Search Results (1,179)

Drone-based chemical spraying in agriculture faces challenges related to operator health hazards, spray deposition, application efficiency, and environmental safety. Electrostatic charging system is a novel technology that minimizes off-target spraying losses and increases droplet deposition on the plant canopy. In electrostatic spraying, chemical consumption and application rates are reduced due to the uniform distribution and enhanced deposition of charged droplets on plant surfaces, thereby improving spraying efficacy. In this study, a drone-based air-assisted electrostatic sprayer was developed to investigate the effect of operational parameters that include forward speed, discharge rate, applied voltage (charged condition) and propeller speed on the droplet density (drops/cm²) in a cotton crop under laboratory conditions. The charge-to-mass ratio (CMR) of the developed air-assisted electrostatic nozzle was found in the range between 1.8–2.5 mC/kg. An Artificial Neural Network–Ant Colony Optimization (ANN–ACO) method was used to optimize the operational parameters for obtaining the highest charged droplet density on the plant canopy surfaces. Results showed that the charged droplet density was significantly affected by discharge rate (DR) and applied voltage (AV) followed by forward speed (FS) and was slightly influenced by the propeller speed (PS). Optimal performance was achieved at FS = 2.58 km/h, PS = 1204 rpm, DR = 558.45 mL/min and AV = 6.18 kV under the charged conditions. At these optimized parameters, an average charged droplet density of 185.83 ± 4.25 drops/cm² (mean ± SE) was achieved. For the uncharged conditions, the optimal performance was achieved at FS = 2.80 km/h, PS = 1065 rpm and DR = 556.75 mL/min, corresponding to an average droplet density of 108.49 ± 2.15 drops/cm². The integration of the ANN–ACO optimization algorithm with the drone-based air-assisted electrostatic spraying system can enhance precision chemical application on the cotton, improving efficiency and sustainability. Full article

APG157DS is a multi-component investigational drug which is currently the subject of multiple cancer trials. It has shown promising efficacy in patients with head and neck cancer. We report its immuno-modulatory effect in a syngeneic mouse model of glioblastoma (GBM). Long-term treatment with APG157DS led to durable tumor remission in 50% of mice, while all vehicle-treated mice reached humane endpoints within 42 days. Mechanistically, the drug induced selective repolarization of tumor-associated macrophages (TAMs) from an immunosuppressive Arg1^high/iNOS^low phenotype to a tumoricidal Arg1^low/iNOS^high state, accompanied by increased intratumoral recruitment of activated (NKp46+) natural killer cells and CD8+ cytotoxic T-cells. APG157DS also suppressed vascular endothelial growth factor (VEGF) and Hypoxia-inducible factor 1-alpha (HIF-1α) expression in tumors, further impairing tumor growth. Notably, APG157DS did not elicit off-target macrophage activation in peripheral tissues such as the spleen, highlighting its selective immune targeting. These findings provide a mechanistic rationale for further clinical development of APG157DS in GBM and potentially other immune-evasive cancers. Full article

This study addresses the inefficiencies and environmental concerns associated with conventional broadcast spraying in agriculture, where uniform chemical application leads to significant off-target losses and excessive agrochemical usage. A plant detection-based nozzle actuation system was developed to enable real-time, selective spraying based on canopy presence. The system integrates a LiDAR sensor for precise canopy detection, an ESP32 microcontroller for signal processing, and a solenoid valve-controlled nozzle for automated on/off spray regulation. Laboratory experiments were conducted using a controlled conveyor-based setup to simulate field conditions and evaluate the effects of forward speed, sensor–nozzle distance, and sensor–canopy distance on spray deposition. Spray performance was assessed using water-sensitive papers and image analysis techniques, while statistical analysis (ANOVA) and optimization using Response Surface Methodology (RSM) were performed. The results indicated that forward speed and sensor–nozzle distance significantly influenced spray coverage, whereas sensor–canopy distance had no significant effect. The optimized parameters (3.0 km h⁻¹ speed, 35 cm sensor–nozzle distance, and 70 cm sensor–canopy distance) achieved effective canopy coverage (~52–55%) while substantially reducing off-target deposition. Compared to continuous spraying, the developed system maintained comparable target coverage while significantly minimizing chemical losses. The findings demonstrate the potential of sensor-based precision spraying for improving input efficiency and environmental sustainability. Full article

Unlike conventional screening methods, which are limited by library size, DNA-encoded chemical library (DEL) technology enables the simultaneous interrogation of billions of compounds, each uniquely barcoded with DNA tags. These libraries can be screened through affinity-based capture and decoded using high-throughput sequencing. DEL-derived ligands can be conjugated to cytotoxic agents or radioactive isotopes, facilitating the creation of highly selective therapeutics that target diseased cells while minimizing off-target effects. This article explores the use of DELs for identifying high-affinity small organic ligands for the development of small molecule–radio conjugates (SMRCs) and small molecule–drug conjugates (SMDCs). Full article

Obesity and type 2 diabetes mellitus (T2DM) are multifactorial disorders characterized by insulin resistance, chronic low-grade inflammation, adipose tissue dysfunction, and multi-organ metabolic impairment. MicroRNAs (miRNAs) act as post-transcriptional gene regulators and play critical roles in metabolic homeostasis, the modulation of insulin signaling, adipogenesis, inflammatory pathways, and energy balance in key insulin-target tissues, including liver, skeletal muscle, and adipose tissue. This review summarizes mechanistic and translational insights into miRNA regulation in obesity, insulin resistance, and T2DM, integrating data from human studies and experimental models on miRNA sequence codes and extracellular vesicle sorting pathways. We focus on the tissue-specific and systemic roles of miRNAs, highlighting their contribution to inter-organ communication and metabolic network regulation. In addition, we emphasize their emerging roles as predictive biomarkers, modulators of treatment response, and promising targets for RNA-based interventions. Advances in sequence-specific miRNA sorting and extracellular vesicle-mediated delivery may provide avenues for therapeutic intervention. However, challenges related to delivery efficiency, tissue specificity, off-target effects, and variability in miRNA quantification remain important barriers to clinical translation. Addressing these limitations may help define the clinical utility of miRNAs as biomarkers and therapeutic targets in metabolic disorders. Full article

Reversible genetic medicines are emerging as controllable alternatives to permanent genome editing by enabling programmable modulation of RNA sequence, transcript abundance, chromatin state, and gene expression without irreversible genomic alteration. However, reversibility is not a single binary property: transient editor exposure, decay of the molecular effect, recovery of cellular function, and clinical capacity to stop, redose, or counteract treatment may diverge. This review therefore distinguishes mechanistic, functional, and clinical reversibility while examining targeted delivery systems for RNA-editing and epigenome-editing therapeutics. Key payloads include ADAR-recruiting oligonucleotides, CRISPR-Cas13 RNA editors, guide RNAs, chemically modified RNAs, editor-encoding mRNAs, dCas9 transcriptional regulators, DNA methylation editors, histone-modifying systems, and CRISPRoff-like platforms. We evaluate extracellular and intracellular delivery barriers, including nuclease degradation, immune recognition, renal clearance, liver uptake, cellular entry, endosomal escape, cytoplasmic release, nuclear localization, chromatin access, editing-window duration, off-target activity, immunogenicity, repeat-dosing feasibility, manufacturing, quality control, potency assays, and regulatory translation. Overall, delivery systems for reversible genetic medicines should be judged by tissue selectivity, functional editing, duration of action, reversibility after treatment withdrawal, safety, manufacturability, and clinical controllability. Full article

Hesperidin is a natural flavonoid derived from citrus plants, which can be hydrolyzed into hesperetin in vivo. Both compounds have anti-inflammatory, antioxidant and antitumor activities. At present, there is a lack of reviews focusing on the epigenetic regulation of cancer stem cells (CSCs) mediated by hesperidin and hesperetin. This review summarizes the molecular crosstalk between hesperidin/hesperetin and CSCs mediated via three major epigenetic pathways, including direct regulatory effects, indirect modulatory actions, and mechanistic relationships proposed based on scientific hypotheses. We elaborate their effects on inhibiting the self-renewal, invasion and metastasis of CSCs as well as reversing chemoresistance, and analyze the crosstalk between epigenetic networks and classical signaling pathways of CSCs. Furthermore, we discuss the core bottlenecks restricting the clinical transformation of these two compounds and introduce improvement strategies such as nanodelivery systems. Current research is still confronted with problems including CSC heterogeneity and the potential off-target toxicity of drugs. In conclusion, hesperidin and hesperetin may serve as potential candidate agents for epigenetic regulation targeting CSCs, which can offer novel theoretical basis for comprehensive tumor therapy. Full article

Background/Objectives: Diclofenac (DCF) and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain and inflammation management; however, their clinical significance is limited by poor aqueous solubility, short biological half-life, and dose-dependent gastrointestinal, renal, and cardiovascular adverse effects. Nanocarrier-based delivery systems have been extensively explored because they can enhance the apparent solubility of poorly water-soluble NSAIDs, provide controlled and sustained drug release, prolong systemic circulation, and improve drug localization at the site of action. By reducing peak plasma concentrations and off-target exposure, these systems may decrease dose-dependent gastrointestinal and systemic adverse effects while maintaining therapeutic efficacy. Most studies focus on optimizing formulation composition, while the manufacturing process is often treated as a secondary parameter. The research critically evaluates conventional and emerging fabrication methods for NSAID nanocarriers, using DCF as the principal reference compound, with emphasis on their impact on physicochemical characteristics, reproducibility, scalability, and translational potential. Methods: A structured literature search was performed in PubMed/MEDLINE, Scopus, and Web of Science (2015–2026, with emphasis on 2022–2026) for DCF and NSAID-loaded submicron delivery systems reporting quantitative formulation data and clearly defined fabrication methods, resulting in a narrative review of approximately 375–395 eligible studies, comprising 75 DCF-specific studies and approximately 300–320 studies involving other NSAIDs that were included as representative surrogate systems when DCF-specific evidence was unavailable for particular fabrication approaches. The review followed Scale for the Assessment of Narrative Review Articles (SANRA) recommendations. Studies were analyzed using a standardized seven-parameter framework including encapsulation efficiency, release profile, particle size control, polydispersity, scalability, reproducibility, and process complexity. Results: Batch-based techniques, such as thin-film hydration for chitosan-coated liposomal systems, consistently provide high encapsulation efficiency, sustained drug release, and good biocompatibility. However, these methods are often associated with batch-to-batch variability, operator dependence, and limited scalability. In contrast, continuous manufacturing approaches, including microfluidic mixing, nanostructured lipid carriers, and Quality-by-Design (QbD)–guided processes, demonstrate improved control over particle size distribution and polydispersity, enhanced reproducibility, and better scalability potential. Conclusions: Manufacturing methodology is an important determinant of DCF and NSAID nanocarrier performance alongside formulation composition. Continuous manufacturing approaches offer promising improvements in reproducibility, process control, and scalability, but current evidence remains uneven across different nanocarrier classes. Further standardized comparative studies are needed to support their broader translation into clinical applications. Full article

Background/Objectives: Pulmonary fibrosis is a progressive and fatal disease characterized by excessive extracellular matrix deposition and irreversible lung remodeling. Although modified mRNA (modRNA) therapeutics offer a promising strategy for regulating disease-driving pathways, effective pulmonary delivery remains challenging due to the inherent liver tropism of conventional lipid nanoparticles (LNPs). This study aimed to establish an optimized platform for lung-selective modRNA delivery and therapeutic screening for pulmonary fibrosis. Methods: A panel of charge-modified LNP formulations was evaluated in vivo for pulmonary tropism following systemic administration of luciferase (Luc) modRNA. Administration routes, biodistribution in healthy and bleomycin (BLM)-induced fibrotic lungs, and endogenous microRNA (miRNA)-mediated de-targeting strategies were assessed. Candidate antifibrotic modRNAs targeting the transforming growth factor-beta (TGF-β) signaling pathway were subsequently evaluated in normal human lung fibroblasts (NHLFs). Results: Among the formulations tested, 50% DOTAP MC3 LNPs demonstrated the most favorable balance of pulmonary transfection, physicochemical properties, and limited off-target expression. Intravenous (IV) administration achieved robust lung expression with a superior safety profile compared with intratracheal (IT) delivery. Importantly, pulmonary biodistribution was preserved in BLM-induced fibrotic lungs despite extensive tissue remodeling. Incorporation of miR-122 recognition sites further enhanced selectivity, resulting in 94.5% of total transgene expression being localized to the lungs while substantially reducing residual hepatic expression. In vitro screening identified dominant-negative TGF-β receptor II (DNTGFBR2) modRNA as a potent inhibitor of TGF-β-induced fibrotic activation, significantly suppressing α-SMA and CTGF expression. Conclusions: These findings establish a comprehensive platform for pulmonary modRNA therapeutic development by integrating lung-selective LNP engineering, optimal systemic delivery, miRNA-mediated de-targeting, and therapeutic payload screening. This strategy provides a foundation for the development of targeted RNA therapies for pulmonary fibrosis and other organ-specific diseases. Full article

Background: Doxorubicin is an effective antineoplastic agent, but its use is constrained by off-target toxicities, including acute liver injury driven by mitochondrial dysfunction, oxidative stress, sterile inflammation, and redox-sensitive signaling pathways. Exenatide, a glucagon-like peptide-1 receptor agonist, exerts antioxidant and anti-inflammatory effects in several experimental liver injury models, but its role in doxorubicin-induced hepatic injury has not been investigated to our knowledge. This study evaluated whether exenatide attenuates acute doxorubicin-induced hepatic injury and examined whether the observed biochemical changes are consistent with modulation of oxidative stress and SIRT1–HMGB1/NF-κB-related signaling. Methods: Male Wistar albino rats were allocated to four groups (n = 7/group): control, exenatide, doxorubicin, and exenatide + doxorubicin. Exenatide (10 µg/kg/day, intraperitoneally) was administered for seven days. Doxorubicin was given intraperitoneally on days 5–7 at a cumulative dose of 18 mg/kg. The pretreatment design was used to test preventive attenuation rather than reversal of established injury. Hepatic injury-associated enzyme activities, serum HMGB1, hepatic SIRT1, NF-κB, TNF-α, IL-6, IL-10, malondialdehyde, glutathione, total antioxidant status, total oxidant status, nitric oxide, and hepatic ^99mTc-pyrophosphate uptake were assessed. Results: Doxorubicin substantially increased intrahepatic ALT and AST activities, serum HMGB1, hepatic NF-κB, TNF-α, IL-6, malondialdehyde, total oxidant status, nitric oxide, and hepatic ^99mTc-pyrophosphate uptake, while reducing SIRT1, IL-10, glutathione, and total antioxidant status. Relative to the doxorubicin group, exenatide lowered HMGB1 by 48.3%, hepatic ^99mTc-pyrophosphate uptake by 48.7%, malondialdehyde by 45.0%, total oxidant status by 37.3%, nitric oxide by 40.7%, NF-κB by 40.4%, TNF-α by 48.6%, and IL-6 by 41.1%, while increasing SIRT1 by 91.7%, IL-10 by 115%, glutathione by 115%, and total antioxidant status by 87.8%. None of the altered parameters returned completely to control levels, indicating attenuation rather than full normalization of acute injury-related changes. Conclusions: Exenatide attenuated doxorubicin-induced acute hepatic injury in this rat model and was associated with reduced oxidative stress, reduced inflammatory activation, higher hepatic SIRT1 levels, lower serum HMGB1 levels, and reduced hepatic ^99mTc-pyrophosphate uptake. The findings are consistent with involvement of SIRT1–HMGB1/NF-κB-related signaling, but they do not establish causality. Hepatic ^99mTc-pyrophosphate uptake should be interpreted as an exploratory imaging correlate of tissue injury rather than an established liver biomarker. Additional studies incorporating histopathology, immunohistochemistry, functional liver indices, mechanistic validation of SIRT1, and tumor-bearing models are required before translational conclusions can be drawn. Full article

Acetaminophen (paracetamol, APAP) is a widely used analgesic and antipyretic drug. Under normal physiological conditions, it does not directly interact with or disrupt cellular membranes. However, in cases of acetaminophen overdose or toxicity, severe cellular damage has been described, involving a broad spectrum of effects at different cellular levels. These toxic effects may involve membrane structures, including mitochondrial, plasma, and other intracellular membranes. Antimicrobial peptides (AMPs) are short, usually cationic and amphipathic peptides produced by both microorganisms and multicellular organisms, serving diverse defensive and competitive functions. In many cases, they exert their antimicrobial activity by direct interaction with bacterial or fungal membranes, leading to membrane destabilization and cell death. Owing to this membrane-targeting mechanism, AMPs may also interact with eukaryotic cell membranes, thereby exerting toxic or off-target effects under certain conditions. Here, we review the current knowledge on the membrane-related effects of acetaminophen toxicity and the mechanisms by which AMPs interact with biological membranes. In the event of combined exposure to acetaminophen and AMPs in therapeutic or experimental settings, the biological consequences remain unexplored. Such combined exposure may give rise to toxic effects and membrane-associated alterations. We further discuss potential mechanisms of interference, additive toxicity, and synergistic interactions between acetaminophen and AMPs, highlighting critical knowledge gaps and directions for future research. Full article

Ischemic priapism, the most prevalent subtype, constitutes over 95% of all priapism cases, with an estimated annual incidence of 5.34 per 100,000 men in the United States. Characterized by impaired venous outflow and reduced cavernosal blood flow, it is commonly confirmed through cavernous blood gas (CBG) analysis. Notably, ischemic priapism occurs in approximately 33% of men with sickle cell disease (SCD). Standard pharmacological management includes penile aspiration combined with intracavernosal injection (ICI) of sympathomimetic agents such as phenylephrine and etilefrine. These therapies encounter several challenges, including ineffectiveness, off-target effects, and possible complications such as pain, penile fibrosis, and deformities. This highlights the need for novel treatment options. Although pharmacological treatments and surgical procedures are available, there is still a significant demand for novel therapies due to the complexities associated with ischemic priapism and its underlying pathophysiology. This review aims to evaluate the potential of novel therapies as modalities for managing ischemic priapism. By utilizing various treatment modalities, it is possible to achieve localized and targeted action, enhanced safety, minimal off-target effects, and improved patient compliance. Furthermore, this review will explore the potential integration of new drug delivery systems for the management of ischemic priapism. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a major global health threat that has outpaced the development of new antibiotics. Drug repurposing has emerged as a promising strategy for identifying alternative antimicrobial therapies. Antidepressants have attracted interest because experimental studies suggest they possess off-target antimicrobial activity, although growing evidence indicates they may also promote antimicrobial resistance. This review critically examines both the therapeutic potential and risks of antidepressant–microbial interactions. Methods: A structured narrative review was conducted using literature identified from major biomedical databases. Experimental, animal, microbiome, environmental, and clinical studies were synthesized according to antidepressant class, antimicrobial mechanisms, interactions with conventional antibiotics, microbiome modulation, and antimicrobial resistance. Results: Experimental evidence demonstrates that several antidepressants inhibit bacterial and fungal pathogens through mechanisms including membrane disruption, oxidative stress induction, efflux pump inhibition, and biofilm interference. Some agents also enhance the activity of conventional antibiotics. However, current evidence is largely preclinical. Multiple studies indicate that antidepressants may also promote antimicrobial resistance through reactive oxygen species-mediated mutagenesis, efflux pump activation, horizontal gene transfer, microbiome dysbiosis, and environmental exposure. Conclusions: Antidepressants represent both a promising drug-repurposing opportunity and a potential contributor to antimicrobial resistance. Although their antimicrobial properties are encouraging, current evidence remains predominantly preclinical, and clinically effective and safe antimicrobial dosing has not been established. At present, their antimicrobial use should be regarded as proof-of-concept rather than a clinically validated therapeutic strategy. Further pharmacokinetic, pharmacodynamic, animal, and clinical studies are required before routine antimicrobial application can be considered. Full article

Nanotechnology has become an important platform in the fields of gene therapy and genome editing, providing delivery strategies that address persistent therapeutic challenges by improving the precision, efficiency, and safety of genetic modifications. This review highlights the central role of nanomaterials in overcoming persistent barriers to genetic interventions, including inefficient delivery, instability of genetic cargo, and off-target effects. Specifically, we emphasize the combined use of nanomaterials with clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) systems, which can improve editing specificity and therapeutic efficacy. Beyond the classical CRISPR/Cas9 platform, this review also discusses next-generation modalities such as base editors, Cas13, prime editing, and the recently described Tandem Interspaced Guide RNA and TIGR-associated protein (TIGR-Tas) system, while considering their therapeutic potential and distinct delivery challenges. By using nanomaterials, the stability and intracellular delivery of genome-editing systems are improved, enabling more effective treatments for genetic disorders and acquired diseases such as cancer and infectious diseases. In addition, nanocarriers provide controlled release, protection from degradation, and better biocompatibility, thereby improving the safety and reliability of gene-editing therapies. Despite these advances, important translational challenges remain, including immunotoxicity, large-scale manufacturing, and regulatory integration. Overall, the continued convergence of nanotechnology and genome engineering may support the development of personalized medicine strategies that adapt genetic engineering tools for patient-specific applications. Full article

Survivin (BIRC5) is a key inhibitor of apoptosis that is highly overexpressed in many cancers, where it promotes tumour cell survival, mitotic progression, and resistance to therapy. Because survivin is largely absent from normal adult tissues, it represents a selective and promising target for cancer treatment. Antisense oligonucleotides (ASOs) provide a precise approach to silence survivin by targeting its transcripts. Preclinical studies have shown that ASO-mediated reduction of survivin is associated with increased cancer cell death, inhibition of tumour growth, and enhanced sensitivity to other treatments. Early-phase clinical trials of survivin-targeting ASOs have shown evidence of target engagement but ultimately failed to demonstrate consistent clinical benefit and/or encountered dose-limiting toxicities, which hindered their further development. This review outlines survivin’s central role in cancer biology, the principles of ASO therapeutics (sequence design, mechanisms of action, chemical modifications, and delivery strategies), and the progress in preclinical and clinical development of survivin-targeting ASOs, while also discussing key challenges that may contribute to their clinical limitations, including inefficient delivery, off-target effects, and systemic toxicities. Collectively, the current status of survivin-targeting ASOs underscores the need for synergistic optimization of delivery platforms and molecular chemistry to improve efficacy and safety, thereby enabling their use in personalised and combination cancer treatment approaches. Full article