Conventional extraction of bioactive alkaloids relies on volatile organic solvents. This study evaluated 21 deep eutectic solvents (DESs) through experimental screening and multi scale computational profiling to extract piperine (PIP) from Piper nigrum and hydroxy sanshools (HAS and HBS) from Zanthoxylum bungeanum. For rigid PIP, a choline chloride/1,2-butanediol (1:4, 20% water) DES achieved 60.11 mg/g (a 1.53-fold increase over methanol). For flexible sanshools, a urea/acetic acid (1:2, 30% water) DES yielded 59.36 mg/g (HAS) and 14.61 mg/g (HBS). Molecular dynamics revealed that extraction efficiency depends on topological and electrostatic complementarity. Specifically, ChCl/1,2-BD extracts PIP via synergistic hydrogen bonding and van der Waals interactions, whereas UR/HAc solubilizes sanshools through network reorganization, anchoring polar terminals while accommodating flexible chains. This work establishes three generalizable principles for rational DES design: electrostatic complementarity matching, spatial topology adaptation for rigid frameworks, and van der Waals compensation for flexible chains.

Early-life nutrition can program gastrointestinal tract development in ruminants; however, the extent to which these effects persist into later life is not fully understood. We hypothesised that early-life diet would have a lasting impact on rumen structure and function in sheep. Fifty-four male lambs were divided into two groups and fed milk replacer (MR) and either a mixture of meadow and alfalfa hay (high-fibre; HF) or concentrate (high-starch; HS) in the first weeks of life. The MR was fed for 7 weeks, and experimental solid feeding was continued for 2 weeks after weaning. Animals were then transitioned to a hay-based diet over 3 weeks (stage 1), which was continued until 7.8 ± 0.53 months of age (stage 2). Subsequently, animals were challenged with a high-starch diet for 7 days (stage 3). In stage 1, absolute and relative DM intake and digestibility were higher for HS (P ≤ 0.03), as was BW (tendency, P = 0.09). Moreover, DM, organic matter and CP digestibility, reticulorumen (RR) tissue mass (g/kg BW), papillae dimensions, rumen epithelium and stratum corneum thickness, number of balloon cells, expression of monocarboxylate transporter 1, putative anion transporter 1 (PAT1) and acetyl-CoA acetyltransferase 2 in rumen epithelium were or tended to be greater, whereas RR pH, RR digesta mass, expression of ten-eleven translocation 1 and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) in the rumen epithelium was or tended to be less for HS (P ≤ 0.09). In stage 2, BW was higher (P ≤ 0.01) and absolute DM intake tended to be higher for HS (P = 0.06), but relative DM intake was higher for HF (P = 0.01). Only minor differences in investigated parameters of RR development and function were observed. In stage 3, the stratum corneum was thicker for HS, whereas the expression of PAT1 and histone deacetylase 3 was higher (P ≤ 0.03) and HMGCS1 tended (P = 0.08) to be higher for HF. Moreover, in stages 2 and 3, plasma urea was higher for HF (P ≤ 0.01). Diet fed early in life had a long-term impact on BW, feed intake and plasma urea, but no long-term impact on nutrient digestibility, digesta passage or global DNA methylation in rumen epithelium. Most of the effects on rumen epithelium function were revealed only after a dietary challenge later in life. These results indicate that early diet affects the response of the rumen epithelium to nutritional changes later in life.

Acute kidney injury (AKI) is a severe complication of burn trauma and is associated with significantly increased mortality. Resveratrol (RES) has shown therapeutic potential in AKI, yet its role in burn-induced AKI, particularly through the modulation of succinylation, remains unclear. This study aimed to investigate the protective effects of RES and the underlying molecular mechanisms in a burn-related AKI model. In vivo, AKI was induced in Sprague-Dawley rats by exposing the dorsal skin to boiling water, while in vitro, human kidney proximal tubular (HK2) cells were stimulated with lipopolysaccharide (LPS) to mimic inflammatory injury. The therapeutic efficacy of RES was assessed by measuring renal function parameters, inflammatory cytokine levels, and kidney injury biomarkers, supported by histopathological and ultrastructural examinations. In vitro, the effects of RES were evaluated through cell viability, apoptosis, and mitophagy assays. Mechanistic insights were obtained using molecular docking, surface plasmon resonance (SPR), western blotting, immunoprecipitation (IP), and co-immunoprecipitation (Co-IP). RES treatment significantly reduced blood urea nitrogen (BUN), serum creatinine (SCr), pro-inflammatory cytokines, and kidney injury molecule-1 (KIM-1) levels, attenuated renal tubular damage, and improved mitochondrial and autophagosomal ultrastructure in burned rats. In LPS-stimulated HK2 cells, RES inhibited apoptosis and promoted mitophagy. Mechanistically, RES upregulated SIRT5 expression, which decreased global succinylation levels and enhanced ATG3 protein stability via K9 desuccinylation. Notably, ATG3 knockdown abrogated the renoprotective effects of RES in both in vivo and in vitro models. Collectively, these findings demonstrate that RES upregulates SIRT5 and inhibits ATG3 succinylation, thereby stabilizing ATG3 and promoting mitophagy, which collectively ameliorate burn-induced AKI.

Type 2 diabetes mellitus (T2DM) complicated by chronic kidney disease (CKD) is associated with persistent hyperglycemia, progressive renal impairment, systemic inflammation, and an increased risk of adverse clinical outcomes. Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists have shown metabolic and cardiorenal benefits, but clinical evidence regarding their combined use in patients with T2DM and CKD remains limited. This retrospective observational study included 126 patients with T2DM complicated by CKD who were treated at our hospital between March 2023 and July 2024. Patients were identified through a review of electronic medical records and the application of predefined eligibility criteria. Treatment groups reflected the actual regimen documented in the medical record rather than random allocation. The final analytic cohort comprised 42 patients in each group; the equal group size reflected the eligible records with complete baseline and 8-week follow-up data available in each treatment category during the study period rather than a prospective 1:1:1 enrollment target. The treatment duration was 8 weeks. Glycemic indices, renal function-related parameters, inflammatory markers, clinical response, and recorded adverse events were compared among the 3 groups. After 8 weeks of treatment, fasting plasma glucose, 2-hour postprandial plasma glucose, hemoglobin A1c, blood urea nitrogen, serum creatinine, 24-hour urinary protein, erythrocyte sedimentation rate, interleukin-6, and high-sensitivity C-reactive protein were significantly reduced in all 3 groups compared with baseline. The combination group showed greater short-term reductions in glycemic indices, renal function-related parameters, and inflammatory markers than either monotherapy group. The overall clinical response rate was significantly higher in the combination group than in the dapagliflozin or semaglutide group. In patients with T2DM complicated by CKD, semaglutide combined with dapagliflozin was associated with greater short-term improvements in glycemic control, inflammatory markers, and renal function-related indicators, as well as a higher exploratory clinical response rate, than either monotherapy. No increase in recorded adverse events was detected during 8 weeks of treatment. Because of the retrospective design, modest sample size, and short observation period, these findings should not be interpreted as demonstrating definitive long-term renal benefit or equivalent long-term safety. Further large-scale prospective studies with standardized renal outcomes are required.

Nanopolysaccharides (NPSs) constitute a rapidly advancing class of biodegradable and biocompatible nanomaterials with strong potential to support sustainable, climate-resilient agriculture. NPSs exhibit high surface area, tunable surface chemistry, and enhanced interactions with biological interfaces, enabling multifunctional roles across soil-plant-microbe systems. This review provides a function-guided synthesis of recent advances in NPS-based agricultural applications, structured around ten interconnected functional domains. These include: (i) structural classes of NPSs and their surface-chemistry-driven functionality; (ii) soil improvement and moisture regulation; (iii) slow and controlled release of mineral fertilizers (e.g., NPK, urea, ammonium and phosphate salts); (iv) foliar delivery for nutrient uptake and stress mitigation; (v) direct antibacterial and antifungal activity against major phytopathogens; (vi) antiviral strategies, including nano-enabled RNA interference delivery; (vii) nano-loading and targeted delivery of agrochemicals, micronutrients, and botanical actives; (viii) induction of plant defense and immune priming; and (ix) encapsulation and nanocoating of agriculturally important microbial inoculants to enhance survival, controlled release, and field performance; and (x) seed nanopriming for improved germination, stress resilience, and early vigor. Emphasis is placed on structure-function relationships linking nanoparticle size, surface charge, crystallinity, functional group density, and cross-linking chemistry to agronomic outcomes, providing a framework for rational design of next-generation NPS-based agricultural formulations.

Therapeutic for Alzheimer's disease (AD) remains a pressing medical challenge in the field of neuroscience. Natural compounds with structural diversity and multi-target regulatory properties have attracted increasing attention for the treatment of complex neurodegenerative disorders. ‌Fraxetin, previously identified through computer-aided virtual screening, C. elegans assays, and in vitro cellular models as a potential anti-AD natural compound, was further investigated in this study using established in vivo and in vitro systems to evaluate its efficacy in ameliorating cognitive function and elucidate underlying mechanisms. A sporadic AD mouse model was established by intracerebroventricular injection of STZ (3 mg/kg). Fraxetin (3, 10, and 30 mg/kg/day, po.) was administered until the mouse sacrifices. Cognitive performance was evaluated using the novel object recognition, passive avoidance, and Morris water maze tests. STZ induced cerebral energy metabolism disturbances accompanied by mitochondrial dysfunction, neuroinflammation, oxidative stress, neuronal and synaptic loss, and cholinergic system impairment. ‌Behavioral tests confirmed that fraxetin ameliorated cognitive deficits in STZ-induced mice. Further studies revealed that fraxetin preserved mitochondrial structural integrity and enhanced mitochondrial biogenesis, accompanied by upregulation of the Sirt1/PGC-1α/Nrf1/TFAM pathway. In parallel, fraxetin attenuated microglial overactivation and neuroinflammatory responses. Consistently, in LPS-stimulated BV2 microglial cells, fraxetin inhibited nitric oxide and inflammatory mediator release, which was associated with modulation of the TLR2/MYD88/NF-κB signaling pathway, while restoring cellular bioenergetic status, indicating coordinated regulation of inflammation-associated metabolic dysfunction. Importantly, fraxetin attenuated neurodegenerative alterations in STZ-treated mice, as evidenced by reduced neuronal loss and synaptic degeneration. These effects were associated with activation of the BDNF/TrkB/ERK/CREB neurotrophic pathway and inhibition of acetylcholinesterase activity, supporting preservation of synaptic and cholinergic function. This study provides experimental evidence supporting fraxetin as a promising natural multi-target candidate for the intervention of AD.

The electronic properties of active M(O)OH catalysts can be effectively modified by tailoring the characteristics of their corresponding precatalysts. Herein, we report a coordination site-modulated precatalyst to access active catalysts for efficient electrocatalytic urea oxidation in an anion exchange membrane (AEM) electrolyzer. A two-dimensional NiFe-coordination polymer (NiFe-2D) was constructed via selective site engineering using hydrazine. Upon electrochemical reconstruction, NiFe-2D was transformed into an active Fe-Ni(O)OH catalyst (AC-2D). X-ray absorption spectroscopy (XAS) confirmed the changes in the coordination and electronic environment of AC-2D with a tuned spin state. Remarkably, AC-2D delivered a current density of 100 mA cm[-2] at 1.50 V vs. RHE for the oxygen evolution reaction (OER) and 1.40 V vs. RHE for the urea oxidation reaction (UOR). AC-2D also delivered outstanding performance in an AEM electrolyzer, achieving a current of 4 A at 2.9 V cell voltage and maintaining operation for over 8 days for UOR-assisted water splitting. In situ electrochemical impedance spectroscopy (EIS) and kinetic analysis suggested facile charge transfer during OER and UOR in AC-2D. In situ Raman studies revealed that Ni[4+] species were identified as the main active centers for OER, while Ni[3+] species served as the catalytic sites for UOR.

The development of hemodialysis membranes capable of simultaneously achieving efficient toxin removal and excellent hemocompatibility remains a major challenge. In this study, a novel dual-layer nanofibrous dialysis membrane was fabricated by combining a solution-electrospun polyurethane-oleic acid-polyethylene glycol (PU-OLE-PEG) top layer with a melt-electrospun polypropylene/zeolite (PP/Zeo) bottom layer. The PU-OLE-PEG layer was designed to enhance hydrophilicity and blood compatibility, while the PP/Zeo layer provided selective adsorption of uremic toxins. The resulting membranes exhibited a molecular weight cut-off of 22-25 kDa, enabling the selective removal of middle-molecular-weight toxins while retaining essential proteins. The 10PP/Zeo-Zeo-ME-PU-OLE-PEG-SE membrane demonstrated the highest adsorption capacity for creatinine (47 ± 5.3 mg g[-1]) and removal efficiencies of 58 ± 5.6% for urea, 65 ± 6.5% for creatinine, and 71 ± 6.8% for β2-microglobulin (β2-MG). Under in vitro simulated dialysis conditions, high recovery of bovine serum albumin (BSA, 98 ± 9.5%) was achieved, indicating effective preservation of valuable proteins. Hemocompatibility studies revealed hemolysis ratios below 1%, markedly reduced protein adsorption (0.0023 ± 0.004 mg mL[-1]), low thrombin-antithrombin complex formation, prolonged activated partial thromboplastin time (35.8 ± 3 s), and minimal platelet adhesion. Furthermore, the membranes exhibited excellent cytocompatibility, with cell viabilities exceeding 90%, favorable cell attachment. These findings demonstrate that the synergistic integration of a hemocompatible PU-OLE-PEG layer and a zeolite-containing adsorption layer provides an effective strategy for developing next-generation dialysis membranes with potential applicability in wearable artificial kidney systems.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in various plastic items and is hazardous for the environment with significant nephrotoxic potential. Edaravone is a potent anti-oxidant that strongly scavenges the free radicals and protects the cells against oxidative stress. The objective of the present study was to examine the ameliorative potential of edaravone against DEHP-induced nephrotoxicity via targeting oxidative stress and ER stress-related proteins. Twenty-four male albino Wistar rats were randomly divided into four groups. The control group received corn oil orally for 28 days. The DEHP group received DEHP (500 mg/kg, p.o.) for 28 days. Additionally, two treatment groups received 500 mg/kg DEHP for 28 days and edaravone (5 and 10 mg/kg) for the last 14 days (Days 15 to 28). On the 29th day, animals were euthanized, and blood and kidney samples were collected. The renal function test, oxido-nitrosative stress parameters, and histopathology analysis were performed along with the western blotting test. Findings revealed that DEHP significantly increased levels of BUN, creatinine, and urea along with a substantial reduction in GSH levels and an increase in MDA and nitrite levels. The DEHP group also showed upregulated protein levels of GRP78, CHOP, and caspase-12. These alterations were accompanied by histological damage. Edaravone treatment alleviated DEHP-induced renal injury by modulation of oxidative stress and ER stress-related markers. These findings give us a mechanistic insight on how edaravone can regulate ER stress-related proteins in DEHP-induced nephrotoxicity and provide its ameliorative effect.