Multiple Vandermonde Decomposition Based Channel Estimation for Mm Wave MIMO High-Mobility Communication in 5G and Beyond

Millimeter wave(mmWave)massive massive multiple input multiple output(MIMO)technique has been regarded as the viable solution for vehicular communications in 5G and beyond.To achieve the substantial increase in date rates,it is important to take an effective channel state information(CSI).However,existing channel estimation strategies are unavailable since the users high-mobility.To solve above issues,in this paper,inspired by a specific antenna structure,we propose a novel approach for fast time-varying channel estimation.Specifically,by considering the vehicle scenario with high-mobility,a corresponding mathematical model is firstly established.Then,based on the special structural of the sparse array,the switch network is used to replace the convention phase shifter of mmWave hybrid system,which can effectively reduce the number of radio-frequency(RF)chains and antennas.Furthermore,by solving the semidefinite programming(SDP)duality problem,the Doppler frequency and path parameters are effectively estimated.Simulation results are shown that the computational complexity and estimation accuracy of the proposed algorithm is superior than that of the traditional schemes.

Scolopendra subspinipes mutilans protected the ceruleininduced acute pancreatitis by inhibiting high-mobility group box protein-1

AIM:To evaluate the inhibitory effects of Scolopendra subspinipes mutilans(SSM) on cerulein-induced acute pancreatitis(AP) in a mouse model.METHODS:SSM water extract(0.1,0.5,or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein.Once AP developed,the stable cholecystokinin analogue,cerulein was injected hourly,over a 6 h period.Blood samples were taken 6 h later to determine serum amylase,lipase,and cytokine levels.The pancreas and lungs were rapidly removed for morphological examination,myeloperoxidase assay,and real-time reverse transcription polymerase chain reaction.To specify the role of SSM in pancreatitis,the pancreatic acinar cells were isolated using collagenase method.Then the cells were pre-treated with SSM,then stimulated with cerulein.The cell viability,cytokine productions and high-mobility group box protein-1(HMGB-1) were measured.Furthermore,the regulating mechanisms of SSM action were evaluated.RESULTS:The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury,as was shown by the reduction in pancreatic edema,neutrophil infiltration,vacuolization and necrosis.SSM treatment also reduced pancreatic weight/body weight ratio,serum amylase,lipase and cytokine levels,and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β.In addition,treatment with SSM inhibited HMGB-1 expression in the pancreas during AP.In accordance with in vivo data,SSM inhibited the cerulein-induced acinar cell death,cytokine,and HMGB-1 release.SSM also inhibited the activation of c-Jun NH2-terminal kinase,p38 and nuclear factor(NF)-κB.CONCLUSION:These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase,p38 and NF-κB.

Inhibition of LOX-1 alleviates the proinflammatory effects of high-mobility group box 1 in Aspergillus fumigatus keratitis

AIM: To investigate the inflammatory amplification effect of high-mobility group box 1(HMGB1) in Aspergillus fumigatus(A. fumigatus) keratitis and the relationship between lectin-like oxidized low-density lipoprotein receptor 1(LOX-1) and HMGB1 in keratitis immune responses.METHODS: Phosphate buffer saline(PBS), and Boxb were injected into BALB/c mice subconjunctivally before the corneas were infected with A. fumigatus. RAW264.7 macrophages and neutrophils were pretreated with PBS and Boxb to determine the HMGB1 inflammatory amplification effects. Abdominal cavity extracted macrophages were pretreated with Boxb and Poly(I)(a LOX-1 inhibitor) before A. fumigatus hyphae stimulation to prove the the relationship between the two molecules. LOX-1, interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), macrophage inflammatory protein-2(MIP-2) and IL-10 were assessed by polymerase chain reaction and Western blot.RESULTS: Pretreatment with Boxb exacerbated corneal inflammation. In macrophages and neutrophils, A. fumigatus induced LOX-1, IL-1β, TNF-α and MIP-2 expression in Boxb group was higher than those in PBS group. Poly(I) treatments before infection alleviated the proinflammatory effects of Boxb in abdominal cavity extracted macrophages. Pretreatment with Boxb did not influence Dectin-1 mRNA levels in macrophages and neutrophils.CONCLUSION: In fungal keratitis, HMGB1 is a proinflammatory factor in the first line of immune response. HMGB1 mainly stimulates neutrophils and macrophages to produce inflammatory cytokines and chemokines during the immune response. LOX-1 participates in HMGB1 induced inflammatory exacerbation in A. fumigatus keratitis.

High-mobility group box 1 expression and lymph node metastasis in intrahepatic cholangiocarcinoma

AIM:To evaluate the prognostic value of high-mobility group box 1(HMGB1) expression in intrahepatic cholangiocarcinoma(IHCC) and the possible underlying mechanism.METHODS:Tissue microarray was constructed from 65 IHCC patients.Immunohistochemistry was performed to validate expression of HMGB1 and Vascular endothelial growth factor C(VEGF-C).Realtime PCR and Western blot analyses were used to study transcript and protein levels.The interaction between HMGB1 and VEGF-C was evaluated by si RNA,real-time PCR,and enzyme-linked immuno assays.The correlation between HMGB1 expression and other clinicopathologic parameters was analyzed byχ2 test,and the univariate as well as multivariate analyses were accomplished by Kaplan-Meier method and Coxregression model,respectively.RESULTS:Overall,overexpression of HMGB1 was found in 38/65(58.8%)IHCCs,whereas VEGF-C overexpression was present in 30/65(46.2%)cases.Overexpression of HMGB1 was significantly correlated with lymphatic microvessel density(P=0.031,r=0.268)and VEGF-C expression(P=0.041,r=0.254).With univariate analysis,both HMGB1(P=0.001)and VEGF-C(P=0.004)were identified to be significantly associated with overall survival rate.Multivariateanalysis indicated that HMGB1 could be served as an unfavorable independent prognostic factor in IHCCs(P=0.005).si RNA knockdown of HMGB1 inhibited transforming growth factor-β-induced epithelialmesenchymal transition(EMT)by elevating E-Cadherin expression and reducing expression of N-Cadherin,Vimentin and Snail in RBE cells.Further in vitro study revealed that HMGB1 silencing significantly decreased the level of VEGF-C,whereas the recombinant HMGB1increased the VEGF-C level in RBE cells(both P<0.05),which suggested that HMGB1 could promote lymphatic microvessel density,and subsequently lymphatic invasion,via promoting VEGF-C expression.CONCLUSION:Our results define an important role of HMGB1 in the progression of cholangiocarcinoma,and HMGB1 may serve as a prognostic marker for IHCC patients.

High-Mobility P-Type MOSFETs with Integrated Strained-Si_(0.73)Ge_(0.27) Channels and High-κ/Metal Gates

Strained-Si0.73Ge0.27 channels are successfully integrated with high-R/metal gates in p-type metai-oxide- semi- conductor field effect transistors （pMOSFETs） using the replacement post-gate process. A silicon cap and oxide inter layers are inserted between Si0.73Ge0.27 and high-κ dielectric to improve the interface. The fab- ricated Si0.73Ge0.27 pMOSFETs with gate length of 3Onto exhibit good performance with high drive current （~428μA/μm at VDD = 1 V） and suppressed short-channel effects （DIBL^77mV/V and SS^90mV/decade）. It is found that the enhancement of effective hole mobility is up to 200% in long-gate-length Si0.73Ge0.27-channel pMOSFETs compared with the corresponding silicon transistors. The improvement of device performance is reduced due to strain relaxation as the gate length decreases, while 26% increase of the drive current is still obtained for 30-nm-gate-length Si0.73Ge0.27 devices.

Oxygen Scavenging Effect of LaLuO_3/TiN Gate Stack in High-Mobility Si/SiGe/SOI Quantum-Well Transistors

Higher-s dielectric LaLuO3, deposited by molecular beam deposition, with TiN as gate stack is integrated into high-mobility Si/SiGe/SOI quantum-well p-type metal-oxide-semiconduetor field effect transistors. Threshold voltage shift and capacitance equivalent thickness shrink are observed, resulting from oxygen scavenging effect in LaLuO3 with ti-rich TiN after high temperature annealing. The mechanism of oxygen scavenging and its potential for resistive memory applications are analyzed and discussed.

Diagnostic significance of serum levels of serum amyloid A,procalcitonin,and high-mobility group box 1 in identifying necrotising enterocolitis in newborns

BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.

Severity of sepsisis is correlated with the elevation of serum high-mobility group box 1 in rats

Background Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine, high-mobility group box 1 （HMGB1）, plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats. Methods To produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide （4, 8 and 16 mg/kg）, and the animals in control group were treated with the same volume of the vehicle （saline）. The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide （LPS） or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed. Results The level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin I, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney. Conclusions The level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.

The m6A reader YTHDF2 alleviates the inflammatory response by inhibiting IL-6R/JAK2/STAT1 pathway-mediated high-mobility group box-1 release

Background:Sepsis is a common severe complication in major burn victims and is characterized by a dysregulated systemic response to inflammation.YTH domain family 2(YTHDF2),a wellstudied N6-methyladenosine(m6A)reader that specifically recognizes and binds to m6A-modified transcripts to mediate their degradation,is connected to pathogenic and physiological processes in eukaryotes,but its effect on sepsis is still unknown.We aimed to discover the effects and mechanisms of YTHDF2 in sepsis.Methods:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and western blot analyses were used to measure the expression of YTHDF2,the interleukin 6 receptor(IL-6R),high-mobility group box-1(HMGB1),Janus kinase 2(JAK2)and signal transducer and activator of transcription 1(STAT1)under different in vitro conditions.Enzyme-linked immunosorbent assays were utilized to evaluate the expression of HMGB1,IL-6,IL-1βand tumor necrosis factor-α.To confirm that YTHDF2 specifically targets IL-6R mRNA,RNA immunoprecipitation and dual-luciferase reporter assays were performed.Finally,we utilized a mouse model of lipopolysaccharide(LPS)-induced sepsis to verify the effects of YTHDF2 in vivo.Results:According to our findings,YTHDF2 was expressed at a low level in peripheral blood mononuclear cells from septic mice and patients as well as in LPS-induced RAW264.7 cells.Overexpression of YTHDF2 alleviated the inflammatory response by inhibiting HMGB1 release and JAK2/STAT1 signalling in LPS-stimulated cells.Mechanistically,YTHDF2 suppressed JAK2/STAT1 signalling by directly recognizing the m6A-modified site in IL-6R and decreasing the stability of IL-6R mRNA,thereby inhibiting HMGB1 release.In vivo experiments showed that YTHDF2 played a protective role in septic mice by suppressing the IL-6R/JAK2/STAT1/HMGB1 axis.Conclusions:In summary,these findings demonstrate that YTHDF2 plays an essential role as an inhibitor of inflammation to reduce the release of HMGB1 by inhibiting the IL-6R/JAK2/STAT1 pathway,indicating that YTHDF2 is a novel target for therapeutic interventions in sepsis.

TLR4-HMGB1-, MyD88- and TRIF-dependent signaling in mouse intestinal ischemia/reperfusion injury

AIM: To characterize high-mobility group protein 1-toll-like receptor 4(HMGB1-TLR4) and downstream signaling pathways in intestinal ischemia/reperfusion(I/R) injury.METHODS: Forty specific-pathogen-free male C57BL/6 mice were randomly divided into five groups(n = 8 per group): sham, control, anti-HMGB1, anti-myeloid differentiation gene 88(My D88), and anti-translocatingchain-associating membrane protein(TRIF) antibody groups. Vehicle with the control Ig G antibody, antiHMGB1, anti-My D88, or anti-TRIF antibodies(all 1 mg/kg, 0.025%) were injected via the caudal vein 30 min prior to ischemia. After anesthetization, the abdominal wall was opened and the superior mesenteric artery was exposed, followed by 60 min mesenteric ischemia and then 60 min reperfusion. For the sham group, the abdominal wall was opened for 120 min without I/R. Levels of serum nuclear factor(NF)-κB p65, interleukin(IL)-6, and tumor necrosis factor(TNF)-α were measured, along with myeloperoxidase activity in the lung and liver. Inaddition,morphologic changes that occurred in the lung and intestinal tissues were evaluated. Levels of m RNA transcripts encoding HMGB1 and NF-κB were measured by real-time quantitative PCR, and levels of HMGB1 and NF-κB protein were measured by Western blot. Results were analyzed using one-way analysis of variance.RESULTS: Blocking HMGB 1, MyD 8 8, and TRIF expression by injecting anti-HMGB1, anti-My D88, or anti-TRIF antibodies prior to ischemia reduced the levels of inflammatory cytokines in serum; NF-κB p65: 104.64 ± 11.89, 228.53 ± 24.85, 145.00 ± 33.63, 191.12 ± 13.22, and 183.73 ± 10.81(P < 0.05); IL-6: 50.02 ± 6.33, 104.91 ± 31.18, 62.28 ± 6.73, 85.90 ± 17.37, and 78.14 ± 7.38(P < 0.05); TNF-α, 43.79 ± 4.18, 70.81 ± 6.97, 52.76 ± 5.71, 63.19 ± 5.47, and 59.70 ± 4.63(P < 0.05) for the sham, control, anti-HMGB1, anti-My D88, and anti-TRIF groups, respectively(all in pg/m L).Antibodies also alleviated tissue injury in the lung and small intestine compared with the control group in the mouse intestinal I/R model. The administration of antiHMGB1, anti-My D88, and anti-TRIF antibodies markedly reduced damage caused by I/R, for which anti-HMGB1 antibody had the most obvious effect.CONCLUSION: HMGB1 and its downstream signaling pathway play important roles in the mouse intestinal I/R injury, and the effect of the TRIF-dependent pathway is slightly greater.

Glycyrrhizic acid promotes sciatic nerves recovery in type 1 diabetic rats and protects Schwann cells from high glucose-induced cytotoxicity

The present study aims to investigate the therapeutic effect and mechanism of glycyrrhizic acid(GA)in diabetic peripheral neuropathy(DPN).GA significantly mitigated nerve conduction velocity(NCV)deficit and morphological abnormality and reduced high-mobility group box-1(HMGB1)expression in the sciatic nerves of diabetic rats independent of blood glucose and body weight.Notably,GA alleviated the increase of HMGB1 and the decrease of cell viability in high glucose-stimulated RSC96 cells.Furthermore,GA obviously reduced the concentration of inflammatory cytokines in the sciatic nerves of diabetic rats and supernatants of high glucose-exposed RSC96 cells,then restored the decreased expression levels of nerve growth factor(NGF)and neuritin-1,and the increased expression levels of cleaved caspase-3 and neuron-specific enolase.Additionally,GA markedly inhibited receptor for advanced glycation end products(RAGE)expression,p38MAPK phosphorylation,and the nuclear translocation of NF-κBp65 in diabetic rats and high glucose-exposed RSC96 cells.The promotional effect of high glucose in RSC96 cells was diminished following Hmgb1 siRNA treatment.Our findings indicate that GA may exert neuroprotection on DPN by suppressing HMGB1,which lead to extenuation of inflammation response,balance of NGF,neuritin-1 and caspase-3,as well as inactivation of RAGE/p38MAPK/NF-κBp65 signaling pathway.

Recent advances in the molecular genetics of type 2 diabetes mellitus

Type 2 diabetes mellitus(T2DM) is a complex disease in which both genetic and environmental factors interact in determining impaired β-cell insulin secretion and peripheral insulin resistance. Insulin resistance in muscle, liver and fat is a prominent feature of most patients with T2DM and obesity, resulting in a reduced response of these tissues to insulin. Considerable evidence has been accumulated to indicate that heredity is a major determinant of insulin resistance and T2DM. It is believed that, among individuals destined to develop T2DM, hyperinsulinemia is the mechanism by which the pancreatic β-cell initially compensates for deteriorating peripheral insulin sensitivity, thus ensuring normal glucose tolerance. Most of these people will develop T2DM when β-cells fail to compensate. Despite the progress achieved in this field in recent years, the genetic causes of insulin resistance and T2DM remain elusive.Candidate gene association, linkage and genome-wide association studies have highlighted the role of genetic factors in the development of T2DM. Using these strategies, a large number of variants have been identified in many of these genes, most of which may influence both hepatic and peripheral insulin resistance, adipogenesis and β-cell mass and function. Recently, a new gene has been identified by our research group, the HMGA1 gene, whose loss of function can greatly raise the risk of developing T2DM in humans and mice. Functional genetic variants of the HMGA1 gene have been associated with insulin resistance syndromes among white Europeans, Chinese individuals and Americans of Hispanic ancestry. These findings may represent new ways to improve or even prevent T2DM.

Prognostic potential of an immune score based on the density of CD8＋ T cells, CD20＋ B cells, and CD33＋/p-STAT1＋ double-positive cells and HMGB1 expression within cancer nests in stage ⅢA gastric cancer patients

Objoctive： There is heterogeneity in the prognosis of gastric cancers staged according to the tumornodes-metastasis （TNM） system. This study evaluated the prognostic potential of an immune score system to supplement the TNM staging system. Mothodsg An immunohistochemical analysis was conducted to assess the density of T cells, B cells, and myeloid-derived suppressor cells （MDSCs） in cancer tissues from 100 stage IIIA gastric cancer patients; the expression of the high-mobility group protein B1 （HMGB1） was also evaluated in cancer cells. The relationship between the overall survival （OS）, disease-free survival （DFS）, and immunological parameters was analyzed.Results： An immune score system was compiled based on the prognostic role of the density ofT cells, B cells, MDSCs, and the expression of HMGB1 in cancer tissues. The median 5-year survival of this group of patient was 32%. However, the 5-year survival rates of 80.0%, 51.7%, 0%, 5.8%, and 0% varied among the patients with an immune score of 4 to those with an immune score of 0 based on the immune score system, respectively. Similarly, differences in DFS rates were observed among the immune score subgroups. Concluslons： An immune score system could effectively identify the prognostic heterogeneity within stage IliA gastric cancer patients, implying that this immune score system may potentially supplement the TNM staging system, and help in identifying a more homogeneous group of patients who on the basis of prognosis can undergo adjuvant therapy.

Boxb mediate BALB/c mice corneal inflammation through a TLR4/MyD88-dependent signaling pathway in Aspergillus fumigatus keratitis

AIM： To investigate whether high-mobility group box 1（HMGB1） Boxb exacerbates BALB/c mice corneal immune responses and inflammatory through the Toll-like receptor 4（TLR4）/myeloid differentiation primary response 88（My D88）-dependent signaling pathway in Aspergillus fumigatus（A. fumigatus） keratitis.METHODS： The mice corneas were pretreated with phosphate buffer saline（PBS）, Boxb before A. fumigatus infection. The abdominal cavity extracted macrophages were pretreated with PBS, Boxb, TLR4 inhibitor（CLI-095）, Dimethyl sulfoxide（DMSO） separately before A. fumigatus hyphae stimulation. HMGB1 was detected in normal and infected mice corneas and macrophages by real-time reverse transcriptase polymerase chain reaction（RT-PCR）, the TLR4, My D88, interleukin-1β（IL-1β）, tumor necrosis factor-α（TNF-α） were detected by Western blot and PCR.RESULTS： In BALB/c mice corneas, the expressions of TLR4, HMGB1, IL-1β, TNF-α were increased after A. fumigatus infection. While pretreatment with Boxb significantly increased the expressions of TLR4, HMGB1, My D88, IL-1β, TNF-α compared with PBS control after infection. In BALB/c mice abdominal cavity extracted macrophages, pretreatment with Boxb increased the expressions of TLR4, HMGB1, My D88, IL-1β, TNF-α, while pretreatment with CLI-095 and Boxb significantly decreased the expressions of TLR4, HMGB1, My D88, IL-1β, TNF-α. CONCLUSION： In A. fumigatus keratitis, Boxb play a proinflammatory role in corneal anti-fungi immune response through the HMGB1-TLR4-My D88 signal pathway.

TEM and STEM Observations of a Flat Continuous Silicon-Germanium Thin Film Epitaxially Grown on Porous Silicon

Strain-relaxed SiGe is an attractive material for use as a substrate of strained Si, in which carrier mobility is higher than that of bulk Si. The concept of this study is the use of porous Si as a sponge like substrate so that a SiGe lattice can relax without introducing dislocations. We produced porous Si specimens by electrochemical anodization and annealed them under a H2 atmosphere. Then, SiGe thin films were grown by gas-source molecular beam epitaxy. We observed the microstructure of the specimens using transmission electron microscopy. The result showed that we succeeded in producing a single-crys- tal continuous Si0.73Ge0.27 film with a 10% relaxation ratio and a low dislocation density on porous Si.

The Concept Study of Recombinant Human Soluble Thrombomodulin in Patients with Acute Respiratory Distress Syndrome

Background: Recombinant human soluble thrombomodulin (rhTM) was approved for the treatment of disseminated intravascular coagulation in Japan, and rhTM has anti-inflammatory effects. Disordered coagulation is a part of the acute respiratory distress syndrome (ARDS) pathophysiology and thus we hypothesize that anticoagulant therapy may help. This preliminary study was to observe the safety of rhTM administration and the improvement on biomarker levels after the therapy for ARDS-patients. Objectives: Case series of ARDS-patients. Methods: Seventeen ARDS-patients that required ventilatory management were treated with rhTM and clinical and laboratory data were collected including platelets, thrombin-antithrombin complex (TAT), fibrinogen degradation products, oxygen saturation/the fraction of inspired oxygen (SpO2/FIO2), and high-mobility group-1 (HMG-1). The administration of rhTM was started during 6 days at a bolus dose of 0.06 mg/kg/day immediately after the diagnosis of ARDS. Results: Eleven of the 17 ARDS-patients were alive at 28 days after the beginning of the administration of rhTM. The serial pattern of the SpO2/FIO2 showed remarkable differences between the survivors and nonsurvivors from day 5 to day 7. The TAT in the survivors significantly decreased after treatment, and there were significantly lower levels in the TAT on day 7 in comparison to that of the nonsurvivors. The serial changes of HMG-1 showed increased levels in the nonsurvivors until day 5 after the administration of rhTM. Conclusions: Additional rhTM administration can safely improve the parameters in survival ARDS-patients, as demonstrated by significant improvements in the SpO2/FIO2, HMG-1 and TAT.

Honokiol Prevents Intestinal Barrier Dysfunction in Mice with Severe Acute Pancreatitis and Inhibits JAK/STAT1 Pathway and Acetylation of HMGB1

Objective To investigate the effect of honokiol(HON)and the role of high-mobility group protein B1(HMGB1)on the pathogenesis of severe acute pancreatitis(SAP).Methods Thirty mice were numbered according to weight,and randomly divided into 5 groups using a random number table,including control,SAP,SAP and normal saline(SAP+NS),SAP and ethyl pyruvate(SAP+EP),or SAP+HON groups,6 mice in each group.Samples of pancreas,intestine,and blood were collected 12 h after SAP model induction for examination of pathologic changes,immune function alterations by enzyme linked immunosorbent assay(ELISA),and Western blot.In vitro experiments,macrophages were divided into 5 groups,the control,lipopolysaccharide(LPS),LPS+DMSO(DMSO),LPS+anti-HMGB1 monoclonal antibody(mAb),and LPS+HON groups.The tight connection level was determined by transmission electron microscopy and fluorescein isothiocyanate-labeled.The location and acetylation of HMGB1 were measured by Western blot.Finally,pyridone 6 and silencing signal transducer and activator of the transcription 1(siSTAT1)combined with honokiol were added to determine whether the Janus kinase(JAK)/STAT1 participated in the regulation of honokiol on HMGB1.The protein expression levels of HMGB1,JAK,and STAT1 were detected using Western blot.Results Mice with SAP had inflammatory injury in the pancreas,bleeding of intestinal tissues,and cells with disrupted histology.Mice in the SAP+HON group had significantly fewer pathological changes.Mice with SAP also had significant increases in the serum levels of amylase,lipase,HMGB1,tumor necrosis factor-α,interleukin-6,diamine oxidase,endotoxin-1,and procalcitonin.Mice in the SAP+HON group did not show these abnormalities(P<0.01).Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability,decreased the levels of junctional adhesion molecule C,and elevated intercellular permeability(P<0.01).HON treatment blocked these effects.Studies of macrophages indicated that LPS led to low nuclear levels of HMGB1,however,HON treatment increased the nuclear level of HMGB1(P<0.01).HON treatment also inhibited the expressions of JAK1,JAK2,and STAT1(P<0.01)and increased the acetylation of HMGB1(P<0.05).Conclusion HON prevented intestinal barrier dysfunction in SAP by inhibiting HMGB1 acetylation and JAK/STAT1 pathway.

Transcription and Secretion of Interleukin-1β and HMGB1 in Keratinocytes Exposed to Stimulations Mimicking Common Inflammatory Damages

Objective:Interleukin-1β(IL-1β)and high-mobility group box 1(HMGB1)are widely known damage-associated molecular patterns(DAMPs).However,their expression and secretion in different skin diseases,especially in inflammatory skin disorders,remain to be further elucidated.This study was performed to explore and compare the transcriptional and secretory levels of IL-1β and HMGB1 in keratinocytes under 3 types of stimulation:ultraviolet B(UVB)irradiation;co-stimulation by tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)(simulation of T helper 1 cell inflammatory challenge);and psoriasis-like stimulation by M5,a mixture of 5 proinflammatory cytokines.Methods:We used quantitative reverse-transcription polymerase chain reaction to determine the transcription levels of IL-1β and HMGB1.Western blotting and enzyme-linked immunosorbent assay were used to detect the secretion levels of IL-1β and HMGB1.The results were statistically analyzed by t test.Results:A rapid transcriptional and secretory response of IL-1β from keratinocytes occurred in all 3 types of stimulation mimicking common inflammatory environments(P<0.05).Transcription of HMGB1 was inhibited in all 3 types of stimulation(P<0.05),but secretion was increased after exposure to UVB irradiation and co-stimulation by TNF-α and IFN-γ(P<0.05).We observed no change in the secretion level of HMGB1 after treatment with M5(P=0.196).Conclusion:IL-1β is a critical cytokine for the immunomodulatory functions of keratinocytes in inflammatory responses.In this study,keratinocytes restrained transcription of HMGB1 when the secretion of HMGB1 was induced in certain stimulations(eg,by UVB exposure or stimulation by TNF-α and IFN-γ).

高拉伸高迁移率半导体纳米纤维共混薄膜应用于完全可拉伸有机晶体管

可拉伸有机场效应晶体管(OFETs)是有机集成电路和可穿戴生物传感器的基本组成部分.可拉伸有机半导体是实现高迁移率可拉伸OFETs的核心材料.目前实现高迁移率高拉伸聚合物半导体仍面临挑战.在此,我们通过混合聚合物半导体和弹性体,制备了高迁移率可拉伸的半导体共混薄膜.通过纳米限域效应,聚合物形成独特的纳米纤维.半导体薄膜具有低结晶度和高聚集度,因此该纤维共混薄膜具有高迁移率和高拉伸性.我们制备的完全可拉伸的有机晶体管在0%和100%应变下空穴迁移率分别为2.74和2.53 m^(2)V^(-1)s^(-1).即使在150%应变下,可拉伸晶体管的迁移率也高达1.57 cm^(2)V^(-1)s^(-1).可拉伸晶体管在30%应变下的1000个拉伸/释放周期中表现出了高的机械鲁棒性.

HMGB1 Inhibitor Effectively Alleviates Psoriasis-Like Lesions and Inflammatory Cytokines in K14-VEGF Transgenic Mice

Objective:Anti-high-mobility group box 1(HMGB1)is involved in the pathogenesis of many inflammatory and autoimmune diseases,including psoriasis.The present study aimed to investigate the therapeutic effects of HMGB1 monoclonal antibody(mAb)in keratin 14(K14)-vascular endothelial growth factor(VEGF)transgenic homozygous mice.Methods:Twelve VEGF transgenic mice were randomly divided into two groups of six mice each:the anti-HMGB1 mAb group and the immune complex(IC)mAb group.The mice underwent intraperitoneal injection of anti-HMGB1 mAb or IC mAb once every 2 days for a total of three treatments.Compare the lesions on the ears of the mice and evaluate the severity of the lesions using the baseline and clinical scores on the last day of treatment.The changes in psoriasis-like lesions,cellular infiltration of T cells,dendritic cells,and neutrophils were detected by hematoxylin-eosin staining and immunohistochemistry.The mRNA expression of the inflammatory cytokines,including interleukin(IL)-6,tumor necrosis factor-α,interferon-γ,and IL-17 in the lesions were assessed by real-time quantitative polymerase chain reaction.The number ofγδT cells in the lesions of two groups were detected by flow cytometry.Thet test was used to compare their differences.Results:The anti-HMGB1 mAb effectively ameliorated the clinical skin lesions.The clinical scores in the anti-HMGB1 mAb group were lower than those in the IC mAb group(6.00±0.52vs.10.83±0.48,P<0.001).Histopathologic changes and improvements in the K14-VEGF transgenic homozygous mice were evident after three treatments.The scores of mice in the anti-HMGB1 mAb group were significantly lower than those in the IC mAb group(3.25±0.71vs.6.95±0.83,P=0.0033).The average epidermal thickness in the anti-HMGB1 mAb group was reduced by about 45%when compared with that in the IC mAb group(32.15±7.08vs.64.69±7.93,P=0.0054).Moreover,anti-HMGB1 mAb also decreased the number of infiltrating CD3+T cells,myeloperoxidase-positive neutrophils,and CD11c+dendritic cells.The ratio of ear skinγδT cells was reduced in anti-HMGB1 mAb treated group.The mRNA expression of IL-6,tumor necrosis factor-α,interferon-γ,and IL-17 in the anti-HMGB1 mAb group were significantly reduced when compared with IC mAb group(0.36±0.070vs.1.98±0.62,P=0.0148;6.43±1.37vs.13.80±1.33,P=0.0006;2.62±0.83vs.7.77±1.32,P=0.0026;4.69±1.13vs.11.41±1.92,P=0.0054).Conclusion:HMGB1 blockade(anti-HMGB1 mAb)reduced leukocyte infiltration and suppressed inflammatory cytokine expression in this K14-VEGF transgenic mouse model,markedly reducing the severity of the psoriasis-like lesions.HMGB1 blockade might serve as a potential target for the treatment of psoriasis.