Exogenous Melatonin Activating Nuclear Factor E2-Related Factor 2 (Nrf2) Pathway via Melatonin Receptor to Reduce Oxidative Stress and Apoptosis in Antler Mesenchymal Stem Cells

Antler growth depends on the proliferation and differentiation of mesenchymal stem cells (MSCs), and this process may be adversely affected by oxidative stress. Melatonin (MLT) has antioxidant functions, but its role in Cervidae remains largely unknown. In this article, flow cytometry, reactive oxygen species (ROS) identification, qPCR, and other methods were used to investigate the protective mechanism of MLT in H₂O₂-induced oxidative stress of antler MSCs. The results showed that MLT significantly increases cell viability by relieving the oxidative stress of antler MSCs. MLT inhibits cell apoptosis by protecting mitochondrial function. We blocked the melatonin receptor with luzindole (Luz) and found that the receptor blockade significantly increases H₂O₂-induced hyperoxide levels and causes significant inhibition of mitochondrial function. MLT treatment activates the nuclear factor E2-related factor 2 (Nrf2) antioxidant signaling pathway, up-regulates the expression of NAD(P)H quinone oxidoreductase 1 (NQO1) and other genes and it could inhibit apoptosis. In contrast, the melatonin receptor blockade down-regulates the expression of Nrf2 pathway-related genes, but significantly up-regulates the expression of apoptotic genes. It was indicated that MLT activates the Nrf2 pathway through the melatonin receptor and alleviates H₂O₂-induced oxidative stress and apoptosis in antler MSCs. This study provides a theoretical basis for further studying the oxidative stress and antioxidant process of antler MSCs and, thereby, increasing antler yields.     

Five New Polyoxypregnane Glycosides from the Vines of Aspidopterys obcordata and Their Antinephrolithiasis Activity

From the dried vines of Aspidopterys obcordata Hemsl, five new polyoxypregnane glycosides, named obcordatas J–N (1–5), were obtained. Their structures were fully elucidated and characterized by HRESIMS and extensive spectroscopic data. In addition, all of the new compounds were screened for their antinephrolithiasis activity in vitro. The results showed that compounds 1–3 have prominent protective effects on calcium oxalate crystal-induced human kidney 2 (HK-2) cells, with EC₅₀ values ranging from 6.72 to 14.00 μM, which is consistent with the application value of A. obcordata in folk medicine for kidney stones.     

MiR-1224-5p modulates osteogenesis by coordinating osteoblast/osteoclast differentiation via the Rap1 signaling target ADCY2

MicroRNAs (miRNAs) broadly regulate normal biological functions of bone and the progression of fracture healing and osteoporosis. Recently, it has been reported that miR-1224-5p in fracture plasma is a potential therapy for osteogenesis. To investigate the roles of miR-1224-5p and the Rap1 signaling pathway in fracture healing and osteoporosis development and progression, we used BMMs, BMSCs, and skull osteoblast precursor cells for in vitro osteogenesis and osteoclastogenesis studies. Osteoblastogenesis and osteoclastogenesis were detected by ALP, ARS, and TRAP staining and bone slice resorption pit assays. The miR-1224-5p target gene was assessed by siRNA-mediated target gene knockdown and luciferase reporter assays. To explore the Rap1 pathway, we performed high-throughput sequencing, western blotting, RT-PCR, chromatin immunoprecipitation assays and immunohistochemical staining. In vivo, bone healing was judged by the cortical femoral defect, cranial bone defect and femoral fracture models. Progression of osteoporosis was evaluated by an ovariectomy model and an aged osteoporosis model. We discovered that the expression of miR-1224-5p was positively correlated with fracture healing progression. Moreover, in vitro, overexpression of miR-1224-5p slowed Rankl-induced osteoclast differentiation and promoted osteoblast differentiation via the Rap1-signaling pathway by targeting ADCY2. In addition, in vivo overexpression of miR-1224-5p significantly promoted fracture healing and ameliorated the progression of osteoporosis caused by estrogen deficiency or aging. Furthermore, knockdown of miRNA-1224-5p inhibited bone regeneration in mice and accelerated the progression of osteoporosis in elderly mice. Taken together, these results identify miR-1224-5p as a key bone osteogenic regulator, which may be a potential therapeutic target for osteoporosis and fracture nonunion.Subject terms: Translational research, Cell signalling     

Simultaneous Determination of Seven Pesticides and Metabolite Residues in Litchi and Longan through High-Performance Liquid Chromatography-Tandem Mass Spectrometry with Modified QuEChERS

This study established a QuEChERS high-performance liquid chromatography/tandem triple-quadrupole mass spectrometry method for determining azoxystrobin, pyraclostrobin, picoxystrobin, difenoconazole, chlorantraniliprole, imidacloprid, and cyantraniliprole and its metabolite (IN-J9Z38) in litchi and longan, and applied this method to the real samples. The residues in samples were extracted with acetonitrile and purified with nano-ZrO₂, C₁₈, and PSA. The samples were then detected with multireactive ion monitoring and electrospray ionization in the positive ion mode and quantified using the external matrix-matched standard method. The results showed good linearities for the eight analytes in the range of 1–100 μg/L, with correlation coefficients (r²) of >0.99. The limit of quantification was 1–10 μg/kg, and the limit of detection was 0.3–3 μg/kg. Average recovery from litchi and longan was 81–99%, with the relative standard deviation of 3.5–8.4% at fortified concentrations of 1, 10, and 100 μg/kg. The developed method is simple, rapid, efficient, and sensitive. It allowed the rapid screening, monitoring, and confirming of the aforementioned seven pesticides and a metabolite in litchi and longan.     

Synthesis of Diversified Pyrazolo[3,4-b]pyridine Frameworks from 5-Aminopyrazoles and Alkynyl Aldehydes via Switchable C≡C Bond Activation Approaches

A cascade 6-endo-dig cyclization reaction was developed for the switchable synthesis of halogen and non-halogen-functionalized pyrazolo[3,4-b]pyridines from 5-aminopyrazoles and alkynyl aldehydes via C≡C bond activation with silver, iodine, or NBS. In addition to its wide substrate scope, the reaction showed good functional group tolerance as well as excellent regional selectivity. This new protocol manipulated three natural products, and the arylation, alkynylation, alkenylation, and selenization of iodine-functionalized products. These reactions demonstrated the potential applications of this new method.     

Comparison of the Antioxidant Activities and Polysaccharide Characterization of Fresh and Dry Dendrobium officinale Kimura et Migo

It is generally believed that fresh Dendrobium officinale (FDO) has more significant pharmacological activity than dried Dendrobium officinale (DDO); however, the difference has not been clearly shown. Our study compared their antioxidant properties both in vitro and in vivo, and the molecular weight arrangement and monosaccharide composition of the fresh Dendrobium officinale polysaccharides (FDOPs) and the dried Dendrobium officinale polysaccharides (DDOPs) were analyzed by HPLC-GPC and GC-MS. The results showed that the FDO and its polysaccharides had more significant effects on scavenging DPPH, ABTS, and hydroxyl radicals than the DDO. In addition, both the FDO and DDO significantly reduced lipid peroxidation levels and increased the SOD, T-AOC, CAT, and GSH levels in mice with acute liver damage caused by CCl₄, while the FDO and its polysaccharides were more effective. Histopathological analysis further verified the protective effect of the Dendrobium polysaccharides on CCl₄-induced liver injury. The determination of the polysaccharides revealed that the polysaccharide and mannose contents of the FDO were significantly higher than their dried counterparts, and the homogeneous arrangement of the polysaccharides in the FDO was degraded into three polysaccharide fragments of different molecular weights in the DDO. Overall, our data identified differences in the antioxidant activities of the FDO and DDO, as well as the reasons for these differences.     

基于碳点的发光材料在潜在手印显现中的应用

遗留在犯罪现场的肉眼不可见的潜在手印是一类重要的痕迹物证,检验鉴定前需要使用一定技术手段将其显现出来。近年来,一些新材料和新技术的引入为手印显现技术的革新注入了新活力,其中稀土发光材料、量子点、荧光金属纳米簇等发光材料在该领域展现出极大潜力。碳点作为具有良好光致发光性能的新型纳米材料,近来逐渐引起了手印显现领域研究人员的广泛关注。本文综述了两类基于碳点材料的手印显现技术国内外研究进展,分别是液体分散碳点用于手印显现和固态发光碳点用于手印显现。具体来说,液体分散碳点显现手印的原理主要基于传统小微粒悬浮液机理或一些特殊效应(咖啡环效应、界面偏析效应);用于手印显现的固态发光碳点包括固态碳点粉末和固态碳点复合粉末两类,合成这些材料时研究人员采用了不同的策略。最后,从三个方面分析了碳点在手印显现应用中面临的问题,即碳点物理形貌和表面性质、碳点光致发光性质以及碳点显现过程与化学生物分析兼容性,并就解决问题的可能途径提出了展望。     

Grain Boundary Electronic Insulation for High-Performance All-Solid-State Lithium Batteries

Sulfide electrolytes with high ionic conductivities are one of the most highly sought for all-solid-state lithium batteries (ASSLBs). However, the non-negligible electronic conductivities of sulfide electrolytes (≈10⁻⁸ S cm⁻¹) lead to electron smooth transport through the sulfide electrolyte pellets, resulting in Li dendrite directly depositing at the grain boundaries (GBs) and serious self-discharge. Here, a grain-boundary electronic insulation (GBEI) strategy is proposed to block electron transport across the GBs, enabling Li−Li symmetric cells with 30 times longer cycling life and Li−LiCoO₂ full cells with three times lower self-discharging rate than pristine sulfide electrolytes. The Li−LiCoO₂ ASSLBs deliver high capacity retention of 80 % at 650 cycles and stable cycling performance for over 2600 cycles at 0.5 mA cm⁻². The innovation of the GBEI strategy provides a new direction to pursue high-performance ASSLBs via tailoring the electronic conductivity.     

Durable Electrocatalytic Reduction of Nitrate to Ammonia over Defective Pseudobrookite Fe2TiO5 Nanofibers with Abundant Oxygen Vacancies

We propose the pseudobrookite Fe₂TiO₅ nanofiber with abundant oxygen vacancies as a new electrocatalyst to ambiently reduce nitrate to ammonia. Such catalyst achieves a large NH₃ yield of 0.73 mmol h⁻¹ mg⁻¹_cat. and a high Faradaic Efficiency (FE) of 87.6 % in phosphate buffer saline solution with 0.1 M NaNO₃, which is lifted to 1.36 mmol h⁻¹ mg⁻¹_cat. and 96.06 % at −0.9 V vs. RHE for nitrite conversion to ammonia in 0.1 M NaNO₂. It also shows excellent electrochemical durability and structural stability. Theoretical calculation reveals the enhanced conductivity of this catalyst and an extremely low free energy of −0.28 eV for nitrate adsorption at the presence of vacant oxygen.     

Enhanced Four-Electron Oxygen Reduction Selectivity of Clamp-Shaped Cobalt(II) Porphyrin(2.1.2.1) Complexes

The molecular structure, electrochemistry, spectroelectrochemistry and electrocatalytic oxygen reduction reaction (ORR) features of two Co^II porphyrin(2.1.2.1) complexes bearing Ph or F₅Ph groups at the two meso-positions of the macrocycle are examined. Single crystal X-ray analysis reveal a highly bent, nonplanar macrocyclic conformation of the complex resulting in clamp-shaped molecular structures. Cyclic voltammetry paired with UV/Vis spectroelectrochemistry in PhCN/0.1 M TBAP suggest that the first electron addition corresponds to a macrocyclic-centered reduction while spectral changes observed during the first oxidation are consistent with a metal-centered Co^II/Co^III process. The activity of the clamp-shaped complexes towards heterogeneous ORR in 0.1 M KOH show selectivity towards the 4e⁻ ORR pathway giving H₂O. DFT first-principle calculations on the porphyrin catalyst indicates a lower overpotential for 4e⁻ ORR as compared to the 2e⁻ pathway, consistent with experimental data.