Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Role of copper in central nervous system physiology and pathology

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

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.

Microglia lactylation in relation to central nervous system diseases

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

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.

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.

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.

Prognostic factors for acute central retinal artery occlusion treated with hyperbaric oxygen:The Hong Kong study report number five

BACKGROUND Central retinal artery occlusion(CRAO)is a potentially blinding disease,and hyperbaric oxygen therapy(HBOT)is becoming increasingly popular with the support of scientific evidence.Despite the presence of various acute management measures,there is no clear evidence on the gold standard treatment for CRAO.AIM To identify factors and imaging parameters associated with good visual outcome,which guide ophthalmologists in the triage of CRAO patients for HBOT.METHODS Patients who suffered from CRAO and had a symptom onset≤6 h were recruited for a course of HBOT in a tertiary hospital after failing bedside treatment.Patient demographics,onset time,CRAO eye parameters,and past medical history were prospectively collected.Visual outcomes after HBOT were also analyzed.RESULTS A total of 26 patients were included;the female-to-male ratio was 1:1.6,and the mean age was 67.5 years±13.3 years(range 44–89 years).The mean duration of follow-up and mean visual acuity(VA)improvement were 10.0 mo±5.3 mo and 0.48 logarithm of minimal angle of resolution(logMAR)±0.57 logMAR(approx-imately 9 letters in ETDRS)(P=0.0001,Z=-3.67),respectively.The 1 mm zone of central macular thickness(CMT)on optical coherence tomography was not associated with VA changes(P=0.119);however,the 1-to-3 mm circular rim of CMT was fairly associated(P=0.02,Spearman's coefficient=0.45).Complete retinal perfusion time during fundus fluorescein angiography(FFA)was mode-rately associated(P=0.01,Spearman's coefficient=0.58)with visual outcome.

Analysis and Modeling of the Central Air-Conditioning System in Intelligent Buildings

The central air conditioning system in an intelligent building (IB) was analyzed and modeled in order to perform the optimization scheduling strategy of the central air conditioning system. A set of models proposed and a type of periodically autoregressive model (PAR) based on the improved genetic algorithms (IGA) were used to perform the optimum energy saving scheduling. The example of the Liangmahe Plaza was taken to show the effectiveness of the methods.

Optimum Energy Management of the Central Air-Conditioning System in Intelligent Buildings

An optimum energy saving scheduling strategy of the central air conditioning system in an intelligent building (IB) was proposed. Based on the system analysis a set of models of the central air conditioning system was established. The periodically autoregressive models (PARM) based on genetic algorithms (GA) were used to predict the next day’s cold load. The improved genetic algorithms (IGA) with stochastic real number coding were used to finish the optimum energy saving scheduling of the system. The simulation results for the building of the Liangmahe Plaza show that the proposed strategy can save energy up to about 24 5%.

Influence of Surrounding Structures upon the Aerodynamic and Acoustic Performance of the Outdoor Unit of a Split Air-Conditioner

DC-inverter split air-conditioner is widely used in Chinese homes as a result of its high-efficiency and energy-saving. Recently, the researches on its outdoor unit have focused on the influence of surrounding structures upon the aerodynamic and acoustic performance, however they are only limited to the influence of a few parameters on the performance, and practical design of the unit requires more detailed parametric analysis. Three-dimensional computational fluid dynamics（CFD） and computational aerodynamic acoustics（CAA） simulation based on FLUENT solver is used to study the influence of surrounding structures upon the aforementioned properties of the unit. The flow rate and sound pressure level are predicted for different rotating speed, and agree well with the experimental results. The parametric influence of three main surrounding structures（i.e. the heat sink, the bell-mouth type shroud and the outlet grille） upon the aerodynamic performance of the unit is analyzed thoroughly. The results demonstrate that the tip vortex plays a major role in the flow fields near the blade tip and has a great effect on the flow field of the unit. The inlet ring＇s size and throat＇s depth of the bell-mouth type shroud, and the through-flow area and configuration of upwind and downwind sections of the outlet grille are the most important factors that affect the aerodynamic performance of the unit. Furthermore, two improved schemes against the existing prototype of the unit are developed, which both can significantly increase the flow rate more than 6 %（i.e. 100 m3·h～（-1）） at given rotating speeds. The inevitable increase of flow noise level when flow rate is increased and the advantage of keeping a lower rotating speed are also discussed. The presented work could be a useful guideline in designing the aerodynamic and acoustic performance of the split air-conditioner in engineering practice.

Environmental Benefits for Phase-Out HCFC-22 in the Residential Air-Conditioner Sector in China

China is the largest producer and consumer of hydrochlorofluorocarbons （HCFCs）, and the production of HCFC-22 accounts for more than 80% of all HCFCs. This paper concentrates on the residential air-conditioner industry and analyzes the environmental benefits of accelerating the phase-out of HCFC-22 in China. According to the comparison of the baseline and phase-out scenarios of HCFC-22, the findings show that using HC-290 （propane） as a refrigerant alternative will directly reduce the greenhouse effect, and indirectly reduce the emission of greenhouse gases due to a reduction in the electricity consumption. The comparison of two scenarios of HC-290 and HFC-410A refrigerant alternatives shows that the use of HC-290 refrigerant will produce significantly higher environmental benefits than the HFC-410A refrigerant.

Forecast of Consumption and Emission of HFC-134a Used in the Mobile Air-conditioner Sector in China

HFC-134a is the most important alternative to CFC-12 used in the mobile air-conditioner sector in China. The con- sumption of HFC-134a has been increasing rapidly in recent years. It becomes the most consumed HFC in the sector. Selecting 2005 as the base line year, future consumption and emission amounts of HFC-134a are estimated through an analysis of a combined scenario： 1） replacement by non-HFC-134a blends, 2） good practice in servicing, 3） technology promotion, and 4） government policies on control of HFC-134a emissions. The analysis shows that HFC-134a consumption and emissions will continue to increase in the next 10 years. The projected HFC-134a consumption will approach 20,150 t and 34,875 t in 2010 and 2015 respectively, while the estimated emission amounts will reach 16,065 t and 30,186 t （i.e., 21 Mt CO2-eq and 39 Mt CO2-eq emissions） correspondingly. Compared with the business-as-usual scenario, the expected emission reductions in 2010 and 2015 will range between 6.7 Mt CO2-eq and 13.0 Mt CO2-eq.

An Energy-Saving Control Strategy on Central Air-Conditioning System

An energy-saving control strategy based on predictive control for central air-conditioning systems is proposed in this paper. The cold load model is developed to describe the dynamic characteristics of temperature control systems, and then parameters in the cold load model and in the central air-conditioning system model are estimated. Generalized predictive control (GPC) is used to establish an optimization model to minimize the consumption of energy and the control error of temperature. The simulated annealing (SA) algorithm, combined with quadratic programming, is adopted to solve the optimal problem. Contrasted with the simulation of traditional PID control, the results prove the effectiveness of this proposed strategy.

A Novel Concept of AI-EV （Air-Conditioner Integrated Electric Vehicle） for the Advanced Smart Community

In order to expand the natural energy and the energy conservation, ＂the smart PV （photovoltaic power generation） ＆ EV （electric vehicle） system＂ has been proposed and the effect has been clarified. In the smart PV ＆ EV system, it is important that electric vehicles become popular. Therefore, the AI-EV （air-conditioner integrated electric vehicle） has been proposed. In this paper, the AI-EV is designed based on the required car air-conditioner capacity. And, the value of AI-EV is compared with a gasoline vehicle, HV （hybrid vehicle） and EV using the mathematical simulation model As a result, it is clarified that the minimum displacement of the small-engine is 120 cc for AI-EV. In the smart PV ＆ EV system, AI-EV can reduce CO_2 emissions by 20% almost the same as EV. Additionally, AI-EV is able to gain the cruising range more than twice as long as EV.

Effect of air-conditioner exposure on semen quality

Aim: To investigate the effect of air-conditioner exposure on semen quality. Methods: The data came from the healthy male volunteers, aged 22 to 30 years, who went to centers for maternity and children health for premarital physical examination in Shanghai, Henan, Zhejiang and Hebei from December 1998 to February 2000. The sampling size is 304. Results: Among the subjects, 90 (29.6 %) had air-conditioner at home and the rest did not. X2-test and multiple logistic regression analyses showed that, the difference between the exposure and control groups was statistically significant in semen volume, sperm density and proportion of sperm with normal morphology. The three indexes were lower in the exposure group. Conclusion: Air-conditioner exposure possibly influences the semen quality.

Intranasal administration of stem cell-derived exosomes for central nervous system diseases

Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

Petroleum geological characteristics and exploration targets of the oil-rich sags in the Central and West African Rift System

Based on seismic,drilling,and source rock analysis data,the petroleum geological characteristics and future exploration direction of the oil-rich sags in the Central and West African Rift System(CWARS)are discussed.The study shows that the Central African Rift System mainly develops high-quality lacustrine source rocks in the Lower Cretaceous,and the West African Rift System mainly develops high-quality terrigenous organic matter-rich marine source rocks in the Upper Cretaceous,and the two types of source rocks provide a material basis for the enrichment of oil and gas in the CWARS.Multiple sets of reservoir rocks including fractured basement and three sets of regional cap rocks in the Lower Cretaceous,the Upper Cretaceous,and the Paleogene are developed in the CWARS.Since the Late Mesozoic,due to the geodynamic factors including the dextral strike-slip movement of the Central African Shear Zone,the basins in different directions of the CWARS differ in terms of rifting stages,intervals of regional cap rocks,trap types and accumulation models.The NE-SW trending basins have mainly preserved one stage of rifting in the Early Cretaceous,with regional cap rocks developed in the Lower Cretaceous strata,forming traps of reverse anticlines,flower-shaped structures and basement buried hill,and two types of hydrocarbon accumulation models of"source and reservoir in the same formation,and accumulation inside source rocks"and"up-source and down-reservoir,and accumulation below source rocks".The NW–SE basins are characterized by multiple rifting stages superimposition,with the development of regional cap rocks in the Upper Cretaceous and Paleogene,forming traps of draping anticlines,faulted anticlines,antithetic fault blocks and the accumulation model of"down-source and up-reservoir,and accumulation above source rocks".The combination of reservoir and cap rocks inside source rocks of basins with multiple superimposed rifting stages,as well as the lithologic reservoirs and the shale oil inside source rocks of strong inversion basins are important fields for future exploration in basins of the CWARS.

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.