The natural product salicin alleviates osteoarthritis progression by binding to IRE1α and inhibiting endoplasmic reticulum stress through the IRE1α-IκBα-p65 signaling pathway

Despite the high prevalence of osteoarthritis (OA) in older populations, disease-modifying OA drugs (DMOADs) are still lacking. This study was performed to investigate the effects and mechanisms of the small molecular drug salicin (SA) on OA progression. Primary rat chondrocytes were stimulated with TNF-α and treated with or without SA. Inflammatory factors, cartilage matrix degeneration markers, and cell proliferation and apoptosis markers were detected at the mRNA and protein levels. Cell proliferation and apoptosis were evaluated by EdU assays or flow cytometric analysis. RNA sequencing, molecular docking and drug affinity-responsive target stability analyses were used to clarify the mechanisms. The rat OA model was used to evaluate the effect of intra-articular injection of SA on OA progression. We found that SA rescued TNF-α-induced degeneration of the cartilage matrix, inhibition of chondrocyte proliferation, and promotion of chondrocyte apoptosis. Mechanistically, SA directly binds to IRE1α and occupies the IRE1α phosphorylation site, preventing IRE1α phosphorylation and regulating IRE1α-mediated endoplasmic reticulum (ER) stress by IRE1α-IκBα-p65 signaling. Finally, intra-articular injection of SA-loaded lactic-co-glycolic acid (PLGA) ameliorated OA progression by inhibiting IRE1α-mediated ER stress in the OA model. In conclusion, SA alleviates OA by directly binding to the ER stress regulator IRE1α and inhibits IRE1α-mediated ER stress via IRE1α-IκBα-p65 signaling. Topical use of the small molecular drug SA shows potential to modify OA progression.Subject terms: Osteoarthritis, Molecularly targeted therapy, Single-molecule biophysics, Drug development     

Binding Modes of Salicylic Acids to Titanium Oxide Molecular Surfaces

A set of titanium oxide clusters (TOCs) comprised of 4 to 16 Ti atoms are synthesized with substituted salicylates (SSAs). The interfacial coordination environment of these SSA/Ti oxide hybrids are surveyed and found to be limited to four binding modes, with the bridging chelate mode being the most common one. The SSA-functionalized TOCs show strong visible light absorption properties. The contribution of the SSAs in the frontier orbitals of the TOCs are analyzed by using TD-DFT calculations based on the molecular geometries determined by X-ray diffraction. For TOCs of relatively high O/Ti ratio, the SSAs narrow the band gap of the TOCs by contributing solely to the HOMOs. Both binding modes and locations of the SSAs are important for the roles of SSAs in changing the HOMOs and thereby the absorption onsets.     

Influence of nature of the fluoride ion on the electrochemical behaviors of Nb(V) in molten NaCl-KCl

Journal of Solid State Electrochemistry - In this research, the reduction mechanism of Nb(V) under various [F−]/[Nbn+] ratios (α) was investigated by a series of electrochemical...     

Iodine‐promoted Intermolecular Dehydrogenation Diamination: Synthesis of Unsymmetrical α,β‐Diamido Ketones

Iodine‐promoted direct diamination of α,β‐unsaturated ketone to form two C?N bonds has been developed starting from chalcone and secondary amine. This reaction was performed in THF at 50 °C in the presence of I₂ and K₂CO_3. The protocol is metal‐free, operationally simple and carried out under mild conditions, providing an effective new way for directing diamination reactions.     

Negative Pressure Pyrolysis Induced Highly Accessible Single Sites Dispersed on 3D Graphene Frameworks for Enhanced Oxygen Reduction

Herein, we report a negative pressure pyrolysis to access dense single metal sites (Co, Fe, Ni etc.) with high accessibility dispersed on three-dimensional (3D) graphene frameworks (GFs), during which the differential pressure between inside and outside of metal–organic frameworks (MOFs) promotes the cleavage of the derived carbon layers and gradual expansion of mesopores. In situ transmission electron microscopy and Brunauer–Emmett–Teller tests reveal that the formed 3D GFs possess an enhanced mesoporosity and external surface area, which greatly favor the mass transport and utilization of metal sites. This contributes to an excellent oxygen reduction reaction (ORR) activity (half-wave potential of 0.901 V vs. RHE). Theoretical calculations verify that selective carbon cleavage near Co centers can efficiently lower the overall ORR theoretical overpotential in comparison with intact atomic configuration.     

燃料及燃料/氧化剂比对LaFeO3纳米粉体的影响

采用溶液燃烧法合成了钙钛矿型LaFeO3纳米粉体,系统考察了不同燃料及燃料/氧化剂的摩尔比对LaFeO3晶相组成和结构的影响.用X射线衍射仪和扫描电子显微镜对纳米粉体的晶相组成、晶粒大小及微观形貌进行了表征.实验结果表明:制备LaFeO3的适宜的燃料/氧化剂比随燃料的不同而变化,甘氨酸为燃料,在燃料/氧化剂比为化学计量比时可得到19.0 nm LaFeO3纳米晶体;柠檬酸为燃料,贫燃时(-50%)产物LaFeO3晶型最好,而乙二醇为燃料,富燃时(+40%)LaFeO3晶型最好,产物为蓬松的多孔网状纳米结构,晶粒尺寸为28.0 nm.     

甲基蓝-铕为光散射探针测定美他环素的共振瑞利散射及共振非线性散射法研究

在pH=5.50的HAc-NaAc缓冲体系中,低浓度的甲基蓝(MB)-铕稀土配合物的光散射较弱,将微量的美他环素(MTC)加入后体系的共振瑞利散射(RRS)、二级散射(SOS)和倍频散射(FDS)均显著增强,且光散射信号与MTC浓度在一定范围内呈良好的线性关系,据此建立了灵敏的测定美他环素的共振瑞利散射和共振非线性散射分析法.实验以RRS法考查了甲基蓝-铕-美他环素体系形成三元离子缔合物的适宜条件、影响因素等,并初步探讨了其反应机制.     

Stochastic virus dynamics with Beddington-DeAngelis functional response

Stochastic virus dynamics modeled by a system of stochastic differential equations with Beddington-DeAngelis functional response and driven by white noise is investigated. The global existence of positive solutions and the existence of stationary distribution are proved. Upper and lower bounds of the pathwise and asymptotic moments for the positive solutions are sharply estimated. The absorbing property in time average is shown and the moment Lyapunov exponents are proved to be nonpositive.     

Determinations of the transient thermal lensing effect in metal cluster Polymer {WS4Cu4I2(bpe)3}n solution by the use of the Z-scan

The nonlinear optical (NLO) properties of a novel cluster Polymer {WS₄Cu₄I₂(bpe)₃}_n solution are studied by using Z-scan technique with laser pulses of 4.5 ns pulse-width at a wavelength of 532 nm. The results show that the cluster solution possesses strong nonlinear absorption and refraction. Nonlinear refraction of the cluster is composed of third-order nonlinear refraction and transient thermal effect. The thermal effect is mainly due to the strong nonlinear absorption. Numerical simulations obtained by solving simultaneously photo-acoustic and electromagnetic wave equations, agrees basically with experimental results.