The isoflavone metabolites, O-desmethylangolensin and (S)-equol, relax isolated arteries ex vivo and decrease arterial blood pressure in vivo.

Synergistic phosphorus-carboxyl co-modification of dolomite for enhanced immobilization and long-term stabilization of Pb in acidic contaminated soils.

S⁰-S²⁻ co-substrate system achieves efficient nitrite accumulation under high alkalinity and ultra-short HRT: Multidimensional responses and metabolic regulation mechanism.

Infective endocarditis (IE) is a life-threatening infection traditionally treated with 4-6 weeks of intravenous (IV) antibiotics. Emerging data, including the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial and recent meta-analyses, suggest that selected clinically stable patients can safely transition early to oral regimens, but practical guidance on implementation is limited. We conducted a comprehensive narrative review of randomized trials, observational studies, ongoing clinical trials, meta-analyses, and contemporary guidelines addressing partial oral antibiotic therapy in adult IE. Evidence consistently shows that after at least 10 days of effective IV treatment, patients who are afebrile, hemodynamically stable, have negative blood cultures, and no uncontrolled infection on imaging can be transitioned to dual oral regimens with high bioavailability and pathogen-directed activity. In this population, oral step-down therapy yields similar rates of death, relapse, embolic events, and unplanned cardiac surgery compared with prolonged IV therapy, while substantially reducing hospital length of stay and line-related complications. Data in people who inject drugs, those with multidrug-resistant pathogens, or severe heart failure remain limited, and robust pharmacokinetic validation of some oral β-lactam-based combinations is still needed. Overall, partial oral antibiotic therapy represents a safe, evidence-based, and stewardship-aligned strategy for many patients with left-sided native or prosthetic valve IE when applied within structured protocols and strict selection criteria.

Although immunotherapy displays potent momentum in cancer treatment, its efficacy is limited due to tumor metabolic reprogramming. Aberrant tumor metabolism is pivotal in sustaining tumorigenesis and resulting in immunosuppression, achieved by the secretion of immunosuppressive metabolites as well as the metabolic competition between tumor cells and immune cells. Therefore, interfering with metabolism-immunity crosstalk via regulating tumor cell and immune cell metabolism is a promising strategy for potentiating antitumor immunity. Nanomaterials have been widely applied in cancer therapy as delivery vehicles due to their small size effect, good biocompatibility, high drug bioavailability, and facile synthesis for on-demand release. In this review, tumor metabolic patterns, including glucose metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism, along with their characteristics, are first reviewed. The recent progress in nanomaterials-based immunometabolism inhibition of tumor cells, cancer-associated fibroblasts, and tumor-associated macrophages, and the metabolism reinforcement of dendritic cells and T lymphocytes, is then systematically summarized. The limitations, challenges, as well as future perspectives of nanomaterials-guided metabolism-immunity crosstalk are highlighted, underscoring the clinical translation needs of future studies.

A new set of quinazolin-4-one-based chalcones was prepared from 3-(4-acetylphenyl)-2- methylquinazolin-4(3H)-one (1) via a base-catalyzed Claisen-Schmidt condensation with substituted aromatic aldehydes. Synthesis was conducted using either a conventional NaOH/EtOH protocol or a solvent-minimized mechanochemical grinding approach. The grinding method delivered chalcones 3a-j and 5 in improved yields (85-94%) within 15-25min, compared with 65-72% over 12-20h for the solution method. Product structures were verified by spectroscopic and elemental analyses. The anti-Alzheimer's potential was investigated through molecular docking of the complete series to propose binding modes and prioritize candidates, followed by in vitro evaluation of the five top-ranked compounds (3e, 3f, 5, 3i, and 3h) for AChE and BuChE inhibition relative to donepezil. In vitro assays revealed the following IC₅₀ values for the compounds against AChE and BuChE: 3e (0.751 ± 0.023µg/mL for AChE, 0.108 ± 0.003µg/mL for BuChE), 3f (1.283 ± 0.039µg/mL for AChE, 0.383 ± 0.01µg/mL for BuChE), and 5 (2.148 ± 0.066µg/mL for AChE, 1.212 ± 0.04µg/mL for BuChE). These values suggest that 3e was the most promising dual inhibitor, outperforming donepezil in both AChE and BuChE inhibition. Docking outcomes agreed with the experimental trends, supporting this scaffold as a promising platform for dual cholinesterase inhibition. In silico ADMET assessment further indicated drug-like characteristics with predicted high oral bioavailability, supporting further lead optimization for Alzheimer's disease therapy.

Yunnan is a major coffee region in China. This study explores mineral sources and bioavailability to identify geochemical indicators for origin traceability. We analyzed 85 soil, 52 coffee beans, and 4 bedrock samples from Pu'er and Baoshan, Yunnan. Eleven elements (Cr, Cu, Mn, Zn, Ca, K, Mg, Fe, Pb, Mo, As) were measured by coupled plasma mass spectrometry, along with soil pH and organic matter. Enrichment factors, bioconcentration factors, principal component analysis, and partial least squares regression were applied to assess elemental mobility, sources, and traceability. K, Ca, Mg, Cu, and Mo showed high bioavailability with greater uptake in Pu'er. Lead, As, Mn, Zn, Fe, and Cu accumulated more in Pu'er beans, while Cr was enriched in Baoshan. Chromium, Mo, and As derived from human activities, whereas Mg, Ca, and K from weathering rock. Elemental sources in Pu'er involved weathering, industry, and agriculture; in Baoshan, coal combustion, mining, and agriculture dominated. Three latent variables were extracted, with higher explanatory power in Pu'er (Xp = 78.07%, Yp = 38.69%) than Baoshan (Xb = 46.26%, Yb = 29.49%). The LV1 axis clearly distinguished origins, identifying Cr, Cu, Ca, and Mg as key soil indicators for coffee traceability. All toxic elements were below safety limits. Pu'er showed higher Pb and As accumulation, while Baoshan had more Zn and Mn. Natural weathering mainly contributed to Mg, Ca, and K; human activities influenced Cr, Mo, and As. Partial least squares regression effectively distinguished origins, highlighting Cr, Cu, Ca, and Mg as effective markers for distinguishing coffee origins.

Plastic composition drives the toxicity of UV-aged melamine-polypropylene microplastics, nanoplastics, and leachates on Raphidocelis subcapitata.

1,3,4-Thiadiazoles constitute an important heterocyclic scaffold with extensive antimicrobial potential. Owing to their unique physicochemical features, such as high lipophilicity, oral bioavailability, and stability in biological systems, this class of compounds has been widely exploited in antibacterial, antifungal, and agrochemical research. In this review, we comprehensively analyzed more than 100 synthetic 1,3,4-thiadiazole derivatives reported between 2007 and 2024, including hybrid molecules, metal complexes, and commercially used agents such as sulfamethizole, cefazolin, and bismerthiazol. Detailed comparison of these structures revealed that subtle changes in substitution patterns, particularly at the 2- and 5-positions of the thiadiazole ring, profoundly influence antimicrobial selectivity and potency. For example, electronwithdrawing groups (-Cl, -NO2) often enhanced Gram-positive activity, while lipophilic substituents improved antifungal efficacy against Candida and Aspergillus spp. Several compounds exhibited minimum inhibitory concentrations comparable to or superior to standard drugs such as Fluconazole, Ciprofloxacin, and Ampicillin, and many retained activity against multidrugresistant clinical isolates. In addition, derivatives targeting plant pathogens demonstrated superior control of Botrytis cinerea, Ralstonia solanacearum, and Rhizoctonia solani, highlighting the agricultural utility of this scaffold. Mechanistic investigations indicate diverse modes of action, including disruption of ergosterol biosynthesis, cell wall inhibition, efflux pump modulation, and interference with bacterial metabolic enzymes. Structure-based design, docking studies, and SAR analyses further underscore the versatility of the scaffold in guiding nextgeneration antimicrobial development. Collectively, this review consolidates structural and pharmacological insights into 1,3,4-thiadiazoles, underscoring their promise as adaptable scaffolds to address the.

Iron deficiency is the most prevalent nutritional disorder globally. Conventional treatment primarily involves oral supplementation with various iron salts, such as ferrous sulfate. While cost-effective and easily administered, these salts are associated with several challenges, including gastrointestinal irritation, prolonged treatment duration, and poor patient compliance due to adverse side effects. To address these limitations, nanotechnology has been employed to develop improved oral iron supplements with varying degrees of success. Utilizing approaches from nanotechnology and materials science, researchers have engineered diverse iron-containing nanomaterials designed to provide bioavailable iron. However, the efficacy of these nanomaterials as oral supplements is highly dependent on their specific physicochemical properties. An effective nano-based replacement for iron salts must exhibit high bioavailability for efficient iron restoration and low toxicity to minimize side effects. This review consolidates in vivo research on various iron nanomaterials evaluated as oral iron supplements. Furthermore, it proposes a framework for the ideal characteristics of an oral iron nanoparticle supplement by consolidating the current understanding of the mechanisms governing nanoparticle absorption and toxicity.

Integrative assessment of cadmium stress adaptation in Ocimum spp.: Linking biochemical defense, anatomical plasticity, and essential oil biosynthesis.

Carboxymethyl β-cyclodextrin-loaded buffalo milk peptide nanoparticles ameliorate DSS-induced intestinal mucosal injury in mice.

Derivation of evidence-based oral-to-parenteral uncertainty factors for medical device toxicological risk assessment.

Metabolic dysfunction-associated steatohepatitis (MASH) presents a growing global health challenge, underscoring the need for effective therapies. Farnesoid X receptor (FXR) represents a promising therapeutic target against MASH. This study reported the rational design of a novel non-carboxylic steroidal FXR agonist, compound 27, which demonstrated effective FXR agonistic activity (TR-FRET: EC50 = 10 ± 3 nM; Luciferase Reporter: EC50 = 128 ± 9 nM) alongside reduced activation of the off-target receptor MRGPRX4 compared to OCA. Compound 27 exhibited high oral bioavailability in rats (F = 70.30%) and activation of hTGR5 (HTRF: EC50 = 1360 nM). In vivo studies confirmed its efficacy: attenuated collagen deposition in the CCl4-induced liver fibrosis model and improved steatosis and inflammatory foci in the MASH model. In summary, compound 27 achieves its promising efficacy and safety profile by the dual-path strategy that enhances FXR/TGR5 activity while suppressing MRGPRX4, supporting its further development as a novel therapeutic agent for MASH.

Arthritis has become a widespread global health issue with the aging population. Wearable transdermal drug delivery offers a promising treatment with high bioavailability and sustained drug concentrations. However, current technologies struggle with issues such as high cost, low comfort, risk of infection, or tissue pain and damage. Here, we present a breathable, stretchable electroporation patch (BSEP) that seamlessly integrates the traditional drug patch with electroporation-enhanced transdermal drug delivery technology in a low-cost manner. Conductive ink was patterned and deposited onto a breathable and stretchable non-woven fabric substrate using screen printing. A unique serpentine interdigitated design for stretchable electrodes was adopted to precisely localize the electric field within the superficial layers of the skin, reducing voltage in deep tissues by >50% and minimizing potential damage. Cytotoxicity tests and histological analyses confirmed the biocompatibility and safety of the materials and device. Finally, animal experiments validated the effectiveness of the BSEP in enhancing drug delivery, achieving a two-threefold increase in skin penetration compared to the control group. These findings collectively suggest that the developed BSEP holds significant promise for transdermal drug delivery applications.

A novel β-casein peptide‑zinc chelate with enhanced zinc transport capacity: Preparation, chelation mechanism, and in vitro stability.

Postoperative sleep disturbance (PSD) is a common complication following laparoscopic cholecystectomy (LC). It is associated with delirium, cognitive decline and delayed recovery. Effective preventive strategies are currently lacking. Dexmedetomidine, a highly selective α₂-adrenergic receptor agonist, offered in a nasal spray formulation with high bioavailability and convenient administration, may present a novel approach for PSD prevention. The primary objective is to evaluate the effect of evening dexmedetomidine nasal spray on the incidence of PSD on the first postoperative day in LC patients. Secondary objectives include assessing its impact on the quality of recovery, anxiety and depression and pain scores. This is a multicentre, prospective, randomised, double-blind, controlled trial. At least 260 patients will be enrolled and randomly allocated in a 1:1 ratio to receive either dexmedetomidine (50 µg nasal spray) or saline placebo the night before and the night of surgery (between 20:00 and 22:00). The primary outcome is the incidence of PSD on postoperative day 1 defined as an Numerical Rating Scale (NRS) >6 or Athens Insomnia Scale >6 score, which will be compared between groups using the χ2 or Fisher's exact test on the full analysis set. Secondary outcomes include quality of recovery (Quality of Recovery-15 scale, QoR-15), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), pain (NRS), postoperative nausea and vomiting and adverse events, analysed using t-tests, rank-sum tests or repeated-measures mixed-effects models as appropriate. The study protocol has been approved by the Ethics Committee of the Affiliated Drum Tower Hospital of Nanjing University Medical School (Approval No.: 2025-0064-02) and registered with the Chinese Clinical Trial Registry. The findings of this study will be disseminated through various channels. Academic dissemination will include publication in peer-reviewed journals and presentations at national and international conferences. ChiCTR2500101205.

The present study investigated efficacy of Ocimum tenuiflorum fermented beverage in the amelioration of renovascular-hypertension in 2K1C model. Hypertension was induced by clipping the left renal artery. The hypertensive rats exhibited elevated systolic, diastolic, and mean arterial pressure; increased heart rate; activity of angiotensin-converting enzyme (ACE); and elevated serum and renal levels of angiotensin II. Additionally, liver and heart functions were impaired, accompanied by increased expression of α-skeletal actin, indicating organ damage associated with hypertension. However, administration of the fermented tulsi beverage for six weeks led to partial restoration of these parameters. The mechanism of action involves the suppression of ACE activity, as supported by gene expression analysis. The observed efficacy may be attributed to the beverage's rich polyphenolic content and high bioavailability. To our knowledge, this is the first report demonstrating the ameliorative potential of a fermented tulsi beverage against renovascular hypertension in a 2K1C rat model.

Effect of pterostilbene on cognitive function, and histone deacetylase and BDNF/CREB pathway following ischemia reperfusion injury in mice.

An engineered micropatch for oral delivery of heterophyllin B in type 2 diabetes treatment.