The Role of AI in Drug Discovery.

The emergence of Artificial Intelligence (AI) in drug discovery marks a pivotal shift in pharmaceutical research, blending sophisticated computational techniques with conventional scientific exploration to break through enduring obstacles. This review paper elucidates the multifaceted applications of AI across various stages of drug development, highlighting significant advancements and methodologies. It delves into AI's instrumental role in drug design, polypharmacology, chemical synthesis, drug repurposing, and the prediction of drug properties such as toxicity, bioactivity, and physicochemical characteristics. Despite AI's promising advancements, the paper also addresses the challenges and limitations encountered in the field, including data quality, generalizability, computational demands, and ethical considerations. By offering a comprehensive overview of AI's role in drug discovery, this paper underscores the technology's potential to significantly enhance drug development, while also acknowledging the hurdles that must be overcome to fully realize its benefits.

Isolation, characterization and anti-inflammatory activity of compounds from the Vernonia amygdalina.

The need to explore the abundance of natural products cannot be overemphasized particularly in the management of various disease conditions. In traditional medical practice, Vernonia amygdalina has been widely adopted in the management of various inflammatory disorders. The objective of this investigation was to isolate the bioactive principles from the stem-bark and root of V. amygdalina and assess the anti-inflammatory (in vitro) activity of both the crude extracts and the isolated compounds. Following extraction with the methanol, the extract was subjected to gravity column chromatography and the resultant fractions was further purified to obtained pure compounds. The structural elucidation of the compounds were based on data obtained from 1H to 13C nuclear magnetic resonance (NMR) spectroscopies as well as fourier transform infrared (FT-IR). Using diclofenac as a control drug, the albumin denaturation assay was used to determine the in vitro anti-inflammatory activity of the extracts and isolates. Three distinct compounds characterized are vernoamyoside D, luteolin-7-α-o-glucuronide, and vernotolaside, a new glycoside. When compared to diclofenac, which has an IC50 of 167.8 µg/mL, luteolin-7-α-o-glucuronide, vernoamyoside D, and vernotolaside all showed significant inhibitions with respective IC50 values 549.8, 379.5, and 201.7 µg/mL. Vernotolaside is reported for the first time from the root. The assertion that the plant is used in traditional medicine for the management of inflammatory disorder is somewhat validated by the confirmation of the existence of the compounds with the biochemical actions. Further validation of the isolated compounds would be required in animal studies.

Integrated approaches for Solenopsis invicta (Hymenoptera: Formicidae) management: insights from laboratory studies with entomopathogenic nematodes and insecticides.

BACKGROUND: In agricultural pest management, especially in combatting the invasive red imported fire ant (RIFA, Solenopsis invicta), significant challenges emerge as a consequence of the constraints of solely depending on chemical insecticides or entomopathogenic nematodes (EPNs). The utilization of chemical insecticides carries environmental and ecological hazards, whereas EPNs, when applied independently, might not offer the immediate effectiveness necessary for adequate RIFA suppression. Acknowledging these hurdles, our study investigates a synergistic method that integrates EPNs with chemical insecticides, aiming to fulfill the urgent demand for more efficient and environmentally friendly pest control solutions. RESULTS: Our evaluation focused on the interaction between the highly pathogenic Steinernema riobrave 7-12 EPN strain and prevalent insecticides, specifically beta-cypermethrin and a mixture of bifenthrin and clothianidin, applied at highly diluted recommended concentrations. The findings revealed a notable increase in RIFA mortality rates when EPNs and these insecticides were used together, outperforming the results achieved with each method individually. Remarkably, this enhanced efficacy was especially evident at lower concentrations of the bifenthrin-clothianidin mixture, indicating a valuable approach to minimizing reliance on chemical insecticides in agriculture. Furthermore, the high survival rates of EPNs alongside the tested insecticides indicate their compatibility and potential for sustained use in integrated pest management programs. CONCLUSION: Our research underscores the effectiveness of merging EPNs with chemical insecticides as a powerful and sustainable strategy for RIFA management. This combined approach not only meets the immediate challenges of pest control in agricultural settings, but also supports wider environmental objectives by reducing the dependency on chemical insecticides. © 2024 Society of Chemical Industry.

Surveillance of catheter-associated bloodstream infections: development and validation of a fully automated algorithm.

BACKGROUND: Most surveillance systems for catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI) are based on manual chart review. Our objective was to validate a fully automated algorithm for CRBSI and CLABSI surveillance in intensive care units (ICU). METHODS: We developed a fully automated algorithm to detect CRBSI, CLABSI and ICU-onset bloodstream infections (ICU-BSI) in patients admitted to the ICU of a tertiary care hospital in Switzerland. The parameters included in the algorithm were based on a recently performed systematic review. Structured data on demographics, administrative data, central vascular catheter and microbiological results (blood cultures and other clinical cultures) obtained from the hospital's data warehouse were processed by the algorithm. Validation for CRBSI was performed by comparing results with prospective manual BSI surveillance data over a 6-year period. CLABSI were retrospectively assessed over a 2-year period. RESULTS: From January 2016 to December 2021, 854 positive blood cultures were identified in 346 ICU patients. The median age was 61.7 years [IQR 50-70]; 205 (24%) positive samples were collected from female patients. The algorithm detected 5 CRBSI, 109 CLABSI and 280 ICU-BSI. The overall CRBSI and CLABSI incidence rates determined by automated surveillance for the period 2016 to 2021 were 0.18/1000 catheter-days (95% CI 0.06-0.41) and 3.86/1000 catheter days (95% CI: 3.17-4.65). The sensitivity, specificity, positive predictive and negative predictive values of the algorithm for CRBSI, were 83% (95% CI 43.7-96.9), 100% (95% CI 99.5-100), 100% (95% CI 56.5-100), and 99.9% (95% CI 99.2-100), respectively. One CRBSI was misclassified as an ICU-BSI by the algorithm because the same bacterium was identified in the blood culture and in a lower respiratory tract specimen. Manual review of CLABSI from January 2020 to December 2021 (n = 51) did not identify any errors in the algorithm. CONCLUSIONS: A fully automated algorithm for CRBSI and CLABSI detection in critically-ill patients using only structured data provided valid results. The next step will be to assess the feasibility and external validity of implementing it in several hospitals with different electronic health record systems.

SKping cell cycle regulation: role of ubiquitin ligase SKP2 in hematological malignancies.

SKP2 (S-phase kinase-associated protein 2) is a member of the F-box family of substrate-recognition subunits in the SCF ubiquitin-protein ligase complexes. It is associated with ubiquitin-mediated degradation in the mammalian cell cycle components and other target proteins involved in cell cycle progression, signal transduction, and transcription. Being an oncogene in solid tumors and hematological malignancies, it is frequently associated with drug resistance and poor disease outcomes. In the current review, we discussed the novel role of SKP2 in different hematological malignancies. Further, we performed a limited in-silico analysis to establish the involvement of SKP2 in a few publicly available cancer datasets. Interestingly, our study identified Skp2 expression to be altered in a cancer-specific manner. While it was found to be overexpressed in several cancer types, few cancer showed a down-regulation in SKP2. Our review provides evidence for developing novel SKP2 inhibitors in hematological malignancies. We also investigated the effect of SKP2 status on survival and disease progression. In addition, the role of miRNA and its associated families in regulating Skp2 expression was explored. Subsequently, we predicted common miRNAs against Skp2 genes by using miRNA-predication tools. Finally, we discussed current approaches and future prospective approaches to target the Skp2 gene by using different drugs and miRNA-based therapeutics applications in translational research.

Investigation of flow behaviour in the nozzle of a Pelton wheel: Effects and analysis of influencing parameters.

The performance of a Pelton wheel is influenced by the jet created by the nozzle. Therefore, a Computational Fluid Dynamics (CFD) simulation was proposed. In this study, the significant output parameters (outlet velocity, outlet pressure, and tangential force component) and input parameters (different pressure and spear locations) were examined. In addition, the influencing parameters and their contributing percentages to the performance of the Pelton wheel were calculated using different optimisation techniques such as Taguchi Design of Experiments (DoE), Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS), Grey Relational Analysis (GRA) and Criteria Importance Through Intercriteria Correlation (CRITIC). The effect of input factors on the output response was examined with DoE, and the results show that the inlet pressure had the most significant impact (97.38%, 99.18%, and 97.38%, respectively, for all different spear sites with a 99% confidence level). In terms of preference values, the TOPSIS and GRA results are comparable (best ranks for simulation runs #24 and #25 and least ranks for simulations #2 and #3, respectively). The CRITIC results for the pressure parameter are in good agreement with the Taguchi ANOVA analysis. The last spear location (5 mm after the nozzle outlet), with an inlet pressure of 413685 Pa generated the best result when employing the TOPSIS and GRA techniques. The outlet pressure of the nozzle was found to have a significant impact on the flow pattern of the Pelton Wheel based on the analysis of the CRITIC, Taguchi, and CFD results.

Physicochemical properties-based hybrid machine learning technique for the prediction of SARS-CoV-2 T-cell epitopes as vaccine targets.

Majority of the existing SARS-CoV-2 vaccines work by presenting the whole pathogen in the attenuated form to immune system to invoke an immune response. On the other hand, the concept of a peptide based vaccine (PBV) is based on the identification and chemical synthesis of only immunodominant peptides known as T-cell epitopes (TCEs) to induce a specific immune response against a particular pathogen. However PBVs have received less attention despite holding huge untapped potential for boosting vaccine safety and immunogenicity. To identify these TCEs for designing PBV, wet-lab experiments are difficult, expensive, and time-consuming. Machine learning (ML) techniques can accurately predict TCEs, saving time and cost for speedy vaccine development. This work proposes novel hybrid ML techniques based on the physicochemical properties of peptides to predict SARS-CoV-2 TCEs. The proposed hybrid ML technique was evaluated using various ML model evaluation metrics and demonstrated promising results. The hybrid technique of decision tree classifier with chi-squared feature weighting technique and forward search optimal feature searching algorithm has been identified as the best model with an accuracy of 98.19%. Furthermore, K-fold cross-validation (KFCV) was performed to ensure that the model is reliable and the results indicate that the hybrid random forest model performs consistently well in terms of accuracy with respect to other hybrid approaches. The predicted TCEs are highly likely to serve as promising vaccine targets, subject to evaluations both in-vivo and in-vitro. This development could potentially save countless lives globally, prevent future epidemic-scale outbreaks, and reduce the risk of mutation escape.

Effect of Dimethyl Sulfoxide Primer on Microtensile Bond Strength and Micromorphological Pattern of HEMA-free Universal Adhesive to Dry/Wet Dentin After Thermomechanical Aging.

Background: To evaluate the effect of dimethyl sulfoxide (DMSO) primer on microtensile bond strength (µTBS) and the micromorphological pattern of a hydroxyethyl methacrylate (HEMA)-free universal adhesive (UA) applied on wet/dry dentin in etch and rinse (E&R) mode before/after thermomechanical aging. Material and Methods: For the µTBS test, the mid-coronal dentin of 80 human mandibular first molars was exposed and etched with 35% phosphoric acid. Teeth were randomly divided into two equal groups: dry and wet dentin (n = 40). Then, each group was subdivided according to dentin pretreatment by DMSO before UA (Gluma Bond Universal, Heraeus Kulzer, Hanau, Germany) application into unpretreated and 10% DMSO/water (OT Primer S100, OT Oy Dent, Turku, Finland) pretreated (n = 20). Resin composite blocks were built up using a specially designed Teflon mold. In every subgroup, both the µTBS test and failure analysis by stereomicroscope were evaluated immediately after 24 h and after thermomechanical aging (n = 10). The data were statistically analyzed using a three-way analysis of variance (ANOVA) (p = 0.05). For the micromorphological pattern, 16 maxillary first premolars were distributed as mentioned in the µTBS test, prepared, and buccolingually sectioned. The dentin-resin interface was examined using an environmental scanning electron microscope (ESEM) (n = 2). Results: Three-way ANOVA revealed that the main effects and interactions between dentin wetness, dentin pretreatment, and evaluation time (thermomechanical aging) were not significant for µTBS (p> 0.05). Adhesive failure was the predominant type in all immediate and delayed specimens. Longer and more prominent resin tags were observed at dentin-resin interfaces after DMSO application. Conclusions: Neither the initial dentin wetness condition, dentin pretreatment, nor thermomechanical aging could affect the dentin bond strength. No correlation was found between the bond strength and the micromorphology findings. Key words:Wet/dry dentin bonding, Microtensile bond strength, Micromorphology, Universal adhesive, Dimethyl sulfoxide, Thermomechanical aging.

Natural compounds targeting YAP/TAZ axis in cancer: Current state of art and challenges.

Cancer has become a burgeoning global healthcare concern marked by its exponential growth and significant economic ramifications. Though advancements in the treatment modalities have increased the overall survival and quality of life, there are no definite treatments for the advanced stages of this malady. Hence, understanding the diseases etiologies and the underlying molecular complexities, will usher in the development of innovative therapeutics. Recently, YAP/TAZ transcriptional regulation has been of immense interest due to their role in development, tissue homeostasis and oncogenic transformations. YAP/TAZ axis functions as coactivators within the Hippo signaling cascade, exerting pivotal influence on processes such as proliferation, regeneration, development, and tissue renewal. In cancer, YAP is overexpressed in multiple tumor types and is associated with cancer stem cell attributes, chemoresistance, and metastasis. Activation of YAP/TAZ mirrors the cellular "social" behavior, encompassing factors such as cell adhesion and the mechanical signals transmitted to the cell from tissue structure and the surrounding extracellular matrix. Therefore, it presents a significant vulnerability in the clogs of tumors that could provide a wide window of therapeutic effectiveness. Natural compounds have been utilized extensively as successful interventions in the management of diverse chronic illnesses, including cancer. Owing to their capacity to influence multiple genes and pathways, natural compounds exhibit significant potential either as adjuvant therapy or in combination with conventional treatment options. In this review, we delineate the signaling nexus of YAP/TAZ axis, and present natural compounds as an alternate strategy to target cancer.

Nicotine sensing behavior of nickel(II) complexes catalyzed oxidation and coupling reactions.

One of the main source of demise during the next ten years will be coronary heart disease and stroke, which are brought on by smoking (nicotine). To identify the percentage (%) of nicotine consumption by electrocatalytic sensor towards nicotine for target-specific prevent stroke, four uninuclear Ni2+ complexes of substituted butanimidamide Schiff base ligands [H2L1-4] was prepared. All the complexes were thoroughly analyzed by using several spectroscopic techniques such as CHNS analysis, FT-IR, NMR (1H & 13C) UV-Vis and NMR. The analyses showed tetradentate binding mode of ligand around nickel(II) metal ion leads to the structure of square planar with N2X2 (X = O, S) donor fashion. In addition, the well-defined nickel(II) complexes were utilized for oxidation of various alcohols such as cyclohexanol, and benzyl alcohol were produced to the assorted oxidized products with high yield respectively using greener co-oxidant (molecular oxygen). In addition, Nickel(II) complexes was further utilized as catalyst for aryl-aryl coupling reaction via Suzuki-Mayura method to obtain biphenyl compound. Furthermore, nickel(II) complexes were exploited for electrochemical detection of nicotine sensing in µM concentration.

Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.

Recent advances have brought forth the complex interplay between tumor cell plasticity and its consequential impact on drug resistance and tumor recurrence, both of which are critical determinants of neoplastic progression and therapeutic efficacy. Various forms of tumor cell plasticity, instrumental in facilitating neoplastic cells to develop drug resistance, include epithelial-mesenchymal transition (EMT) alternatively termed epithelial-mesenchymal plasticity, the acquisition of cancer stem cell (CSC) attributes, and transdifferentiation into diverse cell lineages. Nuclear receptors (NRs) are a superfamily of transcription factors (TFs) that play an essential role in regulating a multitude of cellular processes, including cell proliferation, differentiation, and apoptosis. NRs have been implicated to play a critical role in modulating gene expression associated with tumor cell plasticity and drug resistance. This review aims to provide a comprehensive overview of the current understanding of how NRs regulate these key aspects of cancer biology. We discuss the diverse mechanisms through which NRs influence tumor cell plasticity, including EMT, stemness, and metastasis. Further, we explore the intricate relationship between NRs and drug resistance, highlighting the impact of NR signaling on chemotherapy, radiotherapy and targeted therapies. We also discuss the emerging therapeutic strategies targeting NRs to overcome tumor cell plasticity and drug resistance. This review also provides valuable insights into the current clinical trials that involve agonists or antagonists of NRs modulating various aspects of tumor cell plasticity, thereby delineating the potential of NRs as therapeutic targets for improved cancer treatment outcomes.

Lipid metabolism and its implications in tumor cell plasticity and drug resistance: what we learned thus far?

Metabolic reprogramming, a hallmark of cancer, allows cancer cells to adapt to their specific energy needs. The Warburg effect benefits cancer cells in both hypoxic and normoxic conditions and is a well-studied reprogramming of metabolism in cancer. Interestingly, the alteration of other metabolic pathways, especially lipid metabolism has also grabbed the attention of scientists worldwide. Lipids, primarily consisting of fatty acids, phospholipids and cholesterol, play essential roles as structural component of cell membrane, signalling molecule and energy reserves. This reprogramming primarily involves aberrations in the uptake, synthesis and breakdown of lipids, thereby contributing to the survival, proliferation, invasion, migration and metastasis of cancer cells. The development of resistance to the existing treatment modalities poses a major challenge in the field of cancer therapy. Also, the plasticity of tumor cells was reported to be a contributing factor for the development of resistance. A number of studies implicated that dysregulated lipid metabolism contributes to tumor cell plasticity and associated drug resistance. Therefore, it is important to understand the intricate reprogramming of lipid metabolism in cancer cells. In this review, we mainly focused on the implication of disturbed lipid metabolic events on inducing tumor cell plasticity-mediated drug resistance. In addition, we also discussed the concept of lipid peroxidation and its crucial role in phenotypic switching and resistance to ferroptosis in cancer cells. Elucidating the relationship between lipid metabolism, tumor cell plasticity and emergence of resistance will open new opportunities to develop innovative strategies and combinatorial approaches for the treatment of cancer.

Influence of Immediate Dentin Sealing on Marginal Gaps of Laminate Veneers: Machinable Monolithic Zirconia Versus Pressable Lithium Dislocate. An In Vitro Study.

PURPOSE: To investigate the influence of immediate dentin sealing (IDS) vs delayed dentin sealing (DDS) on the marginal gaps of machinable monolithic zirconia (MMZ) vs pressable lithium disilicate (PLD) laminate veneers. MATERIALS AND METHODS: A total of 40 maxillary lateral incisors were used and received butt-joint laminate veneer preparation. The samples were divided into two groups (n = 20 each) according to ceramic material: PLD ceramic was used in the first group, and MMZ was used in the second. Each group was then divided into two subgroups according to the bonding protocol: IDS was employed in one, and DDS in the other (n = 10 each). The marginal gap widths were measured using digital microscopy and statistically analyzed. RESULTS: The smallest marginal gaps were observed in MMZ-DDS (57.2 ± 8.4 µm), followed by PLD-DDS (62.4 ± 2.7 µm) and MMZ-IDS (63.5 ± 1.9 µm). The largest marginal gaps were observed in PLD-IDS (81.5 ± 6.3 µm). Two-way ANOVA revealed that the bonding technique (P < .001) and ceramic material (P < .001) both showed significant differences. CONCLUSIONS: MMZ produced beIer marginal accuracy than PLD. IDS seems to have a predisposition to significantly wider marginal gaps than DDS, but these gaps are within the clinically acceptable range. The marginal accuracy of ceramic veneers appears to be related to the bonding technique as well as the material of construction.

Design and validation of a pediatric gait assistance exoskeleton system with fast non-singular terminal sliding mode controller.

Existing exoskeletons for pediatric gait assistance have limitations in anthropometric design, structure weight, cost, user safety features, and adaptability to diverse users. Additionally, creating precise models for pediatric rehabilitation is difficult because the rapid anthropometric changes in children result in unknown model parameters. Furthermore, external disruptions, like unpredictable movements and involuntary muscle contractions, add complexity to the control schemes that need to be managed. To overcome these limitations, this study aims to develop an affordable stand-aided lower-limb exoskeleton specifically for pediatric subjects (8-12 years, 25-40 kg, 128-132 cm) in passive-assist mode. The authors modified a previously developed model (LLESv1) for improved rigidity, reduced mass, simplified motor arrangement, variable waist size, and enhanced mobility. A computer-aided design of the new exoskeleton system (LLESv2) is presented. The developed prototype of the exoskeleton appended with a pediatric subject (age: 12 years old, body mass: 40 kg, body height: 132 cm) is presented with real-time hardware architecture. Thereafter, an improved fast non-singular terminal sliding mode (IFNSTSM) control scheme is proposed, incorporating a double exponential reaching law for expedited error convergence and enhanced stability. The Lyapunov stability warrants the control system's performance despite uncertainties and disturbances. In contrast to fast non-singular terminal sliding mode (FNSTSM) control and time-scaling sliding mode (TSSM) control, experimental validation demonstrates the effectiveness of IFNSTSM control by a respective average of 5.39% and 42.1% in tracking desired joint trajectories with minimal and rapid finite time converging errors. Moreover, the exoskeleton with the proposed IFNSTSM control requires significantly lesser control efforts than the exoskeleton using contrast FNSTSM control. The Bland-Altman analysis indicates that although there is a minimal mean difference in variables when employing FNSTSM and IFNSTSM controllers, the latter exhibits significant performance variations as the mean of variables changes. This research contributes to affordable and effective pediatric gait assistance, improving rehabilitation outcomes and enhancing mobility support.

Delineating the role of nuclear receptors in colorectal cancer, a focused review.

Colorectal cancer (CRC) stands as one of the most prevalent form of cancer globally, causing a significant number of deaths, surpassing 0.9 million in the year 2020. According to GLOBOCAN 2020, CRC ranks third in incidence and second in mortality in both males and females. Despite extensive studies over the years, there is still a need to establish novel therapeutic targets to enhance the patients' survival rate in CRC. Nuclear receptors (NRs) are ligand-activated transcription factors (TFs) that regulate numerous essential biological processes such as differentiation, development, physiology, reproduction, and cellular metabolism. Dysregulation and anomalous expression of different NRs has led to multiple alterations, such as impaired signaling cascades, mutations, and epigenetic changes, leading to various diseases, including cancer. It has been observed that differential expression of various NRs might lead to the initiation and progression of CRC, and are correlated with poor survival outcomes in CRC patients. Despite numerous studies on the mechanism and role of NRs in this cancer, it remains of significant scientific interest primarily due to the diverse functions that various NRs exhibit in regulating key hallmarks of this cancer. Thus, modulating the expression of NRs with their agonists and antagonists, based on their expression levels, holds an immense prospect in the diagnosis, prognosis, and therapeutical modalities of CRC. In this review, we primarily focus on the role and mechanism of NRs in the pathogenesis of CRC and emphasized the significance of targeting these NRs using a variety of agents, which may represent a novel and effective strategy for the prevention and treatment of this cancer.

Therapeutic potential of tocotrienols as chemosensitizers in cancer therapy.

Chemoresistance is the adaptation of cancer cells against therapeutic agents. When exhibited by cancer cells, chemoresistance helps them to avoid apoptosis, cause relapse, and metastasize, making it challenging for chemotherapeutic agents to treat cancer. Various strategies like dosage modification of drugs, nanoparticle-based delivery of chemotherapeutics, antibody-drug conjugates, and so on are being used to target and reverse chemoresistance, one among such is combination therapy. It uses the combination of two or more therapeutic agents to reverse multidrug resistance and improve the effects of chemotherapy. Phytochemicals are known to exhibit chemosensitizing properties and are found to be effective against various cancers. Tocotrienols (T3) and tocopherols (T) are natural bioactive analogs of vitamin E, which exhibit important medicinal value and potential curative properties apart from serving as an antioxidant and nutrient supplement. Notably, T3 exhibits a variety of pharmacological activities like anticancer, anti-inflammatory, antiproliferative, and so on. The chemosensitizing property of tocotrienol is exhibited by modulating several signaling pathways and molecular targets involved in cancer cell survival, proliferation, invasion, migration, and metastasis like NF-κB, STATs, Akt/mTOR, Bax/Bcl-2, Wnt/ß-catenin, and many more. T3 sensitizes cancer cells to chemotherapeutic drugs including cisplatin, doxorubicin, and paclitaxel increasing drug concentration and cytotoxicity. Discussed herewith are the chemosensitizing properties of tocotrienols on various cancer cell types when combined with various drugs and biological molecules.

Exploring the nexus of nuclear receptors in hematological malignancies.

Hematological malignancies (HM) represent a subset of neoplasms affecting the blood, bone marrow, and lymphatic systems, categorized primarily into leukemia, lymphoma, and multiple myeloma. Their prognosis varies considerably, with a frequent risk of relapse despite ongoing treatments. While contemporary therapeutic strategies have extended overall patient survival, they do not offer cures for advanced stages and often lead to challenges such as acquisition of drug resistance, recurrence, and severe side effects. The need for innovative therapeutic targets is vital to elevate both survival rates and patients' quality of life. Recent research has pivoted towards nuclear receptors (NRs) due to their role in modulating tumor cell characteristics including uncontrolled proliferation, differentiation, apoptosis evasion, invasion and migration. Existing evidence emphasizes NRs' critical role in HM. The regulation of NR expression through agonists, antagonists, or selective modulators, contingent upon their levels, offers promising clinical implications in HM management. Moreover, several anticancer agents targeting NRs have been approved by the Food and Drug Administration (FDA). This review highlights the integral function of NRs in HM's pathophysiology and the potential benefits of therapeutically targeting these receptors, suggesting a prospective avenue for more efficient therapeutic interventions against HM.

Liquid fertilizers produced by microwave-assisted acid hydrolysis of livestock and poultry wastes and their effects on hot pepper cultivation.

Liquid fertilizers (LFs) produced by microwave-assisted acid hydrolysis of livestock and poultry wastes were applied to potted hot pepper (Capsicum annuum L.) to evaluate their potential to be used as amino acid LFs. A preliminary experiment was conducted to determine the optimum acid-hydrolysis conditions for producing LFs from a mixture of pig hair and faeces (P) and another mixture of chicken feathers and faeces (C). Two LFs were produced under the optimum acid-hydrolysis conditions (acidification by sulphuric acid (7.5 mol L-1) in a microwave (200 W) for 90 minutes), and a commercial amino acid LF (Guo Guang (GG)) was used for comparison. P, C and GG fertilizers were tested in potted hot pepper cultivation at two doses, whereas no fertilizer application served as the control (CK). P and C fertilizers significantly increased the fruit yield compared with GG fertilizer, particularly at the higher dose. Moreover, the treatments improved the fruit vitamin C and soluble sugar contents in the order of C > P > GG compared with CK. These results could be attributed to more types of amino acids in C fertilizer than in P and GG fertilizers. The results also indicated that the prepared fertilizers could significantly increase the shoot and root dry weight, soil available nitrogen and phosphorus contents and nitrogen, phosphorus, and potassium (NPK) uptake by plants compared with CK. In conclusion, microwave-assisted acid hydrolysis could effectively convert unusable wastes into valuable fertilizers comparable or even superior to commercial fertilizers.