Yangyin Tongnao Granules (YYTN) is a contemporary traditional Chinese medicine compound preparation that has proven effective in the treatment of cerebral ischemia-reperfusion injury (CIRI) following ischemic stroke. However, the chemical composition of YYTN remains uncharacterized, which has impeded its pharmacological research progress and clinical utilization. To address this, an analytical strategy based on ultra-high performance liquid chromatography (UHPLC) coupled with Q-Exactive mass spectrometry was developed to evaluate the quality consistency and identify the chemical constituents of YYTN. Using this approach, a total of 242 compounds were tentatively identified, and five major components were identified using UHPLC-UV with a validated method for linearity, precision, repeatability, stability, and recovery. Furthermore, in vitro free radical scavenging assays revealed that YYTN exhibited potential DPPH, ABTS˙+ and hydroxyl radical scavenging capacities. In particular, puerarin, 3'-hydroxypuerarin and 3'-methoxypuerarin demonstrated superior radical scavenging activity, potentially serving as the primary marker compounds for YYTN quality control. The present study successfully established a comprehensive strategy for the chemical characterization and quality assessment of YYTN, which not only elucidates the material basis of YYTN's efficacy against oxidative stress but also provides a robust analytical foundation for its further pharmacological investigation and quality control in clinical applications.
Mid-chain depolymerization enables chemical recycling of conventional plastics with carbon-carbon backbones into high-purity monomers under mild conditions and without any weak bonds typically installed by controlled radical polymerization. However, current reports of mid-chain depolymerization either suffer from poor reaction yields or rely on an excess of chlorinated solvents to generate only a small fraction of chlorinated radicals with corrosive byproducts. Herein, we introduce a chlorine-free photothermal mid-chain depolymerization methodology, which proceeds through a distinct oxygen-centered radical pathway. In the presence of ppm concentrations of anthraquinone, an efficient photocatalyst, up to 97% monomer can be successfully regenerated, while varying the catalyst loading allows the depolymerization rate to be modulated on demand. Notably, a wide range of commercial materials, such as Plexiglas, acrylic tubes, and light guide plates, can undergo efficient depolymerization, while temporal control could also be demonstrated via iterative "on/off" cycles.
Uncontrolled non-compressible visceral hemorrhage and irregular wet wounds remain difficult to manage because many hemostatic powders lack robust wet adhesion and mechanical integrity under continuous blood flow, leading to displacement and rebleeding. Here, a multifunctional, natural-polysaccharide hemostatic powder (CSO) is engineered from carboxymethyl chitosan (CMCS), dopamine-grafted sodium alginate (SA-DA), and oxidized guar gum (OGM), and the mixture is activated by EDC/NHS to enable rapid, in situ self-crosslinking. Upon contact with wound, the CSO powder rapidly absorbs tissue exudate or blood, concentrates coagulation factors and blood cells, and undergoes in situ self-crosslinking to form a stable, adherent hydrogel that seals the wound for rapid hemostasis. The incorporated dopamine moiety endows the hydrogel with potent free radical scavenging ability, effectively mitigating oxidative stress and inflammation to accelerate wound healing. In addition, the CSO powder exhibits notable antimicrobial activity, helping to prevent post-hemostatic infection. In rat tail-amputation and liver-incision models, CSO achieves rapid hemostasis with markedly reduced blood loss, and further accelerates infected full-thickness skin repair by dampening inflammation and improving collagen remodeling. These features, together with favorable biocompatibility and practical applicability, position CSO as a promising powder-to-hydrogel platform for emergency and surgical hemostasis with improved healing outcomes.
This retrospective cohort study evaluated the clinical value and short-term prognostic outcomes of cytoreductive radical prostatectomy using the cytoreductive radical prostatectomy (CRP) technique combined with pharmacotherapy in patients with oligometastatic prostate cancer (OPC). Consecutive OPC patients treated between January 2023 and December 2023 were included. According to the actual treatment received, patients were assigned to a pharmacotherapy group (control) or a CRP technique plus pharmacotherapy group (study), with 47 patients in each group. All patients were followed for 24 months. Baseline demographics and clinical variables were compared between groups. Treatment response was assessed using Prostate Cancer Working Group 3 criteria. Serum prostate-specific antigen levels were recorded at baseline and at 2, 6, and 12 months. Quality of life, pain, and anxiety were evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, visual analog scale, and generalized anxiety disorder-7, respectively. Complications were graded by the Clavien-Dindo classification. Survival outcomes were analyzed using Kaplan-Meier methods. Baseline characteristics were comparable between groups. The CRP combined with intensified systemic therapy showed a higher proportion of complete/partial response and a lower proportion of progression than the pharmacotherapy group. Between-group differences in prostate-specific antigen were evident at the 2-month assessment. Posttreatment European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 scores were higher, whereas visual analog scale and generalized anxiety disorder-7 scores were lower, in the combined-treatment group. Complications were infrequent and limited to grade I events, with no between-group difference. No deaths occurred during follow-up; progression-free survival was longer in the combined-treatment group. Cytoreductive radical prostatectomy using the CRP technique combined with pharmacotherapy was associated with improved short-term disease control and progression-free survival without an apparent increase in complications in OPC.
High-risk non-muscle-invasive bladder cancer (HRNMIBC) has a variable prognosis, managed predominantly by local surgical resection and intravesical Bacillus Calmette-Guérin (BCG), or radical cystectomy (RC). Current treatments are poorly tolerated, have supply limitations and often fail to control the disease. Treatments overcoming these limitations are needed to improve HRNMIBC outcomes. Many novel agents have been approved in recent years (including systemic pembrolizumab, nogapendekin alfa inbakicept-pmln, N-803), but long-term efficacy is unknown. Given advanced bladder cancer findings, we believe direct intravesical administration of atezolizumab may aid with managing HRNMIBC or muscle-invasive bladder cancer in patients who are ineligible for cisplatin-based neoadjuvant chemotherapy. The INtraVESical immunoTherapy (INVEST) trial is a UK-based, open-label, non-randomised, single-centre, Phase Ib dose escalation, window of opportunity study exploring atezolizumab administration via intravesical routes (passive instillation and direct injection [sub-urothelial]) in patients with bladder cancer with all stages undergoing RC. For both routes, an initial dose confirmation stage will determine toxicity and recommended atezolizumab dosage, followed by a dose expansion stage to further evaluate safety and toxicity at the recommended dose. We aim to investigate safety (primary) and preliminary activity (secondary) of intravesical atezolizumab delivered by passive instillation and direct injection into the tumour/bladder wall in patients with bladder urothelial cell carcinoma prior to RC. Primary endpoints include dose limiting toxicities and adverse events. Secondary endpoints include progression-free survival, pathological complete response rate and treatment compliance. Exploratory endpoints include pharmacokinetic profile (assessed by serum and urine concentrations at prespecified timepoints), spatial analysis of atezolizumab distribution within RC tissue by imaging mass spectrometry and overall survival. Atezolizumab will be administered intravesically by either passive instillation or direct injection into the tumour/bladder wall. Cohorts will receive either 600 mg or 1200 mg doses administered as a single dose or as multiple doses (weekly for 3-6 weeks). International Standard Randomised Controlled Trial Number: ISRCTN15842444, registered 2 December 2022.
Nonoxide electrocatalysts hold great promise for high-efficiency seawater oxidation, yet their practical application is hindered by the inevitable surface reconstruction and pronounced corrosion under high anodic potentials. Herein, we solve this longstanding challenge by developing a rational anionic ligand passivation strategy that stabilizes phosphide lattices against oxidative degradation while preserving inherent electrocatalytic activity. Leveraging Lewis acid-base interactions, we grow an ultrathin, undercoordinated TiOx overlayer on a FeNiP (FNP) support. This overlayer withdraws electrons from lattice phosphorus, downshifts the P p-band center, and thermodynamically stabilizes the entire anionic sublattice against oxidative leaching. The oxidation-resistant scaffold further enables the anchoring of atomically ordered Ir arrays with a well-defined interatomic spacing of ∼2.8 Å, promoting direct O-O radical coupling via the oxide pathway mechanism and effectively circumventing the corrosive lattice oxygen route. Operando spectroscopy and 18O isotope tracing confirm fully reconstruction-free OER behavior with negligible lattice oxygen participation. The as-developed TiIr@FNP catalyst achieves ultralow overpotentials (only 310 mV at 1 A cm-2), operates stably for over 1200 h in alkaline seawater, and maintains near-unity Faradaic efficiency. The work demonstrates a generalizable strategy for designing durable, high-performance nonoxide anodic electrocatalysts under industrially relevant conditions.
The efficient dewatering and the deep removal of obstinate emerging contaminants (e.g., perfluorooctanoic acid (PFOA) and antibiotic resistance genes (ARGs) remain critical bottlenecks in current sludge management. Persulfate advanced oxidation processes (PS-AOPs) offer great potential in sludge conditioning and pollutant mineralization, however their efficacy strongly hinges on water-organics binding capacity, solid-liquid interface reactivity, radical generation routes, and iron cycling rate. In this study, a pair of high specific-surface helix-leaf electrodes (a total of 5481.8 mm2 ) was designed and integrated into Fe2+-activated persulfate oxidation processes to drive Fe2+ re-generation and highly active radicals formation. Under the optimal operational conditions of 30 V and 2/1.6 mmol Fe2+-S2O82-/g-VS, the sludge achieved an 87 % decrease in capillary suction time (CST) and low moisture content of 52.2 % after pressure filtration. More importantly, such hybrid option produced a 91.03 % degradation of PFOA from total EPS and an exponential elimination (above 90 %) of ARGs. Mechanistically, the electro-Fe2+-activated persulfate oxidation encouraged the continuous production of highly active radicals (·OH, SO4·⁻, ¹O2, and ·O2⁻) via ensuring efficient Fe³⁺/Fe²⁺ cycling driven by a robust electro-reduced circumstance. These radicals catalyzed the degradation of extracellular polymeric substances (EPS) and microbial cell rupture, notably reconfiguring protein secondary structures-characterized by the reduction of stable α-helix and β-sheet proportions to 17.79 % and 14.44 %, respectively. This profound structural transformation disrupted the hydrophilic gel matrix, thereby significantly enhancing sludge dewaterability. Concurrently, PFOA was destructed via direct free radical attacks on its molecular structure, while ARGs were eliminated primarily through the unwinding and subsequent cleavage of DNA strands. The research results will provide theoretical support and technical paradigms for the "reduction and emerging pollutant control" of sludge, and promote the green and low-carbon transformation in the field of waste treatment.
Cardiovascular diseases are more prevalent and have created an alarming situation worldwide. Nutraceuticals are a class of nutrients that include common foods and fruits for managing various diseases. This paper adopts a narrative review approach, focusing on recent advances in nutraceutical-based interventions and nanotechnology applications for cardiovascular diseases. Extensive literature research on bioactive nutraceuticals was conducted using databases, such as WOS, PubChem, and Scopus, suggesting their potential for target validation and disease identification. Different keywords were used for searching database: Cardiovascular diseases, Nutraceuticals, Antioxidants, Nanoformulations, Targeted drug delivery. Nutraceuticals play a significant role in reducing cardiovascular risk through antioxidant and free-radical scavenging mechanisms. Regular adherence to medicinal foods, such as nutraceuticals, improves health and significantly reduces the risk of chronic diseases. Several free radicals are generated during physiological and pathological reactions in the body, which are responsible for the degradation of organs. Nutraceuticals scavenge reactive oxygen species via antioxidant mechanisms. Various novel nanotechnology approaches have been employed to enhance the therapeutic potential of nutraceuticals. Furthermore, nanotechnology has opened new doors for improving the bioavailability, stability, and targeted delivery of nutraceutical compounds. Nanoformulations, such as liposomes, niosomes, and nanoparticles, are employed to address issues of bioavailability, penetration, solubility, and therapeutic efficacy. It offers researchers cost-effective treatment approaches to improve cardiovascular outcomes. Novel approaches in the field of nutraceuticals possess significant activity in the management of cardiovascular diseases by enhancing stability, bioavailability, solubility, and therapeutic efficacy. Future research should focus on well-designed clinical studies and standardized nanoformulation protocols to facilitate clinical translation.
Antioxidant activity is commonly discussed in fields like chemistry, biology, nutrition, and medicine, but it is often viewed in functional terms rather than as a process controlled by basic radical kinetics. In many cases, antioxidant efficiency is described within a simple scavenging model, where antioxidants mainly intercept reactive radicals stoichiometrically and are then irreversibly consumed. While this model highlights an important aspect of antioxidant behavior, it does not fully capture the complexity of oxidative processes.In this review, antioxidant chemistry is examined as a competitive reaction network where chemical repair and regeneration pathways play a key mechanistic role. These pathways allow for the restoration of radical intermediates before damage terminates and enable the recycling of oxidized antioxidant species, thus extending antioxidant activity beyond just radical trapping. In this context, the identity of radicals, branching ratios, oxygen-dependent competition, and radical lifetimes are crucial factors that determine whether oxidative processes lead to propagation, termination, or repair.Special focus is given to phenolic antioxidants and to reaction networks involving the hydroperoxyl/superoxide couple (HO2•/O2•-). Although superoxide is often described as a weak oxidant or a precursor to more reactive species, its reactivity depends heavily on conditions. Under the right kinetic conditions, superoxide can participate in reductive pathways that contribute to antioxidant regeneration and radical repair.By combining insights from radiation chemistry, electrochemistry, and computational kinetics, this review highlights chemical repair as an important mechanistic component of antioxidant activity and offers a unified framework for understanding antioxidant function in various chemical and biological settings.
Radical fluoroalkylation via electron donor-acceptor (EDA) complex photochemistry stands out as a particularly attractive approach, owing to its mild conditions and the absence of an external metal photocatalyst or organic dye. Fluoroalkyl sulfones, valued for their stability, accessibility, and structural tunability, have emerged as versatile precursors for radical fluoroalkylation. Herein, we present a photocatalyst-free and straightforward method for direct fluoroalkylation through an EDA complex, utilizing inexpensive iodide anion as an electron donor and fluoroalkyl sulfones as acceptors. Upon visible light irradiation, the EDA complex undergoes single-electron transfer (SET) to generate fluoroalkyl radicals, which subsequently react with a diverse array of silyl enol ethers with high efficiency. The method features mild reaction conditions, broad functional group compatibility, and an extensive substrate scope that encompasses bioactive molecules and sterically demanding architectures. Mechanistic investigations indicate the involvement of an iodide-mediated EDA complex and support the proposed radical-generation pathway. This work establishes a practical and sustainable platform for fluoroalkylation, underscoring the utility of iodide in EDA-based photochemistry and broadening the scope of radical synthetic methods.
The introduction of consolidation durvalumab after chemoradiotherapy (CRT) for unresectable stage 3 non-small cell lung cancer (NSCLC), as established by the PACIFIC trial, has transformed survival outcomes. However, its impact remains uncertain in populations characterised by high levels of socioeconomic deprivation, multimorbidity, and historically poorer cancer outcomes compared to other regions. This retrospective observational cohort study included all patients with stage III unresectable NSCLC who received radical (chemo)radiotherapy, between 01/01/2017 - 31/12/2022. Clinical outcomes were compared across treatment groups: radiotherapy alone, sequential CRT, concurrent CRT, and concurrent CRT followed by consolidation durvalumab. Multivariate Cox proportional hazards regression was employed to identify factors associated with outcomes. 656 patients with stage III NSCLC treated with radical radiotherapy were included. The median age was 69 years, and 54% were male. Most patients had a PS of 0 or 1 (81%), the median Charlson Comorbidity Index (CCI) was 3 (2 - 5) and 62% resided in the most deprived socioeconomic quintiles. Radiotherapy alone was the most common treatment (59%). Administration of radiotherapy alone appeared to be influenced by older age and higher performance status, and not by deprivation or objective functional measurements of multimorbidity (i.e. CCI). Reflex biomarker testing improved over time, while the use of sequential CRT declined, and the rates of concurrent CRT, with or without durvalumab, increased.Multivariate regression demonstrated that patients receiving concurrent CRT plus durvalumab achieved superior 2 year progression-free survival (PFS) compared with concurrent CRT alone (HR 0.51, 0.33 - 0.78, p=0.002). Patients treated with radiotherapy alone had the poorest 2-year OS and PFS, independent of other confounders. Delivering a full year of durvalumab was challenging, with 55% of patients who started durvalumab being unable to complete treatment. However, 53% of those who discontinued durvalumab early remained disease-free at 2 years. This study reinforces the progression-free survival benefit of consolidation durvalumab in patients able to undergo concurrent CRT within a large real-world cohort. Although the cohort was socially deprived and comorbid, the high proportion of patients receiving radical radiotherapy alone, and their associated poorer survival outcomes, were not explained by this, revealing a mismatch between objective fitness and clinical decision making, The associated poorer survival outcomes from radiotherapy alone highlights the urgent need to optimise treatment strategies for such patients.
Red blood cells (RBCs) are the most abundant cells in peripheral blood and perform critical functions including oxygen and carbon dioxide transport, acid base buffering, regulation of hemorheology, and modulation of immune signaling. Due to their high content of hemoglobin and labile iron, prolonged exposure to high oxygen tension, membrane enrichment with polyunsaturated fatty acids, and the absence of both nucleus and mitochondria, mature RBCs have limited capacity for damage repair and protein re-synthesis, making them highly susceptible to attack by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Hydrogen peroxide (H2O2) and 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) are the two most commonly used inducers in the in vitro models of RBC oxidative injury: H2O2 primarily generates hydroxyl radicals via hemoglobin/ferrous ion-dependent Fenton reactions, simulating acute oxidative stress. AAPH releases peroxyl radicals upon thermal decomposition, mimicking persistent lipid peroxidation in cell membranes. Curcumin, a representative polyphenolic compound derived from turmeric, exerts multiple effects including free radical scavenging, metal ion chelation, membrane stabilization, anti-inflammatory activity, and regulation of redox homeostasis. This review systematically summarizes the pathological basis of RBC oxidative damage and the protective effects of curcumin on membrane systems, antioxidant defenses, morphology, and function, based on the core evidence chain "H2O2/AAPH-RBCs-curcumin", integrating recent experimental findings on H2O2, AAPH, blood storage-induced injury, and curcumin formulations. It emphasizes that mature RBCs lack nuclei and mitochondria, and therefore mechanisms such as Nrf2/ARE signaling, HO-1 induction, mitochondrial apoptosis, caspase cascades, and inflammasome activation should not be directly equated with transcriptional regulatory pathways within mature RBCs, but rather interpreted as indirect evidence originating from nucleated cells, erythroid progenitors, or the blood microenvironment. The article further proposes that future research should focus on standardized RBC models, physiologically relevant dosages, nanodelivery systems, and translational applications in blood storage, to facilitate the transition of curcumin's in vitro antioxidant evidence into clinical transfusion medicine and precision nutritional interventions.
Background/Objectives: Data on the value of tumor debulking surgery are scarce. We aimed to examine whether tumor debulking surgery followed by non-surgical treatment (cases) improves survival compared to non-surgical treatment alone (controls) in patients with head and neck cancer (HNC). Methods: We performed a systematic review of studies published in the databases PubMed, Scopus and Cochrane Central Register of Controlled Trials up to 10 December 2024. Studies evaluating tumor debulking surgery followed by non-surgical treatment and reporting survival (local recurrence, disease-free survival or overall survival) in subjects with HNC were included; case reports were excluded. We assessed the quality of observational studies with the Newcastle-Ottawa Scale. Results: Among 11 retrospective small studies, three case-control studies (one of high quality, i.e., 7/9, and two of moderate quality, i.e., 6/9 and 5/9) suggested longer survival in 72 cases with predominantly squamous cell carcinoma (SCC) than in 40 controls with predominantly SCC. However, these survival benefits cannot be attributed solely to tumor debulking surgery, as confounding by indication is the most likely explanation. In supraglottic laryngeal SCC, one study reported a local recurrence-free survival rate and overall survival of 80% and 88%, respectively, in 25 cases compared with 86% and 77%, respectively, in 24 controls. In sarcomas, local recurrence-free survival was 25%, 65% and 100% for unknown resection margins, wide local excision and radical excision, respectively. Conclusions: The heterogeneous data indicate the need for higher-quality research. It would be interesting to investigate whether an attempt to surgically debulk paranasal sinus tumors while preserving adjacent vital organs (e.g., the orbit and/or brain) should be incorporated into the treatment strategy for patients with extended paranasal sinus squamous cell carcinoma. Tumor debulking surgery did not improve survival in supraglottic laryngeal SCC or head and neck soft tissue sarcomas.
Sex-related differences in kidney cancer incidence and tumor biology are well established; however, their impact on peri‑operative performance and long-term oncologic outcomes after surgery remains incompletely characterized. We evaluated the association between biological sex and surgical, pathological, and oncologic outcomes in a large contemporary cohort. We retrospectively analyzed a prospectively maintained institutional database including patients undergoing partial or radical nephrectomy as primary treatment for kidney cancer at a high-volume tertiary center (1987-2024). Peri-operative outcomes, adverse pathological features, and long-term oncologic endpoints were compared according to biological sex. Multivariable regression models were used to adjust for baseline clinical, surgical, and tumor-related confounders. Survival outcomes were assessed using Kaplan-Meier estimates and Cox proportional hazards models. In addition, a sensitivity analysis restricted to patients treated between 2005 and 2020 (n = 2,227) was performed to evaluate the robustness and contemporary applicability of the findings. Overall, 3,956 patients were included, of whom 30.5% were female. After multivariable adjustment, male sex was independently associated with longer operative time (β: 13, 95% confidence interval [CI] 6.3-19; P < 0.001) and a higher risk of post-operative acute kidney injury (odds ratio [OR] 1.49, 95% CI 1.21-1.84; P < 0.001), but not with major complications, peri‑operative transfusions, or prolonged length of stay (all P > 0.5). From a pathological standpoint, male patients were more likely to harbor high-grade tumors (OR 1.52, 95% CI 1.19-1.96; P = 0.001) and tumor necrosis (OR 1.38, 95% CI 1.10-1.75; P = 0.006). While biological sex was not independently associated with relapse-free, progression-free, or overall survival (all P > 0.1), male patients exhibited a significantly higher risk of progression at unfavorable metastatic sites (hazard ratio 1.78, 95% CI 1.09-2.89; P = 0.02). Importantly, these findings showed consistent directionality and statistical significance in the contemporary surgical era sensitivity analysis. Biological sex emerged as a relevant determinant of peri‑operative outcomes, tumor aggressiveness, and patterns of disease progression in surgically treated kidney cancer patients. Male sex was independently associated with less favorable peri‑operative metrics, adverse pathological features, and a higher risk of progression at unfavorable metastatic sites, although these differences did not independently translate into worse long-term relapse-free, progression-free, or overall survival.
We report a mild, redox-neutral deacylative SN2'-type alkylation of monochloro- and gem-dichlorocyclobutenones with pro-aromatic ketone-derived dihydroquinazolinones enabled by visible light photocatalysis. The method uniquely combines the C-C bond cleavage of unstrained aliphatic ketones with concurrent C-C bond formation via α-selective radical addition to the enone moiety of gem-dichlorocyclobutenones, contrasting β-selective radical addition in Giese-type addition. This base- and oxidant-free method provides efficient access to highly functionalized 4-alkylated α-chlorocyclobutenones. Furthermore, aldehyde-derived pro-aromatic 4-alkyl-1,4-dihydropyrides served as C-radical precursors, enabling the synthesis of 4-alkylated α-chlorocyclobutenones under similar reaction conditions.
Inflammation is a primary driver of skin ageing. Mussel mucin, a naturally occurring anti-inflammatory protein, suffers from inefficient extraction from its natural source. To overcome the yield limitation of natural sources and to verify the biological activity of the recombinant protein, this study employed synthetic biology techniques to efficiently produce and purify the recombinant mussel mucin Mfp151 and subsequently evaluated its anti-inflammatory and skin barrier repair functions. Using human immortalized keratinocytes (HaCaT), human foreskin fibroblasts (HFF-1), and human monocyte leukemia cells (THP-1) as models, we assessed the skin-repairing, antioxidant, and anti-inflammatory effects of Mfp151 via the CCK-8 assay, qPCR, transmembrane resistance measurement, scratch assay, ELISA, and free radical scavenging assays. In vivo validation was conducted with a zebrafish sunburn model. The results demonstrated that Mfp151 significantly promoted cell proliferation (80 μg/mL treatment increased HaCaT cell proliferation by approximately 32%) and migration, while upregulating the expression of key skin barrier genes IVL, OVOL1, and AQP3 by 2.14-3.88 folds. Mfp151 effectively scavenged DPPH and ABTS free radicals while enhancing cellular antioxidant capacity by activating the Nrf2 pathway. Regarding anti-inflammatory effects, Mfp151 significantly suppressed lipopolysaccharide-induced production of pro-inflammatory factors IL-6, TNF-α, and IL-1β (80 μg/mL treatment reduced expression levels to 59.87%-79.12% of that in the model group), while significantly downregulating the expression of key inflammatory mediators COX-2 and iNOS and their downstream product PGE2 (80 μg/mL treatment reduced COX-2, iNOS expression and PGE2 secretion to 48.91%-67.30% those in the model group.) Zebrafish experiments confirmed the significant promotion of Mfp151 on caudal fin repair following sunburn. The data indicate that the recombinant Mfp151 obtained through synthetic biology techniques possesses skin-repairing functions alongside antioxidant and anti-inflammatory activities, thus demonstrating promising application prospects in fields such as anti-ageing cosmetic ingredients and wound dressings. 炎症是导致皮肤衰老的主要诱因，贻贝黏蛋白是一种天然来源的抗炎蛋白，但其天然提取效率低下。为突破天然来源的产量限制，并验证重组蛋白的生物活性，本研究通过合成生物学技术高效制备并分离纯化得到重组贻贝黏蛋白Mfp151，并对其抗炎和皮肤屏障修复功能进行评价。以人永生化角质形成细胞(human immortalized keratinocytes, HaCaT)、人包皮成纤维细胞(human foreskin fibroblasts, HFF-1)及人单核细胞白血病细胞(human monocytic leukemia cells, THP-1)为模型，采用细胞计数试剂盒-8 (cell counting kit-8, CCK-8)、反转录实时荧光定量聚合酶链式反应(reverse transcription quantitative real-time polymerase chain reaction, RT-qPCR)、跨膜电阻测量、划痕实验、ELISA及自由基清除等方法，评估Mfp151在修复、抗氧化及抗炎方面的功效，同时利用斑马鱼晒伤模型进行体内验证。结果表明，Mfp151可显著促进细胞增殖(80 μg/mL处理使HaCaT细胞增殖率提高约32%)与迁移，并上调皮肤屏障关键基因IVL、OVOL1和AQP3的表达(相比正常对照组，上调2.14-3.88倍)。Mfp151能有效清除1,1-二苯基-2-三硝基苯肼(1,1-diphenyl-2-picrylhydrazyl, DPPH)和2,2′-联氮-双(3-乙基苯并噻唑啉-6-磺酸)[2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS]自由基，并通过激活Nrf2通路增强细胞抗氧化能力。在抗炎方面，Mfp151能有效抑制脂多糖(lipopolysaccharide, LPS)诱导的THP-1细胞产生促炎因子白细胞介素-6 (interleukin-6, IL-6)、肿瘤坏死因子-α (tumor necrosis factor-alpha, TNF-α)和白细胞介素-1β (interleukin-1β, IL-1β) (80 μg/mL处理使其表达水平降低至模型组的59.87%-79.12%)，并显著下调关键炎症介质环氧合酶-2 (cyclooxygenase-2, COX-2)与诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)的编码基因表达及其下游产物前列腺素E2 (prostaglandin E2, PGE2)的水平(80 μg/mL处理使COX-2和iNOS表达及PGE2的分泌降低至模型组的48.91%-67.30%)。斑马鱼实验证实其可显著促进晒伤后的尾鳍修复。本研究结果表明，通过合成生物学技术获得的重组Mfp151蛋白具有促进皮肤修复的功能和抗氧化抗炎活性，在皮肤抗衰化妆品原料及创面敷料等领域展现出良好的应用前景。.
Catalytic antioxidant materials are crucial in medical research, yet current research efforts focus mainly on coordination environments while overlooking physical structures, such as porosity and surface area, a limitation that hinders free radical interaction and reduces antioxidant efficacy. Herein, a conceptual framework is proposed for the development of mesoporous metal-polyphenolic artificial enzymes (MPAEs) (mPDA-Cu), effectively addressing these limitations by integrating catalytically activate centers and maximizing the accessible surface area. The pore confinement achieved by intermediate pore engineering inhibits the densification of active centers and enhances the hydrogen atom transfer and electron transfer processes. Notably, mPDA-Cu with a mesoporous structure displays superior catalase-like (CAT-like) activity, efficiently decomposing H2O2, which is approximately 3.4-fold higher than that of non-mesoporous aPDA-Cu, and its oxygen generation capacity is enhanced by ∼2.9 times. Owing to its CAT-mimetic activity, mPDA-Cu can effectively decrease intracellular ROS levels and facilitate oxygen production, thereby mitigating hypoxia induced by oxidative stress. This study establishes that engineering mesoporous MPAEs is key for enhancing their catalytic antioxidant properties, which offers a straightforward and efficient platform for the development of high-performance, biocompatible antioxidant nanocatalysts aimed at treating oxidative stress-related pathologies.
Chordomas and chondrosarcomas of the skull base are rare, locally aggressive tumors that pose significant therapeutic challenges due to their proximity to critical anatomical structures. While maximal safe surgical resection remains the cornerstone of management, the infiltrative nature of these tumors often precludes radical excision, necessitating adjuvant radiotherapy. Given their relative radioresistance, high-dose radiotherapy exceeding 70 Gray Relative Biological Effectiveness (GyRBE) is required to achieve durable local control. This study evaluated long-term outcomes and toxicity following pencil beam scanning (PBS) proton therapy in patients with skull base chordoma and chondrosarcoma. We retrospectively analyzed 76 patients (50 chordoma, 26 chondrosarcoma) treated with curative-intent PBS between 2016 and 2020. Median prescribed doses were 74.0 GyRBE for chordomas and 70.0 GyRBE for chondrosarcomas. Clinical endpoints included overall survival (OS), local failure-free survival (LFFS), distant metastasis-free survival (DMFS), and toxicity graded according to CTCAE v5.0. At a median follow-up of 70.2 months, 5-year OS, LFFS, and DMFS for the entire cohort were 84.0, 86.9, and 92.7%, respectively. Local control was numerically higher in chondrosarcoma (96.1%) than in chordoma (81.9%; p = 0.116). Tumor contact with the optic apparatus or brainstem was associated with worse OS (p = 0.0034 and p = 0.0151, respectively) and proximity to the optic pathways correlated with poorer local control (p = 0.0182). Grade ≥ 3 late toxicity occurred in 9.2% of patients, predominantly hearing impairment and temporal lobe necrosis. PBS achieves excellent local control and survival with an acceptable safety profile in skull base chordoma and chondrosarcoma. Our findings align with ongoing efforts toward dose intensification, hypofractionation, and particle selection. Moreover, emerging integration of artificial intelligence for contouring, treatment adaptation, and toxicity prediction, along with augmented reality-assisted positioning and patient education, promises to further enhance treatment precision and outcomes. Through long-term follow-up and engagement with international research initiatives, our institution contributes to the global advancement of biologically guided, high-precision radiotherapy for rare skull base malignancies.
The management of cholesterol by using Atorvastatin calcium (ATV) and Ezetimibe (EZE) is often restricted by the fact that they belong to BCS Class II drugs, thus, low aqueous solubility and low systemic bioavailability. The research has created a new pH-responsive hydrogel involving a natural polycationic polysaccharide, chitosan, to increase residence time in the sites of absorption and offer controlled, concurrent delivery of both drugs. The hydrogels were synthesized through a free-radical polymerization process, which entailed dissolving chitosan in aqueous acetic acid, initiation by ammonium persulfate (APS) and addition of acrylic acid (AA) and N,N'-methylene bisacrylamide (MBA) in drops to create a stable 3D cross-linked structure. The numerical optimization was performed with Design Expert software, in which the ratios of components are accurately tuned with the help of the use of the poly equations and 3D response surface plots. This methodology removed hit and trial error leading to a maximized formulation in which the real experimental values, including 87.98% porosity and 98.76% gel fraction, were in good agreement with the software predictions, which confirmed the strength of the design. Findings showed that the internal structure was greatly determined by the formulation parameters; the higher the monomer concentrations, the better the porosity (97.53%) and the gel fraction (97.79%). The system was also very pH-sensitive as it swelled little in acidic environment (pH 1.2) but swelled the most (187.71%) in simulated intestinal fluids (pH 6.8 and 7.2) which allowed the system to dissolve 91.99% of ATV and 90.77% of EZE within 24 h. This mathematically designed platform with dual drug delivery is designed to overcome the drawbacks of a single-drug matrix for cholesterol management and prevent premature leakage from the stomach.
Polycystic ovary syndrome (PCOS), newly named as Polyendocrine Metabolic Ovarian Syndrome (PMOS) is the most common endocrinopathy affecting women of reproductive age, which often leads to infertility due to anovulation and poor oocyte quality. Poor oocyte quality is a major reason for women's infertility in humans and a barrier to efficient assisted reproduction technology (ART) treatment. Supplementation of melatonin, a free radical scavenger, has been reported to show satisfactory results in women undergoing ART. This review investigates whether the endogenous melatonin or supplementation of melatonin impact on oocyte/embryo quality and pregnancy rate in PCOS patients undergoing ART treatment. Articles published between 2010 and 2025 were reviewed to perform a comprehensive search on observational studies and clinical trials that evaluated the use of melatonin in PCOS patients undergoing in vitro fertilization (IVF) or intrauterine insemination (IUI) or intracytoplasmic sperm injection (ICSI). The databases searched included PubMed, Google Scholar, Science Direct, and Cochrane Library. This systematic review indicates that the group that received melatonin had significantly higher clinical pregnancy probabilities than the control group. Similarly, the melatonin administration significantly enhanced the endometrium thickness (p < 0.001) and the chemical pregnancy rate (30% versus 18%, p = 0.012). Additionally, in comparison to the control group that received metformin alone, the group that received melatonin (3 mg) significantly increased the proportion of top-quality embryos (40.3% vs. 29.9%; p < 0.001). According to this systematic review, melatonin significantly improves endometrial thickness, mature oocytes, high-quality embryos, and pregnancy rates, all of which improve ART outcomes in PCOS patients. Because of its safety, affordability, and efficacy, it is a useful supplement to ART procedures. The most popular and well-tolerated dosage is still 3 mg per day, despite variations in research.