阿尔茨海默病居家筛查专家共识

老年人痴呆或认知障碍多由一种以上年龄相关的常见脑部疾病所致。阿尔茨海默病(Alzheimer's disease,AD)是其中最常见的神经变性疾病,且是全球前10位死因中唯一无法治愈或缺乏长期对症疗效的疾病,给个人、家庭和全球经济都带来了巨大的负担。早期及时发现和干预是对抗AD的最佳策略。在过去的30年中,许多研究都提出了降低痴呆风险的方法,2020年《柳叶刀》杂志的痴呆预防报告已阐明通过应对风险因素可以预防或延缓超过40%的痴呆。然而,目前全球医疗体系尚未具备早期或及时发现AD的足够能力。最近的一项研究发现,只有不到10%的轻度认知障碍(mild cognitive impairment,MCI)是在初级医疗机构中诊断出来的。近来,抗淀粉样蛋白β(Amyloid beta,Aβ)抗体药物lecanemab和donanemab被批准上市用于早期AD治疗,以及30年的随访研究证明改善风险因素显著减少AD痴呆的发病率并延长了寿命,使得人们对AD早期识别的关注迅速增加。阿尔茨海默病防治协会(China Association for Alzheimer's Disease,CAAD)认识到居家早期和及时发现AD的重要性,并成立了一个由协会成员、临床医生和研究人员组成的全球AD多领域专家团队,就以下目标达成共识:①为个人、家庭、社区、协会和组织提供专家指导意见;②介绍用于认知障碍和痴呆居家筛查的数字工具和可用资源,并为AD高危人群或疑似患者制定下一步应对策略;③讨论现有可用或将来可能的居家筛查适宜AD生物标志物;④为未来的改进和全球应用建立可行性框架。专家组对于当前可用的证据、工具和资源进行综述,并进一步考量其在AD居家筛查中的价值。

Multiple chemical warfare agent simulant decontamination by self-driven microplasma

Low-temperature plasma is a green and high-efficiency technology for chemical warfare agent(CWA)decontamination.However,traditional plasma devices suffer from the problems of highpower composition and large power-supply size,which limit their practical applications.In this paper,a self-driven microplasma decontamination system,induced by a dielectric-dielectric rotary triboelectric nanogenerator(dd-r TENG),was innovatively proposed for the decontamination of CWA simulants.The microplasma was characterized via electrical measurements,optical emission spectra and ozone concentration detection.With an output voltage of-3460 V,the dd-r TENG can successfully excite microplasma in air.Reactive species,such as OH,O(1D),Hαand O3were detected.With input average power of 0.116 W,the decontamination rate of 2-chloroethyl ethyl sulfide reached 100%within 3 min of plasma treatment,while the decontamination rates of malathion and dimethyl methylphosphonate reached(65.92±1.65)%and(60.88±1.92)%after 7 min of plasma treatment,respectively.In addition,the decontamination rates gradually decreased with the increase in the simulant concentrations.Typical products were identified and analyzed.This study demonstrates the broad spectrum and feasibility of the dd-r TENG-microplasma for CWA elimination,which provides significant guidance for their practical applications in the future.

Large aperture N31 neodymium phosphate laser glass for use in a high power laser facility

Large aperture Nd:phosphate laser glass is a key optical element for an inertial confinement fusion(ICF) facility. N31,one type of neodymium doped phosphate glasses, was developed for high peak power laser facility applications in China. The composition and main properties of N31 glass are given, together with those of LHG-8, LG-770, and KGSS-0180 Nd:phosphate laser glasses, from Hoya and Schott, and from Russia. The technologies of pot melting, continuous melting, and edge cladding of large size N31 phosphate laser glass are briefly described. The small signal gain profiles of N31 glass slabs from both pot melting and continuous melting at various values of the pumping energy of the xenon lamp are presented. N31 glass is characterized by a stimulated emission cross section of 3.8 × 10-20cm2 at 1053 nm,an absorption coefficient of 0.10–0.15% cm-1at laser wavelength, small residual stress around the interface between the cladding glass and the laser glass, optical homogeneity of ～2 × 10-6in a 400 mm aperture, and laser damage threshold larger than 42 J/cm2 for a 3 ns pulse width at 1064 nm wavelength.

绘制小鼠牙胚发育的单细胞图谱并揭示间充质的诱导成牙关键细胞群(CD24^(+)和Plac8^(+)细胞群)

研究人员对牙发育过程中的高分辨时-空关系仍然知之甚少.该文通过高通量(92,688个细胞)单细胞RNA测序追踪牙胚发育过程的细胞轨迹,并结合ATAC测序技术,明确牙胚间充质细胞具显著区分牙齿类型的特异性特征.该文同时发掘起源于间充质细胞的牙本质和牙髓形成中的关键基因调控网络,并绘制具有成牙潜能的间充质细胞空间模式图.在此基础上,该文发现了分别分布于发育晚期牙乳头上半部和预成牙本质细胞层的两个牙胚间充质细胞群,即CD24^(+)和Plac8^(+)细胞,并解析了这两群细胞均可高效诱导非牙源性上皮细胞共同成牙的生理功能.值得关注的是其中的Plac8^(+)组织是迄今为止被证实能在体外诱导再生牙形成的含细胞数量最少且异质性最低的间充质组织模块.综上,该文的工作揭示了牙胚发育过程中由结构和功能决定的时空模式和细胞异质性,为基于干细胞的再生牙构建提供重要的理论基础.

Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells

Background:Tooth is vital not only for a good smile,but also good health.Yet,we lose tooth regularly due to accidents or diseases.An ideal solution to this problem is to regenerate tooth with patients’own cells.Here we describe the generation of tooth-like structures from integration-free human urine induced pluripotent stem cells(ifhU-iPSCs).Results:We first differentiated ifhU-iPSCs to epithelial sheets,which were then recombined with E14.5 mouse dental mesenchymes.Tooth-like structures were recovered from these recombinants in 3 weeks with success rate up to 30%for 8 different iPSC lines,comparable to H1 hESC.We further detected that ifhU-iPSC derived epithelial sheets differentiated into enamel-secreting ameloblasts in the tooth-like structures,possessing physical properties such as elastic modulus and hardness found in the regular human tooth.Conclusion:Our results demonstrate that ifhU-iPSCs can be used to regenerate patient specific dental tissues or even tooth for further drug screening or regenerative therapies.

Comprehensive Proteomic Profiling of Patients'Tears Identifies Potential Biomarkers for the Traumatic Vegetative State

The vegetative state is a complex condition with unclear mechanisms and limited diagnostic, prognostic, and therapeutic methods. In this study, we aimed to explore the proteomic profile of tears from patients in a traumatic vegetative state and identify potential diagnostic markers using tears-a body fluid that can be collected noninvasively. Using iTRAQ quantitative proteomic technology, in the discovery phase, tear samples collected from 16 patients in a traumatic vegetative state and 16 normal individuals were analyzed. Among 1080 identified tear proteins, 57 were upregulated and 15 were downregulated in the patients compared to the controls. Bioinformatics analysis revealed that the differentially-expressed proteins were mainly involved in the wound response and immune response signaling pathways. Furthermore, we verified the levels of 7 differentially-expressed proteins in tears from 50 traumatic vegetative state patients and 50 normal controls （including the samples used in the discovery phase） using ELISA. The results showed that this 7-protein panel had a high discrimination ability for traumatic vegetative state （area under the curve = 0.999）. In sum- mary, the altered tear proteomic profile identified in this study provides a basis for potential tear protein markers for diagnosis and prognosis of the traumatic vegetative state and also provides novel insights into the mechanisms of traumatic vegetative state.

GATA2^(−/−) human ESCs undergo attenuatedendothelial to hematopoietic transition andthereafter granulocyte commitment

Background: Hematopoiesis is a progressive process collectively controlled by an elaborate network of transcriptionfactors (TFs). Among these TFs, GATA2 has been implicated to be critical for regulating multiple steps of hematopoiesisin mouse models. However, whether similar function of GATA2 is conserved in human hematopoiesis, especially duringearly embryonic development stage, is largely unknown.Results: To examine the role of GATA2 in human background, we generated homozygous GATA2 knockout humanembryonic stem cells (GATA2^(−/−) hESCs) and analyzed their blood differentiation potential. Our results demonstratedthat GATA2^(−/−) hESCs displayed attenuated generation of CD34^(+)CD43^(+) hematopoietic progenitor cells (HPCs), due tothe impairment of endothelial to hematopoietic transition (EHT). Interestingly, GATA2^(−/−) hESCs retained the potentialto generate erythroblasts and macrophages, but never granulocytes. We further identified that SPI1 downregulationwas partially responsible for the defects of GATA2^(−/−) hESCs in generation of CD34^(+)CD43^(+) HPCs and granulocytes.Furthermore, we found that GATA2^(−/−) hESCs restored the granulocyte potential in the presence of Notch signaling.Conclusion: Our findings revealed the essential roles of GATA2 in EHT and granulocyte development throughregulating SPI1, and uncovered a role of Notch signaling in granulocyte generation during hematopoiesis modeled byhuman ESCs.

Monolithic edge-cladding process for the elliptical disk of N31-type Nd-doped high-power laser glass

This paper investigates the monolithic edge-cladding process for the elliptical disk of N31-type Nd-doped phosphate laser glass,which will be utilized under liquid cooling conditions for high-power laser systems.The thermal stress,interface bubbles and residual refiectivity,which are due to high-temperature casting and bonding during the monolithic edge-cladding process,are simulated and determined.The applied mould is optimized to a rectangular cavity mould,and the casting temperature is optimized to 1000℃.The resulting lower bubble density makes the mean residual refiectivity as low as 6.75×10^(-5),which is enough to suppress the amplified spontaneous emission generated in the Nd-glass disk,and the resulting maximum optical retardation is converged to 10.2–13.3 nm/cm,which is a favourable base for fine annealing to achieve the stress specification of less than or equal to 5 nm/cm.After fine annealing at the optimized 520℃,the maximum optical retardation is as low as 4.8 nm/cm,and the minimum transmitted wavefront peak-to-valley value is 0.222 wavelength(632.8 nm).An N31 elliptical disk with the size of 194 mm×102 mm×40 mm can be successfully cladded by the optimized monolithic edge-cladding process,whose edge-cladded disk with the size of 200 mm×108 mm×40 mm can achieve laser gain one-third higher than that of an N21-type disk of the same size.

Efficient induction of neural progenitor cells from human ESC/iPSCs on Type I Collagen

A stable,rapid and effective neural differentiation method is essential for the clinical applications of human embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)in treating neurological disorders and diseases.Herein,we established a novel and robust monolayer differentiation method to produce functional neural progenitor cells(NPCs)from human ESC/iPSCs on Type I Collagen.The derived cells not only displayed the requisite markers,but also behaved similarly to classic NPCs both in vitro and in vivo.Upon transplantation into traumatic brain injury model,the derived NPCs facilitated recovery from injury.We also found that SMAD signaling stayed down throughout the differentiation process on Type I Collagen,and the pluripotent signals were rapidly downregulated along with raising up of neural early markers on the third day.Meanwhile,ATAC-seq data showed the related mediation of distinct transcriptome and global chromatin dynamics during NPC induction.Totally,our results thus provide a convenient way to generate NPCs from human ESC/iPSCs for neural diseases’treatment.

Experimental investigation on residual reflectance of Nd:glass amplifier edge cladding

A novel four light ray path test method for measuring residual reflectance has been presented. Residual reflectance spatial distribution at a cladding interface was measured using the technique. Residual reflectance could be on the order of 10-5 by matching the refractive index of Nd:glass, polymer, and cladding glass and eliminating defects in the adhesive layer. Residual reflection spatial distribution appears to be similar to Newton rings due to the edge surface flatness. The relationship between the residual reflectance and the edge surface flatness was discussed, and the results revealed that the edge surface flatness is very important during the cladding process.