Highly thermal conductive shape-stabilized composite phase change materials based on boron nitride and expanded graphite for solar thermal applications.

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.

Effect of regulating the different proportions of Zr to Mn elements on the hydrogen storage properties of titanium-iron-manganese-hydrogen storage alloys.

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 TiFe0.85-x Mn0.15Zr 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 MgZn2 type phases. The MgZn2 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 MgZn2 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.

Albumin-encapsulated HSP90-PROTAC BP3 nanoparticles not only retain protein degradation ability but also enhance the antitumour activity of BP3 in vivo.

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.

A PARP1 PROTAC as a novel strategy against PARP inhibitor resistance via promotion of ferroptosis in p53-positive breast cancer.

Therapeutic targeting of the nuclear enzyme poly (ADP-ribose) polymerase 1 (PARP1) with PARP inhibitors (PARPis) in patients with a homologous recombination (HR)- deficient phenotype based on the mechanism of synthetic lethality has been shown tremendous success in cancer therapy. With the clinical use of various PARPis, emerging evidence has shown that some PARPis offer hope for breakthroughs in triple-negative breast cancer (TNBC) therapy, regardless of HR status. However, similar to other conventional cytotoxic drugs, PARPis are also subject to the intractable problem of drug resistance. Notably, acquired resistance to PARPis caused by point mutations in the PARP1 protein is hard to overcome with current strategies. To explore modalities to overcome resistance and identify patients who are most likely to benefit from PARP1-targeted therapy, we developed a proteolysis-targeted chimaera (PROTAC) to degrade mutant PARP1 in TNBC. Here, we investigated a PARP1 PROTAC termed "NN3″, which triggered ubiquitination and proteasome-mediated degradation of PARP1. Moreover, NN3 degraded PARP1 with resistance-related mutations. Interestingly, compared with other reported PARP1 degraders, NN3 exhibited a unique antitumor mechanism in p53-positive breast cancer cells that effectively promoted ferroptosis by downregulating the SLC7A11 pathway. Furthermore, NN3 showed potent activity and low toxicity in vivo. In conclusion, we propose PROTAC-mediated degradation of PARP1 as a novel strategy against mutation-related PARPi resistance and a paradigm for targeting breast cancer with functional p53 via ferroptosis induction.

Discovery of CN0 as a novel proteolysis-targeting chimera (PROTAC) degrader of PARP1 that can activate the cGAS/STING immunity pathway combined with daunorubicin.

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.

Discovery of BP3 as an efficacious proteolysis targeting chimera (PROTAC) degrader of HSP90 for treating breast cancer.

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.

[Study on chemical constituents of Wedelia trilobata].

A new taraxer-based triterpenoid ester, taraxer-14-en-30-al-3ß-O-palmitate(1), was isolated from the whole plant of Wedelia trilobata, along with six known compounds, ent-kaur-16-en-19-oic acid(2), 16α-hydroxy-ent-kauran-19-oic acid(3), tara-xerol(4), ß-amyrin(5), 1ß-acetoxy-4α, 9α-dihydroxy-6ß-isobutyroxyprostatolide(6), and stigmasterol(7). Their structures were elucidated with use of a combination of spectroscopic techniques(IR, HR-ESI-MS, 1 D, 2 D NMR data) and chemical methods.

Two new cytotoxic glycosides isolated from the green walnut husks of Juglans mandshurica Maxim.

Two new glycosides including an alcohol glycoside and a phenolic glycoside: hexyl-1-O-α-d-arabinofuranosyl-(1 â†’ 6)-ß-d-glucopyranoside (1), 4-hydroxypropiophenone-4-O-ß-d-glucopyranosyl(1 â†’ 6)-ß-d-glucopyranoside(2), along with six known naphthalenyl glucosides (3-8) were isolated from green walnut husks of Juglans mandshurica, and their structures were elucidated on the basis of spectroscopic studies. All compounds were evaluated for their inhibitory effects on tumour cells (BGC-823, HepG-2, MCF-7). The results showed that new compounds 1 and 2 had superior inhibitory activity in comparison with other naphthalenyl glucosides.

[Chemical constituents of Scurrula parasitica].

A new triterpenoid ester, 7ß-hydroxyl-hop-22(29)-en-3ß-O-palmitate (1), was isolated from the stems and leaves of Scurrula parasitica parasitic on Nerium indicum, along with nine known compounds, uvaol (2), 3-epi-ursolic acid (3), 3ß-hydroxyl-hop-22(29)-ene (4), 3ß, 15α-dihydroxyl-lup-20(29)-ene (5), lup-20(29)-en-3-O-α-D-glucoside (6), stigmasterol-3-O-ß-D-glucoside (7), digitoxin-3-O-α-D-glucoside (8), behenic acid (9), octacosyl alcohol (10). Their structures were elucidated using a combination of 1D and 2D NMR techniques (COSY, HMQC, and HMBC) and HR-ESI-MS analyses. Compounds 2-10 were isolated from this plant for the first time.

Chemical of Vitex trifolia.

A new steroidal ester, beta-rosaterol palmitate (1) along with ten known compounds, uvaol(2), 3-epi-ursolic acid (3), 2alpha, 3beta, 24-trihydroxyolean-12-en-28-oic acid (4), 2alpha, 3alpha, 24-trihydroxyurs-12-en-28-oic acid (5), 2alpha, 3alpha, 24-trihydroxyolean-12-en-28-oic acid (6), 2alpha, 3alpha, 24-trihydroxyolean-12-en-28-oic acid-28-O-beta-D-glucopyranosyl ester (7), (Z)-9-hexadecenoic acid (8), octacosyl alcohol (9), beta-sitosterol (10) and beta-daucosterol (11), has been isolated from the stems and leaves of Vitex trifolia. Their structures were elucidated using a combination of 1D and 2D NMR techniques (COSY, HMQC, and HMBC)and HR-ESI-MS analyses. Compounds 2-7 were isolated from this plant for the first time.