NLRP3/1-mediated pyroptosis:beneficial clues for the development of novel therapies for Alzheimer’s disease

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.

Electric Field:A Key Signal in Wound Healing

Wound healing is a complex biological process that involves proliferation,migration,and differentiation.Endogenous electric field(EF)-directed migration of keratinocytes(galvanotaxis)is an essential step in wound re-epithelialization.Endogenous EFs are generated instantaneously after an injury because of the collapse of transepithelial potentials.The application of exogenous EF has become increasingly widespread in promoting wound healing,leading to a paradigm shift in patient outcomes.Here,we summarize the role and value of EF in wound healing through a review of the current research.

Ablation behaviour of C/C-HfC-SiC composites prepared by joint route of precursor infiltration and pyrolysis and gaseous silicon infiltration

C/C-SiC-HfC composites were fabricated by using Precursor Infiltration and Pyrolysis(PIP) combined with Gaseous Silicon Infiltration(GSI) process. Different GSI temperatures(1900 ℃ and 2100 ℃) were selected. The combination of PIP and GSI could significantly reduce the preparation time of the composites. The morphology displaying a rich-Si layer was formed on the surface of the composites prepared at GSI 2100 ℃. Ablation performance of the composites was investigated by oxyacetylene torch. The results showed that after ablation for 120 s, compared to the composites prepared by PIP + 1900 ℃ GSI, the linear and mass ablation rates of the composites fabricated by PIP + 2100 ℃ GSI were decreased from 8.05 μm/s to 5.06 μm/s and from 1.61 mg/s to 1.03 mg/s, respectively. The coverage of the rich-Si surface layer promoted the generation of more SiO_(2) during ablation, which not only benefited for decreasing the surface temperature but also contributed to the formation of H-Si-O glass and the HfO_(2) skeleton, thus better resisting the denudation of the oxyacetylene torch.

CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells

Background:Endogenous electric fields(EFs)play an essential role in guiding the coordinated collective migration of epidermal cells to the wound centre during wound healing.Although polarization of leadercells is essential for collective migration,the signal mechanisms responsible for the EF-induced polarization of leader cells under electrotactic collective migration remain unclear.This study aims to determine how the leader cells are polarized and coordinated during EF-guided collective migration of epidermal cell sheets.Methods:Collective migration of the human epidermal monolayer(human immortalized ker-atinocytes HaCaT)under EFs was observed via time-lapse microscopy.The involvement of tetraspanin-29(CD9)in EF-induced fibrous actin(F-actin)polarization of leader cells as well as electrotactic migration of the epidermal monolayer was evaluated by genetic manipulation.Blocking,rescue and co-culture experiments were conducted to explore the downstream signalling of CD9.Results:EFs guided the coordinated collective migration of the epithelial monolayer to the anode,with dynamic formation of pseudopodia in leader cells at the front edge of the monolayer along the direction of migration.F-actin polarization,as expected,played an essential role in pseudopod formation in leader cells under EFs.By confocal microscopy,we found that CD9 was colocalized with F-actin on the cell surface and was particularly downregulated in leader cells by EFs.Interestingly,genetic overexpression of CD9 abolished EF-induced F-actin polarization in leader cells as well as collective migration in the epidermal monolayer.Mechanistically,CD9 determined the polarization of F-actin in leader cells by downregulating a disintegrin and metalloprotease 17/heparin-binding epidermal growth factor-like growth factor/epidermal growth factor receptor(ADAM17/HB-EGF/EGFR)signalling.The abolished polarization of leader cells due to CD9 overex-pression could be restored in a co-culture monolayer where normal cells and CD9-overexpressing cells were mixed;however,this restoration was eliminated again by the addition of the HB-EGF-neutralizing antibody.Conclusion:CD9 functions as a key regulator in the EF-guided collective migration of the epidermal monolayer by controlling and coordinating the polarization of leader cells through ADAM17/HB-EGF/EGFR signalling.

Advances in ultra-high temperature ceramics,composites,and coatings

Ultra-high temperature ceramics(UHTCs)are generally referred to the carbides,nitrides,and borides of the transition metals,with the Group IVB compounds(Zr&Hf)and TaC as the main focus.The UHTCs are endowed with ultra-high melting points,excellent mechanical properties,and ablation resistance at elevated temperatures.These unique combinations of properties make them promising materials for extremely environmental structural applications in rocket and hypersonic vehicles,particularly nozzles,leading edges,and engine components,etc.In addition to bulk UHTCs,UHTC coatings and fiber reinforced UHTC composites are extensively developed and applied to avoid the intrinsic brittleness and poor thermal shock resistance of bulk ceramics.Recently,high-entropy UHTCs are developed rapidly and attract a lot of attention as an emerging direction for ultra-high temperature materials.This review presents the state of the art of processing approaches,microstructure design and properties of UHTCs from bulk materials to composites and coatings,as well as the future directions.

Micro/nano multiscale reinforcing strategies toward extreme high-temperature applications:Take carbon/carbon composites and their coatings as the examples

Carbon fiber reinforced carbon composites(C/Cs),are the most promising high-temperature materials and could be widely applied in aerospace and nucleation fields,owing to their superior performances.However,C/Cs are very susceptible to destructive oxidation and thus fail at elevated temperatures.Though matrix modification and coating technologies with Si-based and ultra-high temperature ceramics(UHTCs)are valid to enhance the oxidation/ablation resistance of C/Cs,it’s not sufficient to satisfy the increasing practical applications,due to the inherent brittleness of ceramics,mismatch issues between coatings and C/C substrates,and the fact that carbonaceous matrices are easily prone to high-temperature oxidation.To effectively solve the aforementioned problems,micro/nano multiscale reinforcing strategies have been developed for C/Cs and/or the coatings over the past two decades,to fabricate C/Cs with high strength and excellent high-temperature stability.This review is to systematically summarize the most recent major and important advancements in some micro/nano multiscale strategies,including nanoparticles,nanowires,carbon nanotubes/fibers,whiskers,graphene,ceramic fibers and hybrid micro/nano structures,for C/Cs and/or the coatings,to achieve high-temperature oxidation/ablation-resistant C/Cs.Finally,this review is concluded with an outlook of major unsolved problems,challenges to be met and future research advice for C/Cs with excellent comprehensive mechanical-thermal performance.It’s hoped that a better understanding of this review will be of high scientific and industrial interest,since it provides unusual and feasible new ideas to develop potential and practical C/Cs with improved high-temperature mechanical and oxidation/ablation-resistant properties.

High temperature oxidation and ablation behaviors of HfB_(2)-SiC/SiC coatings for carbon/carbon composites fabricated by dipping-carbonization assisted pack cementation

To improve the uniformity and the content of HfBin Hf B-Si-based ceramic coating and alleviate the damage of substrate,and then enhance the high-temperature(1700°C)oxidation and cyclic ablation resistances of carbon/carbon composites,a close-knit double layer HfB_(2)-SiC/SiC coatings with a mosaic structure and high content of HfBwere prepared by a novel dipping-carbonization assisted pack cementation methods(DPC–HS/S).In contrast,a HfB_(2)-SiC/SiC coatings were also fabricated by pack cementation(PC–HS/S).Results revealed that the oxidation and ablation protective performances of the DPC–HS/S coatings were superior to those of PC–HS/S coatings.After 30 thermal cycles between 1500°C and room temperature,the mass gain of the coated sample was 0.78%,and the mass loss was 1.65%after oxidation at 1700°C for 156 h.Moreover,under an oxyacetylene torch ablation for 180 s(3 cycles),the linear ablation rate of the DPC–HS/S coated specimen was 1.62μm/s,which was much lower than that of PC–HS/S coated specimen(3.08μm/s).

Characteristics of burn deaths from 2003 to 2009 in a burn center: A retrospective study

Mortality remains one of the most important end-point quality control parameters to evaluate a burn care system. We retrospectively reviewed the characteristics and multiple organ dysfunction syndrome (MODS) patterns of burn deaths in our center from January 2003 to December 2009. The mortality rate during this time period was 2.3%. Fifty-six patients died, including 49 males and 7 females. The mean survival time was 28.45 ± 24.60 days. The burn percentage was (76.70 ± 26.86) % total burn surface area (TBSA), with (27.74 ± 24.95) % deep-partial thickness burns and (46.88 ± 33.84) % full-thickness burns. Inhalation injury was diagnosed in 36 (64.29%) patients. Patients who had undergone an operation, particularly in the first week post-burn, had a significantly longer survival time. An average of 5.50 ± 1.35 malfunctioning organs per patient and a mean sequential organ failure assessment (SOFA) score of 13.91 ± 3.65 were observed. The most frequently malfunctioning organs were involved in the respiratory, hematologic, circulatory, and central nervous systems. Most of the organ damage occurred during the first week post-burn, followed by 4 weeks later, with relatively less organ damage observed in the third week. Among patients with a TBSA over 50%, non-survivors had larger burn sizes (particularly larger full-thickness burns) and a higher incidence of inhalation injury compared with survivors;nonsurvivors were also more likely to have microorganism-positive blood and sputum cultures. In conclusion, burn deaths are related to a higher burn percentage, inhalation injury, MODS, and infection. Early operation may help improve survival duration.

Epidemiologic and clinical characteristics of severe burn patients: results of a retrospective multicenter study in China, 2011–2015

Background: Severe burns injury is a serious pathology, leading to teratogenicity and significant mortality, and it also has a long-term social impact. The aim of this article is to describe the hospitalized population with severe burns injuries in eight burn centers in China between 2011 and 2015 and to suggest future preventive strategies. Methods: This 5-year retrospective review included all patients with severe burns in a database at eight institutions. The data collected included gender, age, month distribution, etiology, location, presence of inhalation injury, total burn surface area, depth of the burn, the length of hospitalization, and mortality. SPSS 19.0 software was used to analyze the data. Results: A total of 1126 patients were included: 803 (71.3%) male patients and 323 (28.7%) female patients. Scalds were the most common cause of burns (476, 42.27%), followed by fire (457, 40.59%). The extremities were the most frequently affected areas, followed by the trunk. The median length of hospitalization was 30 (15, 52) days. The overall mortality rate was 14.21%. Conclusions: Although medical centers have devoted intensive resources to improving the survival rates of burn patients, expenditures for prevention and education programs are minimal. Our findings suggest that more attention should be paid to the importance of prevention and the reduction of injury severity. This study may contribute to the establishment of a nationwide burn database and the elaboration of strategies to prevent severe burns injury.

The progress of Chinese burn medicine from the Third Military Medical University—in memory of its pioneer,Professor Li Ao

Professor Li Ao was one of the founders of Chinese burn medicine and one of the most renowned doctors and researchers of burns in China. He established one of the Chinese earliest special departments for burns at Third Military Medical University (TMMU) in 1958. To memorialize Professor Li Ao on his 100th birthday in 2017 and introduce our extensive experience, it is our honor to briefly review the development and achievement of the Chinese burn medicine from TMMU. The epidemiology and outcomes of admitted burn patients since 1958 were reviewed. Furthermore, main achievements of basic and clinical research for the past roughly 60 years were presented. These achievements mainly included the Chinese Rule of Nine, fluid resuscitation protocol, experience in inhalation injury, wound treatment strategies, prevention and treatment of burn infections, nutrition therapy, organ support therapies, and rehabilitation. The progress shaped and enriched modern Chinese burn medicine and promoted the development of world burn medicine.

带开槽耗能板的自复位方钢管混凝土柱-钢梁节点抗震性能有限元分析

自复位结构是一种新型可恢复功能结构,它能够有效控制结构震后残余变形,震后不需或经少量维修即可恢复正常使用。近年来,自复位结构成为国内外地震工程界研究的热点。目前的自复位结构主要通过两种方式耗能:金属的塑性变形或设置摩擦阻尼器。但以上两种耗能方式通常存在较大的复位抗力,从而对结构的复位构件提出更高的要求,同时对节点的自复位性能产生不利影响,如何减小复位抗力是此类结构目前亟需解决的重要问题。基于上述问题,提出了一种新型带开槽耗能板的自复位方钢管混凝土柱-钢梁节点,通过在耗能板上开设长槽,可有效减小节点的复位抗力。该节点主要由方钢管混凝土柱、H型钢梁、悬挑梁段、开槽耗能板、盖板、抗剪连接板和钢绞线等构成。为探究该节点的破坏形态、抗震性能、自复位性能及耗能能力,采用有限元软件ABAQUS对带开槽耗能板的自复位方钢管混凝土柱-钢梁节点进行模拟分析,得到弯矩-转角滞回曲线、承载力及特征弯矩、单周滞回耗能及残余变形等。共设计5个节点模型(节点SCJ-1~SCJ-5),对比分析耗能板开槽数量、耗能段宽度、耗能板厚度及钢绞线初始预应力这些参数对节点自复位性能和抗震性能的影响。结果表明:在梁端往复荷载作用下,节点的滞回曲线呈典型的"双旗帜"形,该节点具有良好的承载能力、自复位能力和耗能能力;当加载至4.00%层间位移角时,梁柱主体构件基本处于弹性状态,耗能板发生明显的塑性变形,说明该节点可有效地将损伤控制于局部,从而降低主体构件的塑性损伤;耗能板的开槽数量越多,节点的耗能能力越差,自复位性能越好,而对节点的承载力及特征弯矩没有显著影响;随着耗能段宽度和耗能板厚度的增大,节点的耗能能力增强,自复位能力降低,节点承载力提高。增大钢绞线的初始预应力,节点的初始刚度、承载力和脱开弯矩提高,自复位能力增强,而对节点的耗能能力影响较小。