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Numerous studies have indicated a close association between gut microbiota dysbiosis, inflammation, and cognitive impairment, highlighting their crucial role in the aging process. 2-(3,4-Dihydroxyphenyl)ethyl 3-hydroxybutanoate (HTHB), a novel derivative of hydroxytryrosol (HT), known for its metabolic and anti-inflammatory properties, was investigated for its effects on memory, inflammation, and gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice. The study employed behavioral testing, biochemical detection and 16S RNA analysis. Results revealed that HTHB mitigated memory decline and lymphocyte aberrance, reduced inflammation in the brain cortex, intestine and peripheral system, and modulated gut microbiota dysbiosis. Interestingly, the cognitive function and serum inflammation of mice significantly correlated with differences in gut microbiota in SAMP8 mice. Furthermore, HTHB treatment exhibited an enhancement of gut barrier integrity in colon tissue in SAMP8 mice. In vitro experiments using HCT116 and DLD1 cells further evidenced that HTHB rescued the tight junction protein levels impaired by lipopolysaccharide (LPS). These finding demonstrate that HTHB effectively ameliorates cognitive dysfunction in aged mice, might by modulating gut microbiota, suppressing inflammation and promoting intestinal barrier integrity. This highlights the potential of HTHB as a therapeutic agent for age-related cognitive loss., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Phase change heat storage technology is a good way to solve the problem that the temperature of solar hot water outlet is affected by the time domain. A stearic acid (SA)-benzamide (BA) eutectic mixture is a potential phase change material (PCM), but it still has the disadvantages of low thermal conductivity and liquid leakage. In this work, a new high thermal conductive shape-stabilized composite PCM was prepared by adding boron nitride (BN) and expanded graphite (EG) to a melted SA-BA eutectic mixture using an ultrasonic and melt adsorption method, and its phase change temperature, latent heat, crystal structure, morphology, thermal conductivity, chemical stability, thermal stability, cycle stability and leakage characteristics were characterized. The results indicates that the addition of BN and EG significantly improved the thermal conductivity of the SA-BA eutectic mixture, and they efficiently adsorbed the melted SA-BA eutectic mixture. Besides, when the mass fractions of BN and EG are 15 wt% and 20 wt%, respectively, the 15BN20EG composite has almost no liquid phase leakage. When the melting enthalpy and temperature of 15BN20EG are 132.35 J g -1 and 65.21 °C, respectively, the thermal conductivity of the 15BN20EG is 6.990 W m -1 K -1 , which is 20.601 times that of the SA-BA eutectic mixture. Moreover, 15BN20EG shows good thermal stability after 100 cycles and good chemical stability below 100 °C. Therefore, the 15BN20EG composite is considered as a potential candidate for solar thermal applications., Competing Interests: We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (This journal is © The Royal Society of Chemistry.)

The effect of regulating the different proportions (0, 1 : 3, 1 : 2 and 1 : 1) of Zr to Mn elements on the hydrogen storage properties of TiFe 0.85- x Mn 0.15 Zr x ( x = 0, 0.05, 0.075 and 0.15) alloys was systematically studied in this work. The results showed that all alloys mainly showed TiFe and MgZn 2 type phases. The MgZn 2 type phase went up with the proportion of Zr to Mn elements. At the same time, increasing the proportion of Zr to Mn elements enhanced the first hydrogenation properties. In addition, the x = 0.15 alloy showed the highest hydrogen storage capacity during the first hydrogenation process. This was because the MgZn 2 type phase could improve the penetration of hydrogen atoms and enhance the diffusion of hydrogen atoms. During the test of prolonged air exposure, it was clear that the oxidation resistance also increased with the proportion of Zr to Mn elements. In addition to this, the effect of the starting particle size was also studied. When the length of the starting particle size was around 0.5 cm, the x = 0.05 alloy did not absorb any hydrogen within 1500 seconds. However, the x = 0.15 alloy could be activated in only around 100 seconds. Finally, the rate limiting step of the first hydrogenation and PCT properties were also investigated., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Proteolysis-targeting chimaera (PROTAC) has received extensive attention in industry. However, there are still some limitations that hinder its further development. In a previous study, our group first demonstrated that the HSP90 degrader BP3 synthesised by the principle of PROTACs showed therapeutic potential for cancer. However, its application was hindered by its high molecular weight and water insolubility. Herein, we aimed to improve these properties of HSP90-PROTAC BP3 by encapsulating it into human serum albumin nanoparticles (BP3@HSA NPs). The results demonstrated that BP3@HSA NPs showed a uniform spherical shape with a size of 141.01 ± 1.07 nm and polydispersity index < 0.2; moreover, BP3@HSA NPs were more readily taken up by breast cancer cells and had a stronger inhibitory effect in vitro than free BP3. BP3@HSA NPs also demonstrated the ability to degrade HSP90. Mechanistically, the improved inhibitory effect of BP3@HSA NPs on breast cancer cells was related to its stronger ability to induce cell cycle arrest and apoptosis. Furthermore, BP3@HSA NPs improved PK properties and showed stronger tumour suppression in mice. Taken together, this study demonstrated that hydrophobic HSP90-PROTAC BP3 nanoparticles encapsulated by human serum albumin could improve the safety and antitumour efficacy of BP3.

Poly ADP-ribose polymerase 1 (PARP1) plays an essential role in DNA repair signaling, rendering it an attractive target for cancer treatment. Despite the success of PARP1 inhibitors (PARPis), only a few patients can currently benefit from PARPis. Moreover, drug resistance to PARPis occurs during clinical treatment. Natural and acquired resistance to PARPis has forced us to seek new therapeutic approaches that target PARP1. Here, we synthesized a series of compounds by proteolysis-targeting chimera (PROTAC) technology to directly degrade the PARP1 protein. We found that CN0 (compound 3) with no polyethylene glycol (PEG) linker can degrade the PARP1 protein through the proteasome pathway. More importantly, CN0 could inhibit DNA damage repair, resulting in highly efficient accumulation of cytosolic DNA fragments due to unresolved unrepaired DNA lesions when combined with daunorubicin (DNR). Therefore, CN0 can activate the cyclic GMP-AMP synthase/stimulator of the interferon gene (cGAS/STING) pathway of innate immunity and then spread the resulting inflammatory signals, thereby reshaping the tumor microenvironment, which may eventually enhance T cell killing of tumor cells., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Heat shock protein 90 (HSP90) is involved in the stabilization and activation of oncoproteins, rendering it essential for oncogenic transformation. However, the HSP90 inhibitors evaluated to date have not led to the expected effects in cancer therapy. Herein, we systematically described the design, synthesis, and evaluation of HSP90 degraders based upon the proteolysis-targeting chimera (PROTAC) strategy. The results showed that the candidate compound 16b (BP3) potently degraded HSP90 and effectively inhibited the growth of human breast cancer cells. When used as a single agent, BP3 led to effective tumor suppression in mice. These findings demonstrate that our HSP90-targeting PROTAC strategy has potential novel applications in breast cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)