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We investigate the puzzle of banks contracting the services of external advisors for deals they can self-manage and the role of financial advisors in mergers and acquisitions among European banking firms. We also study the determinants of the choice by bank acquirers and bank targets to either appoint external advisors or manage in-house, as well as between appointing either top or lower tier advisors. Top tier advisors are more likely to be employed in debt financed and cross-border deals. We also find that most European bank mergers are managed in-house, contrary to prior findings reporting mostly externally managed deals attributed to the certification effect. Targets fail to benefit from deals where they do not match acquirer's decision to appoint external advisors. However, there is an overall propensity to match the counter party's tier of advisor. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T (CAR-T) cell therapy has been a milestone breakthrough in the treatment of hematological malignancies, offering an effective therapeutic option for multi-line therapy-refractory patients. So far, abundant CAR-T products have been approved by the United States Food and Drug Administration or China National Medical Products Administration to treat relapsed or refractory hematological malignancies and exhibited unprecedented clinical efficiency. However, there were still several significant unmet needs to be progressed, such as the life-threatening toxicities, the high cost, the laborintensive manufacturing process and the poor long-term therapeutic efficacy. According to the demands, many researches, relating to notable technical progress and the replenishment of alternative targets or cells, have been performed with promising results. In this review, we will summarize the current research progress in CAR-T eras from the "targets" to "alternative cells", to "combinational drugs" in preclinical studies and clinical trials. [ABSTRACT FROM AUTHOR]

This study marks one of the pioneering efforts to compile comprehensive information on Ramsar sites globally. It delves into the significance of wetlands and the designation of Ramsar sites across various countries, incorporating a concise exploration of the utilization of Unmanned Aerial Vehicles (UAVs) for wetland monitoring and assessment. Additionally, the study conducts a comparative evaluation of Ramsar sites, analyzing their percentage area and overall coverage worldwide. Incorporating a Scientometric analysis utilizing the Scopus database, the study features a co‐occurrence map, thematic map, thematic evolution trend, and country collaboration map. Emphasizing the interconnection between wetlands and Sustainable Development Goals (SDGs), particularly SDG6 (Clean Water & Sanitation), SDG12 (Responsible Consumption & Production), SDG13 (Climate‐Action), SDG14 (Life Below Water) and SDG15 (Life on Land), the study delves into associated targets and indicators. Targets such as 6.1, 6.2, 6.3, 6.4, 6.5, 6a, 6b of SDG‐6, 12.1, 12.2, 12.4 of SDG‐12, and 13.2, 13.3 of SDG‐13 align with wetland management and conservation. Moreover, it affirms the role of wetlands in supporting targets 14.1, 14.2, 14.3, 14.4, 14.5, 14.6, 14a‐c of SDG‐14, and 15.1, 15.5, 15.6, 15.7, 15.8, and 15.8 of SDG‐15. Policies, regulations and management plans of different countries relevant for supporting and establishing relationship with SDGs are discussed in details. The study offers a detailed exploration of these targets, elucidating indicator types associated with each SDG target. By doing so, it provides valuable insights for future researchers and policymakers, underlining the indispensable contribution of wetlands to the direct and indirect fulfillment of SDGs 6,12,13,14,15 and 17. [ABSTRACT FROM AUTHOR]

Background: Xiaojin Pill (XJP) is a traditional Chinese medicine prescribed for treating benign prostatic hyperplasia (BPH). It has been proven to have multiple effects, such as regulating sex hormone levels, exhibiting anti-tumor, anti-inflammatory, analgesic, and anti-platelet aggregation properties, and improving immunity. However, the material basis of XJP's therapeutic effect on BPH and its metabolic process in vivo remains to be clarified. At the same time, many microorganisms that exist in the urogenital tract, including those related to BPH, can also affect the health of the host. Methods: Using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), the chemical components of XJP were identified. A BPH model was created through bilateral testicular ablation and injections of testosterone propionate. A comprehensive evaluation of XJP efficacy was conducted using pathological ELISA, TUNEL, and immunohistochemical techniques. In addition, UPLC-MS metabolomics and 16S rRNA sequencing revealed the serum metabolic profile and intestinal microbiota composition. We performed a Spearman correlation coefficient analysis to highlight the interactions between "intestinal microbiota-serum factors" and "intestinal microbiota-metabolites." Results: XJP contains 91 compounds that alleviate pathologies of BPH in rats, decreasing prostate weight, index, and serum levels of Dihydrotestosterone (DHT), Prostate-Specific Antigen (PSA), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) levels. It inhibits prostatic epithelial cell apoptosis and downregulates Bax, TGF-β1, and IGF-1 proteins in the caspase-3 pathway. Metabolomics studies have revealed 10 upregulated and 10 downregulated metabolites in treated rats, with 5-methylcytosine, uracil, and cytosine enriched in pyrimidine metabolism. L-arginine plays a pivotal role in metabolic pathways encompassing pyrimidine metabolism, arginine biosynthesis, and the mammalian target of rapamycin (mTOR) signaling pathway. 16S rRNA sequencing revealed that XJP optimized the diversity and balance of intestinal flora in BPH rats by decreasing the Bacteroidetes/Firmicutes (B/F) ratio, enhancing the beneficial bacteria, such as Eggerthellaceae, Anaerovoracaceae, and Romboutsia, and suppressing the dysfunctional bacteria, such as Atopobiaceae, Prevotellaceae_NK3B31_group, Dorea, and Frisingicoccus. According to the Spearman correlation coefficient analysis, Lactobacillus was found to be most associated with serum factors, whereas Romboutsia showed the highest correlation with metabolites. This finding suggests that XJP modulates pyrimidine metabolism disorders in BPH rats, a regulation that aligns closely with Romboutsia, Prevotellaceae_NK3B31_group, Lactobacillus, Chujaibacter, and Enterorhabdus, thereby providing valuable biological insights. Conclusion: In summary, these findings indicate that XJP possesses a synergistic anti-BHP effect through its multi-component, multi-target, multi-gut microbiota, and multi-metabolic pathway properties. The effect involves the regulation of sex hormone levels, growth factors, and the anti-epithelial cell apoptosis process. The modulation of specific gut microbiota by the host and the involvement of multiple metabolic pathways are likely one of the significant mechanisms of XJP in treating BPH. Notably, pyrimidine metabolism and the intestinal microbial ecosystem are closely intertwined in this process. [ABSTRACT FROM AUTHOR]

The Kunming‐Montreal Global Biodiversity Framework lays out an ambitious set of goals and targets aimed at halting and reversing biodiversity loss. The extent of natural ecosystems has been selected as one of a small set of headline indicators against which countries will report progress under this framework. We evaluate the effectiveness with which this indicator is expected to capture the overall scope of the ecosystem‐focused component of Goal A, and interlinkages with the species‐focused component of this same goal, using extensive global data on the integrity, connectivity, and plant species composition of forests. Results generated for all forest‐supporting countries demonstrate that consideration of these additional factors can profoundly alter understanding of the state of forest biodiversity relative to that based on extent alone. Employment of ecosystem extent as a headline indicator must therefore be augmented by appropriate use of component and complementary indicators addressing other key dimensions of ecosystem change. [ABSTRACT FROM AUTHOR]

The article explores the ongoing debate surrounding the ideal mean arterial pressure (MAP) target for critically ill and surgical patients. It acknowledges the negative outcomes associated with low blood pressure and the potential risks of increasing MAP targets. A recent study found that lower blood pressure targets were associated with lower mortality rates and fewer complications, but there were no differences in rates of acute kidney injury. The article emphasizes the need for personalized MAP targets and further research in this area to address the complexities and limitations of blood pressure target studies. [Extracted from the article]

The study examines whether tourists are targets of terror attacks. Three hypotheses are tested, regarding the annual share of terror attacks against clear and vague tourist targets with foreigners as victims, and the likelihood that tourist targets will be attacked in relation to the number of international tourist arrivals and the annual amount of international tourism receipts. The findings do not show that tourists are being targeted, and the statistical relationship between tourist arrivals and receipts is not robust at best. The study offers some theoretical and practical conclusions for tourism and terrorism studies. [ABSTRACT FROM AUTHOR]

The non-ferrous metallurgy industry in Russia is undergoing profound changes due to geopolitical shifts, the transition to green energy, and the need to develop processing industries. Non-ferrous metals, as strategically important products, can play a decisive role in achieving the global goals of the Russian economy related to economic security, the development of domestic markets, the reconstruction of high-tech industries, the modernization of stably functioning industries, and the improvement of the quality of life for the population. The purpose of this research is to study the trends and risks affecting non-ferrous metal producers and to assess the opportunities and challenges for developing both external and domestic markets, ultimately aiming to ensure sustainable demand for the products of mining companies and metal producers. The primary research methods used include general scientific approaches such as comparative analysis, synthesis, and decomposition. This paper reviews the current state of Russia’s non-ferrous metallurgy sector and explores its development prospects, with a specific focus on Norilsk Nickel, a key player operating in the Arctic. The main results of the study include an assessment of the current global market for non-ferrous metals, their role in the energy transition, and the formation of a low-carbon economy. The study also analyzes and summarizes the challenges facing domestic non-ferrous metallurgy and suggests potential directions for its development in the current economic context. A critical analysis of the Strategy for the Development of the Metallurgical Industry of the Russian Federation for the Period up to 2030 reveals that several important aspects and issues are not adequately addressed in the document. For example, it lacks a strategic planning methodology and fails to consider the specific characteristics and potential of the Arctic’s non-ferrous mineral resource base. The practical significance of this study lies in clarifying the prospects for utilizing non-ferrous metals to support the revitalization of high-tech industries in the national economy.

Abstract Dilated cardiomyopathy (DCM) is a common cause of heart failure, thromboembolism, arrhythmias, and sudden cardiac death. The quality of life and long-term survival rates of patients with dilated DCM have greatly improved in recent decades. Nevertheless, the clinical prognosis for DCM patients remains unfavorable. The primary driving factors underlying the pathogenesis of DCM remain incompletely understood. The present study aimed to identify driving factors underlying the pathogenesis of DCM from the perspective of gene regulatory networks. Single-cell RNA sequencing data and bulk RNA data were obtained from the Gene Expression Omnibus (GEO) database. Differential gene analysis, single-cell genomics analysis, and functional enrichment analysis were conducted using R software. The construction of Gene Regulatory Networks was performed using Python. We used the pySCENIC method to analyze the single-cell data and identified 401 regulons. Through variance decomposition, we selected 19 regulons that showed significant responsiveness to DCM. Next, we employed the ssGSEA method to assess regulons in two bulk RNA datasets. Significant statistical differences were observed in 9 and 13 regulons in each dataset. By intersecting these differentiated regulons and identifying shared targets that appeared at least twice, we successfully pinpointed three differentially expressed targets across both datasets. In this study, we assessed and identified 19 gene regulatory networks that were responsive to the disease. Furthermore, we validated these networks using two bulk RNA datasets of DCM. The elucidation of dysregulated regulons and targets (CDKN1A, SAT1, ZFP36) enhances the molecular understanding of DCM, aiding in the development of tailored therapies for patients.

Colorectal cancer (CRC) affects approximately 2 million people worldwide. Obesity is the major risk factor for CRC. In addition, obesity contributes to a chronic inflammatory stage that enhances tumor progression through the secretion of proinflammatory cytokines. In addition to an increased inflammatory response, obesity-associated cancer presents accrued molecular factors related to cancer characteristics, such as genome instability, sustained cell proliferation, telomere dysfunctions, angiogenesis, and microbial alteration, among others. Despite the evidence accumulated over the last few years, the treatments for obesity-associated CRC do not differ from the CRC treatments in normal-weight individuals. In this review, we summarize the current knowledge on obesity-associated cancer, including its epidemiology, risk factors, molecular factors, and current treatments. Finally, we enumerate possible new therapeutic targets that may improve the conditions of obese CRC patients. Obesity is key for the development of CRC, and treatments resulting in the reversal of obesity should be considered as a strategy for improving antineoplastic CRC therapies. [ABSTRACT FROM AUTHOR]

With the general improvement in living standards in recent years, people's living habits, including their dietary habits, have changed. More people around the world do not follow a healthy diet, leading to an increase in morbidity and even mortality due to digestive system diseases, which shows an increasing trend every year. The advantage of traditional Chinese medicine (TCM) in treating digestive system diseases is evident. Consequently, the mechanisms of action of single Chinese herbs and compound Chinese medicines have become the focus of research. The research method of the network pharmacology system was highly consistent with the holistic concept of TCM, and provided a new perspective and theoretical basis for basic research on digestive system diseases. This article summarizes the common databases currently used in research on TCM. It also briefly introduces the basic methods and technologies of network pharmacology studies. It also summarizes the advancements of network pharmacology technology through a comprehensive literature search on PubMed. Based on this analysis, we further explored the role of TCM in treating digestive system diseases, including chronic gastritis, gastric cancer, ulcerative colitis, and liver cirrhosis. This study provides new ideas and references for treating digestive system diseases with TCM in the future and serves as a reference for relevant researchers. [ABSTRACT FROM AUTHOR]

The increasing resistance to polymyxins in Acinetobacter baumannii has made it even more urgent to develop new treatments. Anti-virulence compounds have been researched as a new solution. Here, we evaluated the modification of virulence features of A. baumannii after acquiring resistance to polymyxin B. The results showed lineages attaining unstable resistance to polymyxin B, except for Ab7 (A. baumannii polymyxin B resistant lineage), which showed stable resistance without an associated fitness cost. Analysis of virulence by a murine sepsis model indicated diminished virulence in Ab7 (A. baumannii polymyxin B resistant lineage) compared with Ab0 (A. baumannii polymyxin B susceptible lineage). Similarly, downregulation of virulence genes was observed by qPCR at 1 and 3 h of growth. However, an increase in bauE, abaI , and pgAB expression was observed after 6 h of growth. Comparison analysis of Ab0, Ab7, and Pseudomonas aeruginosa suggested no biofilm formation by Ab7. In general, although a decrease in virulence was observed in Ab7 when compared with Ab0, some virulence feature that enables infection could be maintained. In light of this, virulence genes bauE, abaI , and pgAB showed a potential relevance in the maintenance of virulence in polymyxin B-resistant strains, making them promising anti-virulence targets. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) is a common cause of heart failure, thromboembolism, arrhythmias, and sudden cardiac death. The quality of life and long-term survival rates of patients with dilated DCM have greatly improved in recent decades. Nevertheless, the clinical prognosis for DCM patients remains unfavorable. The primary driving factors underlying the pathogenesis of DCM remain incompletely understood. The present study aimed to identify driving factors underlying the pathogenesis of DCM from the perspective of gene regulatory networks. Single-cell RNA sequencing data and bulk RNA data were obtained from the Gene Expression Omnibus (GEO) database. Differential gene analysis, single-cell genomics analysis, and functional enrichment analysis were conducted using R software. The construction of Gene Regulatory Networks was performed using Python. We used the pySCENIC method to analyze the single-cell data and identified 401 regulons. Through variance decomposition, we selected 19 regulons that showed significant responsiveness to DCM. Next, we employed the ssGSEA method to assess regulons in two bulk RNA datasets. Significant statistical differences were observed in 9 and 13 regulons in each dataset. By intersecting these differentiated regulons and identifying shared targets that appeared at least twice, we successfully pinpointed three differentially expressed targets across both datasets. In this study, we assessed and identified 19 gene regulatory networks that were responsive to the disease. Furthermore, we validated these networks using two bulk RNA datasets of DCM. The elucidation of dysregulated regulons and targets (CDKN1A, SAT1, ZFP36) enhances the molecular understanding of DCM, aiding in the development of tailored therapies for patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) remains a prevalent and challenging malignancy globally, characterized by its numerous causal factors and generally unfavorable prognosis. In the relentless pursuit of effective treatment modalities, natural products have emerged as a promising and relatively non-toxic alternative, garnering significant interest. The integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of HCC. This review offers a comprehensive overview of the causal factors underlying HCC, and the diverse treatment options available, and highlights the advancements made by natural products in anti-HCC research. Particularly, we provide an outline of the various types of natural products, their corresponding nomenclature, target molecules, and mechanisms of action that exhibit anti-HCC activities. Natural products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer, potentially offering patients improved survival rates and an enhanced quality of life. [ABSTRACT FROM AUTHOR]

Drug discovery is a key process, given the rising and ubiquitous demand for medication to stay in good shape right through the course of one's life. Drugs are small molecules that inhibit or activate the function of a protein, offering patients a host of therapeutic benefits. Drug design is the inventive process of finding new medication, based on targets or proteins. Identifying new drugs is a process that involves time and money. This is where computer-aided drug design helps cut time and costs. Drug design needs drug targets that are a protein and a drug compound, with which the interaction between a drug and a target is established. Interaction, in this context, refers to the process of discovering protein binding sites, which are protein pockets that bind with drugs. Pockets are regions on a protein macromolecule that bind to drug molecules. Researchers have been at work trying to determine new Drug Target Interactions (DTI) that predict whether or not a given drug molecule will bind to a target. Machine learning (ML) techniques help establish the interaction between drugs and their targets, using computer-aided drug design. This paper aims to explore ML techniques better for DTI prediction and boost future research. Qualitative and quantitative analyses of ML techniques show that several have been applied to predict DTIs, employing a range of classifiers. Though DTI prediction improves with negative drug target pairs (DTP), the lack of true negative DTPs has led to the use a particular dataset of drugs and targets. Using dynamic DTPs improves DTI prediction. Little attention has so far been paid to developing a new classifier for DTI classification, and there is, unquestionably, a need for better ones. [ABSTRACT FROM AUTHOR]

Zebrafish being the best animal model to study, every attempt has been made to decipher the toxic mechanism of every fungicide of usage and interest. It is important to understand the multiple targets of a toxicant to estimate the toxic potential in its totality. A total of 22 fungicides of different classes like amisulbrom, azoxystrobin, carbendazim, carboxin, chlorothalonil, difenoconazole, etridiazole, flusilazole, fluxapyroxad, hexaconazole, kresoxim methyl, mancozeb, myclobutanil, prochloraz, propiconazole, propineb, pyraclostrobin, tebuconazole, thiophanate-methyl, thiram, trifloxystrobin and ziram were reviewed and analyzed for their multiple explored targets in zebrafish. Toxic end points in zebrafish are highly informative when it comes to network analysis. They provide a window into the molecular and cellular pathways that are affected by a certain toxin. This can then be used to gain insights into the underlying mechanisms of toxicity and to draw conclusions on the potential of a particular compound to induce toxicity. This knowledge can then be used to inform decisions about drug development, environmental regulation, and other areas of research. In addition, the use of zebrafish toxic end points can also be used to better understand the effects of environmental pollutants on ecosystems. By understanding the pathways affected by a given toxin, researchers can determine how pollutants may interact with the environment and how this could lead to health or environmental impacts. [ABSTRACT FROM AUTHOR]

Phthalates are widespread and commonly used plasticizers that lead to adverse health effects. Several natural products provide a protective effect against phthalates. Moreover, microRNAs (miRNAs) are regulated by natural products and phthalates. Therefore, miRNAs' impacts and potential targets may underlie the mechanism of phthalates. However, the relationship between phthalate-modulated miRNAs and phthalate protectors derived from natural products is poorly understood and requires further supporting information. In this paper, we review the adverse effects and potential targets of phthalates on reproductive systems as well as cancer and non-cancer responses. Information on natural products that attenuate the adverse effects of phthalates is retrieved through a search of Google Scholar and the miRDB database. Moreover, information on miRNAs that are upregulated or downregulated in response to phthalates is collected, along with their potential targets. The interplay between phthalate-modulated miRNAs and natural products is established. Overall, this review proposes a straightforward pathway showing how phthalates modulate different miRNAs and targets and cause adverse effects, which are partly attenuated by several natural products, thereby providing a direction for investigating the natural product–miRNA–target axis against phthalate-induced effects.

Background: Antimicrobial peptides (AMPs) are a critical component of the innate immune system, playing a key role in defending against a variety of pathogenic microorganisms. While many AMPs act primarily on the cell membrane of target pathogens, leading to lysis and subsequent cell death, less is known about their nonlytic membrane activity. This nonlytic activity allows AMPs to target and disrupt bacterial cells without causing lysis, leading to bacterial death through alternative mechanisms.Understanding these nonlytic properties of AMPs is crucial, as they present a promising alternative to traditional antibiotics, which can induce bacterial resistance and have adverse effects on human health and the environment. The mechanisms by which AMPs exhibit nonlytic membrane activity are still being explored. However, it is believed that AMPs penetrate the bacterial membrane and interact directly with internal cellular components such as DNA, RNA, and various enzymes essential for microbial survival and replication. This interaction disrupts metabolic homeostasis, ultimately resulting in bacterial death.The nonlytic activity of AMPs also results in minimal damage to host cells and tissues, making them attractive candidates for the development of new, more effective antibiotics. This review emphasizes the mechanisms by which AMPs nonlytically target cellular components, including DNA, proteins, RNA, and other biomolecules, and discusses their clinical significance. Understanding these mechanisms may pave the way for developing alternatives to conventional antibiotics, offering a solution to the growing issue of antibiotic resistance.

As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and treatment, insight into understanding disease pathology and identifying potential targets. Metabolomics technology is crucial for discovering targets of small-molecule metabolites involved in disease phenotype. Mass spectrometry-based metabolomics has implemented in applications in various fields including target discovery, explanation of disease mechanisms and compound screening. It is used to analyze the physiological or pathological states of the organism by investigating the changes in endogenous small-molecule metabolites and associated metabolism from complex metabolic pathways in biological samples. The present review provides a critical update of high-throughput functional metabolomics techniques and diverse applications, and recommends the use of mass spectrometry-based metabolomics for discovering small-molecule metabolite signatures that provide valuable insights into metabolic targets. We also recommend using mass spectrometry-based metabolomics as a powerful tool for identifying and understanding metabolic patterns, metabolic targets and for efficacy evaluation of herbal medicine. [ABSTRACT FROM AUTHOR]

Play fighting has been one of the most intensely studied forms of play and so has provided some of our deepest insights into the understanding of play in general. As the label implies, this behavior resembles serious fighting, in that the animals compete for an advantage over one another, but unlike true aggression, for play fighting to remain playful, it also incorporates a degree of cooperation and reciprocity - restrained competition seems to be its hallmark. Despite these common features, it should be noted that both the advantage competed over and the mechanisms by which restraint is achieved varies across species. Such variation mitigates simple generalities. For example, how empirical support for a proposed adaptive function in one species not being replicated in another, is to be interpreted. What has emerged over the past few decades is that play fighting is diverse, varying across several dimensions, some superficial, some fundamental, making choosing species to compare a challenge. In this paper,we explore various design features that constitute play fighting and the ways these can be modified across different species and lineages of species. Given that a major pillar of ethology is that description precedes explanation, having a good grasp of the behavioral diversity of play fighting is an essential starting point for detailed analyses of the mechanisms and functions of play. We show that commonalities across species likely involve different mechanisms than do species idiosyncrasies, and that different styles of play fighting likely afford different adaptive opportunities. [ABSTRACT FROM AUTHOR]

The blood-testis barrier (BTB) is formed adjacent to the seminiferous basement membrane. It is a distinct ultrastructure, partitioning testicular seminiferous epithelium into apical (adluminal) and basal compartments. It plays a vital role in developing and maturing spermatocytes into spermatozoa via reorganizing its structure. This enables the transportation of preleptotene spermatocytes across the BTB, from basal to adluminal compartments in the seminiferous tubules. Several bioactive peptides and biomolecules secreted by testicular cells regulate the BTB function and support spermatogenesis. These peptides activate various downstream signaling proteins and can also be the target themself, which could improve the diffusion of drugs across the BTB. The gap junction (GJ) and its coexisting junctions at the BTB maintain the immunological barrier integrity and can be the "gateway" during spermatocyte transition. These junctions are the possible route for toxicant entry, causing male reproductive dysfunction. Herein, we summarize the detailed mechanism of all the regulators playing an essential role in the maintenance of the BTB, which will help researchers to understand and find targets for drug delivery inside the testis. [ABSTRACT FROM AUTHOR]

Neurological disorders are the foremost occurring diseases across the globe resulting in progressive dysfunction, loss of neuronal structure ultimately cell death. Therefore, attention has been drawn toward the natural resources for the search of neuroprotective agents. Plant-based food bioactives have emerged as potential neuroprotective agents for the treatment of neurodegenerative disorders. This comprehensive review primarily focuses on various plant food bioactive, mechanisms, therapeutic targets, in vitro and in vivo studies in the treatment of neurological disorders to explore whether they are boon or bane for neurological disorders. In addition, the clinical perspective of plant food bioactives in neurological disorders are also highlighted. Scientific evidences point toward the enormous therapeutic efficacy of plant food bioactives in the prevention or treatment of neurological disorders. Nevertheless, identification of food bioactive components accountable for the neuroprotective effects, mechanism, clinical trials, and consolidation of information flow are warranted. Plant food bioactives primarily act by mediating through various pathways including oxidative stress, neuroinflammation, apoptosis, excitotoxicity, specific proteins, mitochondrial dysfunction, and reversing neurodegeneration and can be used for the prevention and therapy of neurodegenerative disorders. In conclusion, the plant based food bioactives are boon for neurological disorders. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) -T cell therapy has entered the breakthrough era, characterized by a blend of therapeutic opportunities and challenges. With the integration of genome-editing technology, CAR-T cells will be empowered to become super warriors in eradicating tumor cells and attacking various tumors, including T-cell malignancies and acute myeloid leukemia. Notably, the optimization of CAR-T cells, including efficacy, safety, and manufacturing speed, coupled with other therapeutic strategies such as radiotherapy, hematopoietic stem cell transplantation, small-molecule inhibitors, and bispecific antibodies, could revolutionize the therapeutic landscape of tumors. Consequently, next-generation cellular immunotherapy, including universal CAR-NK cells and synergistic combination approaches, are anticipated to significantly impact cancer treatment in the coming decade. Nevertheless, the failure rates of CAR-T therapy continue to be significant. The challenge lies in determining the optimal combination strategy and identifying reliable and robust biomarkers to effectively select the patients who will derive the greatest benefit from CAR-T therapy. Herein, we highlight recent innovations in CAR-T products, combination strategies and predictive biomarkers of response presented at the 2023 ASH Annual Meeting. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate targets through which Gualou Xiebai Banxia decoction aids in treating myocardial infarction (MI) using network pharmacology in combination with molecular docking. The principal active ingredients of Gualou Xiebai Banxia decoction were identified from the TCMSP database using the criteria of drug-likeness ≥30% and oral bioavailability ≥0.18. Interactions and pathway enrichment were investigated using protein–protein interaction (PPI) networks and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, respectively. Active component structures were docked with those of potential protein targets using AutoDock molecular docking relative softwares. HIF1A was of particular interest as it was identified by the PPI network, GO and KEGG pathway enrichment analyses. In conclusion, the use of network pharmacology prediction and molecular docking assessments provides further information on the active components and mechanisms of action Gualou Xiebai Banxia decoction. [ABSTRACT FROM AUTHOR]

Background: Acute lung injury (ALI) is a serious illness that has few treatment options available. Tribuloside, a natural flavonoid extracted from the Tribulus Terrestris plant in China, is potent in addressing many health issues such as headaches, dizziness, itching, and vitiligo. Objective: This study intends to explore the mechanisms of action of Tribuloside in treating ALI through a combination of network pharmacology and experimental validation. Methods: We obtained the 2D structure and SMILES number of Tribuloside from the PubChem database. We used the SwissTargetPrediction database to identify pharmacological targets. We found 1215 targets linked to ALI by examining the GeneCards database. We used the String database and Cytoscape software to create the "drug or disease-target" network as well as the protein-protein interactions (PPI). Key targets were identified by evaluating associated biological processes and pathway enrichment. A Venny Diagram showed 49 intersection points between Tribuloside and ALI. Molecular docking with AutoDockTools found that Tribuloside had a high affinity for IL6, BCL2, TNF, STAT3, IL1B, and MAPK3, the top 6 targets in the PPI network by Degree values. To test Tribuloside's therapeutic efficacy in ALI, an acute lung damage model in mice was constructed using lipopolysaccharide. Tribuloside treatment reduced inflammatory cell infiltration, decreased fibrotic area, repaired damaged alveoli, and suppressed inflammatory factors IL-6, TNF-α, and IL-1β in the lungs through many pathways and targets. Conclusion: This study reveals that Tribuloside has the potential to treat ALI by targeting various pathways and targets, according to network pharmacology predictions and experimental confirmation. [ABSTRACT FROM AUTHOR]

The UK government's 25 Year Plan to Improve the Environment (25YEP), published in 2018, together with annual progress reports and subsequent periodic revisions, represent the most comprehensive and forward-looking single body of environmental legislation for the United Kingdom. The forthcoming update of the UK National Biodiversity Strategy and Action Plan (NBSAP) addressing targets for the Convention on Biological Diversity's Global Biodiversity Framework to 2030 is also an opportunity to revisit the monitoring framework developed for the 25YEP. Here, we present an evaluation of the goals, targets and indicators of the 25YEP in light of gaps, synergies and opportunities for aligning with the CBD 2030 Framework. We make a number of recommendations for adopting indicators already developed in the context of CBD targets that can also measure progress towards environmental targets within the UK, with a view to more holistic monitoring of biodiversity status and trends. Landscape-scale interventions and, in particular, improvements to farming—exemplified by the new Environmental Land Management Schemes—and fishing policies have the potential for the greatest enhancement to the state of the UK environment and the plants and wildlife within it. [ABSTRACT FROM AUTHOR]

Metal ions are essential trace elements for all living organisms and play critical catalytic, structural, and allosteric roles in many enzymes and transcription factors. Mycobacterium tuberculosis (MTB), as an intracellular pathogen, is usually found in host macrophages, where the bacterium can survive and replicate. One of the reasons why Tuberculosis (TB) is so difficult to eradicate is the continuous adaptation of its pathogen. It is capable of adapting to a wide range of harsh environmental stresses, including metal ion toxicity in the host macrophages. Altering the concentration of metal ions is the common host strategy to limit MTB replication and persistence. This review mainly focuses on transcriptional regulatory proteins in MTB that are involved in the regulation of metal ions such as iron, copper and zinc. The aim is to offer novel insights and strategies for screening targets for TB treatment, as well as for the development and design of new therapeutic interventions. [ABSTRACT FROM AUTHOR]

Powerful pharmaceuticals are readily available for purchase throughout Tanzania and global health policy makers decry this situation as dangerous and disordered, as if no rules govern the use of drugs in Africa. In the prevailing global health understanding, 'truth' lies in the laboratory science that goes into the making and proper prescription of drugs, and such deviations as 'overuse' and 'misuse' result from the fact that locals supposedly misunderstand what these drugs are and how they should be used. However, my ethnographic research in Tanzania reveals that embodied epistemologies frequently enable medical practitioners and patients to evaluate the quality of various drugs and to identify chakachua (substandard or adulterated) pharmaceuticals through their material and sensory qualities—a practice I conceptualize as a form of 'fugitive science' (Rusert 2017). In light of this, I analyze the WHO's National Action Plan for Antimicrobial Resistance in Tanzania, demonstrating how such global health policies disregard this knowledge, employing neocolonial rhetoric that presents 'ignorance' and 'lack of hygiene' as the sources of growing antimicrobial resistance while simultaneously obscuring structural inequalities. I argue that such forms of global health surveillance operate through the logics and epistemologies of war (Chow 2006; Terry 2017) in ways that render populations in the Global South into threats and targets. I conclude by suggesting that fugitive science can work as counter-evidence to health security frameworks and, as such, represents a furtive form of resistance to these militarized logics. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver cancer is one of the most difficult solid tumors to treat and is responsible for one-third of cancer-related deaths worldwide. In particular, the quest for effective therapeutic strategies for hepatocellular carcinoma, which often arises from a chronic inflammatory background, remains an open challenge. In this review, we aim to provide an overview of the current therapeutic options available, focusing on recent advances in targeted therapies and the pursuit of emerging potential targets. Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third in cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, and genetic factors. No specific genetic alterations are unequivocally linked to HCC tumorigenesis. Current standard therapies include surgical options, systemic chemotherapy, and kinase inhibitors, like sorafenib and regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint inhibitors, such as atezolizumab and pembrolizumab, show efficacy, and combination therapies enhance clinical responses. Despite this, the treatment of hepatocellular carcinoma (HCC) remains a challenge, as the complex tumor ecosystem and the immunosuppressive microenvironment associated with it hamper the efficacy of the available therapeutic approaches. This review explores current and advanced approaches to treat HCC, considering both known and new potential targets, especially derived from proteomic analysis, which is today considered as the most promising approach. Exploring novel strategies, this review discusses antibody drug conjugates (ADCs), chimeric antigen receptor T-cell therapy (CAR-T), and engineered antibodies. It then reports a systematic analysis of the main ligand/receptor pairs and molecular pathways reported to be overexpressed in tumor cells, highlighting their potential and limitations. Finally, it discusses TGFβ, one of the most promising targets of the HCC microenvironment. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor-α (PPAR-α) belonging to the nuclear hormone receptor superfamily is a promising target for CVDs which mechanistically improves the production of high-density lipid as well as inhibit vascular smooth muscle cell proliferation. PPAR-α mainly interferes with adenosine monophosphate-activated protein kinase, transforming growth factor-β-activated kinase, and nuclear factor-κB pathways to protect against cardiac complications. Natural products/extracts could serve as a potential therapeutic strategy in CVDs for targeting PPAR-α with broad safety margins. In recent years, the understanding of naturally derived PPAR-α agonists has considerably improved; however, the information is scattered. In vitro and in vivo studies on acacetin, apigenin, arjunolic acid, astaxanthin, berberine, resveratrol, vaticanol C, hispidulin, ginsenoside Rb3, and genistein showed significant effects in CVDs complications by targeting PPAR-α. With the aim of demonstrating the tremendous chemical variety of natural products targeting PPAR-α in CVDs, this review provides insight into various natural products that can work to prevent CVDs by targeting the PPAR-α receptor along with their detailed mechanism. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are generated in a cell endogenously which have a nucleotide length of 18 to 26 and are also known as short non-protein coding RNAs. The majority of them are evolutionarily conserved in nature, suggesting a logical foundation for the anticipation of new miRNAs in association with their clusters in numerous plants. Considering this study, physical, bioinformatics and efficient methods are integrated to predict the fresh miRNA clusters along with their targets in sugar cane. In sugar cane, there were a total of 21 new miRNA clusters identified, which were linked to 15 miRNA families. These families are as 165a, 166b, 528a, 827, 2118, 2120b, 5168, 5564c, 5565g, 5568c, 6220, 6225, 6226, 6232a and 7540a. Multiple characteristics of such miRNA clusters, including web logo, phylogenetic tree and secondary structures have been developed. The minimal free energy (MFE) of the secondary structures has been attained and reported as well. In addition, mature miRNAs have been sought in stem section of the structure. Consequently, 115 miRNA targets were also found. These targets include substantial GO term which have important targets in the reproduction, DNA packaging, multicellular organismal process, gene expression, translation, transcription factors, protein binding, transporter activity, secretion, cell division, binding, growth & development and aging. Hence, the achieved results of novel sugar cane miRNA clusters target several types of significant genes which help in managing the environment for sugar cane for better crop production. [ABSTRACT FROM AUTHOR]

Background: Advanced paramedic practitioners in critical care (APPCCs) are advanced clinical practitioners focused on the delivery of pre-hospital critical care. While working in an ambulance control room setting, APPCCs seek to identify emergency calls appropriate for operational APPCCs to attend. These would include out-of-hospital cardiac arrest (OHCA). Through interrogation of incoming emergency calls they are also able to identify OHCA calls where resuscitation may be futile. In these cases, and within a governance framework, they stand down multiple ambulance responders, leaving only the closest responding resource to attend, thereby ‘saving resources’ that can be re-directed to other waiting emergency calls. It is believed that this is the first initiative of this nature in the United Kingdom. Methods: A three-year retrospective service evaluation of data was undertaken. The aim was to quantify the number of ‘saved resources’, including both double crewed ambulances (DCAs) and solo (single-person) responders, and furthermore to equate those savings into potential hours saved, using average known job cycle times (JCTs). Additionally, safety was assessed by searching all mandated incident reports for occasions where, despite cancellation of resources by an APPCC, resuscitation was commenced by the first response to scene. Results: A total of 13,356 ambulance resources were saved. Of these, 6593 (49.4%) were DCAs and 6763 (50.6%) were solo responders. Using the average JCT for deceased patients of 104.8 minutes, the total time saving equated to 23,328.48 hours of work or 1944.04 12-hour shifts. When considering DCAs alone, the average JCT for obviously deceased patients was 110.9 minutes. This equates to 12,186.1 hours of work or 1015.5 12-hour shifts. A total of 15 incident reports were identified. All had been investigated, revealing appropriate decision making in cancelling ambulance resources. No patient harm was identified. [ABSTRACT FROM AUTHOR]

Licorice, derived from the root of Glycyrrhiza uralensis Fisch, is a key Traditional Chinese Medicine known for its detoxifying, spleen-nourishing, and qi-replenishing properties. Licochalcone A (Lico A), a significant component of licorice, has garnered interest due to its molecular versatility and receptor-binding affinity. This review explores the specific roles of Lico A in various diseases, providing new insights into its characteristics and guiding the rational use of licorice. Comprehensive literature searches using terms such as “licorice application” and “pharmacological activity of Lico A” were conducted across databases including CNKI, PubMed, and Google Scholar to gather relevant studies on Lico A’s pharmacological activities and mechanisms. Lico A, a representative chalcone in licorice, targets specific mechanisms in anti-cancer and anti-inflammatory activities. It also plays a role in post-transcriptional regulation. This review delineates the similarities and differences in the anti-cancer and anti-inflammatory mechanisms of Lico A, concluding that its effects on non-coding RNA through post-transcriptional mechanisms deserve further exploration.

Staphylococcus aureus can readily form biofilm which enhances the drug-resistance, resulting in life-threatening infections involving different organs. Biofilm formation occurs due to a series of developmental events including bacterial adhesion, aggregation, biofilm maturation, and dispersion, which are controlled by multiple regulatory systems. Rapidly increasing research and development outcomes on natural products targeting S. aureus biofilm formation and/or regulation led to an emergent application of active phytochemicals and combinations. This review aimed at providing an in-depth understanding of biofilm formation and regulation mechanisms for S. aureus, outlining the most important antibiofilm strategies and potential targets of natural products, and summarizing the latest progress in combating S. aureus biofilm with plant-derived natural products. These findings provided further evidence for novel antibiofilm drugs research and clinical therapies.

In 2009, elite swimming introduced polyurethane "supersuits," which artificially enhanced performances and facilitated 43 world records at the World Championships, before being prohibited from 2010. This transient, artificial improvement spike created a natural experiment to examine the effect of "impossible" targets on subsequent performances. Analyses revealed that swimming speeds at global championships in the postsupersuit period (2011-2017) were substantially faster than predicted from the presupersuit period (2000-2007). These results suggest that the transient, artificially enhanced performances of the supersuit era recalibrated targets upward-acting as goals-and improved subsequent performances beyond previous trajectories (d = 0.64; 0.70%). Contributing to psychological goal-setting theory, the positive relationship between the size of the transient, artificial improvement (i.e., goal difficulty) and subsequent performance was curvilinear, increasing at a decreasing rate before improvements plateaued. Overall, the research demonstrates the potential for elite athletes to exceed perceived human limits after expectations have been recalibrated upward. [ABSTRACT FROM AUTHOR]

Abstract Background Myelodysplastic syndrome (MDS) is known to arise through the pathogenic bone marrow mesenchymal stem cells (MSC) by interacting with hematopoietic stem cells (HSC). However, due to the strong heterogeneity of MDS patients, it is difficult to find common targets in studies with limited sample sizes. This study aimed to describe sequential molecular changes and identify biomarkers in MSC of MDS transformation. Methods Multidimensional data from three publicly available microarray and TCGA datasets were analyzed. MDS-MSC was further isolated and cultured in vitro to determine the potential diagnostic and prognostic value of the identified biomarkers. Results We demonstrated that normal MSCs presented greater molecular homogeneity than MDS-MSC. Biological process (embryonic skeletal system morphogenesis and angiogenesis) and pathways (p53 and MAPK) were enriched according to the differential gene expression. Furthermore, we identified HOXB3 and HOXB7 as potential causative genes gradually upregulated during the normal-MDS-AML transition. Blocking the HOXB3 and HOXB7 in MSCs could enhance the cell proliferation and differentiation, inhibit cell apoptosis and restore the function that supports hematopoietic differentiation in HSCs. Conclusion Our comprehensive study of gene expression profiling has identified dysregulated genes and biological processes in MSCs during MDS. HOXB3 and HOXB7 are proposed as novel surrogate targets for therapeutic and diagnostic applications in MDS.

• Great progress has been made previously in MicroRNAs-guided gene regulation in plant-parasitic cyst nematodes interactions. Little, however, is known about miRNAs regulation of nematode stress response in Cucumis metuliferus, which is a relative of cultivated cucumber or melon and highly resistant to Meloidogyne incognita. • Five cmu-miR396 precursors were identified and characterized from C. metuliferus. A total of 12 genes were then predicted to be as the potential targets of cmu-miR396 and their function involved in transcription factor, metabolism, signal transduction and stress response. Moreover, three cmu-GRFs genes in roots of C. metuliferus were amplified and confirmed by RT-PCR experimently. The analysis was performed for the phylogeny and subcellular localization of cmu-GRFs protein, and the three transcription factors cmu-GRFs were confirmed as the candidate targets of cmu-miR396 through 5′RLM-RACE assays. • These data laid a foundation for further functional analyses to reveal the roles played by miR396 during the interaction between C. metuliferus and M. incognita. MicroRNAs (miRNAs), a class of non-coding small RNAs, play an important role in biotic and abiotic stresses. Previously, great progress has been made in miRNA-guided gene regulation in plant-parasitic cyst nematodes interactions. However, little is known about miRNAs regulation of nematode stress response in Cucumis metuliferus , which is a relative of cultivated cucumber or melon and highly resistant to the root-knot nematode Meloidogyne incognita. On the basis of our investigation recently, five cmu-miR396 precursors were firstly identified and characterized from C. metuliferus in this study. Subquently, a total of 12 genes were predicted to be as the potential targets of cmu-miR396 and their function involved in transcription factor, metabolism, signal transduction and stress response. Moreover, three cmu-GRFs genes with significant differential expression in roots of C. metuliferus were successfully amplified and confirmed by RT-PCR experimently. Additionally, the analysis was performed for the phylogeny and subcellular localization of cmu-GRFs protein, and the three transcription factors cmu-GRFs were confirmed as the candidate targets of cmu-miR396 through 5′RLM-RACE assays. These data laid a foundation for further functional analyses to reveal the roles played by miR396 during the interaction between C. metuliferus and M. incognita , leading to a better understanding of the mechanisms and underlying regulatory networks of miR396-mediated resistance to M. incognita in C. metuliferus. [ABSTRACT FROM AUTHOR]

Generally, governments and industry have implemented some degree of protection to reduce the impacts of forestry on aquatic ecosystems. Here, we consider the widespread application of streamside management in terms of riparian buffer retention to protect freshwaters from forestry practices across three jurisdictions with large and intensive forestry sectors (British Columbia, Finland and Sweden).This perspective was developed by working with researchers, practitioners and policymakers on mitigation measures to decrease the impacts of forestry on streams. We demonstrate that it is exceedingly rare for policies and guidelines to specify concrete objectives and measurable targets that can be assessed against riparian buffer management outcomes. Most often, policy objectives for riparian management prescribe 'to prevent or mitigate impacts', and this vagueness is insufficient to protect our waters. We argue that we should be clearer about the targets (outcomes) for riparian management and go beyond the simple idea that buffer presence, without further specification of its conditions, is always a successful protection strategy. One cannot measure the effectiveness of rules and guidelines without quantitative targets.Policy implications: In this paper, we suggest that locally developed and adjusted targets for riparian buffers must include quantifiable, measurable goals that specify what is supposed to be achieved and protected with respect to ecological functions, biological communities or other values. It should be relatively simple to move from current vague objectives such as 'protect and prevent' to a defined range of values for ecological parameters that buffers are supposed to provide. For example, these can include region‐specific shading levels and microclimate targets, large wood volumes, or riparian forest species composition. We stress that these targets must be developed through an open dialogue between agencies, practitioners, land owners and scientists. We acknowledge that there are trade‐offs between being too prescriptive and too vague. However, when excessively broad goals are the norm, we lose the capacity to effectively implement, monitor or evaluate the outcomes of protection measures. [ABSTRACT FROM AUTHOR]

Obesity is a major risk factor for morbidity and mortality because it has a close relationship to metabolic illnesses, such as diabetes, cardiovascular diseases, and some types of cancer. With no drugs available, the mainstay of obesity management remains lifestyle changes with exercise and dietary modifications. In light of the tremendous disease burden and unmet therapeutics, fresh perspectives on pathophysiology and drug discovery are needed. The development of epigenetics provides a compelling justification for how environmental, lifestyle, and other risk factors contribute to the pathogenesis of obesity. Furthermore, epigenetic dysregulations can be restored, and it has been reported that certain natural products obtained from plants, such as tea polyphenols, ellagic acid, urolithins, curcumin, genistein, isothiocyanates, and citrus isoflavonoids, were shown to inhibit weight gain. These substances have great antioxidant potential and are of great interest because they can also modify epigenetic mechanisms. Therefore, understanding epigenetic modifications to target the primary cause of obesity and the epigenetic mechanisms of anti‐obesity effects with certain phytochemicals can prove rational strategies to prevent the disease and develop novel therapeutic interventions. Thus, the current review aimed to summarize the epigenetic mechanisms and advances in therapies for obesity based on natural products to provide evidence for the development of several potential anti‐obesity drug targets. [ABSTRACT FROM AUTHOR]