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.

OTFS-Based Efficient Handover Authentication Scheme with Privacy-Preserving for High Mobility Scenarios

Handover authentication in high mobility scenarios is characterized by frequent and shortterm parallel execution.Moreover,the penetration loss and Doppler frequency shift caused by high speed also lead to the deterioration of network link quality.Therefore,high mobility scenarios require handover schemes with less handover overhead.However,some existing schemes that meet this requirement cannot provide strong security guarantees,while some schemes that can provide strong security guarantees have large handover overheads.To solve this dilemma,we propose a privacy-preserving handover authentication scheme that can provide strong security guarantees with less computational cost.Based on Orthogonal Time Frequency Space(OTFS)link and Key Encapsulation Mechanism(KEM),we establish the shared key between protocol entities in the initial authentication phase,thereby reducing the overhead in the handover phase.Our proposed scheme can achieve mutual authentication and key agreement among the user equipment,relay node,and authentication server.We demonstrate that our proposed scheme can achieve user anonymity,unlinkability,perfect forward secrecy,and resistance to various attacks through security analysis including the Tamarin.The performance evaluation results show that our scheme has a small computational cost compared with other schemes and can also provide a strong guarantee of security properties.

Suppressing high mobility group box-1 release alleviates morphine tolerance via the adenosine5'-monophosphate-activated protein kinase/heme oxygenase-1 pathway

Opioids,such as morphine,are the most potent drugs used to treat pain.Long-term use results in high tolerance to morphine.High mobility group box-1(HMGB1) has been shown to participate in neuropathic or inflammatory pain,but its role in morphine tolerance is unclear.In this study,we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days.We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1.HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1β production by increasing Toll-like receptor 4receptor expression in microglia,thereby inducing morphine tolerance.Glycyrrhizin,an HMGB1 inhibito r,markedly attenuated chronic morphine tole rance in the mouse model.Finally,compound C(adenosine 5’-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin(heme oxygenase-1 inhibitor)alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1β production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tole rance,and alleviated morphine tolerance in the mouse model.These findings suggest that morphine induces HMGB1 release via the adenosine 5’-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway,and that inhibiting this signaling pathway can effectively reduce morphine tole rance.

TCP-LTE/5G Cross-layer performance analysis tool for high mobility data networking and a case study on high-speed railway

Nowadays,high mobility scenarios have become increasingly common.The widespread adoption of High-speed Rail(HSR)in China exemplifies this trend,while more promising use cases,such as vehicle-to-everything,continue to emerge.However,the Internet access provided in high mobility environments stllstruggles to achieve seamless connectivity.The next generation of wireless cellular technology 5 G further poses more requirements on the endto-end evolution to fully utilize its ultra-high band-width,while existing network diagnostic tools focus on above-IP layers or below-IP layers only.We then propose HiMoDiag,which enables flexible online analysis of the network performance in a cross-layer manner,i.e.,from the top(application layer)to the bottom(physical layer).We believe HiMoDiag could greatly simplify the process of pinpointing the deficiencies of the Internet access delivery on HSR,lead to more timely optimization and ultimately help to improve the network performance.

High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4(+)CD25(+)CD127(low) Treg cells among CD4(+) cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4(+)CD25(+)CD127(low) Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CIA(+) cells were found in liver failure patients than in CHB patients (82.6+/-20.1 mu g/L vs. 34.2+/-13.7 mu g/L; 4.55+/-1.34% vs. 9.52+/-3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection. Moreover, HMGB1 can weaken the immune activity of Treg cells. It is suggested that effectively inhibiting HMGB1 expression could be a feasible way to treat liver failure by suppressing endotoxemia and enhancing Treg cell activity.

5G High Mobility Wireless Communications: Challenges and Solutions

The fifth generation(5G) network is expected to support significantly large amount of mobile data traffic and huge number of wireless connections,to achieve better spectrum- and energy-efficiency,as well as quality of service(QoS) in terms of delay,reliability and security.Furthermore,the 5G network shall also incorporate high mobility requirements as an integral part,providing satisfactory service to users travelling at a speed up to 500 km/h.This paper provides a survey of potential high mobility wireless communication(HMWC) techniques for 5G network.After discussing the typical requirements and challenges of HMWC,key techniques to cope with the challenges are reviewed,including transmission techniques under the fast timevarying channels,network architecture with mobility support,and mobility management.Finally,future research directions on 5G high mobility communications are given.

Novel insights for high mobility group box 1 proteinmediated cellular immune response in sepsis:A systemic review

BACKGROUND:High mobility group box 1 protein(HMGB1) is a highly conserved,ubiquitous protein in the nuclei and cytoplasm of nearly all cell types.HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine.In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis.METHODS:This systemic review is mainly based on our own work and other related reports.RESULTS:HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes,regulatory T cells(Tregs),dendritic cells(DCs),macrophages,and natural killer cells(NK cells).Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors[e.g.,the receptor for advanced glycation end products(RAGE),Toll-like receptor(TLR)2,and TLR4].Anti-HMGB1 treatment,such as anti-HMGB1 polyclonal or monoclonal antibodies,inhibitors(e.g.,ethyl pyruvate) and antagonists(e.g.,A box),can protect against sepsis lethality and give a wider window for the treatment opportunity.CONCLUSION:HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.

Position-assisted fast handover schemes for LTE-advanced network under high mobility scenarios

Two position-assisted fast handover schemes, scheme A and scheme B, for LTE-A system under very high mobility scenarios, are proposed, together with their performance evaluation. Scheme A is designed to reduce handover delay by making handover preparation before handover starts. Scheme B aims at reducing unnecessary handovers and improving handover success rate, by calculating the geographically best target handover cell, which makes it easier for mobile terminals to access the target cell. A system level simulation is conducted to evaluate the performance of these two schemes. It is shown that, scheme A could reduce inter-site handover delay by about 50 ms, while scheme B could cut down nearly 50% of all handovers when time-to-trigger （TTT） is 0 ms. Besides, as TTT gets larger, Scheme B has much better success rate.

Effect on proliferation and apoptosis of retinoblastoma cell by RNA inhibiting high mobility group protein box-1 expression

AIM： To investigate the effect of high mobility group protein box-1 （HMGB1） siRNA on proliferation and apoptosis of retinoblastoma （Rb） cells.METHODS： The expression of HMGB1 in Rb cells were detected by real-time polymerase chain reaction （RT-PCR） and Western blot. Chemically synthesized HMGB1 siRNA was transfected into Y79 cells. The inhibitory rate was also examined by RT-PCR and Western blot. After HMGB1 siRNA transfection, the cell proliferation was analyzed by MTT, and cell apoptosis was detected by Caspase-3 active detection kit. Cell cycle distribution and apoptosis were detected by flow cytometry. RESULTS： The expression of HMGB1 significantly elevated in Rb cells （P〈0.01）. After transfected by siRNA, the HMGB1 protein level of Y79 cells was significantly reduced （P〈0.01）. After siRNA interference HMGB1, the proportion of proliferating cells reduced, and the proportion of quiescent cells increased （P〈0.05）. In addition, apoptosis rate of Y79 cells increased from 2.03% to 9.10% after interfering with HMGB1 siRNA （P〈0.05）.CONCLUSION： Specific HMGB1 siRNA can inhibit the expression of HMGB1. The effect may be attributed to inhibit the proliferation and promote cell apoptosis.

Changes of High Mobility Group box 1 in Serum of Pig Acute Hepatic Failure Model and Significance

The role of the high mobility group box 1 （HMGB-1） in acute hepatic failure and the effect of artificial liver support system treatment on HMGB-1 level were investigated. Pig models of acute hepatic failure were induced by D-galactosamine and randomly divided into two groups with or without artificial liver support system treatment. Tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） levels were detected by the enzyme linked immunosorbent assay （ELISA）, the expression of HMGB-1 by Western blot, and serum levels of HMGB-1, liver function and hepatic pathology were observed after artificial liver support system treatment. The levels of TNF-α and IL-1β were increased and reached the peak at 24th h in the acute hepatic failure group, then quickly decreased. The serum level of HMGB-1 was increased at 24th h in the acute hepatic failure group and reached the peak at 48th h, then kept a stable high level. Significant liver injury appeared at 24th h and was continuously getting worse in the pig models of acute hepatic failure. In contrast, the liver injury was significantly alleviated and serum level of HMGB-1 was significantly decreased in the group treated with artificial liver support system （P〈0.05）. It was suggested that HMGB-1 may participate in the inflammatory response and liver injury in the late stage of the acute liver failure. Artificial liver support system treatment can reduce serum HMGB-1 level and relieve liver pathological damage.

Guest editorial: special issue on high mobility wireless communications

The high-speed railway and high-way networks are now expanding at a phenomenal speed in Chinaand in many other parts of the world. The related broadband wireless communication over high-speed trains and highway vehicles is a very challenging task due to hostile transmission channel conditions. The demand for such services is growing rapidly, following the proliferation of laptop/tablet computers and smart phones. This motivates the research on wireless communications in the high mobility environments.

Association between thrombomodulin and high mobility group box 1 in sepsis patients

BACKGROUND High mobility group box 1(HMGB1)has been studied as a molecule associated with severe outcomes in sepsis and thrombomodulin(TM)seems to decrease HMGB1 activity.AIM To investigate the role of the thrombomodulin/high mobility group box 1(T/H)ratio in patients with sepsis and their association with their clinic,testing the hypothesis that higher ratios are associated with better outcomes.METHODS Twenty patients diagnosed with sepsis or septic shock,according to the 2016 criteria sepsis and septic shock(Sepsis-3),were studied.Patients were followed until they left the intensive care unit or until they achieved 28 d of hospitalization(D28).The following clinical outcomes were observed:Sequential Organ Failure Assessment(SOFA)score;Need for mechanical pulmonary ventilation;Presence of septic shock;Occurrence of sepsis-induced coagulopathy;Need for renal replacement therapy(RRT);and Death.RESULTS The results showed that patients with SOFA scores greater than or equal to 12 points had higher serum levels of TM:76.41±29.21 pg/mL vs 37.41±22.55 pg/mL among those whose SOFA scores were less than 12 points,P=0.003.The T/H ratio was also higher in patients whose SOFA scores were greater than or equal to 12 points,P=0.001.The T/H ratio was,on average,three times higher in patients in need of RRT(0.38±0.14 vs 0.11±0.09),P<0.001.CONCLUSION Higher serum levels of TM and,therefore,higher T/H ratio in the first 24 h after the diagnosis of sepsis were associated with more severe disease and the need for renal replacement therapy,while those with better clinical outcomes and those who were discharged before D28 showed a tendency for lower T/H ratio values.

Role of high mobility group box protein 1 in depression:A mechanistic and therapeutic perspective

As a common and serious psychiatric disorder,depression significantly affects psychosocial functioning and quality of life.However,the mechanism of depression is still enigmatic and perplexing,which limits its precise and effective therapeutic methods.Recent studies demonstrated that neuroinflammation activation plays an important role in the pathophysiology of depression.In this respect,high mobility group box 1(HMGB1)may be a possible signaling inducer of neuroinflammation and can be a potential mechanistic and therapeutic target for depression.Herein,we review recent studies on the mechanistic and therapeutic targets of HMGB1 in depression and propose potential perspectives on this topic.

Solution-Processed High Mobility Top-Gate N-Channel Polymer Field-Effect Transistors

Polymer field-effect transistors operated in the n-channel model with a top-gate/bottom-contact are processed using a solution method. The transistor performance depends on the gate dielectric layer. A high performance polymer transistor is achieved, with the saturated electron mobility of about 0.46cm2/Vs, threshold voltage nearly 0 V and subthreshold sway of about 0.9 V/decade, employing a polystyrene （PS） dielectric layer. The transistor performances are further improved with increasing current and lower operation voltages by utilizing a bi-layer gate dielectric, comprising a thin PS dielectric layer adjacent to the semiconductor to minimize the density of the interface traps for obtaining a small VT, a large μ and a poly（methyl methacrylate） （PMMA） dielectric layer with a relatively high-k adjacent to the gate electrode for enlarging the capacitance, processed from the orthogonal solvents.

Relationship of plasma homocysteine, soluble intercellular adhesion molecule-1, high mobility group box 1 protein with carotid intima-media thickness in elderly patients with type 2 diabetes mellitus

Objective:To explore the relationship of plasma homocysteine(Hcy),soluble intercellular adhesion molecule-1(sICAM-1)and high mobility group box 1 protein(HMGB1)with carotid intima-media thickness(c-IMT)in elderly patients with type 2 diabetes mellitus.Methods:A total of 100 elderly patients who were diagnosed as type 2 diabetes mellitus in Baogang Hospital of Inner Mongolia from June 2017 to May 2020 were chosen as research objects.According to c-IMT,they were divided into the normal group(n=35),the mild to moderate group(n=41)and the severe group(n=24).The expression levels of plasma Hcy,sICAM-1 and HMGB1 were compared between groups respectively.Pearson’s correlation coefficient was used to analyze the relationship of plasma Hcy,sICAM-1,HMGB1 with c-IMT.Results:The comparison in plasma Hcy,sICAM-1,HMGB1 and c-IMT among the three groups of patients was of statistical significance(p<.05).The results of correlation analysis showed that the expression levels of plasma Hcy,sICAM-1 and HMGB1 were positively correlated with c-IMT in elderly patients with type 2 diabetes mellitus(r=.627,.598,.614;p<.05).Conclusions:The expression levels of plasma Hcy,sICAM-1 and HMGB1 are abnormally increased in elderly patients with type 2 diabetes mellitus,and related to c-IMT,which can provide a strong evidence for clinical diagnosis and treatment by detecting their levels in clinical practice.

Predictive Value of High Mobility Group Box-1 and miR-146b in Septic Shock Patients

In the face of the elevated incidence and mortality rate of septic shock in the ICU,this retrospective study seeks to investigate the indicative and predictive value of high-mobility group box 1(HMGB1)and miR-146b in patients with septic shock.Quantitative RTPCR was employed in this study to quantify the HMGB1 and miR-146b levels in plasma samples obtained from the patient group and healthy controls.The investigation involved the comparison between the two groups and tracking changes in the patient group over time.The finding revealed that upon admission,the patient group exhibited markedly elevated relative expression levels of HMGB1,which subsequently decreased over time.Conversely,the patient group displayed significantly reduced relative expression levels of miR-146b upon admission,which subsequently increased over time compared to the control group.Receiver operating characteristic(ROC)curves showed good predictive value for HMGB1 and miR-146b.The experimental results suggest that HMGB1 and miR-146b serve as valuable and convenient biomarkers for evaluating the severity of septic shock and predicting mortality.Additionally,it is proposed that serum miR-146b may be inducible and potentially exerts a negative regulatory effect on the expression of HMGB1.

Bandgap engineering of high mobility two-dimensional semiconductors toward optoelectronic devices

Over the last few years,great advances have been achieved in exploration of high-mobility two-dimensional(2D)semiconductors such as metal chalcogenide InSe and noble-transition-metal dichal-cogenide PdSe_(2).These materials are competitive candidates for constructing next-generation optoelec-tronic devices owing to their unique crystalline and electronic structures.Moreover,the optical and electronic properties of 2D materials can be efficiently modified via precisely engineering their band structures,which is critical for widening specific applications ranging from high-performance opto-electronics to catalysis and energy harvesting.In this review,we focus on the progress in bandgaps engineering of newly emerging high-mobility 2D semiconductors and their applications in optoelec-tronic devices,incorporating our recent study in the InSe and PdSe_(2)systems.First of all,we discuss the structure-property relationship of typical high-mobility 2D semiconductors(InSe and PdSe 2).Next,we analyze several viable strategies for bandgap engineering,including thickness,strain or pressure,alloying,heterostructure,surface modification,intercalation,and so on.Furthermore,we summarize the optoelectronic devices fabricated with such high-mobility 2D semiconductors.The conclusion and outlook in this topic are finally presented.This review aims to provide valuable insights in bandgap engineering of newly emerging 2D semiconductors and explore their potential in future optoelectronic applications.

Flexible Large-Area Graphene Films of 50-600 nm Thickness with High Carrier Mobility

Bulk graphene nanofilms feature fast electronic and phonon transport in combination with strong light-matter interaction and thus have great potential for versatile applications,spanning from photonic,electronic,and optoelectronic devices to charge-stripping and electromagnetic shielding,etc.However,large-area flexible close-stacked graphene nanofilms with a wide thickness range have yet to be reported.Here,we report a polyacrylonitrile-assisted’substrate replacement’strategy to fabricate large-area free-standing graphene oxide/polyacrylonitrile nanofilms(lateral size~20 cm).Linear polyacrylonitrile chains-derived nanochannels promote the escape of gases and enable macro-assembled graphene nanofilms(nMAGs)of 50-600 nm thickness following heat treatment at 3,000℃.The uniform nMAGs exhibit 802-1,540 cm^(2)V-1s-1carrier mobility,4.3-4.7 ps carrier lifetime,and>1,581 W m^(-1)K^(-1)thermal conductivity(n MAG-assembled 10μm-thick films,mMAGs).nMAGs are highly flexible and show no structure damage even after 1.0×10^(5)cycles of folding-unfolding.Furthermore,n MAGs broaden the detection region of graphene/silicon heterojunction from near-infrared to mid-infrared and demonstrate higher absolute electromagnetic interference(EMI)shielding effectiveness than state-of-the-art EMI materials of the same thickness.These results are expected to lead to the broad applications of such bulk nanofilms,especially as micro/nanoelectronic and optoelectronic platforms.

Packing Adjustment Towards High Mobility Luminescent Conjugated Polymers

Next generation display and lighting technology calls for thinner,cheaper and more-flexible unit devices.Polymer light emitting transistor(PLET),which integrates logic function of organic field effect transistor(OFET),luminescence function of organic light emitting diode(OLED),and potential mechanical properties,is believed to be the raising star in this field.However,great challenges remain in developing the core materials of PLETs,which simultaneously require the integration of high ambipolar mobility and strong solid-state luminescence properties.Herein,high mobility luminescent thienopyrroledione-benzodiathiadiazole-fluorene-based conjugated polymer was chosen as polymer backbone,and polymers TBT-1 and TBT-2(TBT=thienopyrroledione-benzodiathiadiazole-thienopyrrole-dione)with red luminescence were obtained by direct arylation polymerization(DArP).By introducing linear alkyl side chains,the packing orientation is changed from face-on in TBT-1 thin film to edge-on in TBT-2 thin film,which is beneficial for improving the field effect performance.The average hole and electron mobility of TBT-2 are 1.1×10^(-2)and 2.0×10^(-3)cm^(2)·V^(-1)·s^(-1),respectively.This work provides new design strategy for high mobility luminescent conjugated polymers,which can be used in PLETs.

The Effect of a Novel Cytokine,High Mobility Group Box 1 Protein,on the Development of Traumatic Sepsis

Sepsis and subsequent multiple organ dysfunction syndrome(MODS) are frequent complications after severe traumata or burns involving a large area,and these remain as the two most common causes of morbidity and mortality in critical illnesses.Despite the recent rapid advances in intensive