Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

Heterogeneity of mature oligodendrocytes in the central nervous system

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

Transforming growth factor-beta 1 enhances discharge activity of cortical neurons

Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.

Centralized isolation of Helicobacter pylori from multiple centers and transport condition influences

AIM:To evaluate the efficacy of centralized culture and possible influencing factors.METHODS:From January 2010 to July 2012,66452 patients with suspected Helicobacter pylori(H.pylori) infection from 26 hospitals in Zhejiang and Jiangsu Provinces in China underwent gastrointestinal endoscopy.Gastric mucosal biopsies were taken from the antrum for culture.These biopsies were transported under natural environmental temperature to the central laboratory in Hangzhou city and divided into three groups based on their transport time:5,24 and 48 h.The culture results were reported after 72 h and the positive culture rates were analyzed by a χ2 test.An additional 5736 biopsies from H.pylori-positive patients(5646 rapid urease test-positive and 90 14C-urease breath test-positive) were also cultured for quality control in the central laboratory setting.RESULTS:The positive culture rate was 31.66%(21036/66452) for the patient samples and 71.72%(4114/5736) for the H.pylori-positive quality control specimens.In the 5 h transport group,the positiveculture rate was 30.99%(3865/12471),and 32.84%(14960/45553) in the 24 h transport group.In contrast,the positive culture rate declined significantly in the 48 h transport group(26.25%; P < 0.001).During transportation,the average natural temperature increased from 4.67 to 29.14℃,while the positive culture rate declined from 36.67%(1462/3987) to 24.12%(1799/7459).When the temperature exceeded 24℃,the positive culture rate decreased significantly,especially in the 48 h transport group(23.17%).CONCLUSION:Transportation of specimens within 24 h and below 24℃ is reasonable and acceptable for centralized culture of multicenter H.pylori samples.

Analysis of Ornidazole Injection in Clinical Use at Post-marketing Stage by Centralized Hospital Monitoring System

This study aims to analyze the clinical use of ornidazole injection at the post-marketing stage by centralized hospital monitoring system method,and investigate its widespread use in patients,in order to regulate and guide the rational drug use,improve the drug specificity and provide a basis for drug therapy.The study adopts a prospective,multi-center,large sample size,centralized hospital monitoring system.We selected five leading hospitals in Hubei province,and observed the inpatients who received the ornidazole injection from July 1,2015 to October 31,2015.The basic information of patients was recorded,as well as the drug use and adverse events.The statistical analysis was performed based on these data.A total of 4396 individuals were enrolled in this study,most of them were middle-aged female patients and the ornidazole injection was mainly used as prophylactic prior to surgery to prevent the infections,and surgical treatment of anaerobic infections,abdominal infections and pelvic infections.The irrational drug use existed mainly in the prescribing and administration process,including unreasonable dosing frequency,rapid intravenous drip speed and extended duration of drug use.Eleven cases of adverse reactions were collected during the monitoring,incidence rate of adverse reactions was 2.5‰;adverse drug reactions occurred within 30 min.The study results fully reflected the usage of ornidazole injection in the real world.Based on the study,we calculated the adverse reaction incidence of ornidazole and identified the risk factors which may affect the safety of ornidazole injection.Study results strongly recommend that the manufacturers should publish standards for inpatient use and doctors should prescribe with caution accordingly.

Facilities for Centralized Isolation and Quarantine for the Observation and Treatment of Patients with COVID-19

The coronavirus disease 2019(COVID-19)pandemic increased the burden on many healthcare systems and in the process,exposed the need for medical resources and physical space.While few studies discussed the efficient utilization of medical resources and physical space so far.Therefore,this study aimed to summarize experiences related to facilities used for centralized isolation for medical observation and treatment during the COVID-19 pandemic in China and to provide suggestions to further improve the management of confirmed cases,suspected cases,and close contacts.In China,three types of facilities for centralized isolation(Fangcang shelter hospitals,refitted non-designated hospitals,and quarantine hotels)underwent retrofitting for the treatment and isolation of confirmed and suspected cases.These facilities mitigated the immediate high demand for space.Moreover,in order to minimize infection risks in these facilities,regulators and governmental agencies implemented new designs,management measures,and precautionary measures to minimize infection risk.Other countries and regions could refer to China’s experience in optimally allocating social resources in response to the COVID-19 pandemic.As a conclusion,government should allocate social resources and construct centralized isolation and quarantine facilities for an emergency response,health authorities should issue regulations for centralized isolation facilities and pay strict attention to the daily management of these facilities,a multidisciplinary administration team is required to support the daily operation of a centralized isolation facility,in-depth studies and international collaboration on the centralized isolation policy are encouraged.

Monitoring and Assessment of Water Quality of Centralized Drinking Water Sources in Kaixian County during the " Twelfth Five-year Plan " Period

Based on the monitoring data of water quality of more than 40 centralized drinking water sources in 40 towns （townships or streets） of Kaixian County in the first and second half of each year during the ＂Twelfth Five-year Plan＂ period, the changing rules of the water quality were studied to provide scientific references for the improvement of drinking water safety of urban and rural residents and drinking water quality. The re- sults show that the water quality of centralized drinking water sources in Kaixian County improved year by year during the ＂Twelfth Five-year Plan＂ period, and most monitoring sites with water quality exceeding the standard are distributed in reservoirs. Total phosphorus, total nitrogen, chemical oxygen demand, and permanganate index exceeded the standard obviously. Main pollution sources are domestic pollution and non-point source pol- lution caused by excessive discharge of nitrogen, phosphorus and organic pollutants. To improve drinking water quality, it is suggested that some towns can get drinking water from other reservoirs, surface water or underground water with better quality instead of previous reservoirs with water quality exceeding the standard, and the control of non-point source pollution should be enhanced.

Quantitative analysis of distributed and centralized development of renewable energy

Global renewable energy has maintained a steady growth in recent years, mainly fostered by national policies and increasing demand. Analyzing the experience of renewable energy development in developed countries can be important to provide reference and guidance for its adoption in other countries. First, we compare and summarize definitions of distributed generation from 18 leading countries and organizations in renewable energy. On this basis, we provide three basic characteristics for successful distributed generation using renewable resources. Then, we empirically analyze the distributed and centralized development of renewable energy in Germany with focus on wind and photovoltaic power. We determined that 95% of the photovoltaic generation and 85% of the wind power generation is distributed in Germany, suggesting that the most suitable generation mode for renewable energy is the distributed approach.

Research on Model of Guiding Rural Residents' Relatively Centralized Residence——A Case Study of Chongqing City

On the basis of expounding the status quo of rural residents' residence, the thesis notes that influenced by the weak foundation of rural economy, the characteristic of mountain landscape, smallholder consciousness, shortage of capital and other factors, the rural residents in Chongqing City mainly live scattered. In addition to opportunities of the expansion and drive of city, rural market development, rural resources development, rural industrial development, and rural ecological migration, the model of urban development promotion, the model of market development drive, the model of land development drive, the model of rural industry construction and the model of resettlement and reconstruction are advocated in order to guide the rural residents to adopt relative centralized residence. The suggestions concerning guiding rural residents' relative centralized residence are put forward as follows: firstly, act according to circumstances and conduct scientific planning and design; secondly, propagate extensively and activate famers' willingness; thirdly, first experiment and exert the exemplary guide; fourthly, perfect policy and guarantee farmers' benefit; fifthly, strengthen leadership and decrease the risk of centralized residence; sixthly, boost gradually and realize moderate centralized residence.

Return on Investment after Implementation of a Centralized Automated Storage System in a Hospital Pharmacy

An ADS （automated dispensing system） was implemented in our hospital pharmacy in 2008 to optimize and secure the medication process. The main objective of this study was to compare the projected and the real ROI （return on investment）, after seven years of use. ROI was calculated annually （from 2008 to 2015）, by deducting the cost of investment （ADS buying and implementation, maintenance, repairs and ADS upgrade） from the cost saving （drugs stock reduction and decrease of pharmacy staff dedicated to global dispensing）. In 2015, total costs saving （＋$1,141,987） were divided between decreasing drug stock value and reduction of pharmacy staff. Total costs of investment （-$978,656） were acquisition, maintenance, repairs and an unplanned upgrade costs. Finally, the real ROI was ＋$163,331 after seven years of use. In 2008, projected ROI was ＋$410,786. The real payback period has been increased by approximately two years （six years of use, instead of four years as expected）. Despite their cost, ADSs are a worthwhile investment, leading to a ROI within a few years. These economic considerations should be put into perspective with optimization of drugs stock management, greater efficiency of the global dispensing process, securitization of medication process and redeployment of pharmacy staff.

Assessment of Wet Season Precipitation in the Central United States by the Regional Climate Simulation of the WRFG Member in NARCCAP and Its Relationship with Large-Scale Circulation Biases

Assessment of past-climate simulations of regional climate models(RCMs)is important for understanding the reliability of RCMs when used to project future regional climate.Here,we assess the performance and discuss possible causes of biases in a WRF-based RCM with a grid spacing of 50 km,named WRFG,from the North American Regional Climate Change Assessment Program(NARCCAP)in simulating wet season precipitation over the Central United States for a period when observational data are available.The RCM reproduces key features of the precipitation distribution characteristics during late spring to early summer,although it tends to underestimate the magnitude of precipitation.This dry bias is partially due to the model’s lack of skill in simulating nocturnal precipitation related to the lack of eastward propagating convective systems in the simulation.Inaccuracy in reproducing large-scale circulation and environmental conditions is another contributing factor.The too weak simulated pressure gradient between the Rocky Mountains and the Gulf of Mexico results in weaker southerly winds in between,leading to a reduction of warm moist air transport from the Gulf to the Central Great Plains.The simulated low-level horizontal convergence fields are less favorable for upward motion than in the NARR and hence,for the development of moist convection as well.Therefore,a careful examination of an RCM’s deficiencies and the identification of the source of errors are important when using the RCM to project precipitation changes in future climate scenarios.

Crosstalk among mitophagy,pyroptosis,ferroptosis,and necroptosis in central nervous system injuries

Central nervous system injuries have a high rate of resulting in disability and mortality;however,at present,effective treatments are lacking.Programmed cell death,which is a genetically determined fo rm of active and ordered cell death with many types,has recently attra cted increasing attention due to its functions in determining the fate of cell survival.A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain damage.In this review,we provide an ove rview of the role of programmed cell death in central nervous system injuries,including the pathways involved in mitophagy,pyroptosis,ferroptosis,and necroptosis,and the underlying mechanisms by which mitophagy regulates pyroptosis,ferroptosis,and necro ptosis.We also discuss the new direction of therapeutic strategies to rgeting mitophagy for the treatment of central nervous system injuries,with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system injury.In conclusion,based on these properties and effects,interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients.

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells.Oligodendrocytes perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity regulation.They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and apoptosis.Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes.These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function.In this review,we summarize the effects of general anesthetic agents on oligodendrocytes.We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

Symbol Error Probability of Incremental Relaying with Distributed/Centralized Relay Selection

In this paper,we derive the Symbol Error Probability(SEP)of cooperative systems with incremental relaying and Distributed Relay Selection(DRS).The relays remain idle when the Signal to Noise Ratio(SNR)between the source and destination is larger than T.Otherwise,we activate a relay using DRS.Relay nodes transmit only if their SNR is larger than thresholdβ.If the SNRs of more than two relays is larger thanβ,there is a collision and the destination uses only the received signal from the source.If all relays have SNR less thanβ,no relay is chosen.Thresholdβis optimized to yield the lowest SEP at the destination.Our results are compared to centralized relay selection using opportunistic Amplify and Forward(OAF),Partial and Reactive Relay Selection(PRS and RRS).We compare our results to computer simulations for Rayleigh fading channels.

Bromocriptine protects perilesional spinal cord neurons from lipotoxicity after spinal cord injury

Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear.Herein,we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury.We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice.Lipid droplet accumulation could be induced by myelin debris in HT22 cells.Myelin debris degradation by phospholipase led to massive free fatty acid production,which increased lipid droplet synthesis,β-oxidation,and oxidative phosphorylation.Excessive oxidative phosphorylation increased reactive oxygen species generation,which led to increased lipid peroxidation and HT22 cell apoptosis.Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway,thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells.Motor function,lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury.The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.

Use of cognitive-behavioral career coaching to reduce work anxiety and depression in public employees

BACKGROUND Public employees worldwide are increasingly concerned about work anxiety and depression.Cognitive-behavioral career coaching has emerged as a promising strategy for addressing these mental health disorders,which can negatively impact on a person's overall well-being and performance.AIM To examine whether cognitive-behavioral career coaching reduces work anxiety and depression among Nigerian public employees.METHODS A total of 120 public employees(n=60)suffering from severe anxiety and depression were randomly assigned to the treatment or control groups in this study.Cognitive behavioral coaching was provided twice a week to those in the treatment group,whereas no treatment was given to those in the control group.As part of the study,the Hamilton Anxiety Rating Scales and Beck Depression Inventory were used to collect data.RESULTS Analysis of covariance of the data from participants indicates a significant effect of cognitive-behavioral career coaching on work anxiety and depression.CONCLUSION Insights into the underlying mechanisms by which cognitive behavior career coaching exerts its effects have been gained from this study.Also,the study has gathered valuable data that can inform future practice and guide the development of strategies for supporting mental health at work.

An Efficient Routing Tree Algorithm for Combined Uplink and Downlink Subframes on Centralized Scheduling in IEEE 802.16 Based Wireless Mesh Networks

IEEE 802.16 mesh mode defines routing tree for transmitting data in centralized scheduling but it does not define any explicit proposal for combining uplink and downlink subframes. Deploying combined uplink and downlink subframes on the centralized scheduling scheme can be more flexible and utilization is improved. However, existing interferences among the transmission of neighboring nodes lead to performance reduction of the network. In this paper, an efficient routing tree algorithm is proposed with combined uplink and downlink slot allocation on the centralized scheduling scheme which can abate interferences in the network. This algorithm allows more subscriber stations to transmit concurrently and so improves spatial reuse in the network. Also, the algorithm uses multi-channel and single channel systems and considers relay model, smoothing switching frequently between transmitting and receiving in successive time slots and fairness in the network. Extensive simulation results demonstrate the effectiveness of the proposed method in terms of scheduling length, link concurrency ratio, network throughput and Channel Utilization Ratio (CUR).