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Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme environmental conditions. However, pharmacological induction of hypothermia in most mammals remains a huge challenge. Here we show that a natural product P57 promptly induces hypothermia and decreases energy expenditure in mice. Mechanistically, P57 inhibits the kinase activity of pyridoxal kinase (PDXK), a key metabolic enzyme of vitamin B6 catalyzing phosphorylation of pyridoxal (PL), resulting in the accumulation of PL in hypothalamus to cause hypothermia. The hypothermia induced by P57 is significantly blunted in the mice with knockout of PDXK in the preoptic area (POA) of hypothalamus. We further found that P57 and PL have consistent effects on gene expression regulation in hypothalamus, and they may activate medial preoptic area (MPA) neurons in POA to induce hypothermia. Taken together, our findings demonstrate that P57 has a potential application in therapeutic hypothermia through regulation of vitamin B6 metabolism and PDXK serves as a previously unknown target of P57 in thermoregulation. In addition, P57 may serve as a chemical probe for exploring the neuron circuitry related to hypothermia state in mice.

旨在为固体碱催化剂催化油脂裂化制备生物基燃料油提供参考，采用共沉淀法制备Mg-Al水滑石，煅烧后作为催化剂，催化菜籽油裂化制备生物基燃料油。采用XRD、FT-IR、SEM等分析方法对催化剂进行表征分析，并通过对其催化油脂裂化液体产物收率、酸值、皂化值的分析，对其催化性能进行评价，同时采用GC-MS分析了液体产物的组成。结果表明：当催化裂化温度为470 ℃，镁铝比为3∶ 1时，液体产物的收率（60.20%）较高，酸值（KOH）（1.1 mg/g）和皂化值(KOH)(9.3 mg/g)较低；催化剂的最佳使用次数为5次；催化剂的镁铝比为3∶ 1时，液体产物的烷烃和烯烃含量较高。煅烧后的Mg-Al水滑石虽然部分结构遭到破坏，但仍具有很高的结晶度和碱活性，在一定程度上提高了生物基燃料油的品质。 In order to provide a reference for the preparation of bio-based fuel oil by oil cracking catalyzed with solid base catalyst, the Mg-Al hydrotalcite was prepared by co-precipitation method, and then was calcined. The calcined Mg-Al hydrotalcite was used as catalyst to produce bio-based fuel oil by oil cracking.The catalyst was characterized by XRD, FT-IR and electron microscope, and its catalytic performance was evaluated by analyzing the yield, acid value and saponification value of liquid product produced by oil cracking. In addition, the composition of the liquid product was analyzed. The results showed that under the conditions of cracking temperature 470 ℃and ratio of magnesium to aluminum in catalyst 3∶ 1, the yield of liquid product(60.20%) was higher, the acid value (1.1 mgKOH/g)and saponification value(9.3 mgKOH/g) of liquid product were lower. The optimal using times of catalyst were 5. The contents of alkanes and olefins in the liquid product were higher when the ratio of magnesium to aluminum in the catalyst was 3∶ 1. Although part of the structure of calcined Mg-Al hydrotalcite was destroyed, it still had high crystallinity and alkali activity, which improved the quality of bio-based fuel oil to a certain extent.

Aurora A plays a critical role in G2/M transition and mitosis, making it an attractive target for cancer treatment. Aurora A inhibitors showed remarkable antitumor effects in preclinical studies, but unsatisfactory outcomes in clinical trials have greatly limited their development. In this study, the Aurora A inhibitor alisertib upregulated programmed death ligand 1 (PD-L1) expression in a panel of tumor cells both in vitro and in vivo. Upregulation of the checkpoint protein PD- L1 reduced antitumor immunity in immune-competent mice, paradoxically inhibiting the antitumor effects of alisertib. Mechanistically, Aurora A directly bound to and phosphorylated cyclic GMP-AMP synthase (cGAS), suppressing PD-L1 expression in tumor cells. Aurora A inhibition by alisertib activated the cGAS/stimulator of IFN genes (STING)/NF-[kappa]B pathway and promoted PD-L1 expression. Combining alisertib with anti-PD-L1 antibody improved antitumor immunity and enhanced the antitumor effects of alisertib in immune-competent mice. Our results, which reveal the immunomodulatory functions of Aurora A inhibitors and provide a plausible explanation for the poor clinical outcomes with their use, offer a potential approach to improve the antitumor efficacy of these inhibitors., Introduction Aurora A, a member of the evolutionarily conserved Aurora serine/threonine kinase family, is an essential mediator for centrosome maturation and separation and for the ultimate formation of the mitotic [...]

Additive human menopausal gonadotropin (HMG)/recombinant luteinizing hormone (r-LH) to follicle-stimulating hormone (FSH) can improve pregnancy outcomes in patients with poor ovarian response during assisted reproductive procedures. However, their effects on patients with normal ovarian response during such procedures are unclear, which formed the aim of this study. Methods: This retrospective study enrolled 456 infertile women who underwent in vitro fertilization or intracytoplasmic sperm injection treatment. Group 1 received FSH; Group 2 received FSH+HMG/r-LH; Group 3 received FSH+HMG+r-LH. Results: The age and Body Mass Index were significantly greater in Group III. The endometrial thickness was greater in Groups II and III, suggesting better endometrial receptivity. Better pregnancy and birth outcomes were seen in Group 3. In sub-cohorts of women older than 32 years old or with overweight/obesity, pregnancy and birth outcomes were also much better in Group 3, albeit without statistical significance. Conclusion: The addition of both HMG and r-LH to FSH may improve the chance of infertile women with normal ovarian responses to have more success in having live birth babies, specifically in those over 32 years of age or with overweight/obese patients who typically face challenges in conceiving and sustaining a pregnancy. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: OSW‐1 is a well‐known natural saponin with potent antitumor activities. We have designed and prepared a small library of 22 OSW‐1 analogues with a variety of p‐acylamino‐benzoyl groups installed at C2" of the xylose residue, wherein a regioselective (1→3)‐glycosylation of arabinoside 3,4‐diol has been achieved by manipulation of the protecting groups on the imidate donors. Bioassays lead to new structure‐activity relationships as well as two applicable fluorescent probes, which are found to localize to lysosomes in HeLa cells and could be used in further antitumor mechanism studies of OSW‐1 in living cells. [ABSTRACT FROM AUTHOR]