脑脊液ctDNA对非小细胞肺癌脑膜转移患者的临床价值

背景与目的肺癌脑膜转移病死率极高。循环肿瘤DNA(circulating tumor DNA,ctDNA)已被证实含有肿瘤的基因组改变信息,并已被用于监测肿瘤的进展和对治疗的响应。对于存在脑膜转移瘤的患者,由于血脑屏障等因素的存在,外周血ctDNA不能反映脑部病灶的信息,此时脑脊液ctDNA作为检测样本能更好地体现颅内肿瘤的基因状态,指导临床对颅内病灶的靶向治疗。本研究旨在探究脑脊液ctNDA用于监测非小细胞肺癌(non-small cell lung cancer,NSCLC)脑膜转移的可行性以及脑脊液ctDNA检测对NSCLC脑膜转移的临床价值。方法入组NSCLC脑膜转移患者21例,通过二代基因测序技术对患者的脑脊液及外周血样本进行基因检测,并进行脑脊液细胞学病理学检测和头颅核磁共振增强检查。结果入组21例患者脑脊液中均检测到ctDNA。脑脊液ctDNA检测的灵敏性在脑膜转移诊断方面优于细胞学(P<0.001)。脑脊液的基因突变检出率及基因突变丰度均高于血浆(P<0.001)。脑脊液具有独特的基因谱。6例动态检测的患者中,脑脊液中ctDNA丰度变化均同时或早于临床疾病变化出现,可及时揭示耐药机制和监测复发趋势。结论脑脊液ctDNA检出率高于细胞学及影像学;脑脊液ctDNA检测可展现脑膜转移病灶特有的突变图谱;脑脊液ctDNA动态监测对肺癌患者临床疗效具有提示意义。

Energy-Dissipative Hydrogels:A Promising Material for Tissue Regeneration

Hydrogels are promising candidates for mimicking native extracellular matrix(ECM)and are therefore widely adopted as scaffolds in tissue engineering.However,conventional hydrogels composed of static networks are prone to permanent structural damages and lack the ability to provide the time-dependent mechanical cues,which are essential for cell development,ECM remodeling,and tissue regeneration.The recent substantial development in the structurally dynamic hydrogels with energy-dissipative ability has demonstrated the unique capability of such viscoelastic hydrogels to withstand extreme biomechanical loads and regulate cellular behaviors not present in classical hydrogels.This review starts with the general design principles for energy-dissipative hydrogels,followed by recent advancements in fabrication approaches for energy-dissipative hydrogels.We then highlight some applications of energy-dissipative hydrogels in tissue engineering,including bone and cartilage regeneration,vessel regeneration,nerve regeneration,and wound healing.Finally,we discuss about the key current challenges and future development of energy-dissipative hydrogels for biomedical applications.

Complex coacervate-derived hydrogel with asymmetric and reversible wet bioadhesion for preventing UV light-induced morbidities

Protecting the skin from UV light irradiation in wet and underwater environments is challenging due to the weak adhesion of existing sunscreen materials but highly desired.Herein we report a polyethyleneimine/thioctic acid/titanium dioxide(PEI/TA/TiO_(2))coacervate-derived hydrogel with robust,asymmetric,and reversible wet bioadhesion and effective UV-light-shielding ability.The PEI/TA/TiO_(2)complex coacervate can be easily obtained by mixing a PEI solution and TA/TiO_(2)powder.The fluid PEI/TA/TiO_(2)coacervate deposited on wet skin can spread into surface irregularities and subsequently transform into a hydrogel with increased cohesion,thereby establishing interdigitated contact and adhesion between the bottom surface and skin.Meanwhile,the functional groups between the skin and hydrogel can form physical interactions to further enhance bioadhesion,whereas the limited movement of amine and carboxyl groups on the top hydrogel surface leads to low adhesion.Therefore,the coacervate-derived hydrogel exhibits asymmetric adhesiveness on the bottom and top surfaces.Moreover,the PEI/TA/TiO_(2)hydrogel formed on the skin could be easily removed using a NaHCO3 aqueous solution without inflicting damage.More importantly,the PEI/TA/TiO_(2)hydrogel can function as an effective sunscreen to block UV light and prevent UV-induced MMP-9 overexpression,inflammation,and DNA damage in animal skin.The advantages of PEI/TA/TiO_(2)coacervate-derived hydrogels include robust,asymmetric,and reversible wet bioadhesion,effective UV light-shielding ability,excellent biocompatibility,and easy preparation and usage,making them a promising bioadhesive to protect the skin from UV light-associated damage in wet and underwater environments.

Surface decoration of development-inspired synthetic N-cadherin motif via Ac-BP promotes osseointegration of metal implants

Research works on the synergistic effect of surface modified bioactive molecules and bone metal implants have been highlighted.N-cadherin is regarded as a key factor in directing cell-cell interactions during the mesenchymal condensation preceding the osteogenesis in the musculoskeletal system.In this study,the N-cadherin mimetic peptide(Cad)was biofunctionalized on the titanium metal surface via the acryloyl bisphosphonate(Ac-BP).To learn the synergistic effect of N-cadherin mimetic peptide,when tethered with titanium substrates,on promoting osteogenic differentiation of the seeded human mesenchymal stem cells(hMSCs)and the osseointegration at the bone-implant interfaces.Results show that the conjugation of N-cadherin mimetic peptide with Ac-BP promoted the osteogenic gene markers expression in the hMSCs.The biofunctionalized biomaterial surfaces promote the expression of the Wnt/β-catenin downstream axis in the attached hMSCs,and then enhance the in-situ bone formation and osseointegration at the bone-implant interfaces.We conclude that this N-cadherin mimetic peptide tethered on Ti surface promote osteogenic differentiation of hMSCs and osseointegration of biomaterial implants in vitro and in vivo.These findings demonstrate the importance of the development-inspired surface bioactivation of metal implants and shed light on the possible cellular mechanisms of the enhanced osseointegration.

Novel Designed PEG-Dicationic Imidazolium-Based Ionic Liquids as Effective Plasticizers for Sustainable Polylactide

A series of novel polyethylene glycol-dicationic imidazolium-based ionic liquids(mPEG-ILs)were synthesized by facile quaternization reaction from various elaborately designed di-imidazoles and PEG,which were then studied as green plasticizers for sustainable polylactide(PLA)material.

Bisphosphonate-based hydrogel mediates biomimetic negative feedback regulation of osteoclastic activity to promote bone regeneration

The intricate dynamic feedback mechanisms involved in bone homeostasis provide valuable inspiration for the design of smart biomaterial scaffolds to enhance in situ bone regeneration.In this work,we assembled a biomimetic hyaluronic acid nanocomposite hydrogel(HA-BP hydrogel)by coordination bonds with bisphosphonates(BPs),which are antiosteoclastic drugs.The HA-BP hydrogel exhibited expedited release of the loaded BP in response to an acidic environment.Our in vitro studies showed that the HA-BP hydrogel inhibits mature osteoclastic differentiation of macrophage-like RAW264.7 cells via the released BP.Furthermore,the HA-BP hydrogel can support the initial differentiation of primary macrophages to preosteoclasts,which are considered essential during bone regeneration,whereas further differentiation to mature osteoclasts is effectively inhibited by the HA-BP hydrogel via the released BP.The in vivo evaluation showed that the HA-BP hydrogel can enhance the in situ regeneration of bone.Our work demonstrates a promising strategy to design biomimetic biomaterial scaffolds capable of regulating bone homeostasis to promote bone regeneration.