Mechanism of inhibition of melanoma by fucoxanthin simulated in vitro digestion products in cell models constructed using human malignant melanoma cells (A375) and keratinocytes (HaCaT).

Recently, the increasing incidence of malignant melanoma has become a major public health concern owing to its poor prognosis and impact on quality of life. Consuming foods with potent antitumor compounds can help prevent melanoma and maintain skin health. Fucoxanthin (FX), a naturally occurring carotenoid found in brown algae, possesses antitumor properties. However, its bioavailability, safety risks, and in vivo effects and mechanisms against melanoma remain unclear. This research focused on evaluating the safety and prospective antimelanoma impact of simulated gastrointestinal digestion products (FX-ID) on HaCaT and A375 cells.The results indicate that FX-ID exerts negative effects on mitochondria in A375 cells, increases Bax expression, releases Cytochrome C, and activates cleaved caspase-3, ultimately promoting apoptosis. Additionally, FX-ID influences the mitogen-activated protein kinase (MAPK) pathway by enhancing cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) levels, consequently facilitating apoptosis and inflammation without significantly impacting HaCaT cells. These findings provide insight into inhibitory mechanism of FX-ID against melanoma, guiding the development of functional foods for prevention.

Ozonolysis of ketoprofen in polluted water: Reaction pathways, kinetics, removal efficiency, and health effects.

Ketoprofen (KET), as a non-steroidal anti-inflammatory drug frequently detected in aqueous environments, is a threat to human health due to its accumulation and low biodegradability, which requires the transformation and degradation of KET in aqueous environments. In this paper, the reaction process of ozone-initiated KET degradation in water was investigated using density functional theory (DFT) method at the M06-2X/6-311++g(3df,2p)//M06-2X/6-31+g(d,p) level. The detailed reaction path of KET ozonation is proposed. The thermodynamic results show that ozone-initiated KET degradation is feasible. Under ultraviolet irradiation, the reaction of ozone with water can also produce OH radicals (HO·) that can react with KET. The degradation reaction of KET caused by HO· was further studied. The kinetic calculation illustrates that the reaction rate (1.99 × 10-1 (mol/L)-1 sec-1) of KET ozonation is relatively slow, but the reaction rate of HO· reaction is relatively high, which can further improve the degradation efficiency. On this basis, the effects of pollutant concentration, ozone concentration, natural organic matter, and pH value on degradation efficiency under UV/O3 process were analyzed. The ozonolysis reaction of KET is not sensitive to pH and is basically unaffected. Finally, the toxicity prediction of oxidation compounds produced by degradation reaction indicates that most of the degradation products are harmless, and a few products containing benzene rings are still toxic and have to be concerned. This study serves as a theoretical basis for analyzing the migration and transformation process of anti-inflammatory compounds in the water environment.

Hospitalizaciones evitables por problemas de salud sensibles a cuidados ambulatorios: construcción y validación de la lista Uruguaya de patologías

Introducción: Las hospitalizaciones por Ambulatory Care Sensitive Conditions es un indicador que mide la utilización de los servicios hospitalarios por problemas de salud que podrían haber sido prevenidos en el primer nivel de atención. El concepto se refiere a los procesos en que la atención ambulatoria efectiva puede ayudar a disminuir los riesgos de hospitalización, en un segundo nivel de atención. El objetivo del estudio fue construir y validar una lista uruguaya de problemas de salud sensibles a cuidados ambulatorios (PSSCA) según CIE-10. Metodología: Para la construcción de la lista inicial de códigos de PSSCA se realizó una revisión de los listados existentes y se propuso un listado inicial que fue validado a través del Método Delphi. Se propone un listado de 99 códigos diagnósticos de PSSCA adaptado a nuestro entono sanitario. Los mismos permiten identificar y cuantificar problemas de salud que pueden producir hospitalizaciones potenciamente evitables mediante cuidados ambulatorios accesibes y oportunos en el primer nivel de atención. Resultados: Se conformó un panel de 12 expertos. A partir de los datos obtenidos, considerando los 99 diagnósticos clasificados por CIE-10, éstos se pueden subclasificar en función de si la patología es infecciosa o no, obteniendo un resultado general de 62 patologías en un total de 99 que pueden ser clasificadas como infecciosas, lo que se corresponde a un 62 %. Discusión: De la comparación de la lista uruguaya de PSSCA a la que hemos arribado y las listas validadas utilizadas para la construcción inicial del listado de patologías propuesto, podemos decir que la primera presenta un mayor porcentaje de coincidencia con la lista de patologías de Bello Horizonte. Podemos mencionar que la mayoría de los problemas de salud identificados con base en el listado de PSSCA, son sensibles de ser resueltos con la atención primaria oportuna y de calidad que podría evitar o disminuir de una manera significativa su hospitalización. Conclusiones: Este trabajo describe el proceso de construcción y validación de una lista de códigos de PSSCA adaptados al contexto uruguayo a través del método Delphi. Hemos arribado a un listado que comprende un total de 99 diagnósticos, agrupadas en un total de diecinueve categorías que considera la especificidad del contexto uruguayo del indicador.

Introduction: Hospitalizations for Ambulatory Care Sensitive Conditions is an indicator that measures the use of hospital services for health problems that could have been prevented at the first level of care. The concept refers to the processes in which effective outpatient care can help reduce the risks of hospitalization, at a second level of care. The objective of the study was to build and validate a Uruguayan list of health problems sensitive to outpatient care (PSS-CA) according to ICD-10. Methodology: To construct the initial list of PSSCA codes, a review of the existing lists was carried out and an initial list was proposed that was validated through the Delphi Method. A list of 99 PSSCA diagnostic codes adapted to our healthcare environment is proposed. They make it possible to identify and quantify health problems that can lead to potentially avoidable hospitalizations through accessible and timely outpatient care at the first level of care. Results: A panel of 12 experts was formed. From the data obtained, considering the 99 diagnoses classified by ICD-10, these can be subclassified depending on whether the pathology is infectious or not, obtaining a general result of 62 pathologies in a total of 99 that can be classified as infectious, which corresponds to 62%. Discussion: From the comparison of the Uruguayan list of PSSCA that we have arrived at and the validated lists used for the initial construction of the proposed list of pathologies, we can say that the first presents a higher percentage of coincidence with the list of pathologies of Bello Horizonte . We can mention that most of the health problems identified based on the PSSCA list are sensitive to being resolved with timely and quality primary care that could prevent or significantly reduce hospitalization. Conclusions: This work describes the process of construction and validation of a list of PSSCA codes adapted to the Uruguayan context through the Delphi method. We have arrived at a list that includes a total of 99 diagnoses, grouped into a total of nineteen categories that consider the specificity of the Uruguayan context of the indicator.

Introdução: As Internações por Condições Sensíveis à Atenção Ambulatorial são um indicador que mede a utilização de serviços hospitalares para problemas de saúde que poderiam ter sido evitados no primeiro nível de atenção. O conceito refere-se aos processos em que um atendimento ambulatorial eficaz pode auxiliar na redução dos riscos de internação, em um segundo nível de atenção. O objetivo do estudo foi construir e validar uma lista uruguaia de problemas de saúde sensíveis à atenção ambulatorial (PSS-CA) segundo a CID-10. Metodologia: Para construir a lista inicial de códigos PSSCA foi realizada uma revisão das listas existentes e foi proposta uma lista inicial que foi validada através do Método Delphi. É proposta uma lista de 99 códigos de diagnóstico PSSCA adaptados ao nosso ambiente de saúde. Permitem identificar e quantificar problemas de saúde que podem levar a hospitalizações potencialmente evitáveis ​​através de cuidados ambulatórios acessíveis e oportunos no primeiro nível de cuidados. Resultados: Foi formado um painel de 12 especialistas. A partir dos dados obtidos, considerando os 99 diagnósticos classificados pela CID-10, estes podem ser subclassificados consoante a patologia seja infecciosa ou não, obtendo-se um resultado geral de 62 patologias num total de 99 que podem ser classificadas como infecciosas, o que corresponde para 62%. Discussão: A partir da comparação da lista uruguaia de PSSCA a que chegamos e das listas validadas utilizadas para a construção inicial da lista de patologias proposta, podemos dizer que a primeira apresenta um maior percentual de coincidência com a lista de patologias de Belo Horizonte. Podemos mencionar que a maioria dos problemas de saúde identificados com base na lista PSSCA são sensíveis para serem resolvidos com cuidados primários oportunos e de qualidade que possam prevenir ou reduzir significativamente a hospitalização. Conclusões: Este trabalho descreve o processo de construção e validação de uma lista de códigos PSSCA adaptados ao contexto uruguaio através do método Delphi. Chegamos a uma lista que inclui um total de 99 diagnósticos, agrupados em um total de dezenove categorias que consideram a especificidade do contexto uruguaio do indicador.

Chemical Constituents, Anti-Tumor Mechanisms, and Clinical Application: A Comprehensive Review on Scutellaria barbata.

With the increasing global incidence and mortality rates of cancer, the development of novel anti-tumor drugs has become particularly urgent. Scutellaria barbata D. Don, a perennial herb belonging to the genus Scutellaria in the family Lamiaceae, has aroused extensive attention for its medicinal value in recent years. This article presents an exhaustive review of the flavonoid, diterpene, and other chemical constituents harbored within Scutellaria barbata, delving into the intricate mechanisms by which these compounds orchestrate their anti-tumor effects via diverse biological pathways. Remarkably, these compounds distinguish themselves through their capability to regulate cellular signaling, inhibit cancer cell proliferation, trigger apoptosis, disrupt angiogenesis, and bolster immune responses. These anti-tumor effects are achieved through strategic modulation of pivotal signaling cascades, particularly the PI3K/Akt/mTOR, MAPK, and NFκB pathways. In addition, this article also summarizes the clinical applications of Scutellaria barbata in tumor treatment, especially its potential in alleviating the side effects of radiotherapy and chemotherapy and improving patients' quality of life. In conclusion, this review comprehensively summarizes and analyzes the chemical constituents, anti-tumor mechanisms, and clinical applications of Scutellaria barbata, with the aim of systematically reviewing the existing research results and exploring potential future research directions.

Natural products for the treatment of hypertrophic scars: Preclinical and clinical studies.

Hypertrophic scarring (HS) is a complication of wound healing that causes physiological and psychological distress in patients. However, the possible mechanism underlying HS is not fully understood, and there is no gold standard for its treatment. Natural products are more effective, economical, convenient, and safe than existing drugs, and they have a wide application prospect. However, there is a lack of literature on this topic, so we reviewed in vivo, in vitro, and clinical studies and screened natural products showing beneficial effects on HS that can become potential therapeutic agents for HS to fill in the gaps in the field. In addition, we discussed the drug delivery systems related to these natural products and their mechanisms in the treatment of HS. Generally speaking, natural products inhibit inflammation, myofibroblast activation, angiogenesis, and collagen accumulation by targeting interleukins, tumor necrosis factor-α, vascular endothelial growth factors, platelet-derived growth factors, and matrix metalloproteinases, so as to play an anti-HS effects of natural products are attributed to their anti-inflammatory, anti-proliferative, anti-angiogenesis, and pro-apoptotic (enhancing apoptosis and autophagy) roles, thus treating HS. We also screened the potential therapeutic targets of these natural compounds for HS through network pharmacology and constructed a protein-protein interaction (PPI) network, which may provide clues for the pharmacological mechanism of natural products in treating this disease and the development and application of drugs.

The role of Rhizoma Paridis saponins on anti-cancer: The potential mechanism and molecular targets.

Cancer is a disease characterized by uncontrolled cell proliferation, leading to excessive growth and invasion that can spread to other parts of the body. Traditional Chinese medicine has made new advancements in the treatment of cancer, providing new perspectives and directions for cancer treatment. Rhizoma Paridis is a widely used Chinese herbal medicine with documented anti-cancer effects dating back to ancient times. Modern research has shown that Rhizoma Paridis saponins (RPS) have various pharmacological activities. RPS can inhibit cancer in multiple ways, such as suppressing tumor growth, inducing cell cycle arrest, promoting cell apoptosis, enhancing cell autophagy, inducing ferroptosis, reducing inflammation, inhibiting angiogenesis, as well as inhibiting metastasis and invasion, and these findings demonstrate the potent anti-cancer activity of RPS. Polyphyllin I, polyphyllin II, polyphyllin VI, and polyphyllin VII have been widely reported as the main active ingredients with anti-cancer properties. Polyphyllin D, polyphyllin E, and polyphyllin G have also been confirmed to possess strong anti-cancer activity in recent years. Therefore, this review dives deep into the molecular mechanisms underlying the anti-cancer effects of RPS to serve as a valuable reference for future scientific research and their potential applications in cancer treatment.

Individual mono and co-interactions of butylated hydroxytoluene and its metabolite with pepsin: Multi-pronged research strategies.

In this study, the interactions between butylated hydroxytoluene (BHT) and its metabolite 2,6-Di-tert-butyl-p-benzoquinone (BHT-Q) with pepsin (PEP) were explored using multispectral measurements and computer prediction techniques. UV-vis absorption spectra, fluorescence lifetime, and Stern-Volmer quenching analysis showed static fluorescence quenching of PEP by BHT/BHT-Q. Negative thermodynamic parameters indicated that the spontaneous formation of complexes was primarily driven by van der Waals (vdW) forces and hydrogen bonds (HB). Synchronous fluorescence and circular dichroism spectroscopy revealed conformational changes induced by BHT/BHT-Q on PEP. Furthermore, BHT and BHT-Q inhibited PEP's enzymatic activity, while PEP suppressed their antioxidant activity. Interestingly, BHT-Q weakened BHT's binding strength to PEP, affecting the enzyme inhibition rate. Computer predictions highlighted the integral role of hydrophobic interactions. Moreover, BHT and BHT-Q exhibited different effects on the stability and compactness of PEP, the residue environment of PEP became more flexible or rigid in the presence of BHT and BHT-Q. Changes in the hydrophobic solvent accessible surface area (SASA) elucidated that the microenvironment of hydrophobic residues of PEP was changed after binding with BHT and BHT-Q. Ultimately, BHT's stronger binding affinity to PEP than BHT-Q was attributed mainly to its larger negative surface area, facilitating interactions with more amino acid residues.

Paracoccidioides spp.: escape mechanisms and their implications for the development of this mycosis.

Paracoccidioidomycosis (PCM) is a systemic granulomatous mycosis prevalent in individuals who carry out rural activities. Its etiological agent is a thermodimorphic fungus belonging to the genus; Paracoccidioides spp. Seven species of this fungus are known: Paracoccidioides brasiliensis, Paracoccidioides lutzii, Paracoccidioides americana, Paracoccidioides restrepiensis, Paracoccidioides venezuelensis, Paracoccidioides loboi and Paracoccidioides ceti. For a long time, Paracoccidioides brasiliensis was attributed as the only causal agent of this mycosis. What is known about adhesins, virulence, escape mechanisms and fungal involvement with the host's immune system is correlated with the species Paracoccidioides brasiliensis. Interactions between Paracoccidioides spp. and the host are complex and dynamic. The fungus needs nutrients for its needs and must adapt to a hostile environment, evading the host's immune system, thus enabling the development of the infectious process. On the other hand, the host's immune system recognizes Paracoccidioides spp. and employs all protective mechanisms to prevent fungal growth and consequently tissue invasion. Knowing this, understanding how Paracoccidioides spp. escapes the host's immune system, can help to understand the pathogenic mechanisms related to the development of the disease and, therefore, in the design of new specific treatment strategies. In this review we discuss these mechanisms and what are the adhesion molecules of Paracoccidioides spp. uses to escape the hostile environment imposed by the host's defense mechanisms; finally, we suggest how to neutralize them with new antifungal therapies.

Lonicerae Japonicae Flos with the homology of medicine and food: a review of active ingredients, anticancer mechanisms, pharmacokinetics, quality control, toxicity and applications.

Lonicerae Japonicae Flos (LJF, called Jinyinhua in China), comes from the dried flower buds or flowers to be opened of Lonicera japonica Thunb. in the Lonicera family. It has a long history of medicinal use and has a wide range of application prospects. As modern research advances, an increasing number of scientific experiments have demonstrated the anticancer potential of LJF. However, there is a notable absence of systematic reports detailing the anti-tumor effects of LJF. This review integrates the principles of Traditional Chinese Medicine (TCM) with contemporary pharmacological techniques, drawing upon literature from authoritative databases such as PubMed, CNKI, and WanFang to conduct a comprehensive study of LJF. Notably, a total of 507 compounds have been isolated and characterized from the plant to date, which include volatile oils, organic acids, flavonoids, iridoids, triterpenes and triterpenoid saponins. Pharmacological studies have demonstrated that LJF extract, along with components such as chlorogenic acid, luteolin, rutin, luteoloside, hyperoside and isochlorogenic acid, exhibits potential anticancer activities. Consequently, we have conducted a comprehensive review and summary of the mechanisms of action and clinical applications of these components. Furthermore, we have detailed the pharmacokinetics, quality control, and toxicity of LJF, while also discussing its prospective applications in the fields of biomedicine and preventive healthcare. It is hoped that these studies will provide valuable reference for the clinical research, development, and application of LJF.

YOLOv8-Coal: a coal-rock image recognition method based on improved YOLOv8.

To address issues such as misdetection and omission due to low light, image defocus, and worker occlusion in coal-rock image recognition, a new method called YOLOv8-Coal, based on YOLOv8, is introduced to enhance recognition accuracy and processing speed. The Deformable Convolution Network version 3 enhances object feature extraction by adjusting sampling positions with offsets and aligning them closely with the object's shape. The Polarized Self-Attention module in the feature fusion network emphasizes crucial features and suppresses unnecessary information to minimize irrelevant factors. Additionally, the lightweight C2fGhost module combines the strengths of GhostNet and the C2f module, further decreasing model parameters and computational load. The empirical findings indicate that YOLOv8-Coal has achieved substantial enhancements in all metrics on the coal rock image dataset. More precisely, the values for AP50, AP50:95, and AR50:95 were improved to 77.7%, 62.8%, and 75.0% respectively. In addition, optimal localization recall precision (oLRP) were decreased to 45.6%. In addition, the model parameters were decreased to 2.59M and the FLOPs were reduced to 6.9G. Finally, the size of the model weight file is a mere 5.2 MB. The enhanced algorithm's advantage is further demonstrated when compared to other commonly used algorithms.

The key mechanisms of multi-system responses triggered by central nervous system damage in hand, foot, and mouth disease severity.

Hand, foot, and mouth disease (HFMD) is a prevalent infectious affliction primarily affecting children, with a small portion of cases progressing to neurological complications. Notably, in a subset of severe HFMD cases, neurological manifestations may result in significant sequelae and pose a risk of mortality. We systematically conducted literature retrieval from the databases PubMed (1957-2023), Embase (1957-2023), and Web of Science (1957-2023), in addition to consulting authoritative guidelines. Subsequently, we rigorously selected the most relevant articles within the scope of this review for comprehensive analysis. It is widely recognized that the severity of HFMD is attributed to a multifaceted array of pathophysiological mechanisms. The implication of multi-system dysfunction appears to be perturbances of the human defense system; therefore, it contributes to the severity of HFMD. In this review, we provide an overview and analysis of recent insights into the molecular mechanisms contributing to the severity of HFMD, with a particular focus on cytokine release syndrome, the involvement of the renin-angiotensin system, regional immunity, endothelial dysfunction, catecholamine storm, viral invasion, and the molecular mechanisms of neurological damage. We speculate that the domino effect of diverse physiological systems, initiated by damage to the central nervous system, serve as the primary mechanisms governing the severity of HFMD. Simultaneously, we emphasize the knowledge gaps and research urgently required to delineate a quick roadmap for ongoing and essential studies on HFMD.

The dual role of TRPV1 in peripheral neuropathic pain: pain switches caused by its sensitization or desensitization.

The transient receptor potential vanilloid 1 (TRPV1) channel plays a dual role in peripheral neuropathic pain (NeuP) by acting as a "pain switch" through its sensitization and desensitization. Hyperalgesia, commonly resulting from tissue injury or inflammation, involves the sensitization of TRPV1 channels, which modulates sensory transmission from primary afferent nociceptors to spinal dorsal horn neurons. In chemotherapy-induced peripheral neuropathy (CIPN), TRPV1 is implicated in neuropathic pain mechanisms due to its interaction with ion channels, neurotransmitter signaling, and oxidative stress. Sensitization of TRPV1 in dorsal root ganglion neurons contributes to CIPN development, and inhibition of TRPV1 channels can reduce chemotherapy-induced mechanical hypersensitivity. In diabetic peripheral neuropathy (DPN), TRPV1 is involved in pain modulation through pathways including reactive oxygen species and cytokine production. TRPV1's interaction with TRPA1 channels further influences chronic pain onset and progression. Therapeutically, capsaicin, a TRPV1 agonist, can induce analgesia through receptor desensitization, while TRPV1 antagonists and siRNA targeting TRPV1 show promise in preclinical studies. Cannabinoid modulation of TRPV1 provides another potential pathway for alleviating neuropathic pain. This review summarizes recent preclinical research on TRPV1 in association with peripheral NeuP.

Characteristics of tetracycline antibiotic resistance gene enrichment and migration in soil-plant system.

Tetracycline Resistance Genes (TRGs) have received widespread attention in recent years, as they are a novel environmental pollutant that can rapidly accumulate and migrate in soil plant systems through horizontal gene transfer (HGT), posing a potential threat to food safety and public health. This article systematically reviews the pollution sources, enrichment, and migration characteristics of TRGs in soil. The main sources of TRGs include livestock manure and contaminated wastewater, especially in intensive farming environments where TRGs pollution is more severe. In soil, TRGs diffuse horizontally between bacteria and migrate to plant tissues through mechanisms such as plasmid conjugation, integron mediation, and phage transduction. The migration of TRGs is not limited to the soil interior, and increasing evidence suggests that they can also enter the plant system through plant root absorption and the HGT pathway of endophytic bacteria, ultimately accumulating in plant roots, stems, leaves, fruits, and other parts. This process has a direct impact on human health, especially when TRGs are found in crops such as vegetables, which may be transmitted to the human body through the food chain. In addition, this article also deeply analyzed various factors that affect the migration of TRGs, including the residual level of tetracycline in soil, the type and concentration of microorganisms, heavy metal pollution, and the presence of new pollutants such as microplastics. These factors significantly affect the enrichment rate and migration mode of TRGs in soil. In addition, two technologies that can effectively eliminate TRGs in livestock breeding environments were introduced, providing reference for healthy agricultural production. The article concludes by summarizing the shortcomings of current research on TRGs, particularly the limited understanding of TRG migration pathways and their impact mechanisms. Future research should focus on revealing the migration mechanisms of TRGs in soil plant systems and developing effective control and governance measures to reduce the environmental transmission risks of TRGs and ensure the safety of ecosystems and human health.

Potential toxicity of carbonaceous nanomaterials on aquatic organisms and their alleviation strategies: A review.

Carbonaceous nanomaterials (CNMs) are widely used in electronics, biomedicine, agriculture, environmental remediation, and catalysis due to their excellent biocompatibility, high reactivity, and high specific surface area. However, the extensive applications of CNMs cause their inevitable release into water, which may result in toxic effects on the aquatic ecological environment and organisms. CNMs can cause lipid peroxidation damage and neurotoxicity in aquatic organisms, affecting embryo hatching and larval morphology. The effects of CNMs on aquatic organisms vary depending on their structures and physicochemical properties, as well as the species, age, and tolerance of the tested organisms. The above uncertainties have increased the difficulty of exploring the impact of carbonaceous nanomaterials on the toxicity of aquatic organisms to a certain extent. Solving these issues is of great significance and reference value for promoting the research and safe utilization of carbon nanomaterials. Therefore, a systematic review of the effects of potential toxicity of carbonaceous nanomaterials on aquatic organisms and their alleviation strategies is needed. This paper firstly summarizes the toxic effects of commonly used CNMs (i.e., carbon nanotubes, graphene, and fullerene) on different aquatic organisms, which include developmental toxicity, behavioral and metabolic toxicity, reproductive toxicity, and organ toxicity. Then the main mechanisms of CNMs to aquatic organisms are further explored, and the methods to reduce the toxicity of CNMs are also summarized. Finally, the current challenges and future perspectives for studying CNM toxicity to aquatic organisms are proposed.

Cellular thermal shift assay: an approach to identify and assess protein target engagement.

INTRODUCTION: A comprehensive and global knowledge of protein target engagement is of vital importance for mechanistic studies and in drug development. Since its initial introduction, the cellular thermal shift assay (CETSA) has proven to be a reliable and flexible technique that can be widely applied to multiple contexts and has profound applications in facilitating the identification and assessment of protein target engagement. AREAS COVERED: This review introduces the principle of CETSA, elaborates on western blot-based CETSA and MS-based thermal proteome profiling (TPP) as well as the major applications and prospects of these approaches. EXPERT OPINION: CETSA primarily evaluates a given ligand binding to a particular target protein in cells and tissues with the protein thermal stabilities analyzed by western blot. When coupling mass spectrometry with CETSA, thermal proteome profiling allows simultaneous proteome-wide experiment that greatly increased the efficiency of target engagement evaluation, and serves as a promising strategy to identify protein targets and off-targets as well as protein-protein interactions to uncover the biological effects. The CETSA approaches have broad applications and potentials in drug development and clinical research.

Obesity, herbal extracts, dietary supplements, mechanisms of action, medicinal plants, phytochemicals, clinical studies, management.

Obesity and associated health impairments are proven to exhibit multifocal health disorders along with increasing co-morbidity. Underlying obesity pathology is linked up with almost every major disease, which may increase the risk of heart disease, hypertension, diabetes, cancer, osteoarthritis, etc. The prevalence of overweight and obesity is on the rise around the world, which enormously affects the life span of individuals. Due to the foggier nature of the underlying pathology, the efficacy is questionable for conventional treatments. The traditional therapy of obesity may involve synthetic moieties and surgical procedures, which have many harmful side effects and chances of recurrent severity. Scientists are continuously focusing on prophylactic remedies alongside maintaining a proper lifestyle. In that context, nature always helped with traditional medications. As per folklore medicine reports, many plants have been used to treat obesity and its associated complications. This review compiles a vast array of datasets, including the impact of obesity and the need for the introduction of phytochemicals in place of conventional pharmacotherapies, the impact of phytochemicals along with the reported mechanisms of action, recent clinical trial reports, and recently explored dietary supplements. The primary objective of this presentation is to chart the future trajectory of phytochemical research for metabolic disorders, establishing a foundational framework for future investigations to build upon.

Evaluation of Differentially Expressed Candidate Genes in Benzo[a]pyrene Degradation by Burkholderia vietnamiensis G4.

Bacteria-mediated bioremediation is widely employed for its environmental benefits. The genus Burkholderia can degrade persistent organic compounds, however, little is known about its mechanisms. To increase this knowledge, Burkholderia vietnamiensis G4 bacteria were exposed to benzo[a]pyrene, a recalcitrant compound, and the expression of twelve genes of interest was analyzed at 1, 12 and 24 h. In addition, benzo[a]pyrene degradation, evaluation of cell viability and fluorescence emission of assimilated benzo[a]pyrene was performed over 28 days. The up-regulated genes were xre, paaE, livG and pckA at the three times, ACAD, atoB, bmoA and proV at 1 h and AstB at 12 h. These genes are important for bacterial survival in stress situations, breakdown and metabolization of organic compounds, and nutrient transport and uptake. Furthermore, a 52% reduction of the pollutant was observed, there was no significant variation in the viability rate of the cells, and fluorescence indicated an accumulation of benzo[a]pyrene after 24 h. Our study demonstrates the bacteria adaptability and ability to modulate the expression of genes at different times and as needed. This increases our understanding of biodegradation processes and opens new possibilities for using this bacterial strain as a tool for the bioremediation of contaminated areas.

Changing hearts and minds: theorizing how, when, and under what conditions three social influence implementation strategies work.

Background: Opinion leadership, educational outreach visiting, and innovation championing are commonly used strategies to address barriers to implementing innovations and evidence-based practices in healthcare settings. Despite voluminous research, ambiguities persist in how these strategies work and under what conditions they work well, work poorly, or work at all. The current paper develops middle-range theories to address this gap. Methods: Conceptual articles, systematic reviews, and empirical studies informed the development of causal pathway diagrams (CPDs). CPDs are visualization tools for depicting and theorizing about the causal process through which strategies operate, including the mechanisms they activate, the barriers they address, and the proximal and distal outcomes they produce. CPDs also clarify the contextual conditions (i.e., preconditions and moderators) that influence whether, and to what extent, the strategy's causal process unfolds successfully. Expert panels of implementation scientists and health professionals rated the plausibility of these preliminary CPDs and offered comments and suggestions on them. Findings: Theoretically, opinion leadership addresses potential adopters' uncertainty about likely consequences of innovation use (determinant) by promoting positive attitude formation about the innovation (mechanism), which results in an adoption decision (proximal outcome), which leads to innovation use (intermediate outcome). As this causal process repeats, penetration, or spread of innovation use, occurs (distal outcome). Educational outreach visiting addresses knowledge barriers, attitudinal barriers, and behavioral barriers (determinants) by promoting critical thinking and reflection about evidence and practice (mechanism), which results in behavioral intention (proximal outcome), behavior change (intermediate outcome), and fidelity, or guideline adherence (distal outcome). Innovation championing addresses organizational inertia, indifference, and resistance (determinants) by promoting buy-in to the vision, fostering a positive implementation climate, and increasing collective efficacy (mechanisms), which leads to participation in implementation activities (proximal outcome), initial use of the innovation with increasing skill (intermediate outcome) and, ultimately, greater penetration and fidelity (distal outcomes). Experts found the preliminary CPDs plausible or highly plausible and suggested additional mechanisms, moderators, and preconditions, which were used to amend the initial CPD. Discussion: The middle-range theories depicted in the CPDs furnish testable propositions for implementation research and offer guidance for selecting, designing, and evaluating these social influence implementation strategies in both research studies and practice settings.

Unraveling the Complexity of Parkinson's Disease: Insights into Pathogenesis and Precision Interventions.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss, leading to motor and non-motor symptoms. Early detection before symptom onset is crucial but challenging. This study presents a framework integrating circuit modeling, non-equilibrium dynamics, and optimization to understand PD pathogenesis and enable precision interventions. Neuronal firing patterns, particularly oscillatory activity, play a critical role in PD pathology. The basal ganglia network, specifically the subthalamic nucleus-external globus pallidus (STN-GPe) circuitry, exhibits abnormal activity associated with motor dysfunction. The framework leverages the non-equilibrium landscape and flux theory to identify key connections generating pathological activity, providing insights into disease progression and potential intervention points. The intricate STN-GPe interplay is highlighted, shedding light on compensatory mechanisms within this circuitry may initially counteract changes but later contribute to pathological alterations as disease progresses. The framework addresses the need for comprehensive evaluation methods to assess intervention outcomes. Cross-correlations between state variables provide superior early warning signals compared to traditional indicators relying on critical slowing down. By elucidating compensatory mechanisms and circuit dynamics, the framework contributes to improved management, early detection, risk assessment, and potential prevention/delay of PD development. This pioneering research paves the way for precision medicine in neurodegenerative disorders.

Poisoning Mechanism Map for Metal Hydride Hydrogen Storage Materials.

The effective utilization of hydrogen storage materials (HSMs) is hindered by impurity gas poisoning, posing a significant challenge for large-scale applications. This study elucidates the poisoning mechanisms of various impurities gases (CO, CO2, O2, Ar, He, CH4, N2) on ZrCo, Pd, U and LaNi5. Impurities gases are categorized into active and inactive types based on their effecting behaviors and mechanisms on the hydrogenation of HSMs. During the hydrogenation process, active impurities chemically poison the hydrogenation reaction by limiting hydrogen absorption at interface, while inactive impurities physically hinder hydrogenation reaction by impeding hydrogen diffusion in hydrogen-impurity mixed gas. In situ Scanning Tunneling Microscope clarifies these behaviors, and a novel criterion based on hydrogen spontaneous dissociation energy is introduced to explain and predict impurity-substrate interaction characteristics. The novel findings of this work provide a comprehensive framework for designing long-lived HSMs with poisoning resistance, guiding the development of more resilient hydrogen storage systems.