Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

TurboID Proximity Labeling of a Protocadherin Protein to Characterize Interacting Protein Complex

The study of the neuron has always been a fundamental aspect when it came to studying mental illnesses such as autism and depression. The protein protocadherin-9 (PCDH9) is an important transmembrane protein in the development of the neuron synapse. Hence, research on its protein interactome is key to understanding its functionality and specific properties. A newly discovered biotin ligase, TurboID, is a proximity labeler that is designed to be able to label and observe transmembrane proteins, something that previous methods struggled with. The TurboID method is verified in HEK293T cells and primary cultured mouse cortical neurons. Results have proven the validity of the TurboID method in observing PCDH9-interacting proteins.

Development of an Agrobacterium-mediated CRISPR/Cas9 system in pea(Pisum sativum L.)

Pea(Pisum sativum L.)is an annual cool-season legume crop.Owing to its role in sustainable agriculture as both a rotation and a cash crop,its global market is expanding and increased production is urgently needed.For both technical and regulatory reasons,neither conventional nor transgenic breeding techniques can keep pace with the demand for increased production.In answer to this challenge,CRISPR/Cas9 genome editing technology has been gaining traction in plant biology and crop breeding in recent years.However,there are currently no reports of the successful application of the CRISPR/Cas9 genome editing technology in pea.We developed a transient transformation system of hairy roots,mediated by Agrobacterium rhizogenes strain K599,to validate the efficiency of a CRISPR/Cas9 system.Further optimization resulted in an efficient vector,PsU6.3-tRNA-PsPDS3-en35S-PsCas9.We used this optimized CRISPR/Cas9 system to edit the pea phytoene desaturase(PsPDS)gene,causing albinism,by Agrobacterium-mediated genetic transformation.This is the first report of successful generation of gene-edited pea plants by this route.

GRB 220408B:A Three-episode Burst from a Precessing Jet

Jet precession has previously been proposed to explain the apparently repeating features in the light curves of a few gamma-ray bursts(GRBs).In this paper,we further apply the precession model to a bright GRB 220408B by examining both its temporal and spectral consistency with the predictions of the model.As one of the recently confirmed GRBs observed by our GRID CubeSat mission,GRB 220408B is noteworthy as it exhibits three apparently similar emission episodes.Furthermore,the similarities are reinforced by their strong temporal correlations and similar features in terms of spectral evolution and spectral lags.Our analysis demonstrates that these features can be well explained by the modulated emission of a Fast-Rise-Exponential-Decay(FRED)shape light curve intrinsically produced by a precessing jet with a precession period of 18.4_(-0.2)~(+0.2)s,a nutation period of11.1_(-0.2)~(+0.2)s and viewed off-axis.This study provides a straightforward explanation for the complex yet similar multiepisode GRB light curves.

Development of a Rehabilitation Instrument of Neurological Training for Cervical Spine

Objective: To develop a kind self active resistance movement training equipment for cervical spine, so as to restore the dynamic balance of the front and back muscle strength of the cervical spine in order to correct the abnormal physiological radian of the cervical spine, thereby relieving the clinical symptoms. Methods: The air spring with adjustable strength was used to provide the power of resistance active movement, and the neurological training cervical audio-visual synthesis training software was used to automatically guide patients to perform resistance active movement training of the cervical spine. Thirty two patients with cervical spondylosis were enrolled for treatment, and SPSS26 was used to statistically analyze the VAS, Lovett muscle strength, head and neck range of motion and C2-3 vertebral body curvature before and after the treatment. Result: There were significant differences in posterior cervical muscle strength (Lovett), dizziness, shoulder and neck pain (VAS) and C2-3 vertebral curvature before and after training in 32 patients (p˂0.001). Conclusion: The application of neurological training cervical vertebra self rehabilitation training instrument can effectively relieve clinical symptoms, restore head and neck range of motion, improve nape muscle strength, restore the dynamic balance of front and rear cervical muscle strength, and also can correct the abnormal physiological radian of the cervical vertebra.

Study on the Treatment Strategy of Batches of the Wounded and Partial First-Aid Procedures in Public Emergencies in Tertiary General Hospitals

Objective: The purpose is to formulate treatment strategies of batches of the wounded and partial first-aid procedures, and further improve the emergency rescue capability of hospitals. Methods: This study analyzed the emergency treatment case that we participated in. In this case, we used various means to start the emergency plan, run the emergency procedures, optimize diagnosis, treatment, and rescue procedures, mobilize medical rescue resources, provide a reference for emergency command decisions, formulate a set of coping strategies of tertiary general hospitals on public emergencies. Results: Through the scientific and effective management of our hospital, 20 wounded have been discharged from the hospital and achieved the ideal effect of zero deaths in the hospital. Conclusions: The new mode of first-aid and health emergency management on the scene of modern disaster needs to find ways to minimize the loss of life and property brought by public emergencies, integrate the various sections of modern disaster medicine, integrate a large number of international and domestic basic and clinical research achievements of disaster first-aid, and upgrade to information, digital system.

Effect of Polyethylene (LDPE) Microplastic on Remediation of Cadmium Contaminated Soil by <i>Solanum nigrum</i>L.

Solanum nigrum L. has a delightful prospect as a hyperaccumulation plant for cadmium pollution remediation, and microplastic is a new type of pollution that has received wide attention. In this study, the effects of polyethylene microplastics (LDPE) (0.135, 0.27, 0.81 and 1.35 mg·kg-1) and cadmium (20 mg·kg-1) on the growth indexes and soil physical and chemical properties of Solanum nigrum L. were investigated in a 17-day microcosm experiment. The results showed that single LDPE contamination showed a trend of low concentration promotion and medium-high concentration inhibited the growth index of Solanum nigrum L. and soil physicochemical index, and single Cd contamination was more stressful to plants than single LDPE contamination, while low concentration of LDPE could reduce the effect of Cd on soil physical and chemical properties and promote plant growth and uptake of soil nutrients. These findings suggest that high concentrations of microplastics can inhibit the growth of Solanum nigrum L. alone or in combination with Cd, rather than reducing the toxicity of Cd.

70岁及以上临床晚期胃癌患者化疗相关不良反应的列线图预测模型的构建与验证

目的:本研究拟在≥70岁临床晚期胃癌患者中探索化疗相关毒性(chemotherapy related toxicities,CRT)相关危险因素并建立列线图预测CRT的风险。方法:选取2003年7月至2020年8月就诊于北京协和医院的≥70岁临床晚期胃癌患者,收集其临床资料,通过Logistic回归模型探索与CRT相关的危险因素,随后构建列线图模型来预测CRT发生的概率,通过自举重采样技术验证模型,采用校准曲线检验模型的一致性。结果:纳入研究的178例患者中CRT的发生率为41%。其中女性、ECOG≥1分、体质量减轻、化疗前血白蛋白<30 g/L、化疗前中性粒细胞与淋巴细胞比值(neutrophil and lymphocyte ratio,NLR)<4和化疗前血小板水平是CRT的独立危险因素。基于上述6个潜在危险因素构建列线图模型,该模型具有良好的诊断能力[曲线下面积(AUC)=0.716,95%CI:0.677~0.755]和良好的校准和拟合能力。结论:本研究构建了一个列线图模型预测≥70岁临床晚期胃癌患者CRT发生的概率。该模型可作为一种无创的、方便的模型早期预测这些患者CRT的发生。

海藻酸钠-海泡石-聚磷酸铵三元杂化灭火凝胶及其在粮棉储备中的应用

以海藻酸钠、海泡石、聚磷酸铵(APP)为原料,采用简便的一锅法制备了一种环保型生物基三元杂化凝胶材料。流变学测试表明,这种三元杂化凝胶材料具有剪切变稀行为。模拟灭火实验表明,采用水灭火的棉包容易复燃,而三元混合凝胶由于其能紧密附着在棉包表面,有效地防止了棉包的阴燃和复燃。此外,在对粮堆的模拟灭火实验中,三元杂化凝胶材料能够覆盖在粮堆的上层,在有效灭火的同时不破坏中下层的粮食,而水在扑灭火灾的同时则完全浸泡了稻谷堆,使其丧失了食用价值。进一步研究表明,该三元杂化凝胶材料的灭火机理涉及多种作用模式:凝胶中高含量水分的挥发吸收了大量热量(冷却燃烧区);APP在加热时分解为不易燃的氨气(稀释易燃挥发物和氧气);APP和海泡石的分解产物有助于形成连续且致密的炭层(充当可燃气体、热量和氧气交换的阻隔层)。本工作为棉花和粮食等物资储备提供了一种环境友好、经济高效、天然来源的灭火凝胶材料。

Folic acid-conjugated liposomal vincristine for multidrug resistant cancer therapy

We encapsulated vincristine into folic acid-conjugated PEGylated liposomes to improve the anti-tumor efficacy on multidrug resistant cancers.It was observed that the drug delivery system we constructed exhibited maximum cytotoxicity on KBv200 cells(multidrug resistant variant)compared with any other formulations.The semi-quantitative analysis of region of interest revealed that there was a great increase in area under curve(AUC)of a near-infrared fluorescein in solid tumors due to folic acid-mediated accumulation.Folic acid-conjugated PEGylated liposomes showed a significant tumor growth inhibiting effect in vitro and in vivo.TUNEL assay revealed that folic acid-conjugated PEGylated liposomes could induce cell apoptosis much more greatly than others.This study demonstrated that it had potential application prospective for the treatment of multidrug resistant cancer.

Effects of shape and particle size on the photocatalytic kinetics and mechanism of nano-CeO_(2)

Nanomaterials have been widely applied to many fields because of their excellent photocatalytic performance.The performance is closely related to the catalytic kinetics,but it is not completely clear about the influencing regularities of shape and particle size on the photocatalytic kinetics of nanomaterials and the photocatalytic kinetic mechanism.In this paper,nano-CeO_(2)with different shapes and particle sizes were prepared,the kinetic parameters of adsorption and photocatalytic degradation were determined,and the effects of shape and particle size on the kinetics of adsorption and photocatalysis and photocatalytic mechanism were discussed.The results show that the shape and particle size have significant influences.With the decreases of diameter,the performances of adsorption and photocatalysis of nano-CeO_(2)are improved;and these performances of spherical nano-CeO_(2)are greater than those of linear nano-CeO_(2).The shape and particle size have no effects on the kinetic order and mechanism of the whole photocatalytic process.Then a generalized mechanism of photocatalytic kinetics of nanomaterials was proposed and the mechanism rate equation was derived.Finally,the conclusion can be drawn:the desorption of photodegradation products is the control step of photocatalytic kinetics,and the kinetic order of photocatalytic degradation reaction is 1.The mechanism is universal and all nanomaterials have the same photocatalytic kinetic mechanism and order.

Enhancing the robustness of object detection via 6G vehicular edge computing

Academic and industrial communities have been paying significant attention to the 6th Generation (6G) wireless communication systems after the commercial deployment of 5G cellular communications. Among the emerging technologies, Vehicular Edge Computing (VEC) can provide essential assurance for the robustness of Artificial Intelligence (AI) algorithms to be used in the 6G systems. Therefore, in this paper, a strategy for enhancing the robustness of AI model deployment using 6G-VEC is proposed, taking the object detection task as an example. This strategy includes two stages: model stabilization and model adaptation. In the former, the state-of-the-art methods are appended to the model to improve its robustness. In the latter, two targeted compression methods are implemented, namely model parameter pruning and knowledge distillation, which result in a trade-off between model performance and runtime resources. Numerical results indicate that the proposed strategy can be smoothly deployed in the onboard edge terminals, where the introduced trade-off outperforms the other strategies available.

Comparison between fluctuation of floating potential gradient and velocity of blob structure on HL-2A tokamak

Several results based on the Langmuir probes’data on the HL-2A tokamak are presented.The blob structures’radial and poloidal drift velocities,estimated by the gradient of floating potential and by time delay evaluation,are compared in different line-averaged density and electron cyclotron resonance heating conditions.A positive correlation is observed in the comparison between blobs’radial velocity estimated by the two methods mentioned above,regardless of the situation differences mentioned above.Correlation is also observed in the comparison between the blobs’poloidal velocity estimated by the two methods in different situations,while a shift due to the different line-averaged density is observed.These results imply that the radial gradient of floating potential may have some value as a reference during data analysis in low-parameter discharge.

Correction to “Folic acid-conjugated liposomal vincristine for multidrug resistant cancer therapy”

In the original version of this article on p 122, two inappropriate images were placed in B and C of Fig. 1, which didn’t represent the group of FA-PEG-LS and PEG-LS/VCR. In the revised graphic provided below, the appropriate images are used.These corrections do not change the results and conclusions of this work.

The Importance of Food Security from the Perspective of Food Issue of the Roman Empire

This paper firstly introduced characteristics of the food production( or grain production) and regulation of the prosperous period of the Roman Empire. Then,it discussed the shortcomings and summarized the experience and lessons. It is expected to provide some references for construction of China's food security.

A Novel Dual Helical Magnetorheological Fluid Micro-Robot

To address the problem of flexible drive control of gastrointestinal(GI)tract micro-capsule robot posture,a novel dual helix magnetorheological fluid(MRF)micro-robot(DHMRFMR)is proposed and developed in this paper.Based on the mechanical properties of magnetorheological fluid,the relationship model of magnetic field force is obtained,and the thrust model is established.Double micro DC deceleration motor is used to drive the two ends of the helical actuator to make the DHMRFMR forward and backward,by changing the external magnetic field rotation speed,direction and distance,adjust the attitude direction of the robot.Numerical simulation software ANSYS is used to analyze the motion law of external fluid of DHMRFMR,and the visualization of fluid velocity and pressure distribution is realized.The front-end helix actuator can change the flow path of the fluid,and the middle and tail of the DHMRFMR bear less pressure,which improves the stability and flexibility of the robot.The novel DHMRFMR is suitable for internal drive in bending environment,and has a good application prospect in biomedical engineering field in human intestinal unstructured environment.

Meta-Analysis of the Efficacy of Cimetidine in the Treatment of Mumps

Objective:To compare the efficacy of cimetidine and ribavirin in the treatment of mumps by meta-analysis.Methods:Controlled trials of cimetidine and ribavirin in the treatment of mumps were searched through China National Knowledge Infrastructure(CNKI),Wanfang data,Cqvip,Pubmed,The Cochrane Library and EMBase databases up to September 2022.The effective rate,the time of swelling regression in parotid gland area and the rate of adverse reactions were analyzed by Review Manager 5.3 software.Results:The final 10 articles included 920 children,including 427 in the trial group and 447 in the control group.Meta analysis showed that the effective rate of cimetidine in the treatment of mumps was higher than that of ribavirin in routine treatment,with a statistically significant difference(odds ratio[OR]=5.2,P<0.00001);The time of swelling regression was statistically significant(OR=-1.28,P<0.00001);The difference of adverse reaction rate was not statistically significant(OR=0.73,P=0.62).Conclusions:Compared with ribavirin,cimetidine is more effective in the treatment of mumps,with shorter swelling regression time without increases of adverse reactions.

Identification of a novel MYO1D variant associated with laterality defects,congenital heart diseases,and sperm defects in humans

The establishment of left–right asymmetry is a fundamental process in animal development.Interference with this process leads to a range of disorders collectively known as laterality defects,which manifest as abnormal arrangements of visceral organs.Among patients with laterality defects,congenital heart diseases(CHD)are prevalent.Through multiple model organisms,extant research has established that myosin-Id(MYO1D)deficiency causes laterality defects.This study investigated over a hundred cases and identified a novel biallelic variant of MYO1D(NM_015194:c.1531G>A;p.D511N)in a consanguineous family with complex CHD and laterality defects.Further examination of the proband revealed asthenoteratozoospermia and shortened sperm.Afterward,the effects of the D511N variant and another known MYO1D variant(NM_015194:c.2293C>T;p.P765S)were assessed.The assessment showed that both enhance the interaction withβ-actin and SPAG6.Overall,this study revealed the genetic heterogeneity of this rare disease and found that MYO1D variants are correlated with laterality defects and CHD in humans.Furthermore,this research established a connection between sperm defects and MYO1D variants.It offers guidance for exploring infertility and reproductive health concerns.The findings provide a critical basis for advancing personalized medicine and genetic counseling.

Prediction and Regulation of Delamination at Flexible Film/Finite-Thickness-Substrate Structure Interfaces

Regulating the surface instability of thin film/substrate structures has been successfully applied to prepare new ductile electronic devices.However,such electronic devices need to be subjected to external loads during operation,which can easily induce delamination of the thin-film electronic device from the substrate.This study aims to investigate the instability characteristics of hard films on flexible substrate surfaces from theoretical analysis and numerical simulation perspectives.Considering finite-thickness substrates,this paper establishes theoretical models for pure bending,bent wrinkle,partial delamination,and total delamination buckling of film/substrate structures based on the nonlinear Euler–Bernoulli beam theory and the principle of minimum energy;then the effects of material and geometric parameters of the structure,interfacial adhesion strength,and pre-strain on the evolutionary path of the four patterns are discussed.The study results show that:the greater Young’s modulus of the substrate is,the larger the parameter region where partial delamination of the film/substrate structure occurs,and the smaller the parameter region where bent wrinkle occurs.By varying Young’s modulus,thickness of the film and substrate,interfacial adhesion coefficient,and pre-strain,the buckling pattern of the structure can be predicted and regulated.The parametric design intervals for each pattern are summarized in the phase diagram.The results of this paper provide theoretical support for the design and reliability evaluation of flexible electronic devices.