Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Determination of the best materials for development and designing product using a multi-criteria decision-making

Purpose–Material selection,driven by wide and often conflicting objectives,is an important,sometimes difficult problem in material engineering.In this context,multi-criteria decision-making(MCDM)methodologies are effective.An approach of MCDM is needed to cater to criteria of material assortment simultaneously.More firms are now concerned about increasing their productivity using mathematical tools.To occupy a gap in the previous literature this research recommends an integrated MCDM and mathematical Bi-objective model for the selection of material.In addition,by using the Technique for Order Preference by Similarity to Ideal Solution(TOPSIS),the inherent ambiguities of decision-makers in paired evaluations are considered in this research.It goes on to construct a mathematical bi-objective model for determining the best item to purchase.Design/methodology/approach–The entropy perspective is implemented in this paper to evaluate the weight parameters,while the TOPSIS technique is used to determine the best and worst intermediate pipe materials for automotive exhaust system.The intermediate pipes are used to join the components of the exhaust systems.The materials usually used to manufacture intermediate pipe are SUS 436LM,SUS 430,SUS 304,SUS 436L,SUH 409 L,SUS 441 L and SUS 439L.These seven materials are evaluated based on tensile strength(TS),hardness(H),elongation(E),yield strength(YS)and cost(C).A hybrid methodology combining entropy-based criteria weighting,with the TOPSIS for alternative ranking,is pursued to identify the optimal design material for an engineered application in this paper.This study aims to help while filling the information gap in selecting the most suitable material for use in the exhaust intermediate pipes.After that,the authors searched for and considered eight materials and evaluated them on the following five criteria:(1)TS,(2)YS,(3)H,(4)E and(5)C.The first two criteria have been chosen because they can have a lot of influence on the behavior of the exhaust intermediate pipes,on their performance and on the cost.In this structure,the weights of the criteria are calculated objectively through the entropy method in order to have an unbiased assessment.This essentially measures the quantity of information each criterion contribution,indicating the relative importance of these criteria better.Subsequently,the materials were ranked using the TOPSIS method in terms of their relative performance by measuring each material from an ideal solution to determine the best alternative.The results show that SUS 309,SUS 432L and SUS 436 LM are the first three materials that the exhaust intermediate pipe optimal design should consider.Findings–The material matrix of the decision presented in Table 3 was normalized through Equation 5,as shown in Table 5,and the matrix was multiplied with weighting criteriaß_j.The obtained weighted normalized matrix V_ij is presented in Table 6.However,the ideal,worst and best value was ascertained by employing Equation 7.This study is based on the selection of material for the development of intermediate pipe using MCDM,and it involves four basic stages,i.e.method of translation criteria,screening process,method of ranking and search for methods.The selection was done through the TOPSIS method,and the criteria weight was obtained by the entropy method.The result showed that the top three materials are SUS 309,SUS 432L and SUS 436 LM,respectively.For the future work,it is suggested to select more alternatives and criteria.The comparison can also be done by using different MCDM techniques like and Choice Expressing Reality(ELECTRE),Decision-Making Trial and Evaluation Laboratory(DEMATEL)and Preference Ranking Organization Method for Enrichment Evaluation(PROMETHEE).Originality/value–The results provide important conclusions for material selection in this targeted application,verifying the employment of mutual entropy-TOPSIS methodology for a series of difficult engineering decisions in material engineering concepts that combine superior capacity with better performance as well as cost-efficiency in various engineering design.

我国化工、盐类矿产资源开发利用现状及存在的问题

文章对我国重要化工、盐类矿产,包括钾、磷、硫、锂、铷、铯、石墨、萤石、硼、镁、重晶石,共11个矿种的资源情况、生产现状以及存在问题进行了分析。并将国内盐湖矿产品相关产业发展情况与世界典型矿产资源强国相比,我国在国内外资源获取能力,产业链延伸,产业集中度情况,参与国际定价方面尚存在很大差距。针对我国现阶段化工、盐类资源产业发展存在的问题及与世界矿产资源强国的差距,提出了化工、盐类矿产品产业发展途径,并在管理机制体制、金融政策、人才队伍建设、国际合作方面,给出了一些初步的意见和建议。未来10 a,与大宗矿产下降趋势不同,我国化工、盐类需求呈明显增长趋势,并将在之后相当长时间维持高位运行,加之"一带一路"中相关资源战略的实施,我国化工、盐类矿产资源产业及发展将面临新的机遇和挑战。

一种机械臂分段插值轨迹规划方法

针对工业机械臂在运动过程中的角速度与角加速度突变引起的机械系统冲击问题,结合五次B样条曲线和五次多项式的高阶连续性,提出了一种新的分段插值轨迹规划算法即"B-5-B算法"。通过SOLIDWORKS建立样机模型,利用Adams进行虚拟样机的运动学仿真,得到关节的角位移、角速度、角加速度以及关节力矩图。通过与"3-5-3算法"所得到的图进行比较,表明了该算法提高了工业机械臂的角速度和角加速度曲线的平滑性,并降低了机械系统的冲击力,同时由于B样条具有局部支撑性,为轨迹优化提供了一种新的方法,也为机械臂实物验证做了充分的理论支撑。

Initial coin offerings(ICOs):Why do they succeed?

Recent literature has addressed initial coin offering(ICO)projects,which are an innovative form of venture financing through cryptocurrencies using blockchain technology.Many features of ICOs remain unexplored,leaving much room for additional research,including the success factors of ICO projects.We investigate the success of ICO projects,with our main purpose being to identify factors that influence a project’s outcome.Following a literature review,from which several potential variables were collected,we used a database comprising 428 ICO projects in the banking/financial sector to regress several econometric models.We confirmed the impacts of several variables and obtained particularly valuable results concerning project and campaign variables.We confirmed the importance of a well-structured and informative white-paper.The proximity to certain markets with high availability of financial and human capital is also an important determinant of the success of an ICO.We also confirm the strong dependency on cryptocurrency and the impact of cryptocurrency valuations on the success of a project.Furthermore,we confirm the importance of social media in ICO projects,as well as the importance of human capital characteristics.Our research contributes to the ICO literature by capturing most of the success factors previously identified and testing their impacts based on a large database.The current research contributes to the building of systems theory and signaling theory by adapting their frameworks to the ICO environment.Our results are also important for regulators,as ICOs are mainly unregulated and have vast future potential,and for investors,who can benefit from our analysis and use it in their due diligence.

Assessing the relationship between the rumen microbiota and feed efficiency in Nellore steers

Background:Ruminants rely upon a complex community of microbes in their rumen to convert host-indigestible feed into nutrients.However,little is known about the association between the rumen microbiota and feed efficiency traits in Nellore(Bos indicus)cattle,a breed of major economic importance to the global beef market.Here,we compare the composition of the bacterial,archaeal and fungal communities in the rumen of Nellore steers with high and low feed efficiency(FE)phenotypes,as measured by residual feed intake(RFI).Results:The Firmicutes to Bacteroidetes ratio was significantly higher(P<0.05)in positive-RFI steers(p-RFI,low feed efficiency)than in negative-RFI(n-RFI,high feed efficiency)steers.The differences in bacterial composition from steers with high and low FE were mainly associated with members of the families Lachnospiraceae,Ruminococcaceae and Christensenellaceae,as well as the genus Prevotella.Archaeal community richness was lower(P<0.05)in p-RFI than in n-RFI steers and the genus Methanobrevibacter was either increased or exclusive of p-RFI steers.The fungal genus Buwchfawromyces was more abundant in the rumen solid fraction of n-RFI steers(P<0.05)and a highly abundant OTU belonging to the genus Piromyces was also increased in the rumen microbiota of highefficiency steers.However,analysis of rumen fermentation variables and functional predictions indicated similar metabolic outputs for the microbiota of distinct FE groups.Conclusions:Our results demonstrate that differences in the ruminal microbiota of high and low FE Nellore steers comprise specific taxa from the bacterial,archaeal and fungal communities.Biomarker OTUs belonging to the genus Piromyces were identified in animals showing high feed efficiency,whereas among archaea,Methanobrevibacter was associated with steers classified as p-RFI.The identification of specific RFI-associated microorganisms in Nellore steers could guide further studies targeting the isolation and functional characterization of rumen microbes potentially important for the energy-harvesting efficiency of ruminants.

Evaluation of the diagnostic and therapeutic utility of retrograde through-the-scope balloon enteroscopy and single-balloon enteroscopy

BACKGROUND Retrograde single balloon enteroscopy(SBE)is a minimally invasive procedure which is less frequently performed compared with antegrade SBE.There are few studies on the retrograde through-the-scope enteroscopy(TTSE),a novel technique for evaluation of the small bowel.AIM To compare the clinical utility and safety of retrograde TTSE with retrograde SBE.METHODS Clinical data and complications of retrograde TTSE(2014-2018)and retrograde SBE(2011-2018)performed in a community hospital were reviewed and presented as mean±SD or frequency(%)and compared using proper statistical tests.Technical success was defined as insertion of the enteroscope>20 cm beyond ileocecal valve.RESULTS Data obtained from 54 retrograde SBE in 49 patients and 27 retrograde TTSE in 26 patients were studied.The most common indication for retrograde enteroscopy was iron deficiency anemia(41 patients)followed by gastrointestinal bleeding(37 patients),and chronic diarrhea(7 patients).The duration of retrograde SBE procedure(91.9±34.2 min)was significantly longer compared with retrograde TTSE(70.5±30.7 min)(P=0.04).Technical success was comparable in TTSE[23/27(85.2%)]and SBE[41/54(75.9%)(P=0.33)].The mean depth of insertion beyond the ileocecal valve in retrograde SBE(92.5±70.0 cm)tended to be longer compared with retrograde TTSE(64.6±49.0 cm)(P=0.08).No complication was observed in this study.CONCLUSION Both retrograde TTSE and retrograde SBE are feasible and safe.Retrograde TTSE takes a shorter time and has a comparable technical success with SBE.TTSE has a lower capacity of small bowel insertion.

Development of hepatorenal syndrome in bile duct ligated rats

AIM: To evaluate in bile duct ligated rats whether there were progressive alterations of renal function without changes in histopathology. METHODS: Male Wistar rats were submitted to sham-surgery or bile duct ligation (BDL) and divided according to the post-procedure time (2, 4 and 6-wk). To determine renal function parameters, rats wereplaced in metabolic cages and, at the end of the experiment, blood and urine samples were obtained. Histology and hydroxyproline content were analyzed in liver and renal tissue. RESULTS: Rats with 2 wk of BDL increased free water clearance (P = 0.02), reduced urinary osmolality (P = 0.03) and serum creatinine (P = 0.01) in comparison to the sham group. In contrast, rats at 6 wk of BDL showed features of HRS, including signif icant increase in serum creatinine and reductions in creatinine clearance, water excretion and urinary sodium concentration. Rats with 4 wk of BDL exhibited an intermediate stage of renal dysfunction. Progressive hepatic f ibrosis according to post-procedure time was confirmed by histology. The increased levels of liver hydroxyproline contrasted with the absence of structural changes in the kidney, as assessed by histology and unchanged hydroxyproline content in renal tissue. CONCLUSION: Our data show that BDL produced progressive renal dysfunction without structural changes in the kidney, characterizing HRS. The present model will be useful to understand the pathophysiology of HRS.

Communicating in Product Harm Crises: Do the Right Thing

Food recalls can have very serious aftermath from many points of view: starting from the outbreak consequences on public health, on company’s reputation, sell-out, finance, up to putting at risk the survival of the firm itself. From a formal point of view, a product harm crisis presents similarities with other emergency situations: both of them consist in unpredictable events, often due to unknown or undervalued causes, which can significantly alter normal business and compromise the safety of the company, of its employees and customers. Given the potential damage resulting from a dangerous product crisis, it is surprising that in the food industry alongside mere procedures (often reducible to botched manuals compiled solely because their presence reassures auditors and authorities) there is still little attention to an approach based on a method. Formal corporate procedures (manuals and crisis management plans) are important, but can cause a false sense of security and preparedness, if executives do not possess an adequate crisis management culture, which depends, as well as on experience and training, also on the ability to assume the correct behavioral posture, and which involves psychological, organizational and communicational skills that can not be undervalued. The purpose of this article is to provide a practical approach based on the experience of crisis-management (applied in emergency situations by health professionals, armed forces and civil protection) useful to support food industry during a food recall, in order to avoid the most classic errors that can undermine speed of reaction, corrective measures effectiveness and leadership, in the most delicate moments for a company life. If it is true the way a firm manages the recall affects its impact, it is necessary to assess the fundamental factors to be observed at such times: timeliness, lucidity, responsibility, leadership.

民乐交响化的思考

本文通过对中西音乐的器乐声学、乐团编制、乐器伴奏从属性改革、律制改革的对比,阐述了中西乐器交响化的差距所在,明确了中国民乐交响改革的方向。

基层、文化和人性在认识和优先考虑未来的设计教育方面起着重要作用

《设计》:根据您的观察,在过去三年的毕业设计中,毕业生们都在探讨哪些话题?您认为为什么会这样?周传美:近年来,我们的毕业生所探讨的最常见的主题与以下问题有关:1.环境与可持续发展;2.未来主义/机器人;3.游戏;4.虚拟现实;5.文化;6.身份认同;7.场所制造(Place-making)。他们热衷于讨论这些问题,我相信这是由于当前的趋势以及社会媒体的影响,因为大多数毕业生都是Z世代,他们一出生就与网络信息时代无缝对接,受数字信息技术、即时通信设备、社交媒体的影响极大,这种由科技发展塑造的社群关系与价值观深深影响了他们。

Recent applications of isotope analysis to forensic anthropology

Isotope analysis has become an increasingly valuable tool in forensic anthropology case-work over the past decade. Modern-day isotopic investigations on human remains have integrated the use of multi-isotope profiles (e.g. C, N, O, H, S, Sr, and Pb) as well as iso-topic landscapes ("isoscapes") from multiple body tissues (e.g. teeth, bone, hair, and nails) to predict possible region-of-origin of unidentified human remains. Together, data from various isotope analyses provide additional lines of evidence for human identification, including a decedent's possible region-of-birth, long-term adult residence, recent travel history, and dietary choices. Here, we present the basic principles of isotope analysis and provide a brief overview of instrumentation, analytical standards, sample selection, and sample quality measures. Finally, we present case studies that reflect the diverse applications of isotope analysis to the medicolegal system before describing some future research directions. As shown herein, isotope analysis is a flexible and powerful geolocation tool that can provide new investigative leads for unidentified human remains cases.

Salmonella enterica Flagellin Is Recognized via FLS2 and Activates PAMP-Triggered Immunity in Arabidopsis thaliana

Infections with Salmonella enterica belong to the most prominent causes of food poisoning and infected fruits and vegetables represent important vectors for salmonellosis. Recent evidence indicates that plants recognize S. enterica and raise defense responses. Nonetheless, the molecular mechanisms controlling the interaction of S. enterica with plants are still largely unclear. Here, we show that flagellin from S. enterica represents a prominent pathogenassociated molecular pattern （PAMP） in Arabidopsis thaliana, which induces PAMP-triggered immunity （PTI） via the recognition of the fig22 domain by the receptor kinase FLS2. The Arabidopsis fls2 mutant shows reduced though not abolished PTI activation, indicating that plants rely also on recognition of other S. enterica PAMPs. Interestingly, the S. enterica type III secretion system （T3SS） mutant prgH- induced stronger defense gene expression than wild-type bacteria in Arabidopsis, suggesting that T3SS effectors are involved in defense suppression. Furthermore, we observe that S. enterica strains show variation in the fig22 epitope, which results in proteins with reduced PTI-inducing activity. Altogether, these results show that S. enterica activates PTI in Arabidopsis and suggest that, in order to accomplish plant colonization, S. enterica evolved strategies to avoid or suppress PTI.

Cell specialization and coordination in Arabidopsis leaves upon pathogenic attack revealed by scRNA-seq

Plant defense responses involve several biological processes that allow plants to fight against pathogenic attacks.How these different processes are orchestrated within organs and depend on specific cell types is poorly known.Here,using single-cell RNA sequencing(scRNA-seq)technology on three independent biological replicates,we identified several cell populations representing the core transcriptional responses of wild-type Arabidopsis leaves inoculated with the bacterial pathogen Pseudomonas syringae DC3000.Among these populations,we retrieved major cell types of the leaves(mesophyll,guard,epidermal,companion,and vascular S cells)with which we could associate characteristic transcriptional reprogramming and regulators,thereby specifying different cell-type responses to the pathogen.Further analyses of transcriptional dynamics,on the basis of inference of cell trajectories,indicated that the different cell types,in addition to their characteristic defense responses,can also share similar modules of gene reprogramming,uncovering a ubiquitous antagonism between immune and susceptible processes.Moreover,it appears that the defense responses of vascular S cells,epidermal cells,and mesophyll cells can evolve along two separate paths,one converging toward an identical cell fate,characterized mostly by lignification and detoxification functions.As this divergence does not correspond to the differentiation between immune and susceptible cells,we speculate that this might reflect the discrimination between cellautonomous and non-cell-autonomous responses.Altogether our data provide an upgraded framework to describe,explore,and explain the specialization and the coordination of plant cell responses upon pathogenic challenge.

Self-assembling protein nanocarrier for selective delivery of cytotoxic polypeptides to CXCR4^(+) head and neck squamous cell carcinoma tumors

Loco-regional recurrences and distant metastases represent the main cause of head and neck squamous cell carcinoma(HNSCC) mortality. The overexpression of chemokine receptor 4(CXCR4) in HNSCC primary tumors associates with higher risk of developing loco-regional recurrences and distant metastases, thus making CXCR4 an ideal entry pathway for targeted drug delivery. In this context, our group has generated the self-assembling protein nanocarrier T22-GFP-H6, displaying multiple T22 peptidic ligands that specifically target CXCR4. This study aimed to validate T22-GFP-H6 as a suitable nanocarrier to selectively deliver cytotoxic agents to CXCR4^(+)tumors in a HNSCC model. Here we demonstrate that T22-GFP-H6 selectively internalizes in CXCR4^(+)HNSCC cells, achieving a high accumulation in CXCR4^(+)tumors in vivo, while showing negligible nanocarrier distribution in non-tumor bearing organs. Moreover, this T22-empowered nanocarrier can incorporate bacterial toxin domains to generate therapeutic nanotoxins that induce cell death in CXCR4-overexpressing tumors in the absence of histological alterations in normal organs. Altogether, these results show the potential use of this T22-empowered nanocarrier platform to incorporate polypeptidic domains of choice to selectively eliminate CXCR4^(+)cells in HNSCC. Remarkably, to our knowledge, this is the first study testing targeted proteinonly nanoparticles in this cancer type, which may represent a novel treatment approach for HNSCC patients.

COMPARING PERFORMANCE OF CROP SPECIES MIXTURES AND PURE STANDS

Intercropping is the planned cultivation of species mixtures on agricultural land.Intercropping has many attributes that make it attractive for developing a more sustainable agriculture,such as high yield,high resource use efficiency,lower input requirements,natural suppression of pests,pathogens and weeds,and building a soil with more organic carbon and nitrogen.Information is needed which species combinations perform best under different circumstances and which management is suitable to bring out the best from intercropping in a given production situation.The literature is replete with case studies on intercropping from across the globe,but evidence synthesis is needed to make this information accessible.Meta-analysis requires a careful choice of metric that is appropriate for answering the question at hand,and which lends itself for a robust meta-analysis.This paper reviews some metrics that may be used in the quantitative synthesis of literature data on intercropping.

Evaluation of method performance for osteometric sorting of commingled human remains

Evaluation of method performance involves the consideration of numerous factors that can contribute to error.A variety of measures of performance can be borrowed from the signal detection literature and others are drawn from statistical science.This article demonstrates the principles of performance evaluation by applying multiple measures to osteometric sorting models for paired elements run against data from known individuals.Results indicate that false positive rates are close,on average,to expected values.As assemblage size grows,the false positive rate becomes unimportant and the false negative rate becomes significant.Size disparity among the commingled individuals plays a significant role in method performance,showing that case-specific circumstances(e.g.assemblage size and size disparity)will determine method power.

Grain landscape and dielectric properties of ceramics based on sodium,calcium,strontium niobates,depending on the synthesis and sintering conditions,and mechanical processing

The properties studying results of ceramics based on strontium,calcium and sodium niobates,which vary from the conditions of synthesis,sintering,and mechanical processing,are presented.The evolution of the grain structure of objects is traced depending on their phase filling during concentration changes in the composition and thermodynamic prehistory(preparation conditions).

Bidirectionally polarizing surface chemistry of heteroatom-doped carbon matrix towards fast and longevous lithium-sulfur batteries

Herein, a bidirectional polarization strategy is proposed for hosting efficient and durable lithium-sulfur battery(Li-S) electrochemistry. By co-doping electronegative N and electropositive B in graphene matrix(BNrGO), the bidirectional electron redistribution enables a higher polysulfide affinity over its monodoped counterparts, contributing to strong sulfur immobilization and fast conversion kinetics. As a result,BNrGO as the cathode host matrix realizes excellent cycling stability over 1000 cycles with a minimum capacity fading of 0.027% per cycle, and superb rate capability up to 10 C. Meanwhile, decent areal capacity(6.46 m Ah/cm^(2)) and cyclability(300 cycles) are also achievable under high sulfur loading and limited electrolyte. This work provides instructive insights into the interaction between doping engineering and sulfur electrochemistry for pursuing superior Li-S batteries.

Advancing knowledge of plasma spraying coatings for Li||Sb-Sn liquid metal batteries by X-ray micro-CT

The performance of Li||Sb-Sn liquid metal batteries(LMBs) is hindered by the corrosion of the Sb-Sn cathode on its current collector. Herein, a uniform, dense, and low-oxidized W coating was prepared by plasma spraying, which can effectively resist the corrosion of the cathode and improve the cycle stability of the Li||Sb-Sn LMBs. For the first time, micro-CT nondestructive inspection is applied in the field of LMBs. The corrosion micromorphology and composition evolution of the SS304 matrix and Sb-Sn cathode with or without the plasma-sprayed W coating is obtained without disassembling the battery, which proves that the W coating can effectively protect the SS304 matrix. Our autonomous new LMB device for nondestructive inspection is universal and can be applied to different LMBs systems for advancing knowledge of corrosion mechanism and protection. This work guarantees the ability to directly visualize the inner critical positions in three dimensions and fills the knowledge gap in the field of LMB detection technology.