Natural Products Improve Organ Microcirculation Dysfunction Following Ischemia/Reperfusion-and Lipopolysaccharide-Induced Disturbances:Mechanistic and Therapeutic Views

Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell interactions,plasma albumin leakage,microvascular hemorrhage,and thrombosis.These disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism,the mitochondrial respiratory chain,oxidative stress,inflammatory factors,adhesion molecules,the cytoskeleton,vascular endothelial cells,caveolae,cell junctions,the vascular basement membrane,neutrophils,monocytes,and platelets.In clinical practice,aside from drugs that target abnormal vasomotor responses and platelet adhesion,there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory disturbances.Natural products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion(I/R)-and lipopolysaccharide(LPS)-induced microcirculatory disturbances.In recent years,numerous research papers on the improvement of microcirculatory function by natural products have been published in international journals.In 2008 and 2017,the first listed author of this review was invited to publish reviews in the journal of Pharmacology&Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine,respectively.This review systematically summarizes the effects,targets of action,and mechanisms of natural products regarding improving I/R-and LPSinduced microcirculatory disturbances and tissue injury.Based on this summary,scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.

Multi-circular formation control with reinforced transient profiles for nonholonomic vehicles:A path-following framework

This article investigates a multi-circular path-following formation control with reinforced transient profiles for nonholonomic vehicles connected by a digraph.A multi-circular formation controller endowed with the feature of spatial-temporal decoupling is devised for a group of vehicles guided by a virtual leader evolving along an implicit path,which allows for a circumnavigation on multiple circles with an anticipant angular spacing.In addition,notice that it typically imposes a stringent time constraint on time-sensitive enclosing scenarios,hence an improved prescribed performance control(IPPC)using novel tighter behavior boundaries is presented to enhance transient capabilities with an ensured appointed-time convergence free from any overshoots.The significant merits are that coordinated circumnavigation along different circles can be realized via executing geometric and dynamic assignments independently with modified transient profiles.Furthermore,all variables existing in the entire system are analyzed to be convergent.Simulation and experimental results are provided to validate the utility of suggested solution.

Path-Following Based on Nonlinear Model Predictive Control with Adaptive Path Preview

This paper presents a Nonlinear Model Predictive Controller(NMPC)for the path following of autonomous vehicles and an algorithm to adaptively adjust the preview distance.The prediction model includes vehicle dynamics,path following dynamics,and system input dynamics.The single-track vehicle model considers the vehicle’s coupled lateral and longitudinal dynamics,as well as nonlinear tire forces.The tracking error dynamics are derived based on the curvilinear coordinates.The cost function is designed to minimize path tracking errors and control effort while considering constraints such as actuator bounds and tire grip limits.An algorithm that utilizes the optimal preview distance vector to query the corresponding reference curvature and reference speed.The length of the preview path is adaptively adjusted based on the vehicle speed,heading error,and path curvature.We validate the controller performance in a simulation environment with the autonomous racing scenario.The simulation results show that the vehicle accurately follows the highly dynamic path with small tracking errors.The maximum preview distance can be prior estimated and guidance the selection of the prediction horizon for NMPC.

Effects of serum containing natural cerebrolysin on glucose-regulated protein 78 and CCAAT enhancer-binding protein homologous protein expression in neuronal PC12 cells following tunicamycin-induced endoplasmic reticulum stress

BACKGROUND： Glucose-regulated protein 78 （GRP78）, a marker of endoplasmic reticulum stress, can prolong cell survival. Alternatively, CCAAT enhancer-binding protein homologous protein （CHOP）, a transcription factor specific for endoplasmic reticulum stress, can cause cell cycle arrest and cell apoptosis. OBJECTIVE： To study the protective effects of serum containing natural cerebrolysin on endoplasmic reticulum stress in tunicamycin-induced neuronal PC12 cells, and analyze the influence on GRP78 and CHOP expressions. DESIGN, TIME AND SETTING： A parallel controlled study was performed at the Institute of Integrated Western and Traditional Chinese Medicine, Shenzhen Hospital, Southern Medical University, between March 2006 and August 2008. MATERIALS： Adult Sprague-Dawley rats were perfused with natural Cerebrolysin aqueous extract （0.185 g/kg/d） to produce serum containing natural Cerebrolysin. Physiological saline was used to produce blank serum. PC12 cell line was provided by Shanghai Institute of Cell Biology, Chinese Academy of Science. Tunicamycin was provided by Sigma （St. Louis, USA）, and natural Cerebrolysin, containing ginseng, rhizoma gastrodiae, and gingko leaf （1：2：2）, by Shengzhen Institute of Integrated Western and Traditional Chinese Medicine. METHODS： PC12 cells were treated with DMEM culture media containing 10% blank serum （normal control group）, tunicamycin （1 μg/mL; model group）, and 5%, 10%, and 15% serum containing natural cerebrolysin and tunicamycin （1 μ g/mL; low-, moderate-, and high-dose serum containing natural cerebrotysin groups）, for 2 hours. MAIN OUTCOME MEASURES： PC12 cells were treated with tunicamycin for 48 hours after which apoptosis was measured using the TUNEL method to calculate apoptotic index. GRP78 expression was detected using immunocytochemistry. After 24 hours of treatment with tunicamycin, GRP78 and CHOP mRNA expressions were measured using RT-PCR. RESULTS： The apoptotic index and CHOP mRNA expression were in the model group and three cerebrolysin groups were significantly increased when compared to the normal control group （P 〈 0.05）. In contrast, GRP78 mRNA and protein expressions were significantly decreased （P 〈 0.05）. CONCLUSION： Serum containing natural cerebrolysin significantly reduced apoptosis in neuronal PC12 cells following tunicamycin-induced endoplasmic reticulum stress. These results may be related to an up-regulation of GRP78 expression and down-regulation of CHOP expression, both of which displayed dose-dependent effects.

A Novel Prescribed-Performance Path-Following Problem for Non-Holonomic Vehicles

The issue of achieving prescribed-performance path following in robotics is addressed in this paper,where the aim is to ensure that a desired path within a specified region is accu-rately converged to by the controlled vehicle.In this context,a novel form of the prescribed performance guiding vector field is introduced,accompanied by a prescribed-time sliding mode con-trol approach.Furthermore,the interdependence among the pre-scribed parameters is discussed.To validate the effectiveness of the proposed method,numerical simulations are presented to demonstrate the efficacy of the approach.

Natural history of sensory nerve recovery after cutaneous nerve injury following foot and ankle surgery

Cutaneous nerve injury is the most common complication following foot and ankle surgery. However, clinical studies including long-term follow-up data after cutaneous nerve injury of the foot and ankle are lacking. In the current retrospective study, we analyzed the clinical data of 279 patients who underwent foot and ankle surgery. Subjects who suffered from apparent paresthesia in the cutaneous sensory nerve area after surgery were included in the study. Pa- tients received oral vitamin B^2 and methylcobalamin. We examined final follow-up data of 17 patients, including seven with sural nerve injury, five with superficial peroneal nerve injury, and five with plantar medial cutaneous nerve injury. We assessed nerve sensory function using the Medical Research Council Scale. Follow-up immediately, at 6 weeks, 3, 6 and 9 months, and 1 year after surgery demonstrated that sensory function was gradually restored in most patients within 6 months. However, recovery was slow at 9 months. There was no significant difference in sensory function between 9 months and 1 year after surgery. Painful neuromas occurred in four patients at 9 months to 1 year. The results demonstrated that the recovery of sensory func- tion in patients with various cutaneous nerve injuries after foot and ankle surgery required at least 6 months.

博士后对学术职业环境满意吗?——基于Nature全球博士后调查数据比较分析

本研究基于已有成果,将博士后学术职业环境划分为学术资源、职业保障、组织管理、科研强度四个维度。利用2020年Nature全球博士后教育调查数据,通过比较分析博士后对学术职业环境的感知与评价。研究发现,相比较国外发达国家博士后而言,我国接近四成博士后对学术职业环境感到满意。为了优化博士后学术职业环境,大学需强化对博士后科研资金的支持力度,保障博士后科研参与机会,减少非学术事务对博士后科研时间的挤占,规范导师指导;大学不断调适大学基层学术组织治理模式,优化院系对博士后学术职业发展的组织支持与服务质量;大学与博士后建立稳定性雇佣关系,不断提升工资薪酬水平,疏通博士后学术职业晋升渠道,营造良好的工作环境;高校实行服务型、便捷式的科研管理方式,制定灵活多元的学术评价机制,破除博士后对“学术GDP主义”的崇拜。

Effects of natural cerebrolysin on protective proteins and pro-apoptotic molecules in mesenchymal stem cells following beta-amyloid peptide1-40-induced endoplasmic reticulum stress

BACKGROUND： Studies have demonstrated that β-amyloid peptide （Aβ）, a characteristic pathological product of Alzheimer＇s disease （AD）, results in neuronal endoplasmic reticulum stress （ERS）. However, the mechanisms of traditional Chinese medicine against ERS in AD are poorly understood. OBJECTIVE： To measure expression levels of protective proteins （GRP78 and GRP94） of ER molecular partners and pro-apoptotic Caspase-12 ER membrane expression following application of traditional Chinese medicine natural cerebrolysin （NC） to treat Aβ1-40-induced ERS. DESIGN, TIME AND SETTING： A parallel-controlled study was performed at the Institute of Integrated Western and Traditional Chinese Medicine, Shenzhen Hospital of Southern Medical University between September 2006 and November 2008. MATERIALS： Sprague Dawley male rats, 6-8 weeks old, were used to harvest tibial and femoral bone marrow. Isolation and purification of mesenchymal stem cells （MSCs） were established from the whole bone marrow by removing non-adherent cells in primary and passage cultures. Aβ1-40 was provided by Sigma, USA. NC was provided by Shenzhen Institute of Integrated Chinese and Western Medicine, China. NC was predominantly composed of Renshen （Radix Ginseng）, Tianma （Rhizoma Gastrodiae）, and Yinxingye （Ginkgo Leaf） in a proportion of 1 ： 2： 2. Following conventional water extraction technology, an extract （1 ： 20） was prepared. Six adult, male, New Zealand rabbits underwent intragastric administration of NC extract （0.976 g/kg per day） for 1 month to prepare NC-positive serum, and the remaining 6 rabbits received intragastric administration of physiological saline to prepare normal blank serum. METHODS： A total of 500 nmol/L Aβ1-40 was used to establish ERS models of primary cultured MSCs. AD cell models were incubated with different doses of NC-positive serum （2.5%, 5%, and 10%）. MSCs treated with normal blank serum served as normal blank controls. MAIN OUTCOME MEASURES： Reverse transcription-polymerase chain reaction and fluorescent immunocytochemistry were respectively used to measure mRNA and protein expression levels of GRP78, GRP94, and Caspase-12 in MSCs. RESULTS： Following Aβ1-40 exposure, mRNA and protein expression levels of GRP78 and GRP94, as well as Caspase-12, significantly increased （P 〈 0.05）, suggesting successful establishment of ERS models. Following NC-positive serum application, mRNA and protein expression levels of GRP78 and GRP94 in MSCs significantly increased （P 〈 0.05 or P 〈 0.01）. However, mRNA and protein expression levels of Caspase-12 significantly decreased （P 〈 0.05, or P 〈 0.01） compared with the ERS model group. These effects were dose-dependent. CONCLUSION： NC downregulated Caspase-12 expression and upregulated GRP78 and GRP94 expression in MSCs in a dose-dependent manner under the state of Aβ1-40-induced ERS.

The Alienation of Nature in Emily Dickinson’s Poems through the Prism of Taoism

In the poems created by the renowned American poet Emily Dickinson,those related to nature constitute a considerable proportion.However,Dickinson’s attitude toward nature is,in fact,contradictory.On the one hand,Dickinson perceives nature as gentle and kind,akin to a mother.Nature is regarded as“heaven”and embodies harmony.On the other hand,nature possesses its own operational principles and harbors inherent cruelty.According to Dickinson,humans should refrain from excessive interference in the natural order.This article attempts to analyze the similarities in attitude towards nature between Dickinson’s poetry and Taoist philosophy.

Problems and Development Suggestions of Nature Education in Jiangxi Province

The forest coverage rate of Jiangxi Province ranks second in China.It has rich natural resources,a long history of ancient color culture and rich red culture.In the development of nature education,Jiangxi Province has great potential and advantages.This paper introduces the development conditions of nature education in Jiangxi Province,summarizes the problems existing in the development of nature education in Jiangxi Province from the aspects of the types of nature education and the construction of nature education base,such as simple content and single form,imperfect infrastructure and lack of professionals,and puts forward some suggestions on the development of nature education in Jiangxi Province.

The Macrolichens of Barluk Mountain National Nature Reserve, Xinjiang Province, China

A checklist of the macrolichens (foliose, fruticose & squamulose) of Barluk Mountain National Nature Reserve located in northwestern China is presented. It was derived from 47 inventories of preserved and undeveloped areas which yielded more than 670 collections containing 102 taxa (99 species, 1 subspecies, 2 varieties). Eight species were found that were new to Xinjiang, China. Twenty-eight species and 2 varieties were found on rock, 31 species on bark of deciduous and coniferous trees, 26 species on soil and 14 species and 1 subspecies over mosses. Foliose lichens were dominant with 76 species, followed by 16 species of squamulose lichens and 7 species of fruticose lichens.

Adaptive Network Sustainability and Defense Based on Artificial Bees Colony Optimization Algorithm for Nature Inspired Cyber Security

Cyber Defense is becoming a major issue for every organization to keep business continuity intact.The presented paper explores the effectiveness of a meta-heuristic optimization algorithm-Artificial Bees Colony Algorithm(ABC)as an Nature Inspired Cyber Security mechanism to achieve adaptive defense.It experiments on the Denial-Of-Service attack scenarios which involves limiting the traffic flow for each node.Businesses today have adapted their service distribution models to include the use of the Internet,allowing them to effectively manage and interact with their customer data.This shift has created an increased reliance on online services to store vast amounts of confidential customer data,meaning any disruption or outage of these services could be disastrous for the business,leaving them without the knowledge to serve their customers.Adversaries can exploit such an event to gain unauthorized access to the confidential data of the customers.The proposed algorithm utilizes an Adaptive Defense approach to continuously select nodes that could present characteristics of a probable malicious entity.For any changes in network parameters,the cluster of nodes is selected in the prepared solution set as a probable malicious node and the traffic rate with the ratio of packet delivery is managed with respect to the properties of normal nodes to deliver a disaster recovery plan for potential businesses.

《Nature》揭示:禁食机制下的脂肪依赖性肿瘤会消退

近日,一篇发表在《Nature》上的研究显示,研究发现了一种能让小鼠摆脱胰腺癌的新方法,该疗法通过抑制脂肪代谢,切断肿瘤的能量供应,只要小鼠持续遵循生酮饮食,肿瘤生长便会停滞。研究中,研究团队聚焦于机体在禁食状态下如何转向脂肪作为能源的问题。研究者发现直接关联到胰腺癌的生物学研究,首次揭示了真核生物翻译起始因子(eukaryotic translation initiation factor,eIF4E)在禁食期间如何调控机体代谢,使其从消耗碳水化合物转变为消耗脂肪。

Nature’s Gift

NATURAL WONDERS IN CHINA AND AFRICA Qilian Mountains National Park Located in Northwest China’s Gansu and Qinghai provinces,Qilian Mountains National Park spans 50,200 square km,serving as a vital ecological security barrier and water source conservation area in west China.Established in 2017 to address ecosystem damage,intensive food chain protection and wildlife monitoring in the area began in early 2011.

《Nature》子刊:苏佳琪等开发基于牛奶的水凝胶,用作酒精中毒的解毒剂

近日,苏黎世联邦理工学院Raffaele Mezzenga、苏佳琪等人在《Nature》子刊《Nature Nanotechnology》上发表的一篇研究显示,该研究开发了一种口服的、基于牛奶蛋白的水凝胶——FeSA@FibBLG,或可作为急性酒精中毒的有效解毒剂,能够稳定耐受胃酸消化且持续显著降低酒精中毒小鼠血液中的酒精水平,同时避免额外积累有毒的乙醛,还可增强肝脏保护,并显著减轻肠道损伤和生态失调,强调了其作为酒精相关疾病的新疗法的潜力。

Spatiotemporal Evolution of Ecological Quality in Alpine Freshwater Lake Nature Reserves in the Past 20 Years

The Caohai Nature Reserve is one of the three major plateau freshwater lakes in China.Since the 1950s,human activities such as land reclamation and population relocation have greatly damaged Caohai.A rapid evaluation of the spatiotemporal evolution trend of the ecological quality of the Caohai Nature Reserve is significant for the maintenance and construction of the ecosystem in this area.The research is based on the Google Earth Engine(GEE)remote sensing cloud computing platform.Landsat TM/OLI images from May to October in five time periods:2000-2002,2004-2006,2009-2011,2014-2016,and 2019-2021 were obtained to reconstruct the optimal cloud image set by averaging the images in each time period.By constructing four ecological indicators:Greenness(NDVI),Wetness(Wet),Hotness(LST),and Dryness(NDBSI),and using Principal Component Analysis(PCA)method to obtain the Remote Sensing Ecological Index(RSEI)for the corresponding years,the spatiotemporal variation of ecological quality in the Caohai Nature Reserve over 20 years was analyzed.The results indicate:①the mean value of RSEI increased from 0.460 in 2000-2002 to 0.772 in 2019-2021,a 67.83%increase,indicating a significant improvement in the ecological quality of the reserve over the 20 years;②from the perspective of functional zoning of the Caohai Nature Reserve,the ecological quality of the core area showed a degrading trend,while the ecological quality of the buffer zone and experimental zone significantly improved;③with the implementation of ecological restoration projects,the ecological quality of the reserve gradually recovered and improved from 2014 to 2021.The trend of RSEI value changes is well correlated with human interventions,indicating that the PCA-based RSEI model can be effectively used for ecological quality assessment in lake areas.

《Nature》:新开发的可穿戴超声贴片可连续、无创监测大脑血流

近日,一篇发表在《Nature》上的研究显示,研究人员开发出一种可穿戴超声贴片(wearable ultrasound patch),其可对大脑血流进行连续、无创的监测。该研究将贴片在36名健康志愿者身上进行了测试,以检验其测量脑部主要动脉血流速度(收缩期峰值、平均流速和舒张末期速度)的能力,发现测量结果与传统超声探头的测量结果非常吻合。

A Study of the People’s Nature in Woodcuts During the Anti-Japanese War in Shanxi

The anti-Japanese woodcuts focus on the red revolutionary culture and describe the connotation of the Anti-Japanese War era,which is self-evident in the commemorative value of China’s revolutionary struggle history.For example,in Shanxi,China,woodcut art activities and social practice promotion activities organized around the theme of the Anti-Japanese War are also everywhere,which all show the people’s nature of the Chinese people during the revolutionary struggle from the two aspects of the red culture of the Anti-Japanese War and traditional art and culture,and its humanistic connotation is quite profound.In this paper,we first introduce the historical origin of woodcut during the Anti-Japanese War,and then show the people’s value connotation of woodcut art activities in Shanxi.This paper mainly discusses the image narration,language and picture narration and construction significance of woodcuts in Shanxi’s War of Resistance,fully reveals the narrative nature of image media,strives to arouse people’s recognition of this period of Shanxi’s War of Resistance culture and history,and reflects the realistic value and significance of Shanxi’s War of Resistance Woodcuts art activities.

《Nature》:科学家发现能驱动患者狼疮发生的两种细胞缺陷

近日,一篇发表在《Nature》上的研究显示,研究发现了一种特殊的分子缺陷或会促进系统性红斑狼疮的病理性免疫反应,同时揭示了逆转这一缺陷或有望逆转疾病。该研究中,研究人员报道了驱动狼疮发生的新通路,研究者表示,患者体内血液中的多种分子都会发生疾病相关的改变,最终,这些变化会导致芳香烃受体(aryl hydrocarbon receptor,AHR)所控制的通路激活不足,AHR能调节细胞对环境污染物、细菌或代谢产物的反应。

Gene expression in rat mesenchymal stem cells following treatment with natural cerebrolysin-containing serum Validation of a whole genome microarray technique

BACKGROUND： Natural cerebrolysin （NC）, a Chinese herbal drug for the treatment of Alzheimer＇s disease （AD）, induces mesenchymal stem cell （MSC） differentiation into neuron-like cells, with low toxicity. But the mechanisms involved in NC effects on MSCs remain poorly understood. OBJECTIVE： We used a whole genome microarray technique to further investigate the molecular, genetic, and pharmacodynamic mechanisms of NC on MSC gene expression profiles. DESIGN, TIME AND SETTING： A parallel, controlled, in vitro experiment was performed at the First Affiliated Hospital of Shenzhen University, Shenzhen Institute of Integrated Chinese and Western Medicine, China, between September 2006 and October 2008. MATERIALS： NC was provided by Shenzhen Institute of Integrated Chinese and Western Medicine China. It was predominantly composed of Renshen （Radix Ginseng）, Tianma （Rhizoma Gastrodiae） and Yinxingye （Ginkgo Leaf） and prepared by conventional water extractJon technology. Twelve adult, male, New Zealand rabbits were included, six of which underwent intragastric administration of NC extract for 1 month to create NC-containing serum. METHODS： Bone marrow was collected from the tibia and femur of Sprague Dawley rats, aged 6 8 months old. Rat MSCs were isolated and purified by the whole bone marrow adherence method. After in vitro culture, MSCs from passage 4 were treated with NC-containing serum for 48 hours, and total RNA was extracted. Gene expression in MSCs was analyzed using Affymetrix whole genome microarray analysis. MAIN OUTCOME MEASURES： Differentially expressed genes in NC serum-treated MSCs. RESULTS： NC treated MSCs displayed 46 differentially expressed genes, 22 with upregulated expression （fold change 〉 2） and 24 with downregulated expression （fold change 〈 -2）. Differentially expressed genes participated in neuronal growth, differentiation, and function, cell growth, differentiation, proliferation, apoptosis, signal transduction, substance/energy metabolism, ion transport, and immune responses. NC treatment changed levels of transforming growth factor β/ bone morphogenetic proteins, Hedgehog, Bmp, and Wntsignaling pathways, which regulate nerve cell differentiation, development and function, as well as learning and memory; Ras, G protein- coupled receptor signal pathways that are related to cell growth, proliferation, and apoptosis; and mitogen-activated protein kinase kinase kinase signaling cascades. CONCLUSION： NC can regulate gene expression for many signal transduction pathways related to nerve cell differentiation, development and function, learning and memory function, as well as regulation of cell growth, differentiation, proliferation, or apoptosis to mediate the genetic effects of NC treatment on AD.