Molecules最新文献

Testosterone, an androgenic steroid hormone, regulates primary sexual characteristics and influences mood, cognition, social behavior, and sexual function. Deficiency, caused by factors such as aging and genetics, is linked to multiple disease conditions. However, current testosterone therapies are limited by extensive metabolism, poor solubility, and undesirable side effects. To address these limitations, we synthesized a four-armed star PEG-OH-linked testosterone (PEG-T). The in vitro release of testosterone from PEG-T was evaluated in buffer (pH 7.4) and mouse plasma. PEG-T was stable in the buffer, but released testosterone in plasma via esterase-mediated hydrolysis. Pharmacokinetics of testosterone and PEG-T were compared following intraperitoneal (IP) and subcutaneous (SC) administration. Following IP dosing, PEG-T exhibited a ~6-fold improvement in half-life compared to testosterone (1.18 h vs. 0.21 h), and a 54-fold increase in exposure (AUC_0-t = 36.0 μM·h vs. 0.67 μM·h) at equimolar doses; furthermore, following SC dosing, PEG-T showed a 4-fold improvement in both half-life (3.57 h vs. 0.91 h) and plasma exposure (11.5 μM·h vs. 3.1 μM·h). Additionally, PEG-T showed lower liver and kidney to plasma ratios, which could potentially result in reduced hepatotoxicity and nephrotoxicity. Overall, PEG-T provides sustained release pharmacokinetics, representing a promising candidate for safer testosterone replacement therapy.

Huperzine A is a preferred treatment option for Alzheimer's disease. Huperzia serrata (Thunb. ex Murray) Trev. (H. serrata) has garnered significant attention for its ability to produce Huperzine A (HupA). However, natural populations of wild H. serrata (WH) are rapidly declining. Fortunately, our group obtained two types of H. serrata thalli (OT and ST) capable of stably producing Huperzine A, which have the potential to serve as an alternative resource to WH. To evaluate the feasibility of this strategy, we conducted a comprehensive assessment of both WH and H. serrata thallus. The results indicated that compared to WH, ST and OT exhibited stronger anti-inflammatory and antioxidant activities, with lower cytotoxicity. Notably, ST demonstrated a strong radical scavenging activity, reaching 93.23% (DPPH at 0.2 μg/mL) and 99.87% (ABTS at 4 μg/mL), and reduced nitrite production from 10.29 μM to 6.51 μM at 50 µg/mL. GC-MS and widely targeted metabolomics analyses revealed that the higher antioxidant and anti-inflammatory activities for ST and OT were due to higher concentrations of phenolic acids and flavonoids compared to WH. In addition, the HupA content in ST reached 36.56% of that found in WH. KEGG enrichment analysis revealed that the flavonoid, phenylalanine, and phenylpropanoid biosynthesis pathways may be involved in regulating the antioxidant activity. P-coumaroyl quinic acid and caffeoyl quinic acid are the crucial metabolites for antioxidant activity. These findings suggested that the H. serrata thallus could serve as a sustainable alternative to WH.

Haloketoesters are synthetic intermediates in various cyclization reactions that facilitate the production of biologically active compounds. Nonetheless, the selective synthesis of dihaloketoesters and trihaloketoesters, which are expected to be highly versatile, presents significant challenges. In this study, we designed a new synthetic approach that selectively and efficiently produces haloketoesters through the halogenative C-C bond cleavage and ring-opening reactions of cyclic 1,3-diketones. This convenient method enables the direct synthesis of di- and trichloro-functionalized ketoesters from 1,3-cyclohexadiones under mild conditions. Na₂HPO₄, employed as a buffer salt, proved to be effective in facilitating the alcoholytic ring-opening reaction of 2,2-dichloro-1,3-cyclohexadiones, which were generated as synthetic intermediates.

Tetranuclear rhodium carbonyl clusters are vital catalytic precursors; yet derivatives featuring bidentate phosphines are less common, due to the propensity for cluster fragmentation during synthesis. This study reports the successful isolation of five new heteroleptic species by reacting Rh₄(CO)₁₂ with various bidentate diphosphines under homogeneous conditions and at room temperature, namely the mono-substituted Rh₄(CO)₁₀(dppe) (1) and Rh₄(CO)₁₀(dppb) (3), the rare bis-substituted derivative Rh₄(CO)₈(dppe)₂ (2), and the two unique dimeric assemblies {Rh₄(CO)₁₀(dpp-hexane)}₂ (4) and {Rh₄(CO)₁₀(trans-dppe)}₂ (5). The tetrahedral Rh₄ core of the cluster precursor was preserved in all cases. The new compounds were characterized via infrared (IR) spectroscopy and single-crystal X-ray diffraction (SC-XRD). Furthermore, variable-temperature (VT) ³¹P{¹H} NMR spectroscopy elucidated the dynamic behavior of the phosphorus atoms. This work reports a robust methodology for accessing stable, low-nuclearity rhodium phosphine clusters with tunable properties.

This work presents the results of the synthesis and investigation of new antibacterial composite materials based on acrylonitrile-butadiene-styrene (ABS) copolymer and o-, m-, p-carboxyphenylmaleimides (CPhMI). The composites were obtained by thermal mixing with varying contents of different CPhMI isomers in the polymer matrix. The structural and thermal characteristics of the synthesized materials were investigated using IR and UV spectroscopy, as well as thermogravimetric (TGA) and differential thermal analysis (DTA). The results indicate that the o-isomer imparts the highest thermal stability, while the p-isomer shows slightly lower stability. In terms of processability, the m-isomer exhibits the highest melt flow, the p-isomer an intermediate level, and the o-isomer the lowest. The antibacterial activity of the composites was evaluated by the agar diffusion method against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) microorganisms. All synthesized samples exhibited strong antibacterial activity against S. aureus and E. coli at a concentration of 0.5 wt%, confirming their potential for application in medical devices, as well as in sanitary polymer coatings and packaging.

Corilagin is a hydrolyzable ellagitannin and naturally occurring polyphenolic compound widely distributed in medicinal plants. It is also present in longan (Dimocarpus longan), known as lumyai in Thailand, a subtropical fruit extensively cultivated across China and Southeast Asia. Corilagin has been reported to exhibit strong antioxidant, anti-inflammatory, hepatoprotective, and anticancer activities through modulation of multiple cellular signaling pathways. However, despite these well-established pharmacological properties, its potential role in regulating bone marrow mesenchymal stem cell (BM-MSC) differentiation has not been fully explored in biomedical applications. In this study, we investigated the effects of corilagin on BM-MSC viability, protein-binding interactions, and lineage-specific differentiation toward osteogenic and chondrogenic pathways. Cytotoxicity assessment using human synovial SW-982 cells demonstrated that corilagin maintained cell viability at concentrations ranging from 1.56 to 50 µg/mL within 48 h, whereas prolonged exposure resulted in a time-dependent reduction in viability. In BM-MSCs, corilagin significantly enhanced osteogenic and chondrogenic differentiation in a dose-dependent manner, as evidenced by increased mineral deposition and cartilage matrix formation, as revealed by Alizarin Red S, Toluidine Blue, and Alcian Blue staining. Quantitative analyses further showed the upregulation of key lineage-specific genes, including Runx2 and osteopontin (OPN) for osteogenesis and Sox9 and aggrecan for chondrogenesis. Protein-binding assays confirmed the molecular interaction capacity of corilagin, supporting its biological activity. Overall, these findings demonstrate that corilagin promotes MSC-mediated osteogenic and chondrogenic differentiation while maintaining acceptable cytocompatibility, highlighting its potential as a natural small-molecule candidate for bone and cartilage tissue engineering and other biomedical fields with regenerative medicine applications.

Activation of microglia and resulting neuroinflammation are central processes that significantly contribute to neurodegenerative disease progression. Treatments capable of attenuating neuroinflammation are therefore an urgent medical need. Vitis vinifera L., cultivated since ancient times for its fruits, is known for its antioxidant and anti-inflammatory activities. However, polyphenols, the main bioactive molecules in V. vinifera extracts, exhibit considerable variability due to numerous hard-to-control factors, which complicates the production of standardized extracts with consistent biological activity. To address this issue, plant cell culture biotechnology was used to produce a highly standardized V. vinifera phytocomplex (VP), and its anti-neuroinflammatory profile was investigated in LPS-stimulated microglial cells, an in vitro model of neuroinflammation. VP reduced the LPS-induced pro-inflammatory phenotype, improved cell viability and cell number, attenuated NF-κB activation and ERK1/2 phosphorylation, and increased SIRT1 levels. To overcome VP's poor water solubility, water-soluble cellulose nanocrystal (CNC)-based formulations were developed and tested. VP-CNC formulations markedly reduced the BV2 pro-inflammatory phenotype and increased cell viability under both basal and LPS-stimulated conditions. The nanoformulations also decreased pERK1/2 levels and increased SIRT1 expression, exhibiting biological activities comparable to VP alone. V. vinifera phytocomplex derived from plant cell cultures represents an innovative and standardized product with promising anti-neuroinflammatory properties.

Hydrodynamic cavitation (HC) is a green and readily scalable platform for the recovery and upgrading of bioactives from agri-food and forestry byproducts. This expert-led narrative review examines HC processing of citrus and pomegranate peels, softwoods, and plant protein systems, emphasizing process performance, ingredient functionality, and realistic routes to market, and contrasts HC with other green extraction technologies. Pilot-scale evidence repeatedly supports water-only operation with high solids and short residence times; in most practical deployments, energy demand is dominated by downstream water removal rather than the extraction step itself, which favors low water-to-biomass ratios. A distinctive outcome of HC is the spontaneous formation of stable pectin-flavonoid-terpene phytocomplexes with improved apparent solubility and bioaccessibility, and early studies indicate that HC may also facilitate protein-polyphenol complexation while lowering anti-nutritional factors. Two translational pathways appear near term: (i) blending HC-derived dry extracts with commercial dry protein isolates to deliver measurable functional benefits at low inclusion levels and (ii) HC-based extraction of plant proteins to obtain digestion-friendly isolates and conjugate-ready ingredients. Priority gaps include harmonized reporting of specific energy consumption and operating metrics, explicit solvent/byproduct mass balances, matched-scale benchmarking against subcritical water extraction and pulsed electric field, and evidence from continuous multi-ton operation. Overall, HC is a strong candidate unit operation for circular biorefineries, provided that energy accounting, quality retention, and regulatory documentation are handled rigorously.

This study investigates the adsorption and migration of sulfadiazine (SDZ) in soda saline-alkali soils under Cu/Zn co-pollution using equilibrium adsorption and soil column experiments. Freundlich and Langmuir isothermal models, combined with Hydrus-1D two-site modeling, revealed concentration-dependent interactions. Low Cu (10-100 mg kg^-1) and Zn (10-100 mg kg^-1) enhanced SDZ adsorption via charge regulation and complexation, while high concentrations (300 mg kg^-1) suppressed adsorption through competitive adsorption and hydroxide precipitation. Synergistic Cu-Zn coexistence further reduced adsorption to 3.035 mg kg^-1. Freundlich modeling (R² = 0.922-0.995) outperformed Langmuir, confirming adsorption site heterogeneity. Column experiments showed Cu (300 mg kg^-1) and Zn (300 mg kg^-1) accelerated SDZ migration (peaks 0.93-0.94), delaying breakthrough versus Br^-. Hydrus-1D simulations (R² ≥ 0.915, RMSE < 0.1) effectively quantified nonlinear dynamics between instantaneous adsorption sites (f = 0.101-0.554) and metal concentrations. Results demonstrate heavy metals critically regulate antibiotic fate via concentration-dependent mechanisms in saline-alkali ecosystems.

Surface-Enhanced Raman Spectroscopy (SERS) is highly attractive as an analytical technique owing to its high sensitivity, distinctive molecular specificity, and speed of analysis. It offers the potential to match the sensitivity and molecular specificity of established techniques like Gas Chromatography-Mass Spectrometry in a more affordable, faster, and portable format, providing unique solutions for challenging analytical problems such as bedside diagnostics and in-field forensic analysis. Despite these benefits, SERS currently remains a specialized technique and has not yet successfully entered the mainstream of analytical chemistry. This transition is hindered primarily by challenges in achieving robust, reliable, and especially quantitative measurements in real-world applications. Achieving quantitative SERS requires addressing core issues arising from the heterogeneous nature of enhancing substrates and the complexity of real-life samples. This perspective summarizes the fundamental challenges associated with signal variability and matrix interference. It then details modern strategies focused on standardizing performance metrics, with particular emphasis on the newly proposed SERS Performance Factor for substrate evaluation, alongside the development of advanced quantification methods (e.g., internal standardization and digital SERS) and rapid sample pretreatment protocols. Finally, emerging prospects, including the deployment of Artificial Intelligence for enhanced analysis and advancements in deep-tissue SERS sensing, are explored as critical drivers for integrating SERS into routine analytical practice.