Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments.This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke.However,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical translation.To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke.We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis.The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor.These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.Finally,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile.Therefore,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

Design Principles and Mechanistic Understandings of Non-Noble-Metal Bifunctional Electrocatalysts for Zinc-Air Batteries

Zinc-air batteries(ZABs)are promising energy storage systems because of high theoretical energy density,safety,low cost,and abundance of zinc.However,the slow multi-step reaction of oxygen and heavy reliance on noble-metal catalysts hinder the practical applications of ZABs.Therefore,feasible and advanced non-noble-metal elec-trocatalysts for air cathodes need to be identified to promote the oxygen catalytic reaction.In this review,we initially introduced the advancement of ZABs in the past two decades and provided an overview of key developments in this field.Then,we discussed the work-ing mechanism and the design of bifunctional electrocatalysts from the perspective of morphology design,crystal structure tuning,interface strategy,and atomic engineering.We also included theoretical studies,machine learning,and advanced characterization technologies to provide a comprehensive understanding of the structure-performance relationship of electrocatalysts and the reaction pathways of the oxygen redox reactions.Finally,we discussed the challenges and prospects related to designing advanced non-noble-metal bifunctional electrocatalysts for ZABs.

Emerging roles of exosomes in oral diseases progression

Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine.

Study on Influence Factors of Pressure Injury Risk in the Elderly Inpatients with Kidney Disease Based on LASSO Regression

Objective: This paper aims to explore clinical status and related influence factors of pressure injury (PI) in the elderly inpatients with kidney disease, so as to provide reference for the prevention and treatment of PI in the elderly inpatients with kidney disease. Methods: Retrospective collection method is adopted to collect 158 clinical cases of the elderly inpatients with kidney disease aged ≥ 60 in the Nephrology Department, the First Affiliated Hospital of Jinan University from January 2017 to December 2019, and then least absolute shrinkage and selection Operator (LASSO) regression analysis is used to analyze 17 possible influence factors;finally Logistic regression model is established to analyze and screen influence factors of risk. Results: 1) Among 158 elderly inpatients with medium and high risk of PI, the incidence of PI is 20.25%;the most common stage of injury is stage I (42.5%);sacrococcygeal (60%) is the high-risk site of pressure injury. 2) LASSO regression analysis shows that history of present respiratory infection/respiratory failure (β = 1.2714. P < 0.05) and hospitalization time (β = 0.4177. P < 0.05) are independent factors influencing PI risk in the elderly inpatients with kidney disease. Conclusion: The elderly patients with kidney disease and PI risk are the high incidence population of hospital acquired PI;for the elderly inpatients with kidney disease and having respiratory infection history or respiratory failure, prolonged hospitalization will significantly increase the risk of PI. Therefore, targeted preventive and control measures should be taken to reduce the incidence of PI.

Universal antibacterial and anti-inflammatory treatment using chitosan-prussian blue nanozyme

Bacterial infections are a growing global public health problem,exacerbated by the widespread and often inappropriate use of antibiotics,leading to the emergence of non-antibiotic pathogens.Herein,we synthesized a chitosan-Prussian blue nanozyme(CS@PB),a non-antibiotic agent,for universal antibacterial and antiinflammatory treatment of bacterial infections.Confocal microscopy images showed that CS@PB significantly enhanced the physical interaction between chitosan and bacteria,thereby increasing the antibacterial ability.Moreover,these nanozymes exhibited potent antioxidant and anti-inflammatory properties,promoting macrophage polarization toward the M2-like phenotype,reducing oxidative stress,and alleviating inflammation.This dual-action approach effectively accelerates the healing of bacteria-infected inflammatory wounds.The synergistic bactericidal and anti-inflammatory properties of CS@PBs inhibited wound infection and promoted the healing of skin infections in a mouse model.In addition,CS@PB displayed remarkable lung retention and potent bactericidal effects,resulting in significantly improved survival rates in mouse models of acute pulmonary bacterial infections.In conclusion,CS@PBs exhibited exceptional bactericidal capabilities,anti-inflammatory properties,and minimal toxicity,suggesting that they are promising candidates for a new generation of non-antibiotic antimicrobial agents for the treatment of bacterial infections.

Droplet Characterization Based on the Simulated Secondary Rainbows

The droplet size, size distribution, refractive index, and temperature can be measured simultaneously by the rainbow technique. In the present work, the rainbow scattering diagram for a spherical droplet in the secondary rainbow region is simulated by the use of the generalized Lorenz-Mie theory. For achieving high spatial resolution in denser droplet sprays, a focused Gaussian beam is used. For droplet characterization, different inversion algorithms are investigated, which includes trough-trough (θmin1 and θmin2) method and inflection-inflection (θinf1 and θinf2) method. For the trough-trough algorithm, the absolute error of the refractive index is between −6.4 × 10−4 and 1.7 × 10−4, and the error of the droplet radius is only between −0.55% and 1.77%. For the inflection-inflection algorithm, the maximum absolute error of the inverted refractive index is less than −1.1 × 10−3. The error of the droplet radius is between −0.75% and 5.67%.

铁死亡的发生机制及其在肺癌中的研究进展

铁死亡是近年来发现的一种铁依赖性的程序性细胞死亡,这种死亡是脂质过氧化物和活性氧堆积引起的。而肺癌作为病死率最高的恶性肿瘤之一,关于肺癌中铁死亡的研究甚少。本文中我们综述了肺癌中铁死亡受抑制的研究进展,从铁死亡发生的不同途径来解释肺癌中铁死亡受抑制现象。此外,诱导铁死亡治疗癌症越来越受到重视,本文中我们介绍了四种铁死亡激活剂以及铁死亡治疗肺癌的新展望,以期为肺癌治疗提供新的思路。

双取代苯的亲电取代反应区域选择性规则的理论解释和实验依据

芳香化合物的亲电取代反应是合成不同取代芳香化合物的重要方法,芳香亲电取代反应的区域选择性规则是实现控制合成所需目标分子的理论依据。本文从中间体稳定性、反应活化能和相对反应速率的角度讨论了双取代苯的芳香亲电取代反应区域选择性规则的理论解释和实验依据,为学生正确理解该选择性规则提供了合理的解释和实验证据。

Chemical probing reveals insights into the signaling mechanism of inflammasome activation

Caspase-1-mediated IL-1β production is generally controlled by two pathways. Toll-like receptors （TLRs） recognize pathogen-derived products and induce NF-KB-dependent pro-IL-1β transcription; NOD-like receptors （NLRs） assemble caspase-l-activating inflammasome complexes that sense bacterial products/danger signals. Through a targeted chemical screen, we identify bromoxone, a marine natural product, as a specifc and potent inhibitor of the caspase-1 pathway. Bromoxone is effective over diverse inflammatory stimuli including TLR ligands plus ATP/nigeri- cin, cytosolic DNA, flagellin and Bacillus anthracis lethal toxin. Bromoxone also efficiently suppresses easpase-1 acti- vation triggered by several types of bacterial infection. Bromoxone acts upstream or at the level of the inflammasome in a transcription-independent manner. Bromoxone also inhibits pro-IL-1β expression by targeting components up- stream of IKK in the TLR-NF-kB pathway. The unique dual activities of bromoxone are shared by the known TAK1 inhibitor that specifically blocks Nalp3 inflammasome activation. Hinted from the mechanistic and pharmacological properties of bromoxone, we further discover that several known NF-KB inhibitors that act upstream of IKK, but not those targeting IKK or IKK downstream, are potent blockers of different NLRs-mediated caspase-1 activation. Our study uncovers a possible non-transcriptional molecular link between the NLR （Nalp3）-mediated inflammasome pathway and TLR-NF-kB signaling, and suggests a potential strategy to develop new anti-inflammatory drugs.

Analysis of ethoxyquin and its oxidation products in swine tissues by gas chromatography-tandem mass spectrometry for evaluating the feed-toanimal tissue transfer of ethoxyquin and its metabolites

Background:Ethoxyquin(EQ)is a common antioxidant which is widely used in animal feed.But the supplement of EQ in animal feed may lead to the residues of EQ and its major oxidation products:ethoxyquin quinone imine(EQI)and ethoxyquin dimer(EQDM)in animal tissue.Thus,it would pose potential health hazards to consumers.However,the method for the simultaneous determination of EQ,EQI and EQDM in animal tissues is currently not available,and the accumulation extend of these chemicals in animal tissues after EQ administration remains to be evaluated.Results:A gas chromatography-tandem mass spectrometry method was successfully developed for the simultaneous determination of EQ,EQI and EQDM in swine tissues.The quantitative limits of EQ,EQI and EQDM can achieve to 0.5,5.0 and 5.0μg/kg in swine tissues,respectively.The spiked-recovery ratios of the three analytes(5–2000μg/kg)were in the range of 64.7%–100.7%with relative standard deviations below 11.6%.Moreover,the utilization of this method for the analysis of actual swine tissue samples revealed that the application of commercial EQ additive in swine diet would produce the residues of all the three chemicals(EQ,EQI and EQDM)in fat,kidney,liver and muscle.Conclusions:The assay accuracy and precision of this GC-MS/MS method can meet the requirement of quantitative analysis.Meanwhile,the safety of EQ as a feed additive should be seriously considered with regard to food safety concerns since the oxidation product of EQ may have potential carcinogenicity.

Next generation of neurological therapeutics:Native and bioengineered extracellular vesicles derived from stem cells

Extracellular vesicles(EVs)-based cell-free therapy,particularly stem cell-derived extracellular vesicles(SC-EVs),offers new insights into treating a series of neurological disorders and becomes a promising candidate for alternative stem cell regenerative therapy.Currently,SC-EVs are considered direct therapeutic agents by themselves and/or dynamic delivery systems as they have a similar regenerative capacity of stem cells to promote neurogenesis and can easily load many functional small molecules to recipient cells in the central nervous system.Meanwhile,as non-living entities,SC-EVs avoid the uncontrollability and manufacturability limitations of live stem cell products in vivo(e.g.,low survival rate,immune response,and tumorigenicity)and in vitro(e.g.,restricted sources,complex preparation processes,poor quality control,low storage,shipping instability,and ethical controversy)by strict quality control system.Moreover,SC-EVs can be engineered or designed to enhance further overall yield,increase bioactivity,improve targeting,and extend their half-life.Here,this review provides an overview on the biological properties of SC-EVs,and the current progress in the strategies of native or bioengineered SC-EVs for nerve injury repairing is presented.Then we further summarize the challenges of recent research and perspectives for successful clinical application to advance SC-EVs from bench to bedside in neurological diseases.

Doping of group IVB elements for nickel-rich cobalt-free cathodes

Hetero-element doping is a promising strategy to improve the cycling stability of nickel-rich cobalt-free cathodes for the next-generation high energy-density Li ion batteries.To make doping effective,it is important to understand the mechanism of how the dopants regulate the electronic band,lattice parameter adjusting,or hetero-phase formation to achieve high stability.In this study,we investigate LiNi_(0.9)Mn_(0.1)O_(2)cathodes doped with IVB grouping elements via multiple characterization techniques.By utilizing in situ XRD and TEM methods,we found that the stronger Ti-O bond effectively improves the cathode stability via a dual protection mechanism.Specifically,the bulk lattice of cathode is wellpreserved during cycling as a result of the suppressed H_(2)-H_(3)phase transition,while a in situ formed Ti-rich surface layer can prevent continuous surface degradation.As a result,the 5%Ti doped LiNi_(0.9)Mn_(0.1)O_(2)cathode exhibits a high capacity retention of 96%after 100 cycles.Whereas,despite IVB group elements Zr and Hf have stronger bonding energy with oxygen,their larger ionic radii actually impede their diffusion into the cathode,thereby they can not improve the cycling stability.Our findings uncover the functional origin of doped elements with their dynamic modification on cathode structure,providing mechanistic insights into the design of nickel-rich cobalt-free cathodes.

Genetic Improvement in Juglans mandshurica and Its Uses in China:Current Status and Future Prospects

Juglans mandshurica is an economically and ecologically valuable species that is used for various construction purposes,making luxurious furniture,as food and sources of medicinal substances and landscaping because of its excellent wood,edible fruits and rich in various types of chemical compounds.In the past few decades,several genetic improvements of J.mandshurica were made,with a focus on the selection of improved varieties and on breeding technology.Many elite provenances and families were selected based on growth traits or wood properties.In recent years,with the increasing demand for high-quality seedlings in Chinese forestry production,the breeding goals of genetic improvement for J.mandshurica were redefined to include other traits,such as fruit yield and contents of medicinal component.However,the improvement processes were still slow due to the long breeding cycle and the limited use of advanced breeding technologies,resulting in the selection of fewer improved varieties.In this review,we summarized the research progresses on genetic improvements of J.mandshurica and other related works,and discussed research gaps and suggested future directions for genetic improvement of the species.The review provides valuable insight for the selection of improved varieties and production of excellent germplasms.

Mediating effect of undergraduate nursing students’ professional commitment on positive psychological capital and learning burnout

Objective:The objective of this study is to explore the mediating role of professional commitment of undergraduate nursing students between positive psychological capital(PsyCap)and learning burnout.Materials and Methods:A cluster sampling method was used to survey 442 students of a bachelor’s degree in freshman to the junior in a medical college in Shaanxi Province.Results:Professional commitment was positively related to positive PsyCap(=0.487,P<0.01),while positive PsyCap and professional commitment were negatively related to learning burnout(r=−0.456,r=−0.411,P all<0.01).There are certain mediating effects of professional commitment in the relationship between positive PsyCap and learning burnout.The mediating effect value of professional commitment is−0.065,accounting for 16.08%of the total effect.Conclusion:Nursing educators in medical colleges and universities should focus on developing and training the positive PsyCap of undergraduate nursing students,thereby enhancing and stabilizing their professional commitment level and reducing the risk of learning burnout.

Rapid one-step enzyme immunoassay and lateral flow immunochromatographic assay for colistin in animal feed and food

Background:Colistin(polymyxin E)is a kind of peptide antibiotic which has been approved in animal production for the purposes of disease prevention,treatment,and growth promotion.However,the wide use of colistin in animal feed may accelerate the spread of colistin-resistance gene MCR-1 from animal production to human beings,and its residue in animal-origin food may also pose serious health hazards to humans.Thus,it is necessary to develop corresponding analytical methods to monitor the addition of colistin in animal feed and the colistin residue in animal-origin food.Results:A one-step enzyme-linked immunosorbent assay(ELISA)and a lateral flow immunochromatographic assay(LFIA)for colistin were developed based on a newly developed monoclonal antibody.The ELISA showed a 50%inhibition value(IC50)of 9.7 ng/m L with assay time less than 60 min,while the LFIA had a strip reader-based detection limit of 0.87 ng/m L in phosphate buffer with assay time less than 15 min.For reducing the non-specific adsorption of colistin onto sample vial,the components of sample extraction solution were optimized and proved to greatly improve the assay accuracy.The spiked recovery experiment showed that the recoveries of colistin from feed,milk and meat samples were in the range of 77.83%to 113.38%with coefficient of variations less than 13%by ELISA analysis and less than 18%by LFIA analysis,respectively.Furthermore,actual sample analysis indicated that the two immunoassays can produce results consistent with instrumental analysis.Conclusions:The developed assays can be used for rapid qualitative or quantitative detection of colistin in animal feed and food.

CG hypermethylation of the bHLH39 promoter regulates its expression and Fe deficiency responses in tomato roots

Iron(Fe)is an essential micronutrient for all organisms,including plants,whose limited bioavailability restricts plant growth,yield,and nutritional quality.While the transcriptional regulation of plant responses to Fe deficiency have been extensively studied,the contribution of epigenetic modulations,such as DNA methylation,remains poorly understood.Here,we report that treatment with a DNA methylase inhibitor repressed Fe deficiency-induced responses in tomato(Solanum lycopersicum)roots,suggesting the importance of DNA methylation in regulating Fe deficiency responses.Dynamic changes in the DNA methylome in tomato roots responding to short-term(12 hours)and long-term(72 hours)Fe deficiency identified many differentially methylated regions(DMRs)and DMR-associated genes.Most DMRs occurred at CHH sites under short-term Fe deficiency,whereas they were predominant at CG sites following long-term Fe deficiency.Furthermore,no correlation was detected between the changes in DNA methylation levels and the changes in transcript levels of the affected genes under either short-term or long-term treatments.Notably,one exception was CG hypermethylation at the bHLH39 promoter,which was positively correlated with its transcriptional induction.In agreement,we detected lower CG methylation at the bHLH39 promoter and lower bHLH39 expression in MET1-RNA interference lines compared with wild-type seedlings.Virus-induced gene silencing of bHLH39 and luciferase reporter assays revealed that bHLH39 is positively involved in the modulation of Fe homeostasis.Altogether,we propose that dynamic epigenetic DNA methylation in the CG context at the bHLH39 promoter is involved in its transcriptional regulation,thus contributing to the Fe deficiency response of tomato.

Analysis of Risk Factors of Fever among Inpatients in Rehabilitation Department Based on Lasso Regression Analysis

Purpose: To explore the fever-related risk factors of inpatients in Rehabilitation Department, and to provide reference for patients with high risk of fever to take corresponding nursing measures. Methods: The study was conducted on the Rehabilitation Department of The First Affiliated Hospital of Jinan University from July 2019 to December 2019. The fever group included 51 patients and the non-fever group included 49 patients without fever. The two groups of clinical data, comorbidities, related laboratory values, possible risk factors of fever were analyzed by case regression analysis, and the relevant risk factors were screened out by LASSO (least absolute shrinkage and selection operator) regression analysis. Results: According to the results of Lasso regression analysis, pressure sore or skin infection, history of hypertension, current history of respiratory tract infection, feeding patterns were the higher risk factors of fever in inpatients in Rehabilitation Department, while the first course of disease, main diagnosis, history of respiratory tract infection within half a year, kidney damage and hospitalization days were lower risk factors. Conclusion: This study is helpful to early identify the fever risk of inpatients in Rehabilitation Department, and provide reference basis for high-risk fever patients to take positive and effective nursing measures.

Mechanical-Hydraulic Co-Simulation of Full Hydraulic Articulated Steering System

With the development and improvement of the hydraulic steering system,the articulated steering system became the research focus of numerous domestic and foreign scholars.The full hydraulic steering system with a compact structure and ease of operation,is widely used in articulated steering mode.Furthermore,its performance can directly impact the steering sensitivity and stability.This paper studies the working principle and actual structure of the priority valve and the steering control valve,which are very important.By setting up a mathematic model,the system’s load-sensing characteristics and the impact of steering control valve bypass throttle damping on steering stability can be analyzed.The Hydraulic Components Design(HCD)model was established for the hydraulic part of this system.It is proved that the model can reflect the system’s actual properties by comparing simulation and experimental results.The dynamic model is based on its actual prototype parameters by taking the tire and ground forces into account.The steering process’s dynamic characteristics are co-simulated in the 1D+3D system model by combining AMESim and Virtual.Lab Motion.The simulation results show that the system’s load-sensing characteristics ensure the sensitivity of the steering operation,and the bypass throttle damping has significantly improved the operation stability and lowered down the cylinder pressure fluctuations.This can improve the system performance by appropriate optimization.

Why is Asian Infrastructure Investment Bank So Attractive?

The target of the AIIB is to focus on supporting the infrastructure construction in Asia as well as to promote regional cooperation and partnership so that countries can jointly address the challenges during the developing process.As the first China-led multilateral international institution,AIIB is targeted for focusing on supporting the infrastructure construction

Formation Characteristics of N-Nitrosodimethylamine during Chloramines of PolyDADMAC

Interactions of chloramine with organic nitrogen compounds during purification of water for drinking may generate carcinogenic N-nitrosodime-thylamine (NDMA) as byproduct, and it has been found that cationic amine-based water treatment polymers may be one of the important precursors of NDMA. We have analyzed experimentally the influence rule of NDMA formation during chlorination and disinfection, in order to provide technical support for reducing or even avoiding the formation of NDMA. The formation characteristics of nitrosamines during the chlorination of poly-diallyldimethylammonium chloride (polyDADMAC) have been studied during our experiments. The results show that the type of chlorinating agent is crucial for the generation of NDMA;if pH = 7, NDMA has the great potential formation;the NDMA potential formation increases with temperature. The yield of NDMA will be higher as the concentration of monochloramine is 1.5 to 2.5 times of the precursor;the variation of polymer with reaction time can explain the concentration of NDMA in terminal water of pipe network is higher than that in drinking water.