The use of computational tools has become widespread in drug discovery as an effective approach to guide the development of new therapeutic agents, including potential cancer drugs. In addition, plant-derived secondary metabolites have attracted considerable interest as a valuable source of bioactive compounds. Among these, alkannin and shikonin, two enantiomeric phyto naphthoquinones, have emerged as promising candidates for cancer therapy because of their anti-inflammatory properties and their ability to induce oxidative DNA damage in malignant cells. Related to the above commentaries, in the present study, the phyto naphthoquinones alkannin, shikonin, and their corresponding indole derivatives were evaluated employing density functional theory (DFT), followed by chemoinformatic analyses and molecular docking studies to evaluate, in silico, their potential activity against the cancer-related enzymes PARP-1, COX-2, and HDAC2, which are overexpressed in several types of cancer. The presence of the indole moiety in the phytomolecules increased their chemical reactivity, as exhibited by the calculated properties and the smaller LUMO-HOMO energy gap. In addition, the bioinformatic evaluation predicted that the target molecules may act as potential apoptosis agonists and antineoplastic agents. Finally, the performed molecular docking analysis suggested a stereoselective effect on the stability of ligand-protein binding complexes, particularly for alkannin, including relevant interactions with His201 and its indole derivative displaying interactions with His201, Tyr235, and Glu327 from the PARP-1 catalytic triad. Additionally, alkannin (-11.2 kcal/mol) and the corresponding indole derivative of shikonin (-10.14 kcal/mol) showed better interaction energies with COX-2 than naproxen (-8.75 kcal/mol). In the latter case, the inclusion of the indole moiety improved the binding affinity. In contrast, the affinity of the target compounds for HDAC2 decreased considerably with the indole derivatives in comparison with the reference compound BIZ.

This study investigated the sorption of three widely detected non-steroidal anti-inflammatory drugs, naproxen, diclofenac, and ibuprofen, onto biochars and activated carbons derived from coconut shell and orange peel. Activated carbons were prepared under chemical activation with ZnCl2 and H3PO4. The sorbent materials were characterized in terms of surface functional groups, acid-base properties, and pzc, while the pH was monitored along the sorption experiments. Results suggest that the activating agent played an important role in controlling surface chemistry and acid-base properties; ZnCl2-activated carbons exhibited near-neutral pzc values and a balanced distribution of functional groups, while H3PO4-activated materials showed highly acidic surfaces with lower pzc. The solution pH evolved during sorption instead of remaining at its initial value. The sorption performance showed a clear dependance on surface chemistry, ZnCl2-activated carbons exhibited a superior sorption capacity as well as faster kinetics under neutral conditions, this behavior may be associated to reduced electrostatic repulsion toward anionic model molecules. Under acidic conditions, some H3PO4-activated materials showed comparatively favorable sorption behavior, consistent with possible contribution from hydrogen bonding and hydrophobic interactions. Kinetic analysis showed time-dependent uptake profiles consistent with more than one mass-transfer contribution; however, no single rate-controlling mechanism could be established from the available data. The results indicate that NSAID sorption under the investigated conditions was associated with the surface acid-base properties of the carbon materials, the initial-to-final pH shifts, and the pH-dependent speciation of the pharmaceuticals. These findings provide an empirical basis for evaluating the performance of agroindustrial waste-derived carbon materials toward ionizable pharmaceuticals and highlight the importance of considering both surface chemistry and the measured solution pH when interpreting sorption behavior.

Airplane headache (AH) is a headache disorder recognized in the International Classification of Headache Disorders, 3rd edition (ICHD-3) and characterized by severe, short-lasting, fronto-orbital pain occurring during aircraft take-off or, more typically, landing. Despite growing clinical recognition, evidence regarding its epidemiology, pathophysiology and management remains fragmented across heterogeneous studies.

Gitelman syndrome (GS) is an inherited renal salt wasting tubulopathy caused by variants in SLC12A3 and classically associated with hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. We describe an 18-year-old professional baseball player with an approximately 6-month history of recurrent, exertional muscle cramping, fatigue, and profuse sweating that persisted despite hydration and commercial electrolyte supplementation. Laboratory evaluation demonstrated blood urea nitrogen (BUN) levels of 24-27 mg/dL, creatinine levels of 1.20-1.38 mg/dL, bicarbonate of 29-31 mmol/L, and 24-h urinary sodium of 163 mmol/L. The serum potassium measurements did not indicate levels below 3.5 mmol/L. Persistent symptoms and the urinary sodium finding raised concern for abnormal renal salt handling. Evaluation was complicated by limited, episodic access to the athlete while he trained and competed in the Dominican Republic, restricting opportunities for serial biochemical testing. Genetic sequencing identified a heterozygous SLC12A3 gene c.2990C>T variant. Management included individualized potassium and magnesium supplementation, naproxen sodium 220 mg daily, and pre-exercise iontophoresis to reduce sweating. At the 6-month follow-up, the athlete reported less cramping and improved endurance; BUN was 17.4 mg/dL, creatinine was 1.20 mg/dL, and potassium was 4.59. This case highlights the diagnostic challenge posed by an incomplete GS phenotype in a high-performance athlete and the importance of correlating clinical, biochemical, and genetic findings. Heterozygous SLC12A3-associated salt-wasting physiology should be considered in athletes with persistent compatible symptoms and evidence of inappropriate renal electrolyte loss, while alternative acquired and endocrine causes are evaluated.

Development of chiral sensors for determining amino acid enantiomers is an important topic in the biosensing field. However, the inherent non-electroactivity or weak electroactivity of many chiral amino acids poses a fundamental challenge for direct electrochemical detection, necessitating alternative transduction strategies. In this work we developed a sensitive electrochemical sensor for selective detection of chiral amino acids based on covalent organic framework-cyclodextrin-gold nanocomposite.

Non-steroidal anti-inflammatory drugs （NSAIDs） are often used to treat horses' injuries and pain due to long-term training and competitions. In equestrian competitions， NSAIDs do not affect the upper limit of a horse's athletic ability， but they can enable the horse to perform close to its maximum capacity by reducing inflammation and pain. This not only affects the competition results， but also fails to ensure the health and welfare of the horses. Therefore， it has become crucial to effectively monitor and control NSAIDs residues during equestrian competition. In this study， a rapid screening and determination method for 33 NSAIDs in horse urine was established using QuEChERS pretreatment combined with ultra performance liquid chromatography-tandem mass spectrometry （QuEChERS-UPLC-MS/MS）. The pretreatment process， chromatographic conditions， and mass spectrometric conditions were also optimized. In brief， the target analytes in 1 mL of horse urine samples were extracted with 5 mL of acetonitrile. During extraction， 100 mg of NaCl was added as a salting-out agent， and the mixture was shaken for 3 min. Subsequently， the extract was purified using a QuEChERS method with 300 mg of anhydrous MgSO4， 40 mg of octadecylsilane-bonded silica （C18）， and 40 mg of primary secondary amine （PSA） as sorbents. After centrifugation， the supernatant was dried under nitrogen and reconstituted. The 33 NSAIDs were separated on an Agilent Poroshell 120 EC-C18 analytical chromatographic column （100 mm×3.0 mm，2.7 μm） with gradient elution using （A） 0.1% formic acid aqueous solution and （B） methanol solution as the mobile phases. The gradient elution program was as follows： 0-1 min， 30%B； 1-3 min， 30%B-60%B； 3-12 min， 60%B-85%B； 12-12.1 min， 85%B-95%B； 12.1-14 min， 95%B； 14-14.1 min， 95%B-30%B； 14.1-17 min， 30%B. Then， the target analytes were determined by UPLC-MS/MS in dynamic multiple reaction monitoring （dMRM） mode with positive/negative ion switching. Quantification was performed using the matrix-matched external standard method. The results showed that the method can rapidly and simultaneously determine the 33 NSAIDs in horse urine. The analytes had good linear relationships within their respective ranges， with correlation coefficients of >0.99. The limits of detection （LODs） and quantification （LOQs） were 0.1-1.0 μg/L and 0.9-5.4 μg/L， respectively. The recoveries of the 33 NSAIDs in horse urine were between 70.8% and 123.8% at three spiked levels of LOQ， 20 μg/L and 200 μg/L. The relative standard deviations of all targeted compounds ranged from 1.9% to 14.8%. The method was applied to 10 actual horse urine samples. The results revealed the presence of three NSAIDs， including ketorolac， lornoxicam and naproxen， with contents ranging from < LOQ to 6.87 μg/L. According to the Equine Prohibited Substances List published by the Federation Equestre Internationale （FEI）， ketorolac and naproxen are controlled medications. They are prohibited for use during competition period， as they may mask symptoms and aggravate clinical conditions. However， they are permitted for use during non-competition times. Lornoxicam is a banned substance and is strictly prohibited for use in horses at any time. The proposed method is simple， efficient and accurate， and is suitable for the simultaneous determination of the 33 NSAIDs residues in horse urine samples.

Chronic nonbacterial osteomyelitis is an autoinflammatory bone disease characterized by pronounced dysregulation of proinflammatory and anti-inflammatory cytokine production and release. Through innate immune dysregulation, patients with chronic nonbacterial osteomyelitis develop bone inflammation, pathological bone remodeling, and associated pain. Notably, secondary activation of adaptive immune mechanisms may contribute to phenotypic variability and the onset of additional tissue and organ involvement (joints, skin, gut). Currently used treatments are empiric, targeting inflammation and/or osteoclasts. While deemed efficacious across clinical cohorts internationally, in the absence of randomized controlled trials, they lack regulatory approval. While chronic nonbacterial osteomyelitis limited to bones frequently responds to anti-inflammatory treatment with naproxen or, in more severe cases, tumor necrosis factor inhibitors and/or osteoclast inhibition with bisphosphonates, patients with additional symptoms may require additional/different treatments targeting effector T cells and associated cytokines (such as interleukin-17 blockers, Janus kinase inhibitors). Thus, changing molecular, cellular, and phenotypic patterns throughout the disease course offer an opportunity for personalized treatment and suggest a 'window of opportunity' preventing the onset of additional organ involvement. However, 'tools' to guide personalized treatment approaches are currently lacking, and treatment is guided by clinical features, following a trial-and-error approach. This article reviews the available literature, deciphering shared immune mechanisms between chronic nonbacterial osteomyelitis and associated diseases that may guide individualized care. It focuses on shared and disease-specific molecular and cellular patterns of chronic nonbacterial osteomyelitis and associated diseases, delivering arguments for disease stage and phenotype specific treatments, including cytokine blockers and synthetic small-molecule inhibitors.

Irregular fracture edges and gaps present significant challenges to bone healing. As versatile scaffolds for bone regeneration, hydrogels can effectively guide and facilitate tissue repair. Compared to preformed hydrogels, in situ gelation via a responsive sol-gel transition at the defect site offers superior flexibility, adaptability, and conformity, minimizing void cavities and establishing a more favorable environment for healing complex fractures. Peptides, as biogenic building blocks, can self-assemble into hierarchically structured hydrogels under specific stimuli. Given that alkaline phosphatase (ALP) is a key enzyme in bone mineralization and is highly expressed at the fracture site, we developed a phosphorylated peptide (N[f]FpYO) that undergoes ALP-triggered dephosphorylation, enabling direct in situ gelation on irregular fracture surfaces. Our results show that the resulting nanofibrous three-dimensional scaffold, functionalized with Gly-Pro-Hyp (GPO) motifs, promotes the migration, proliferation, and osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. Moreover, the resulting nanofibrous hydrogel, which presents peptide-bound naproxen and fluorinated motifs, was associated with a less inflammatory and more repair-supportive macrophage-associated marker profile, enhanced osteogenic marker expression, and improved radiographic and histological fracture repair in a murine model. This study adapts a promising ALP-instructed peptide self-assembly strategy to the fracture-repair microenvironment through a multifunctional precursor design, providing a local shape-conformal and bioactive hydrogel platform with potential for complex fracture repair.

Lanthanide-based metal-organic frameworks (Ln-MOFs) offer a unique combination of adsorption capabilities and tunable luminescent properties, making them promising materials for environmental applications. This study details the synthesis of a family of isoreticular Ln-MOFs (Ln = Sm, Eu, Tb, Dy) using benzene-1,4-dicarboxylic acid (BDC) as a linker, yielding materials with nanometric crystallite sizes. We explore their efficiency in removing four emerging contaminants (ECs) and systematically evaluate the impact of adsorption on their luminescent properties. While exhibiting a maximum adsorption of 50.2% for naproxen on Dy 2 (BDC) 3 , highlighting the influence of EC functional groups, the materials demonstrate superior functionality as a luminescent sensor. Notably, ciprofloxacin adsorption induces a significant and specific luminescence enhancement (up to 202.24% for Eu-MOF), suggesting great potential for luminescence-based chemical sensing applications. The consistent fitting to the Freundlich model supports the occurrence of adsorption on energetically heterogeneous surfaces. These findings underscore the versatility of Ln-MOF for environmental monitoring through a mechanism that combines adsorption and modulated luminescence.

L-β-Cyclodextrin (L-CD), the mirror-image isomer of native β-cyclodextrin, provides a conceptually novel chiral microenvironment for pharmaceutical enantioseparation; however, its full separation potential and recognition mechanism remain largely unexplored, hindering its rational development. Herein, a multiscale computational framework integrating high-throughput molecular docking, molecular dynamics (MD) simulations, and density functional theory (DFT) calculations was developed to elucidate the chiral recognition mechanism of L-CD toward three clinically drugs, namely baclofen (Bacl), naproxen (Nap), and propranolol (Prop). Batch docking of 150 enantiomer pairs reveals that L-CD discriminates approximately 57% of the evaluated species, with a distinct preference for R-enantiomers in the 200-300 Da range. Subsequent MD simulations further demonstrated that R-enantiomer complexes possess enhanced structural stability, tighter cavity adaptation, and more persistent hydrogen bonds. Binding free energy calculations consistently yield stronger binding affinities of L-CD for R-enantiomers across all three drugs, exemplified by R-Bacl/CD (-72.05 kJ/mol) vs. S-Bacl/CD (-67.99 kJ/mol), R-Nap/CD (-67.46 kJ/mol) vs. S-Nap/CD (-66.03 kJ/mol), and R-Prop/CD (-79.51 kJ/mol) vs. S-Prop/CD (-73.59 kJ/mol). Energy decomposition analysis further reveals that reduced steric hindrance and favorable electrostatic interactions contribute to the enhanced stability of R-enantiomer complexes. This multiscale framework provides atomic-level insights into dynamic chiral recognition by L-CD and establishes a robust theoretical foundation for the rational design of next-generation L-CD-based chiral separation materials.

Since the publication of the Taiwan Headache Society's 2022 Guidelines for the Acute Treatment of Migraine Attacks, advances in headache medicine and the approval of new drugs in Taiwan have necessitated an update. To address clinical needs, the Guideline Committee of the Taiwan Headache Society reviewed evidence for pharmacological and non-pharmacological acute treatments using evidence-based principles. Drawing from the latest European, American, and international guidelines, and through expert consensus, this revision updates treatment roles, grades of recommendation, efficacy, and adverse-effect profiles. Currently, a broad range of medications is available in Taiwan for acute migraine management, categorised into "specific" and "non-specific" agents. Specific treatments include oral and intranasal triptans, and gepants, i.e., oral calcitonin gene-related peptide (CGRP) receptor antagonists. Non-specific agents include acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs: diclofenac, ibuprofen, naproxen). Injectable prochlorperazine is also strongly recommended. Ergotamine/caffeine combinations are less effective and are second-line agents, while high-dose aspirin is limited by gastrointestinal risk. Considering the potential risk of dependency, tramadol or tramadol/paracetamol combinations should be reserved until all other agents fail, and should be limited to oral forms. Other opioids, such as morphine, butorphanol, etc., lack evidence and are not recommended. Treatment should follow the principle of stratified care: oral NSAIDs for mild disability, with combination analgesics or parenteral NSAIDs as alternatives, and oral or intranasal triptans for moderate to severe disability, ideally administered early. Antiemetics may be added, and combining triptans with NSAIDs enhances efficacy. Rimegepant can be considered a first-line therapy, particularly for patients who are unresponsive or intolerant to triptans, have cardiovascular contraindications, or are at risk of developing medication overuse. In status migrainosus, parenteral corticosteroids with intravenous fluids are advised. Acetaminophen remains first-line for children and pregnant women. To prevent medication-overuse headache, acute treatments, including NSAIDs, acetaminophen, triptans, ergot derivatives, and combination analgesics, should not exceed two days per week, probably with the exception of rimegepant.

Because dental implant post-surgical pain is mainly driven by inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (eg, Advil\'ae, Motrin\'ae IB) or naproxen sodium (Aleve\'ae) are logical choices to address it. These drugs are highly efficacious, non-addicting, and generally well tolerated. Dental implant patients, however, are generally older than those having their impacted third molars removed and are, therefore, likely to present with more comorbidities and drug intake, leading to potentially more adverse effects and serious adverse drug interactions. Fortunately, pain following dental implant surgery is generally milder than that of impacted third molar surgery and is amenable to low over-the-counter (OTC) dosing regimens. Administering NSAIDs immediately after surgery before the local anesthesia has worn off and then around the clock for 2 to 3 days appears to be an effective strategy at not only preventing the onset of postoperative pain, but also diminishing breakthrough pain, which is typically seen with as-needed (PRN) dosing. Implant surgeons must be able to identify those patients in whom a short course of NSAIDs can be used safely and employ dosing strategies that provide optimal analgesic efficacy while limiting untoward events. This article discusses current recommendations for postoperative pain management in dental implant patients, emphasizing the role of NSAIDs while addressing patient-specific safety considerations.