1,4-Benzodioxane scaffold is an important active unite in many natural ligans such as haedoxans. Herein, we have achieved synthesis of chiral 1,4-benzodioxane using a linear route. The concise sequence includes several key transformations, such as a Horner-Wadsworth-Emmons (HWE) olefination, Sharpless asymmetric dihydroxylation (AD), epoxidation of sulfonate-diol, and a Mitsunobu reaction for fragment coupling. The crucial chiral 1,4-benzodioxane ring system was efficiently constructed through a Lewis acid-promoted epoxide opening, followed by a second Mitsunobu cyclization. Rieche formylation was utilized for functional group manipulation. A significant tosylate intermediate 13 was successfully crystallized, and its structure was definitively confirmed using X-ray crystallographic analysis. Density Functional Theory (DFT) calculations provided additional insights into the structural and energetic aspects of the synthesis. The present establishes a versatile and stereo controlled method to access the target neolignan scaffold, thereby laying the groundwork for the synthesis and biological evaluation of haedoxan analogues derived from Phryma leptostachya L.

Divergent syntheses of two epimeric nardosinane sesquiterpenoids are achieved through a DABCO-promoted Michael–Aldol cascade, a scaffold-controlled stereochemical diversion, and late-stage divergent functionalizations from a common intermediate.

Glioblastoma multiforme (GBM) remains a lethal brain cancer with poor prognosis, largely due to the limitations of current therapies. Focal adhesion kinase (FAK) is a promising therapeutic target, given its central role in driving GBM progression, invasion, and microenvironment adaptation. While several FAK inhibitors, such as TAE-226, have entered clinical trials, none have achieved approval, underscoring the need for novel, more effective agents. Through a structure-based molecular hybridization strategy that integrated key pharmacophores from TAE-226 and the clinical candidate GSK2256098, a novel series of N-methoxy-2-(pyrimidin-4-ylamino)benzamide derivatives were designed and synthesized. Among the eighteen synthesized compounds, 7h emerged as the most potent compound. It demonstrated superior enzymatic and cellular activity, with FAK inhibitory activity (IC50 = 3.62 nM) and potent anti-proliferative activity against U87-MG glioblastoma cell line (IC50 = 71 nM), outperforming the positive control TAE-226 (IC50 = 4.81 nM and 0.49 µM, respectively). Furthermore, in the PAMPA-BBB assay, the passive permeability (Pe) of 7h reached 25.97 × 10−6 cm∙s⁻1, which was comparable to and slightly higher than TAE-226 (24.80 × 10−6 cm∙s⁻1), suggesting favorable passive permeation potential that warrants further in vivo brain distribution studies. Mechanistic studies in U87-MG cells revealed that compound 7h induced apoptosis and pronounced G2/M cell cycle arrest compared to TAE-226 at equivalent concentrations, suggesting a potent anti-proliferative effect associated with FAK inhibition. In a U87-MG xenograft mouse model, 7h exhibited favorable in vivo dose-dependent antitumor efficacy with this specific model. At 10 mg/kg/day, its tumor growth inhibition (TGI = 54.1

A series of isoquinolone compounds Ia-Iq containing amide moiety were rationally designed and synthesized based-on isoquinolone alkaloids. Their structures were confirmed by 1H NMR,13C NMR and HRMS. Most of the title compounds showed medium to excellent antifungal activity in vitro at 50 mg/L. Especially, the EC50 of Im (13.155 mg/L) against P. piricola was slightly better than chlorothalonil (14.323 mg/L). The in vivo activity of Im against P. piricola on apples was comparable to chlorothalonil. Preliminary mechanistic exploration illustrated that Im strongly damage the mycelium morphology. Furthermore, molecular electrostatic potential and molecular docking analysis revealed that Im could interact with the residues of SDH via hydrogen bond.

The meticulous control of micromorphology in high power conversion efficiency (PCE) of polymer solar cells (PSCs) typically relies on halogenated solvents, which pose serious threats to both environmental sustainability and human health. In this work, a green and efficient method for fabricating high PCE PSCs with halogen-free solvents is developed. By introducing volatile solid additives 1-bromo-2,6-dichlorobenzene (DIB) and 1-bromo-2,3,5-trichlorobenzene (TIB) into toluene solvents, the aggregation behaviors of PM6:L8-BO were meticulously regulated, forming distinct fibrous morphology; in detail, the micromorphology of vertical direction exhibited a distinct pattern of acceptor enrichment at the top and donor enrichment at the bottom, which leads to enhanced exciton dissociation efficiency, improved charge transport performance, significantly reducing charge recombination, and finally improved PCEs, as the maximum PCEs were 18.56 and 17.67%, respectively, which are notably higher than those of devices without additives. Furthermore, since the solid additives can be completely removed from the active layer, the additive-treated devices exhibit superior morphology and photovoltaic stability. This work, therefore, unveils a straightforward and environmentally friendly method for preparing efficient PSCs, which is instrumental in facilitating the large-scale commercialization of PSC technology.

BACKGROUND:Using microbes and their metabolites as material to develop new biological fungicides is still vital for pesticide development. Our preliminary study found that the endophytic fungi Arthrinium sp. 2-65 of Thymus mongolicus (Ronniger) Ronniger showed a certain inhibitory effect on pathogenic fungi. RESULTS:In this study, the antifungal activity of Arthrinium sp. 2-65 was evaluated. The ethyl acetate extract of Arthrinium sp. 2-65 exhibited significant inhibitory activity against pathogenic fungi, especially Botrytis cinerea. The main compounds of Arthrinium sp. 2-65 metabolites were isolated and purified, and the two compounds were identified by infrared spectroscopy (IR), high-performance liquid chromatography (HPLC), 1H nuclear magnetic resonance (NMR), 13C NMR, and high-resolution mass spectrometry (HRMS) as 2-hexyl-3-methylmaleic anhydride (A) and 2-carboxymethyl-3-n-hexylmaleic acid anhydride (B). CONCLUSIONS:The main compounds (A and B) isolated and characterised from the fermentation broth of Arthrinium sp. 2-65 showed satisfactory inhibitory effects against pathogenic fungi, especially B. cinerea. These compounds could be used as potential molecules for the development of novel pesticides to control grey mould.

Chronic refractory diabetic wound healing remains a significant clinical problem due to hyperglycaemia-induced complicated wound microenvironments characterized by serious vascular dysfunction, dysregulated inflammatory responses, excessive reactive oxygen species (ROS) production, and recurrent bacterial infections. In this study, we developed an engineered composite termed BMn@H-Abs by encapsulating endothelial cell-derived apoptotic bodies (H-Abs) with manganese dioxide nanozymes (BMn). This BMn@H-Abs composite was further integrated into a microneedle (MN) patch using porous gelatin methacryloyl (GelMA) as the needle matrix, forming BMn@H-Abs MNs capable of penetrating dense wound eschar to achieve localized and sustained therapeutic delivery. Within diabetic wounds, the encapsulated H-Abs with inherent tissue regeneration and immunomodulatory properties effectively enhanced angiogenesis by promoting endothelial cell migration and tubulogenesis, while regulating macrophages polarization toward pro-regenerative and anti-inflammatory M2 phenotypes. The insertion of BMn@H-Abs MNs further restored oxygen supply, scavenged ROS levels, and inhibited bacterial growth through the catalase-mimetic and superoxide dismutase-mimetic activities of BMn nanozymes, as well as Mn2 + -mediated antibacterial effects. This study demonstrates a novel MN-based therapeutic strategy that not only effectively penetrates the physical barriers within wounds but also implements multi-targeted interventions addressing the etiology, offering a promising approach for diabetic wound treatment.

We report a straightforward and robust protocol for synthesizing unsymmetric propargylic acetals through single-step alkoxypropargylation of aliphatic alcohols. This method employs allenyl ethers and hypervalent iodine reagents to achieve direct functionalization under mild conditions, producing 26 distinct acetals in 60-94% yields. The reaction's broad substrate compatibility accommodates diverse hydroxyl-containing molecules, offering a versatile and scalable platform for installing alkynyl moieties in complex molecular architectures.

Plant-derived extracellular vesicles have considerable potential as natural pharmaceutical and nutraceutical delivery systems. However, the impact of plant maturity on the physicochemical and structural properties of isolated extracellular vesicles is currently unknown. In this work, extracellular vesicles isolated from oranges at different maturity stages were first characterized and compared. Afterwards, polyphenol-load orange juices were successfully prepared by incorporating polyphenols (mainly curcumin) into extracellular vesicles originated from orange juices. Encapsulation in vesicles was found to increase the solubility, stability, bioaccessibility, and antioxidant activity of curcumin, but the effects depended on the maturity of oranges. Specifically, the vesicles from unripe and ripe orange juices were more effective for curcumin delivery than those from overripe orange juice. Conclusively, this study has provided important new information about the optimum maturity for isolating fruit-derived extracellular vesicles. Moreover, the extracellular vesicle-based delivery systems developed in this study may facilitate the design of more effective functional foods and beverages.

1-Indanone is a prominent scaffold recognized for its wide range of biological activities. Numerous studies have demonstrated that 1-indanone derivatives are crucial for Alzheimer's disease, antidiarrheal, anti-proliferative, antibacterial, anti-inflammatory, anticancer agents, etc. In recent years, it has been found that this type of compound also has significant anti-plant disease activity. Novel 1-indanone derivatives were designed and synthesized based on their extensive biological activities. The compounds were characterized using 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS). Compound 11 (CCDC number: 2391,391) was crystallized, and its structure was determined through X-ray analysis. Additionally, density functional theory (DFT) calculations for compound 11 were conducted at the B3LYP/6-311 level. Ultimately, systematic biological assays indicated that the intermediate 6 exhibited significant inhibitory activity in vitro against the four tested plant pathogenic bacteria.

As a traditional Chinese medicinal herb, ginseng (Panax ginseng C. A. Mey.) is commonly used to treat common diseases, for example, esophageal cancer and myasthenia gravis. Furthermore, ginseng is also processed into a functional food additive that is utilized to improve the freshness of chicken soup and make health wine. Unfortunately, ginseng (Panax ginseng C. A. Mey.) has already shown a noticeable bitterness during its application process. In this research, the bitter substances in ginseng (Panax ginseng C. A. Mey.) after two common preparation processes (water extraction and ethanol extraction) were separated, purified and identified by preparative high performance liquid chromatography (prep-HPLC), high performance liquid chromatography with diode array detector (HPLC-DAD), ultra-performance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and an electronic tongue. The results indicated that compared with the other four bitter compounds, the ginsenoside Rb1 had the highest bitterness value, followed by 20(S)-ginsenoside Rg2, ginsenoside Rg1, ginsenoside Rf and ginsenoside Rb3. Upon the evaluation of results to reduce the bitterness of ginseng extract, we found that the composite embedding system of chitosan adsorption in the ginseng carrageenan gel microsphere (K/MC/MCG) could effectively reduce the bitterness.

Current research on tumor fibrosis has focused on cancer-associated fibroblasts, which may exert dual functions of tumor promotion and inhibition. Little attention has been paid to whether tumor cells themselves can undergo fibrotic transformation and whether they can inhibit parenchymal cells similar to pulmonary fibrosis, thus achieving the goal of inhibiting the malignant progression of tumors. To explore the significance of inducing tumor fibrosis for cancer treatment. This study utilizes mesoporous silica nanoparticles (MSN) loaded with Trehalose dimycolate (TDM) to induce tumor cell fibrosis through the dual effects of TDM-induced inflammatory granuloma and MSN-induced foreign body granuloma. The results show that TDM/MSN (TM) can effectively induce tumor fibrosis, manifested specifically by collagen internalization, and suppression of proliferation and invasion capabilities, suggesting the potential role of tumor fibrosis therapy. However, further investigation reveals that extrachromosomal DNA (ecDNA) mediates resistance to fibrosis induction. To comprehensively enhance the efficacy, WRN exonuclease is conjugated to TM to form new nanoparticles (TMW) capable of effectively eliminating ecDNA, globally promoting tumor cell fibroblast-like transformation, and validated in a PDX model to inhibit cancer progression. Therefore, TMW, through inducing tumor cell fibrosis to inhibit its malignant progression, holds great potential as a clinical treatment strategy.

Although immunotherapy of hepatocellular carcinoma using immune checkpoint inhibitors has achieved certain success, only a subset of patients benefits from this therapeutic strategy. The combination of immunostimulatory chemotherapeutics represents a promising strategy to enhance the effectiveness of immunotherapy. However, it is hampered by the poor delivery of conventional chemotherapeutics. Here, it is shown that H-ferritin nanocages loaded with doxorubicin (DOX@HFn) show potent chemo-immunotherapy in hepatocellular carcinoma tumor models. DOX@HFn is constructed with uniform size, high stability, favorable drug loading, and intracellular acidity-driven drug release. The receptor-mediated targeting of DOX@HFn to liver cancer cells promote cellular uptake and tumor penetration in vitro and in vivo. DOX@HFn triggers immunogenic cell death to tumor cells and promotes the subsequent activation and maturation of dendritic cells. In vivo studies in H22 subcutaneous hepatoma demonstrate that DOX@HFn significantly inhibits the tumor growth with >30% tumors completely eliminated, while alleviating the systemic toxicity of free DOX. DOX@HFn also exhibits robust antitumor immune response and tumoricidal effect in a more aggressive Hepa1-6 orthotopic liver tumor model, which is confirmed by the in situ magnetic resonance imaging and transcriptome sequencing. This study provides a facile and robust strategy to improve therapeutic efficacy of liver cancer.

Experimental Section Materials Phospholipid was purchased from Avanti (Shanghai, China). RLA (RLASHLRKLRKRLLREEQAQQIRLQAEAFQARLKSWFEPLVEDM) and Aβ1-42 were from Top-Peptide Co., Ltd (Shanghai, China). DSPE-NH2, HOOC-TK-COOH, NH2-PEG2000, DSPE-NHS, NH2-TK-NH2, NHS-PEG3400-MAL and ANG (Angiopep-2, TFFYGGSRGKRNNFKTEEY) were purchased from Ruixi biotechnology Co., Ltd (Xi’ an, China). Mouse anti-human Aβ1-42 antibody and FITC-Aβ1-42 were purchased from China Peptides Co., Ltd (Shanghai, China). Colloidal gold labeled goat anti-mouse IgG and peroxidase-conjugated goat anti-mouse IgG were from Beijing Biodragon Immunotechnologies Co., Ltd (Beijing, China). Thioflavin-T was purchased from Aladdin (Shanghai, China). The rest were commercially qualified reagents.

The discovery of novel and easily available leads provides a convincing solution to agrochemical innovation. A bioassay-guided scaffold subtraction of the previous "Chem-Bio Model" isoquinoline-3-oxazoline MIQOX was conducted for identifying the easily available isoquinoline-3-hydrazide as a novel antifungal scaffold. The special and practical potential of this model was demonstrated by a phenotypic antifungal bioassay, molecular docking, and cross-resistance evaluation. A panel of antifungal leads (LW2, LW3, and LW11) was acquired, showing much better antifungal performance than the positive controls. Specifically, compound LW3 exhibited a broad antifungal spectrum holding EC50 values as low as 0.54, 0.09, 1.52, and 2.65 mg/L against B. cinerea, R. solani, S. sclerotiorum , and F. graminearum, respectively. It demonstrated a curative efficacy better than that of boscalid in controlling the plant disease caused by B. cinerea. The candidate LW3 did not show cross-resistance to the extensively used succinate dehydrogenase inhibitor (SDHI) fungicides and can efficiently inhibit resistant B. cinerea strains. The molecular docking of compound LW3 is quite different from that of the positive controls boscalid and fluopyram. This progress highlights the practicality of isoquinoline hydrazide as a novel model in fungicide innovation.

Probes such as carbon dots (C-dots) have extensive and important applications in the quantitative analysis of complex biological and environmental systems. However, the development of probes is often hindered by incomplete selectivity, i.e., a probe that responds to one substance is also prone to respond to coexisting structurally similar substances. Therefore, the above dilemma often leads to be developed as semi-selective probes, so that the development of probes is abandoned halfway. This work shows how a semi-selective probe can enhance selectivity by combining a proper multivariate calibration model. Primarily, we developed a semi-selective fluorescent probe that responded to tetracyclines (TCs) with discarded tobacco leaves. Then, we introduced the multivariate quantitative fluorescence model (QFM) to enhance its selectivity and solve the problem of fluorescence spectral shift. For the determination of chlortetracycline (CTC) with this semi-selective C-dots probe in mineral and lake water samples and compared to the traditional quantitative model, the introduced QFM resulted in an average relative predictive error (ARPE) in mineral water spiked samples decreased from 57.1 to 5.6%, which reduced the ARPE in the lake water spiked samples from 18.1 to 4.7%. The above results show that the QFM-assisted semi-selective probe C-dots strategy (QFMC-dots) can enhance selectivity, and QFMC-dots achieved high-selective and accurate determination of CTC in interfering mineral and lake water samples, with the limit of detection and limit of quantitation of 0.55 and 1.66 μM, respectively. The proposed strategy of enhancing selectivity by introducing a proper multivariate calibration model can reduce the difficulty and increase success rate of developing probes, which can be expected to provide an interesting alternative for the development of probes, especially when encountering semi-selective problems.

Botanical pesticides are one of the sources of third-generation pesticides, which have received much attention at home and abroad in recent years due to their degradable and pollution-free advantages in nature. This article explored a concise approach toward synthesizing a series of novel L-pyroglutamic acid analogues from L-hydroxyproline. Furthermore, bioassay studies of these sulfonyl ester derivatives against Pyricularia oryzae, Fusarium graminearum, Alternaria brassicae, Valsa mali, and Alternaria alternariae showed moderate antifungal activity. For instance, C08a and C08l provide potential lead agents for controlling Fusarium graminearum because of their inhibitory activity.

The first palladium-catalyzed asymmetric addition of arylboronic acids to coumarins was successfully established, providing a straightforward asymmetric approach to achieving pharmaceutically important 4-aryl-3,4-dihydrocoumarins. This methodology features easily accessible and bench-stable ligands, a wide substrate scope, mild conditions, and accommodation of electron-withdrawing arylboronic acids.

The first palladium/chiral nitrogenous ligand-catalyzed enantioselective addition of aryl boronic acids to various maleimides was reported. This protocol features mild conditions combined with good functional group tolerance. The resultant 3-arylsuccinimides were shown to be novel chiral antifungal leads and inspired the discovery of novel ligands to address the challenging issues of this transformation.

Sulfonylurea herbicides are the most widely used herbicides in the world.They have the advantages of high efficiency, good selectivity, and no toxicity to human and animals.In this study, sulfonylureas containing imidazole heterocycles were synthesized on the basis of computer simulation of molecular docking, and the biological activity was evaluated.It shows that the compound has a good inhibitory effect on the ALS and a certain inhibitory effect on the phytopathogenic fungi of Curvularia lunata and Curvularia mebaldsii.Its inhibitory rate at concentration of 50 mg/L is similar to that of the carbendazim.This research provides the basis for further optimization of the structure of imidazolium heterocyclic sulfonylurea and the synthesis of its derivatives.