二(2-重氮-2-苯乙酸)-1,4-丁二醇酯交联剂的合成及在聚己内酯交联中的应用

重氮化合物在一定条件下可以放出氮气生成卡宾结构,这种高活性的卡宾可以与低表面能的聚己内酯材料进行交联反应,得到具有形状记忆效应的交联聚己内酯材料。文中成功合成了一种重氮型交联剂——二(2-重氮-2-苯乙酸)-1,4-丁二醇酯,并优化了该交联剂的合成条件,使其产率可达92.8%。将二(2-重氮-2-苯乙酸)-1,4-丁二醇酯交联剂加入聚己内酯(PCL)中,成功实现了PCL的交联。当二(2-重氮-2-苯乙酸)-1,4-丁二醇酯添加量为PCL质量的20%时,测得凝胶含量为61.1%,得到的交联PCL具有良好的形状记忆性能,其形状恢复率大于95%、形状固定率可达100%。

生物降解性形状记忆聚合物的研究进展

形状记忆聚合物(SMP)可以在特定的刺激下改变形状,是一类应用前景广阔的智能材料。生物降解性SMP可以在人体内分解。这种材料符合生物医学应用中的严格要求,是微创手术和可触发生物医学设备的理想选择,对其中部分材料已经进行了深入的研究,并有着广泛的用途。文中综述了聚乳酸(PLA)、聚己内酯(PCL)、聚三亚甲基碳酸酯(PTMC)、聚十二烷甘油酯(PGD)、聚(ω-十五酸内酯)(PPDL)等几种主要的生物降解性形状记忆聚合物的研究进展,并对其形状记忆效应的机理进行了分析和介绍。

Foodborne toxin Aflatoxin B_(1)induced glomerular podocyte inflammation through proteolysis of RelA,downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.

Discovery of novel covalent selective estrogen receptor degraders against endocrine-resistant breast cancer

Endocrine-resistance remains a major challenge in estrogen receptorαpositive(ERα^(+))breast cancer(BC)treatment and constitutively active somatic mutations in ERαare a common mechanism.There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrineresistance.Given aberrant ERαactivity,we herein report the identification of novel covalent selective estrogen receptor degraders(cSERDs)possessing the advantages of both covalent and degradation strategies.A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERa+breast cancer cell lines including mutant ERα.Crystal structure of ERα-29c complex alongside intact mass spectrometry revealed that 29c disrupted ERa protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11,thus enforcing a unique antagonist conformation and driving the ERαdegradation.These significant effects of the cSERD on ERαhomeostasis,unlike typical ERαdegraders that occur directly via long side chains perturbing the morphology of H12,demonstrating a distinct mechanism of action(MoA).In vivo,29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity.This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

Visible transparent,infrared stealthy polymeric films with nanocoating of ITO@MXene enable efficient passive radiative heating and solar/electric thermal conversion

Visible transparent yet low infrared-emissivity(ε)polymeric materials are highly anticipated in many applications,whereas the fabrication of which remains a formidable challenge.Herein,visible transparent,flexible,and low-εpolymeric films were fabricated by nanocoating decoration of indium tin oxide(ITO)and MXene on polyethylene terephthalate(PET)film surface through magnetron sputtering and spray coating,respectively.The obtained PET-ITO@MXene(PET-IM)film exhibits lowεof 24.7%and high visible transmittance exceeding 50%,endowing it with excellent visible transparent infrared stealthy by reducing human skin radiation temperature from 32 to 20.8°C,and remarkable zero-energy passive radiative heating capability(5.7°C).Meanwhile,the transparent low-εPET-IM film has high solar absorptivity and electrical conductivity,enabling superior solar/electric to thermal conversion performance.Notably,the three heating modes of passive radiative and active solar/electric can be integrated together to cope with complex heating scenarios.These visible transparent low-εpolymeric films are highly promising in infrared stealth,building daylighting and thermal management,and personal precision heating.

Super-enhancer-associated TTC8 alters the nucleocytoplasmic distribution of PHOX2B and activates MAPK signaling in neuroblastoma

Super-enhancers are regions of the mammalian genome comprising multiple enhancers in close proximity and often enriched at cancer genes.^(1)Recent studies suggest the emerging roles of super-enhancer-associated genes in un-derlying the cell identity of neuroblastoma(NB)2 which rises from neural crest-derived cells and is one of the most common malignant solid tumors in children.

Optimized weak measurement of orbital angular momentum-induced beam shifts in optical reflection

Tiny but universal beam shifts occur when a polarized light beam is reflected upon a planar interface.Although the beam shifts of Gaussian beams have been measured by the weak measurement technique, the weak measurement for orbital angular momentum(OAM)-induced spatial shifts of vortex beams is still missing.Here, by elaborately choosing the preselection and postselection states, the tiny OAM-induced Goos–H?nchen and Imbert–Fedorov shifts are amplified at an air–prism interface. The maximum shifts along directions both parallel and perpendicular to the incident plane are theoretically predicted and experimentally verified with optimal preselection and postselection states. These maximum shifts can be used to determine the OAM of vortex beams.

Signatures of functional constraint at Fgfr1a Genes in schizothoracine fishes (Pisces: Cypriniformes): The dermal skeleton variation adapted to high-altitude environments

Fishes harbor a huge resource of phenotypic diversity and are useful for understanding the genetic basis of mor­phological variation.However,it is difficult to transfer classical genetic mapping to most non-model species.In this study,we performed a comparative sequence analysis of Fgfr1a to first interpret the evolution of this candi­date scale-loss gene in 15 schizothoracine fishes with various scale phenotypes.While considerable amino acid(AA)substitutions were observed,molecular evolution analysis indicates that the overall coding regions were subject to functional constraint.We also identified extra copies of Fgfr1a in 4 scale-loss fishes and detected ac­celerated evolution in one AA substitution specific to these duplicates.We speculate that Fgfr1a had accumulat­ed mutations in the ancestral lineage of scale-loss schizothoracine fishes before experiencing duplication events,which was further followed by the diversification of species.In silico mutation analysis predicted deleterious ef­fects of the mutations while no disruptive molecular mechanism was detected.Collectively,our results highlight the important role of Fgfr1a gene in the adaptive evolution of schizothoracine fishes during their radiation in the Qinghai-Tibetan Plateau.

Zooming on T cells in cancer

Immunotherapies have had tremendous progress in treating numerous cancer types since the late twentieth century(Waldman et al.,2020).Accompanied with this,there has been an unprecedented wave of understanding the dynamic changes and the functional mechanisms of immune cells that are tumor-infiltrating and systematically circulating in cancer patients(Waldman et al.,2020).