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关键词： Drug delivery   Teriparatide   Core-shell microspheres   Osteoporosis   Pulsatile release  

摘要： Teriparatide is a representative anabolic agent for the treatment of osteoporosis; however, its therapeutic efficacy relies on intermittent exposure, necessitating frequent administration and thereby limiting long-term patient compliance. To address this limitation, we developed a programmable pulsatile delivery platform based on uniform core-shell microspheres fabricated via a W₁/O/W₂ double-emulsion process combined with premix membrane emulsification (PME). Through precise regulation of polymer phase separation, teriparatide is preferentially localized within the microsphere core. Core-shell microspheres constructed with PLLA shells of 7, 36, and 78 kDa exhibit well-defined pulsatile release profiles in vitro, each generating a major release event at approximately 7, 14, and 21 days, respectively, with about 40% of the loaded drug discharged during each pulse. In ovariectomized mice, a single administration of the combined microsphere combination formulation enhances bone formation, suppresses bone resorption, and markedly restores trabecular bone microarchitecture over a one-month treatment period, achieving therapeutic outcomes comparable to those of weekly teriparatide solution injections. Collectively, these findings demonstrate that PME-assisted phase separation core-shell microspheres enable synchronized and temporally programmable pulsatile delivery of teriparatide, offering a versatile platform for long-acting peptide therapeutics in osteoporosis management.

关键词： 1,3-pentadiene   Quantum cascade laser   Supersonic expansion  

摘要： The high-resolution infrared spectrum of the ν₂₆ band of trans-1,3-pentadiene near 1003 cm⁻¹ has been observed under supersonic jet-cooled conditions. The spectrum was assigned and fit using a standard asymmetric top Hamiltonian, though it was necessary to include two sub-bands to account for splitting observed in the rotational structure of the spectrum, likely due to the presence of a methyl rotor in the molecule. The spectral assignment was aided by quantum chemical calculations, which were used to predict vibrational frequencies and excited state rotational constants. The calculated vibrational frequencies were used to update the vibrational assignment of trans-1,3-pentadiene where there were discrepancies between the previous vibrational assignment and present computational predictions. The spectroscopic constants derived from the jet-cooled data were also used to create a simulated spectrum at 300 K which showed good agreement with a previously measured room temperature spectrum of this band at high resolution. This work provides a foundation for future studies that explicitly include the methyl rotor in analyzing the rotational structure of the ground and excited states of this vibrational band.

关键词： Combined exposure to arsenic and lipid   Endothelial dysfunction   Endothelial progenitor cells   Caveolin-1   Arsenic  

摘要：

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  EPCs can repair VED caused by the combined exposure to arsenic and lipid.
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  Cav-1 is a pivotal protein which has comparable effects as EPCs injection.
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  Cav-1 was found linked to vascular disease through the high urinary arsenic.

关键词： L-rhamnose   Propionate   Pdu operon   Glycyl radical enzyme   Food biopreservation  

摘要： Lactobacillaceae have a long history as natural or starter cultures in food and produce antimicrobial short-chain carboxylic acids (SCCA) during fermentation. Recently, Loigolactobacillus coryniformis was shown to metabolize the deoxyhexose L-rhamnose to the antifungal SCCA propionate with 1,2-propanediol (1,2-PD) as an intermediate. This study aimed to investigate whether deoxyhexose metabolism is more widespread among food-related Lactobacillaceae. We tested nine Lactobacillaceae species (one strain each) for their ability to produce propionate combining genome analysis with anaerobic cultivation in Hungate tubes. Substrate utilization included ¹³C-labeled L-rhamnose. Bioreactor runs were performed for 72 h at 30 °C and pH 6.5 under aerobic and anaerobic conditions and expression of key genes was monitored. Seven out of nine strains including four Liquorilactobacillus species harbored deoxyhexose metabolism-related genes and produced 1,2-PD. In addition, Latilactobacillus fuchuensis that possessed the pdu operon encoding glycerol/diol dehydratase, and Liquorilactobacillus ghanensis with a gene encoding a glycyl radical enzyme (GRE) formed propionate, which was confirmed by ¹³C-stable isotope probing. In bioreactors, L. ghanensis gre expression and propionate formation were regulated by the presence of oxygen. This study identified new strains that were able to use deoxyhexoses and uncovered a new deoxyhexose utilization pathway in L. ghanensis. Propionate-producing Lactobacillaceae have potential to produce antifungal fermentates for food biopreservation.

关键词： 2:1 resonance   Resonant capture   Resonant jump   Space debris  

摘要： The Global Positioning System (GPS) constellation operates at altitudes that are strongly affected by Earth’s 2:1 gravitational resonance. Unlike the 1:1 resonance, the 2:1 resonance is driven by three dominant harmonic terms of comparable magnitude, which gives rise to more intricate nonlinear dynamics than in the 1:1 resonance. The dynamical models adopted in this work incorporate $J_2$, the three dominant terms of 2:1 resonance, Poynting–Robertson drag, and lunisolar secular perturbations. Based on these models, the resonance width, the equilibrium semi-major axis, and Fast Lyapunov Indicator maps in the resonant angle and semi-major axis phase plane are computed as functions of the initial orbital elements. These indicators reveal the domains of influence of the three dominant terms of 2:1 resonance, as well as the shapes of the resonance islands. The Poynting–Robertson drag, in turn, drives a slow but secular decay of the semi-major axis, causing orbits to drift quasi-statically across the resonant region. As a result, space debris initially above the resonant region is gradually brought into the 2:1 resonance zone, where it may undergo long-term resonant capture, or experience resonant jumps. For space debris located near GPS altitudes with high area-to-mass ratios, the combined action of the 2:1 resonance and the lunisolar secular resonances leads to simultaneous capture into the 2:1 resonance and the lunisolar secular resonance. These results characterize the resonant features of the 2:1 resonance, quantify how resonant capture and resonant jumps depend on the initial orbital elements, and provide new insights into the potential role of the 2:1 resonance in debris mitigation and orbit maintenance strategies in the GPS altitude region.

关键词： TANK结合激酶1(TBK1)   核因子κB激活激酶   CiteSpace   Web of Science   文献计量学   可视化   共被引   研究热点   前沿  

摘要： 背景:肿瘤双向调控因子核因子κB激活激酶的研究成果逐年增多,但是却没有相关文献计量学分析。目的:通过文献计量学分析肿瘤逃避因子核因子κB激活激酶的研究现状、热点及趋势。方法:基于Web of Science核心合集中的SCIE数据库筛选近10年来核因子κB激活激酶相关研究文献,导入Cite Space 6.3.R1软件中分别以国家(地区)、作者、机构、参考文献和关键词5个选项进行文献计量及可视化分析,并运用Origin 2021软件绘制相关统计图。结果与结论:核因子κB激活激酶的发文量、文献共被引次数呈现上升的趋势,Chen,Dan-Dan、Gui,Jian-Fang、Qin,Qiwei和Li,Shun 4位作者发文量最多(11篇),中国科学院、中国科学院大学、浙江大学、中国农业科学院、武汉大学的发文量较大(>50篇)。近10年来关于核因子κB激活激酶的研究热点主要集中在innate immunity、c GAS-STING pathway、NF-κB、inflammation、optineurin、expression、cancer等模块。结果表明,近年来各国学者在相关领域进行了持续且深入的研究,核因子κB激活激酶在自身免疫系统、信号通路、基因表达、肿瘤防治等方面显示出巨大的科研潜力。但是学者之间、机构之间的学术合作并不紧密,今后学者应加强合作与交流,把握核因子κB激活激酶的研究热点与趋势,拓展在疾病领域中的研究范围,为进一步阐明疾病的药效机制和病理变化提供更多证据。

关键词： Immune checkpoint blockade   Immunogenic cell death   Ferroptosis   Calcium overload   Metal-polyphenol network   Thyroid cancer  

摘要：

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  An innovative PEI "electrostatic bridge" strategy enables robust HA coating on negatively charged MPNs, overcoming interfacial repulsion for enhanced tumor targeting and lysosomal escape.
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  The CaO₂@MPN-HA nanoreactor degrades in the TME, enabling self-supplied H₂O₂, Fe²⁺/Fe³ ⁺ cycling, and Ca²⁺ burst to synergistically amplify oxidative stress via ferroptosis and calcium overload.

关键词： Engeletin   Hepatic fibrosis   Inflammation   Oxidative injury   Risperidone  

摘要： Risperidone (RIS) is a potent atypical antipsychotic drug that has gained widespread attention owing to its toxic effects on the body organs such as liver. The current research experiment was executed to elucidate the alleviative efficacy of engeletin (ENG) against risperidone (RIS) induced hepatic dysfunction. Thirty-six Sprague Dawley rats were divided into four groups including control, RIS (2 mg/kg), RIS (2 mg/kg) + ENG (10 mg/kg), and ENG (10 mg/kg) alone administered group for 10 weeks orally. RIS intoxication induced hepatic fibrosis as well as inflammation via upregulating the gene expression of transforming growth factor beta receptor 2 (TGFBR2), transforming growth factor beta receptor 1 (TGFBR1), nuclear factor- kappa B (NF-κB), transforming growth factor beta-1 (TGF-β1), collagen type I alpha 1 (COL1A1), tumor necrosis factor-alpha (TNF-α), SMAD3, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), SMAD4 & interleukin-1beta (IL-1β). The administration of RIS promoted the levels of ROS and MDA while diminishing the activities of HO-1, GPx, SOD, GSR, CAT and GST. RIS intakes abruptly uplifted levels of gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), & alkaline phosphatase (ALP) while lowering the concentrations of albumin & total proteins in hepatic tissues. RIS exposure promoted the levels of Caspase-3, Bax & Caspase-9 while demolishing levels of Bcl-2. RIS intoxication dysregulated the normal architecture of hepatic tissues. Nonetheless, ENG therapy ameliorated hepatic dysregulations owing to its antioxidative, anti-inflammatory, anti-fibrotic as well as anti-apoptotic properties. In addition, advanced molecular docking analysis demonstrated strong binding affinity of engeletin with the key regulatory proteins SMAD3 (−9.3 kcal/mol) and NF-κB p65 (−9.1 kcal/mol), providing strong evidence that ENG can directly interact with the central regulators of the TGF-β1/Smad and NF-κB signaling pathway

关键词： MIRI   MARCHF6   Ferroptosis   Ubiquitination   ADAMTS4   SDC-1  

摘要：

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  Reports indicate that MARCHF6 can regulate ferroptosis.
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  The high expression of MARCHF6 alleviates myocardial ischemia-reperfusion injury.
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  Elevated MARCHF6 expression inhibits ferroptosis in CMECs.
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  MARCHF6 regulates ferroptosis through the ADAMTS4/SDC-1 pathway.
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  MARCHF6 is a promising therapeutic target for MIRI.