamic changes in miRNA expression in A. macrocephala infected by F. oxysporum at 0, 6, and 12 days after inoculation. Furthermore, we using degradome sequencing and quantitative real-time PCR (qRT-PCR), validated four miRNA/target regulatory units involved in A. macrocephala-F. oxysporum interactions. Discussion: This study provides new insights into the molecular mechanisms underlying A. macrocephala's early defense against F. oxysporum infection, suggesting directions for enhancing resistance against this pathogen. [ABSTRACT FROM AUTHOR]

Fibrosis is a prevalent pathological condition observed in various organs and tissues. It primarily arises from the excessive and abnormal accumulation of the extracellular matrix, resulting in the structural and functional impairment of tissues and organs, which can culminate in death. Many forms of fibrosis, including liver, cardiac, pulmonary, and renal fibrosis, are considered irreversible. Maternally expressed gene 3 (MEG3) is an imprinted RNA gene. Historically, the downregulation of MEG3 has been linked to tumor pathogenesis. However, recent studies indicate an emerging association of MEG3 with fibrotic diseases. In this review, we delve into the current understanding of MEG3's role in fibrosis, aiming to shed light on the molecular mechanisms of fibrosis and the potential of MEG3 as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Interactions between proteins and small organic compounds play a crucial role in regulating protein functions. These interactions can modulate various aspects of protein behavior, including enzymatic activity, signaling cascades, and structural stability. By binding to specific sites on proteins, small organic compounds can induce conformational changes, alter protein–protein interactions, or directly affect catalytic activity. Therefore, many drugs available on the market today are small molecules (72% of all approved drugs in the last 5 years). Proteins are composed of one or more domains: evolutionary units that convey function or fitness either singly or in concert with others. Understanding which domain(s) of the target protein binds to a drug can lead to additional opportunities for discovering novel targets. The evolutionary classification of protein domains (ECOD) classifies domains into an evolutionary hierarchy that focuses on distant homology. Previously, no structure‐based protein domain classification existed that included information about both the interaction between small molecules or drugs and the structural domains of a target protein. This data is especially important for multidomain proteins and large complexes. Here, we present the DrugDomain database that reports the interaction between ECOD of human target proteins and DrugBank molecules and drugs. The pilot version of DrugDomain describes the interaction of 5160 DrugBank molecules associated with 2573 human proteins. It describes domains for all experimentally determined structures of these proteins and incorporates AlphaFold models when such structures are unavailable. The DrugDomain database is available online: http://prodata.swmed.edu/DrugDomain/. [ABSTRACT FROM AUTHOR]

Purpose: Bladder cancer (BLCA) is a prevalent malignancy. Dysregulated propionate metabolism, a key cancer factor, suggests a potential target for treating metastatic cancer. However, a complete understanding of the link between propionate metabolism-related genes (PMRGs) and bladder cancer is lacking. Methods: From the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we gathered BLCA patient data, which was classified into distinct subgroups using non-negative matrix factorization (NMF). Survival and pathway analyses were conducted between these clusters. The PMRGs model, created through univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses, was assessed for prognostic significance using Kaplan–Meier and receiver operating characteristic (ROC) curves. A comprehensive evaluation included clinical, tumor microenvironment (TME), drug sensitivity, and immunotherapy analyses. Finally, the expression of HSD17B1 essential genes was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR), with further validation through Transwell, wound healing, colony-formation, and EDU assays. Results: We discovered two distinct subcategories (CA and CB) within BLCA using NMF analysis, with CA demonstrating significantly better overall survival compared to CB. Additionally, six PMRGs emerged as critical factors associated with propionate metabolism and prognosis. Kaplan–Meier analysis revealed that high-risk PMRGs were correlated with a poorer prognosis in BLCA patients. Moreover, significant differences were observed between the two groups in terms of infiltrated immune cells, immune checkpoint expression, TME scores, and drug sensitivity. Notably, we found that suppressing HSD17B1 gene expression inhibited the invasion of bladder cancer cells. Conclusion: Our study proposes molecular subtypes and a PMRG-based score as promising prognostic indicators in BLCA. Additionally, cellular experiments underscore the pivotal role of HSD17B1 in bladder cancer metastasis and invasion, suggesting its potential as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Male breast cancer (MaBC) has limited data on genomic alterations. We aimed to comprehensively describe and compare MaBC's genomics with female breast cancer's (FBC) across subtypes. Methods: Using genomic data from Foundation Medicine, we categorized 253 MaBC into estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 210), ER-positive/HER2-positive (n = 22) and triple-negative (n = 20). One ER-negative/HER2-positive case was excluded due to n-of-1. The genomics of the final MaBC cohort (n = 252) were compared to a FBC cohort (n = 2708) stratified by molecular subtype, with adjusted p-values. In the overall MaBC and FBC cohorts, we compared mutational prevalence in cancer susceptibility genes (CSG) (ATM/BRCA1/BRCA2/CHEK2/PALB2). Results: Comparing ER-positive/HER2-negative cases, MaBc had increased alterations in GATA3 (26.2% vs. 15.9%, p = 0.005), BRCA2 (13.8% vs. 5.3%, p < 0.001), MDM2 (13.3% vs. 6.14%, p = 0.004) and CDK4 (7.1% vs. 1.8%, p < 0.001); and decreased frequency of TP53 (11.0% vs. 42.6%, p < 0.001) and ESR1 mutations (5.7% vs. 14.6%, p < 0.001). Comparing ER-positive/HER2-positive cases, MaBC had increased short variants in ERBB2 (22.7% vs. 0.6%, p = 0.002), GATA3 (36.3% vs. 6.2%, p = 0.004), and MDM2 (36.3% vs. 4.9%, p = 0.002); decreased frequency of TP53 alterations was seen in MaBC versus FBC (9.1% vs. 61.7%, p < 0.001). Within triple-negative cases, MaBC had decreased alterations in TP53 compared to FBC (25.0% vs. 84.4%, p < 0.001). MaBC had higher frequency of CSG variants than FBC (22.6% vs. 14.6%, p < 0.05), with increased BRCA mutations in MaBC (14.6% vs. 9.1%, p < 0.05). Conclusions: Although MaBC and FBC share some common alterations, our study revealed several important differences relevant to tumor biology and implications for targeted therapies. [ABSTRACT FROM AUTHOR]

Repression has long been regarded as the main response of the state when encountering contentious actions. Although recent studies point out that repression may vary by regime types and state-level concerns regarding international reputation, few analyses to date have analyzed how movement dynamics and movement targets jointly shape state responses. In this article, I analyze over 7,500 episodes of labor protests in mainland China to advance scholarship on state responses to social movements. I develop a typology of state responses, from active coercion to accommodation and even tolerance. I then explore differences in state responses based on protest tactics and whether they are against private or state-affiliated targets. My results show that state responses differ based on the tactics that movements employ. Furthermore, these effects are moderated by whether activists target state-affiliated or private entities. This research offers important insights into the dynamic relations between state and social movement, the diverse ways highly bureaucratic governments use to manage social unrest, and the conflict between maintaining legitimacy and social control in both authoritarian and democratic contexts. [ABSTRACT FROM AUTHOR]

Some scholars endorse the idea that a necessary condition for qualifying as fake news is being consumed by a minimum number of people. Call this requirement ‘the minimum audience condition’. I claim that each version of this condition is either incompatible with the damage that fake news does to our beliefs or unable to capture the case of outlandish fake stories. Drawing inspiration from an online scam, I then propose to distinguish the audience of fake news from its target. Lastly, I replace the minimum audience condition with a new requirement stating that fake news must be designed and published in a way that is conducive to the goal of persuading one or more target groups, regardless of its audience. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma, a malignancy of melanocytes, presents a significant challenge due to its aggressive nature and rising global incidence. Despite advancements in treatment, the variability in patient responses underscores the need for further research into novel therapeutic targets, including the role of programmed cell death pathways such as necroptosis. The melanoma datasets used for analysis, GSE215120, GSE19234, GSE22153 and GSE65904, were downloaded from the GEO database. The melanoma data from TCGA were downloaded from the UCSC website. Using single‐cell sequencing, we assess the heterogeneity of necroptosis in cutaneous melanoma, identifying distinct cell clusters and necroptosis‐related gene expression patterns. A combination of 101 machine learning algorithms was employed to construct a necroptosis‐related signature (NRS) based on key genes associated with necroptosis. The prognostic value of NRS was evaluated in four cohorts (one TCGA and three GEO cohorts), and the tumour microenvironment (TME) was analysed to understand the relationship between necroptosis, tumour mutation burden (TMB) and immune infiltration. Finally, we focused on the role of key target TSPAN10 in the prognosis, pathogenesis, immunotherapy relevance and drug sensitivity of cutaneous melanoma. Our study revealed significant heterogeneity in necroptosis among melanoma cells, with a higher prevalence in epithelial cells, myeloid cells and fibroblasts. The NRS, developed through rigorous machine learning techniques, demonstrated robust prognostic capabilities, distinguishing high‐risk patients with poorer outcomes in all cohorts. Analysis of the TME showed that high NRS scores correlated with lower TMB and reduced immune cell infiltration, indicating a potential mechanism through which necroptosis influences melanoma progression. Finally, TSPAN10 has been identified as a key target for cutaneous melanoma and is highly associated with poor prognosis. The findings highlight the complex role of necroptosis in cutaneous melanoma and introduce the NRS as a novel prognostic tool with potential to guide therapeutic decisions. [ABSTRACT FROM AUTHOR]

The largest cause of cancer-related fatalities worldwide is lung cancer. In its early stages, lung cancer often exhibits no signs or symptoms. Its signs and symptoms often appear when the condition is advanced. The Kirsten rat sarcoma virus oncogene homolog is one of the most frequently mutated oncogenes found in non-small cell lung cancer. Patients who have these mutations may do worse than those who do not, in terms of survival. To understand the nuances in order to choose the best treatment options for each patient, including combination therapy and potential resistance mechanisms, given the quick development of pharmaceuticals, it is necessary to know the factors that might contribute to this disease. It has been observed that single nucleotide polymorphisms altering let-7 micro-RNA might impact cancer propensity. On the other hand, gefitinib fails to stop the oncogenic protein from directly interacting with phosphoinositide3-kinase, which may explain its resistance towards cancer cells. Additionally, Atorvastatin may be able to overpower gefitinib resistance in these cancer cells that have this mutation regardless of the presence of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha. De novo lipogenesis is also regulated by this virus. To overcome these effects, several targeted therapies have been proposed. One such therapy is to use inhibitors of focal adhesion kinases. When this is inhibited, viral oncogene mutant cancers are effectively stopped because it functions downstream of the virus. Mutant oncoproteins like epidermal growth factor receptor may depend on Heat Shock protein90 chaperones more frequently than they do on natural counterparts that make it more attractive therapeutic target for this virus. Inhibition of the phosphoinositide 3-kinase pathway is frequent in lung cancer, and fabrication of inhibitors against this pathway can also be an effective therapeutic strategy. Blocking programmed cell death ligand1 is another therapy that may help T cells to recognize and eliminate cancerous cells. This homolog is a challenging therapeutic target due to its complex structural makeup and myriad biological characteristics. Thanks to the unrelenting efforts of medical research, with the use of some inhibitors, immunotherapy, and other combination methods, this problem is currently expected to be overcome. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) play an important role in the occurrence and development of diseases. However, the role of circRNAs in male smokers with chronic obstructive pulmonary disease (COPD) remains unclear. Methods: Stable COPD patients and healthy controls were recruited. Peripheral blood mononuclear cells (PBMCs) were extracted. After high-throughput RNA sequencing (RNA-Seq) of PBMCs, a bioinformatics method was used to analyse differentially expressed (DE) circRNAs (DEcircRNAs) and mRNAs (DEmRNAs). Results: Total of 114 DEcircRNAs and 58 DEmRNAs were identified. Functional enrichment analysis showed that processes related to COPD include the regulation of interleukin (IL)-18, IL-5 and the NLRP3 inflammasome; differentiation of T helper type 1 (Th1), Th2, and Th17 cells, and the AMPK, Wnt, JAK-STAT, and PI3K-Akt signalling pathways. In the protein-protein interaction (PPI) network, the core genes were MYO16, MYL4, SCN4A, NRCAM, HMCN1, MYOM2, and IQSEC3. Small-molecule prediction results revealed potential drugs for the COPD treatment. Additionally, the circRNAmiRNA-mRNA competitive endogenous RNA (ceRNA) regulatory network was constructed. Conclusion: This study identified a set of dysregulated circRNAs and mRNAs and revealed potentially important genes, pathways, new small-molecule drugs and ceRNA regulatory networks in male smokers with COPD. These circRNAs might be prospective biomarkers or potential molecular targets of the ceRNA mechanism for COPD. [ABSTRACT FROM AUTHOR]

Matrine has been reported inhibitory effects on ovarian cancer (OC) cell progression, development, and apoptosis. However, the molecular targets of matrine against OC and the underlying mechanisms of action remain elusive. This study endeavors to unveil the potential targets of matrine against OC and to explore the intricate relationships between these targets and the pathogenesis of OC. The effects of matrine on the OC cells (A2780 and AKOV3) viability, apoptosis, migration, and invasion was investigated through CCK-8, flow cytometry, wound healing, and Transwell analyses, respectively. Next, Matrine-related targets, OC-related genes, and ribonucleic acid (RNA) sequence data were harnessed from publicly available databases. Differentially expressed analyses, protein-protein interaction (PPI) network, and Venn diagram were involved to unravel the core targets of matrine against OC. Leveraging the GEPIA database, we further validated the expression levels of these core targets between OC cases and controls. Mendelian randomization (MR) study was implemented to delve into potential causal associations between core targets and OC. The AutoDock software was used for molecular docking, and its results were further validated using RT-qPCR in OC cell lines. Matrine reduced the cell viability, migration, invasion and increased the cell apoptosis of A2780 and AKOV3 cells (P< 0.01). A PPI network with 578 interactions among 105 candidate targets was developed. Finally, six core targets (TP53, CCND1, STAT3, LI1B, VEGFA, and CCL2) were derived, among which five core targets (TP53, CCND1, LI1B, VEGFA, and CCL2) differential expressed in OC and control samples were further picked for MR analysis. The results revealed that CCND1 and TP53 were risk factors for OC. Molecular docking analysis demonstrated that matrine had good potential to bind to TP53, CCND1, and IL1B. Moreover, matrine reduced the expression of CCND1 and IL1B while elevating P53 expression in OC cell lines. We identified six matrine-related targets against OC, offering novel insights into the molecular mechanisms underlying the therapeutic effects of matrine against OC. These findings provide valuable guidance for developing more efficient and targeted therapeutic approaches for treating OC. [ABSTRACT FROM AUTHOR]

Summary: Multiagent chemoimmunotherapy remains the standard of care treatment for Burkitt lymphoma leading to a cure in the majority of cases. However, frontline treatment regimens are associated with a significant risk of treatment related toxicity especially in elderly and immunocompromised patients. Additionally, prognosis remains dismal in refractory/relapsed Burkitt lymphoma. Thus, novel therapies are required to not only improve outcomes in relapsed/refractory Burkitt lymphoma but also minimize frontline treatment related toxicities. Recurrent genomic changes and signalling pathway alterations that have been implicated in the Burkitt lymphomagenesis include cell cycle dysregulation, cell proliferation, inhibition of apoptosis, epigenetic dysregulation and tonic B‐cell receptor‐phosphatidylinositol 3‐kinase (BCR‐PI3K) signalling. Here, we will discuss novel targeted therapy approaches using small molecule inhibitors that could pave the way to the future treatment landscape based on the understanding of recurrent genomic changes and signalling pathway alterations in the lymphomagenesis of adult Burkitt lymphoma. [ABSTRACT FROM AUTHOR]

This paper develops a model in which a country, which only has access to a dirty technology for producing electric power in the short run, looks to expand its production in the long run by only permitting new power plants based on clean technology. The model mimics current reality in which major developing countries are being pushed by factors, such as the Paris Climate agreement of 2015 and the large burden of mortality and morbidity resulting from use of fossil fuels, to rely more on clean technologies. Our model shows how emissions and emission intensity of power output after the adoption of clean technologies are increasing in the targets for power production set by the government before availability of such technology and supply variables such as the wage rate and expenses on fixed capital, and decreasing in the tax on power production before the availability of clean technologies. Finally, it is seen that for low enough cost of the clean resource input, a country with a higher demand is able to set a higher target for production with the dirty technology when the clean technology is not available and yet achieves lower emissions and emission intensity in the long run. [ABSTRACT FROM AUTHOR]

Lung cancer remains one of the leading causes of cancer-related mortality worldwide necessitating the development of innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents a promising advancement in the field of oncology offering a novel approach to target and eliminate tumor cells with high specificity and reduced risk of immune-related adverse effects. This paper reviews the mechanism, potential targets, and recent advances in CAR-NK cell therapy for lung cancer, including the design and engineering of CAR-NK cells, preclinical studies, and the outcomes of early-phase clinical trials. We highlight the unique advantages of using NK cells, such as their innate ability to recognize and kill cancer cells and their reduced potential for inducing graft-versus-host disease (GvHD) and cytokine release syndrome (CRS) compared to CAR T-cell therapies. Results from recent studies demonstrate significant antitumor activity in lung cancer models with improved targeting and persistence of CAR-NK cells observed in vitro and in vivo. Finally, we discuss the challenges in optimizing CAR-NK cell therapies, including the potential resistance mechanisms. The paper concludes with an outlook on the future directions of CAR-NK cell research and its implications for lung cancer treatment emphasizing the importance of continued innovation and collaboration in the field. [ABSTRACT FROM AUTHOR]

A growing body of evidence suggests that miR-5189-3p plays a critical role in multiple diseases. This study aimed to investigate the function of miR-5189-3p in laryngeal squamous cell carcinoma (LSCC) and explore its underlying mechanisms. qRT-PCR was designed to determine the expression levels of miR-5189-3p and eukaryotic translation initiation factor 5A2 (EIF5A2), while CCK-8 assay was performed to measure the effects of miR-5189-3p on cell proliferation. Transwell assay was performed to evaluate cell invasion as well as migration, and wound healing assay was applied to demonstrate cell migratory ability. Target gene prediction and luciferase reporter assay were developed to screen the possible target gene of miR-5189-3p, and Western blot was designed to measure EIF5A2 protein expression. MiR-5189-3p was down-regulated in LSCC tissues and cell lines. Up-regulation of miR-5189-3p notably inhibited cell proliferation, invasion, and migration in HEP2 and FADU cells. EIF5A2 was the potential downstream gene of miR-5189-3p, and overexpression of miR-5189-3p apparently reduced EIF5A2 expression. Moreover, reintroduction of EIF5A2 rescued the tumor suppressive effects of miR-5189-3p. MiR-5189-3p functions as a tumor inhibitor in LSCC progression via directly regulating EIF5A2 and may be a potential therapeutic target for LSCC. [ABSTRACT FROM AUTHOR]

Interpersonal emotion regulation involves having emotions changed in a social context. While some research has used the term to refer to instances where others are used to alter one's own emotions (intrinsic), other research refers to goal-directed actions aimed at modifying others' emotional responses (extrinsic). We argue that the self-other distinction should be applied not only to the target (who has their emotion regulated) but also to the means (whether the agent uses themselves or others to achieve the regulation). Based on this, we propose interpersonal emotion regulation can take place when an agent changes a target's emotions by affecting a third party's emotion who will shift the emotion of the target in turn (direct other-based interpersonal ER) or by impacting a third party's emotion (indirect other-based interpersonal ER). We discuss these processes and the conditions that lead to their emergence reconciling findings from different fields and suggesting new research venues. [ABSTRACT FROM AUTHOR]

To elucidate the active ingredients and potential mechanism of Solanum lyratum in the treatment of rheumatoid arthritis (RA), we employed a comprehensive strategy that combined network pharmacology and molecular docking. First, we systematically retrieved relevant compounds from S. lyratum documented in the literature. We obtained RA-related targets by querying GeneCards, DisGeNET, and the OMIM database. Subsequently, we constructed drug-compound-target and protein-protein interaction (PPI) networks to predict the promising protein targets of S. lyratum and identify the primary interactions between these protein targets and compounds. To validate our predicted candidate targets, we employed docking techniques. Finally, we conducted an in vitro intervention and validation using the ethyl acetate extract of S. lyratum on human RA synovial fibroblasts (MH7A). Our analysis identified a total of 41 potential active compounds and 126 intersecting pharmacological targets. GO enrichment analysis revealed that positive regulation of gene expression, response to hypoxia, and apoptotic processes were closely associated with S. lyratum treatment in RA. KEGG pathway analysis suggested that the TNF signaling pathway, IL-17 signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and Toll-Like receptor signaling pathway might play a pivotal role in S. lyratum intervention in RA. Consequently, key targets could include AKT1, TP53, VEGF, CASP3, TNF, and IL6. Molecular docking analysis indicated that diosgenin, strychnine, solamargine, solamarine, solasodine, and ursolic acid exhibited strong binding affinities with STAT3, JUN, MAPK1, TNF, TP53, IL6, MAPK8, IL1B, MMP1, and MMP3. These active compounds in S. lyratum had the potential to regulate multiple signaling pathways and target molecules, thereby exerting preventive and therapeutic effects in RA. In our in vitro experiment, we observed that the ethyl acetate extract of S. lyratum inhibited the proliferation of MH7A cells and reduced the release of cytokines. These experimental results aligned with the predictions generated through the network pharmacology approach. This study not only provided a theoretical foundation for the use of S. lyratum in the treatment of RA but also offered valuable insights for further investigations into the action mechanisms of Chinese herbal extract compounds. [ABSTRACT FROM AUTHOR]

T-cell immunoglobulin and mucin structural domain 1 (TIM-1, also known as hepatitis A virus cell receptor 1) is a co-stimulatory molecule that is expressed predominantly on the surface of T cells. TIM-1 promotes the activation and proliferation of T cells, cytokine secretion, and can also be overexpressed in various types of cancer. Upregulation of TIM-1 expression may be associated with the development and progression of cancer. After reviewing the literature, we propose that TIM-1 affects tumour development mainly through two pathways. In the Direct pathway: overexpression in tumours activates tumour-related signaling pathways, mediates the proliferation, apoptosis, invasion and metastasis, and directly affects tumour development directly. In the indirect pathway: In addition to changing the tumour microenvironment and influencing the growth of tumours, TIM-1 binds to ligands to encourage the activation, proliferation, and generation of cytokines by immune cells. This review examines how TIM-1 stimulates the development of tumours in direct and indirect ways, and how TIM-1 is exploited as a target for cancer therapy. [ABSTRACT FROM AUTHOR]

This paper presents two experiments in which, using artificial intelligence (specifically Deep Learning with convolutional neural networks), we were able to predict Alzheimer's disease based on MRI images. In order to have better results and to minimize the computational effort in the laboratory, two pre-trained AI models were used, models trained previously on more than a million images from the ImageNet database (which provide tens of millions of clean, labelled and sorted images). The top-layers of the models were trained, for our specific task of Alzheimer’s prediction, with 500 public MRI images from Kaggle, an online community of data scientists and machine learning engineers and a subsidiary of Google. In this paper we describe the code used in the laboratory for the specific task. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are a major hindrance to clinical cancer treatment. Owing to their high tumorigenic and metastatic potential, CSCs are vital in malignant tumor initiation, growth, metastasis, and therapeutic resistance, leading to tumorigenesis and recurrence. Compared with normal tumor cells, CSCs express high levels of surface markers (CD44, CD90, CD133, etc.) and activate specific signaling pathways (Wnt/β-catenin, Notch, and Hedgehog). Although Current drug delivery systems (DDS) precisely target CSCs, the heterogeneity and multidrug resistance of CSCs impede CSC isolation and screening. Conversely, hydrogel DDSs exhibit good biocompatibility and high drug delivery efficiency. Hydrogels are three-dimensional (3D) spatial structures for drug encapsulation that facilitate the controlled release of bioactive molecules. Hence, hydrogels can be loaded with drugs to precisely target CSCs. Their 3D structure can also culture non-CSCs and facilitate their transformation into CSCs. for identification and isolation. Given that their elastic modulus and stiffness characteristics reflect those of the cellular microenvironment, hydrogels can simulate extracellular matrix pathways and markers to regulate CSCs, disrupting the equilibrium between CSC and non-CSC transformation. This article reviews the CSC microenvironment, metabolism, signaling pathway, and surface markers. Additionally, we summarize the existing CSC targeting strategies and explore the application of hydrogels for CSC screening and treatment. Finally, we discuss potential advances in CSC research that may lead to curative measures for tumors through targeted and precise attacks on CSCs.

Tuberculosis (TB) has been troubling humans for hundreds of years, is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, Mtb can infect almost all organs of the body and is one of the deadly infectious diseases in the world. At present, the first-line treatment regimen has a long treatment cycle and is prone to multiple drug resistance. Anti-tuberculosis drugs and latent tuberculosis infection (LTBI) resistance are increasing year by year, and new targets and new bioactive compounds are urgently needed to treat this disease. This review focuses on the latest reported anti-TB drug targets and related compounds in recent years, reviews the current TB drug regimen and major defects, outlines the key drug targets developed to date in Mtb, and the current situation of newly discovered anti-TB resistant forms of drugs. To provide a reference for the research and development of new anti-TB drugs and bring new treatment strategies for TB patients.