Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Physiological and pathological functions of circular RNAs in the nervous system

Circular RNAs(circRNAs)are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues.CircRNAs play crucial roles in physiological and pathological processes by sponging microRNAs,modulating gene transcription,controlling the activity of certain RNA-binding proteins,and producing functional peptides.A key focus of research at present is the functionality of circRNAs in the nervous system and several advances have emerged over the last 2 years.However,the precise role of circRNAs in the nervous system has yet to be comprehensively reviewed.In this review,we first summarize the recently described roles of circRNAs in brain development,maturity,and aging.Then,we focus on the involvement of circRNAs in various diseases of the central nervous system,such as brain cancer,chronic neurodegenerative diseases,acute injuries of the nervous system,and neuropathic pain.A better understanding of the functionality of circRNAs will help us to develop potential diagnostic,prognostic,and therapeutic strategies to treat diseases of the nervous system.

The effects and potential of microglial polarization and crosstalk with other cells of the central nervous system in the treatment of Alzheimer’s disease

Microglia are resident immune cells in the central nervous system. During the pathogenesis of Alzheimer’s disease, stimulatory factors continuously act on the microglia causing abnormal activation and unbalanced phenotypic changes;these events have become a significant and promising area of research. In this review, we summarize the effects of microglial polarization and crosstalk with other cells in the central nervous system in the treatment of Alzheimer’s disease. Our literature search found that phenotypic changes occur continuously in Alzheimer’s disease and that microglia exhibit extensive crosstalk with astrocytes, oligodendrocytes, neurons, and penetrated peripheral innate immune cells via specific signaling pathways and cytokines. Collectively, unlike previous efforts to modulate microglial phenotypes at a single level, targeting the phenotypes of microglia and the crosstalk with other cells in the central nervous system may be more effective in reducing inflammation in the central nervous system in Alzheimer’s disease. This would establish a theoretical basis for reducing neuronal death from central nervous system inflammation and provide an appropriate environment to promote neuronal regeneration in the treatment of Alzheimer’s disease.

Research progress of sphingosine 1-phosphate and its signal transduction in central nervous system diseases

Sphingosine 1-phosphate(S1P),as a sphingolipid metabolite,has become a key substance in regulating various physiological processes,involved in differentiation,proliferation,migration,morphogenesis,cytoskeleton formation,adhesion,apoptosis,etc.process.Sphingosine 1-phosphate can not only activate the S1P-S1PR signaling pathway by binding to the corresponding receptors on the cell membrane,but also play a role in the cell.In recent years,studies have found that there is a certain relationship between its level changes and the occurrence and development of central nervous system diseases.This article reviews the latest knowledge of sphingosine-1-phosphate in the occurrence and treatment of nervous system diseases,and further clarifies its molecular mechanism in the treatment and development of central nervous system diseases.

Novel Computer-Aided Diagnosis System for the Early Detection of Alzheimer’s Disease

Aging is a natural process that leads to debility,disease,and dependency.Alzheimer’s disease(AD)causes degeneration of the brain cells leading to cognitive decline and memory loss,as well as dependence on others to fulfill basic daily needs.AD is the major cause of dementia.Computer-aided diagnosis(CADx)tools aid medical practitioners in accurately identifying diseases such as AD in patients.This study aimed to develop a CADx tool for the early detection of AD using the Intelligent Water Drop(IWD)algorithm and the Random Forest(RF)classifier.The IWD algorithm an efficient feature selection method,was used to identify the most deterministic features of AD in the dataset.RF is an ensemble method that leverages multiple weak learners to classify a patient’s disease as either demented(DN)or cognitively normal(CN).The proposed tool also classifies patients as mild cognitive impairment(MCI)or CN.The dataset on which the performance of the proposed CADx was evaluated was sourced from the Alzheimer’s Disease Neuroimaging Initiative(ADNI).The RF ensemble method achieves 100%accuracy in identifying DN patients from CN patients.The classification accuracy for classifying patients as MCI or CN is 92%.This study emphasizes the significance of pre-processing prior to classification to improve the classification results of the proposed CADx tool.

A necessary and sufficient condition for transforming autonomous systems into linear autonomous Birkhoffian systems

The problem of transforming autonomous systems into Birkhoffian systems is studied. A reasonable form of linear autonomous Birkhoff equations is given. By combining them with the undetermined tensor method, a necessary and sufficient condition for an autonomous system to have a representation in terms of linear autonomous Birkhoff equations is obtained. The methods of constructing Birkhoffian dynamical functions are given. Two examples are given to illustrate the application of the results.

Exact Solutions to Maccari's System

Based on the generalized Riccati relation,an algebraic method to construct a series of exact solutionsto nonlinear evolution equations is proposed.Being concise and straightforward,the method is applied to Maccari'ssystem,and some exact solutions of the system are obtained.The method is of important significance in exploring exactsolutions for other nonlinear evolution equations.

Entanglement and non-Markovianity of a spin-S system in a dephasing environment

We study the entanglement （measured by negativity） evolution and the non-Markovianity for the dynamical process of a spin-S system embedded in dephasing environments. The exact analytical solution is presented, which shows that the decoherence function governs the evolutions of coherence, entanglement, and the non-Markovianity of the correspond- ing dynamical processes. For Ohmic and sub-Ohmic reservoirs, the negativity decreases monotonically in time and the corresponding dynamics is Markovian. While for super-Ohmic reservoirs with non-monotonic decoherence function, the negativity appears as the phenomenon of revival and the corresponding dynamics is non-Markovian. The relation between non-Markovianity and the system dimension is studied.

The U.S. School Bus System:What Can China Learn?

The school bus system in the United States took its form in 1939 when Frank W. Cyr, from the New York-based Teachers College of Columbia University, organized a national standards conference for school transportation. Representatives of education and transportation depart- ments from all 48 states, together with school bus manufacturers, attended the 7-day meeting. They worked out 45 standards and rules concerning school bus safety, specifying in detail school bus length, roof height, aisle width, etc.

ZTE's Broadband Wireless Access System

1 IntroductionWith the rapid development of backbonenetworks,the subscriber accessnetwork,a major component of publictelecom network equipment and so-called the“last kilometer”,has turned out to bethe focus of attention.Among various access technologies,thebroadband wireless access system featuresquick network construction,rapid investmentreturn and large bandwidth.It enables newnetwork operators to provide services quickly

Review on the Effect of Resveratrol on Central Nervous System Disease

Resveratrol (3,5,4’-trihydroxy-trans-stilbene, RV) is a kind of phytoalexin found in many kinds of plants and food. As a natural antioxidant, RV shows significant biological activity, including anti-tumor activity, antitubulin activity, cardiovascular disease resistance activity, etc. Many experiments confirm that resveratrol displays a wide range of beneficial effects on human diseases including heart disease and cancer, especially in the treatment of central nervous system disease, such as Huntington’s disease (HD), Alzheimer’s disease (AD) and Parkinson’s disease (PD). This paper summarizes the positive effects of RV on several central nervous system diseases.

China's first plasma pyrolysis system for treating solid wastes

A research team from the CAS Institute of Mechanics has been recently successful in developing China’s first plasma pyrolysis system for the treatment of solid chemical wastes.

People's Complaints System in China——Chinese way of human rights relief

The people＇s complaints system is a mechanism of democracy and human rights relief under the traditional legal system of China. It has displayed positive roles during different historical periods after 1949 when the new China was founded.

Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload

Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer＇s dis- ease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer＇s disease patients. An APPs,~JPSI^E9 double transgenic mouse model of Alzheimer＇s disease was used. The intragas- tric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer＇s disease. These com- pounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer＇s disease.

The Yin-Yang of osteopontin in nervous system diseases: damage versus repair

Osteopontin is a broadly expressed pleiotropic protein,and is attracting increased attention because of its role in the pathophysiology of several inflammatory,degenerative,autoimmune,and oncologic diseases.In fact,in the last decade,several studies have shown that osteopontin contributes to tissue damage not only by recruiting harmful inflammatory cells to the site of lesion,but also increasing their survival.The detrimental role of osteopontin has been indeed well documented in the context of different neurological conditions(i.e.,multiple sclerosis,Parkinson’s,and Alzheimer’s diseases).Intriguingly,recent findings show that osteopontin is involved not only in promoting tissue damage(the Yin),but also in repair/regenerative mechanisms(the Yang),mostly triggered by the inflammatory response.These two apparently discordant roles are partly related to the presence of different functional domains in the osteopontin molecule,which are exposed after thrombin or metalloproteases cleavages.Such functional domains may in turn activate intracellular signaling pathways and mediate cell-cell and cell-matrix interactions.This review describes the current knowledge on the Yin and Yang features of osteopontin in nervous system diseases.Understanding the mechanisms behind the Yin/Yang would be relevant to develop highly specific tools targeting this multifunctional protein.

Oxidation of KCNB1 K^+ channels in central nervous system and beyond

KCNB1, a voltage-gated potassium(K+) channel that conducts a major delayed rectifier current in the brain, pancreas and cardiovascular system is a key player in apoptotic programs associated with oxidative stress. As a result, this protein represents a bona fide drug target for limiting the toxic effects of oxygen radicals. Until recently the consensus view was that reactive oxygen species trigger a pro-apoptotic surge in KCNB1 current via phosphorylation and SNARE-dependent incorpora-tion of KCNB1 channels into the plasma membrane. However, new evidence shows that KCNB1 can be modified by oxidants and that oxidized KCNB1 channels can directly activate pro-apoptotic signaling pathways. Hence, a more articulated picture of the pro-apoptotic role of KCNB1 is emerging in which the protein induces cell's death through distinct molecular mechanisms and activation of multiple pathways. In this review article we discuss the diverse functional, toxic and protective roles that KCNB1 channels play in the major organs where they are expressed.

Research on Supply Chain Operation of Connecting Agriculture with Supermarkets Based on Agricultural Brokers System

On the basis of expounding the research results of using relevant knowledge about Game Theory for supply chain of agricultural products at home and abroad,we use principal-agent model in Game Theory to research the new function that the supermarkets entrust supervision and control over quality of agricultural products to agricultural brokers in the circulation model of connecting agriculture with supermarkets;then design the optimal incentive contract and influencing factors between agricultural broker and supermarket,and explain the fundamental role of agricultural brokers in the process of circulation;finally in light of the role of government in promoting development and application of agricultural brokers,put forward corresponding policy suggestions:establish government support policy;set relevant standard of industry;establish cooperative organizations of agricultural brokers.

Proteolysis targeting chimera technology:a novel strategy for treating diseases of the central nervous system

Neurological diseases such as stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease are among the intractable diseases for which appropriate drugs and treatments are lacking.Proteolysis targeting chimera(PROTAC)technology is a novel strategy to solve this problem.PROTAC technology uses the ubiquitin-protease system to eliminate mutated,denatured,and harmful proteins in cells.It can be reused,and utilizes the protein destruction mechanism of the cells,thus making up for the deficiencies of traditional protein degradation methods.It can effectively target and degrade proteins,including proteins that are difficult to identify and bind.Therefore,it has extremely important implications for drug development and the treatment of neurological diseases.At present,the targeted degradation of mutant BTK,mHTT,Tau,EGFR,and other proteins using PROTAC technology is gaining attention.It is expected that corresponding treatment of nervous system diseases can be achieved.This review first focuses on the recent developments in PROTAC technology in terms of protein degradation,drug production,and treatment of central nervous system diseases,and then discusses its limitations.This review will provide a brief overview of the recent application of PROTAC technology in the treatment of central nervous system diseases.

Two uncommon manifestations of leptospirosis:Sweet's syndrome and central nervous system vasculitis

To leptospirosis is the commonest spirocheatal infection in the tropical and temperate countries of Indian sub-continent and Africa and the most common zoonosis worldwide.The protean manifestation of this infectious disease is a challenge for practising clinicians across the world. In poor developing countries,at most clinical suspicion it is essential in the diagnosis of this disease.In this report,we are able to document two uncommon manifestations of leptospirosis, namely Sweet’s syndrome and central nervous system vasculitis.