Prognostic value of circulating tumor cells combined with neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma

BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in HCC.METHODS Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the Affiliated Hospital of Southwest Medical University,Sichuan,China,from 2021 to 2023.The optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile software.Patients were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was assessed.RESULTS Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and mOS.Cox regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of OS.The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low survival.CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.

The Geoscience Frontier of Gulong Shale Oil:Revealing the Role of Continental Shale from Oil Generation to Production

The clay mineral content of Daqing Gulong shale is in the range of about 35%–45%,with particle sizes less than 0.0039 mm.The horizontal fluidity of oil in Gulong shale is poor,with near-zero vertical flowability.As a result,Gulong shale has been considered to lack commercial value.In recent years,however,interdisciplinary research in geoscience,percolation mechanics,thermodynamics,and surface mechanics has demonstrated that Gulong shale oil has a high degree of maturity and a high residual hydrocarbon content.The expulsion efficiency of Gulong shale in the high mature stage is 32%–48%.Favorable storage spaces in Gulong shale include connecting pores and lamellar fractures developed between and within organic matter and clay mineral complexes.The shale oil mainly occurs in micro-and nano-pores,bedding fractures,and lamellar fractures,with a high gas–oil ratio and medium–high movable oil saturation.Gulong shale has the characteristics of high hardness,a high elastic modulus,and high fracture toughness.This study achieves breakthroughs in the exploration and development of Gulong shale,including the theories of hydrocarbon generation and accumulation,the technologies of mobility and fracturing,and recoverability.It confirms the major transition of Gulong shale from oil generation to oil production,which has extremely significant scientific value and application potential for China’s petroleum industry.

Strengthening and toughening of additively manufactured Ti-6Al-4V alloy by hybrid deposition and synchronous micro-rolling

To overcome the disadvantages of inhomogeneous microstructures and poor mechanical properties of additively manufactured Ti-6Al-4V alloys,a novel technique of hybrid deposition and synchronous micro-rolling is proposed.The micro-rolling leads to equiaxed prior β grains,thin discontinuous intergranular α,and equiaxed primary α,in contrast to the coarse columnar prior β grains without the application of micro-rolling.The recrystallization by micro-rolling results in discontinuous intergranular α via the mechanism of strain and interface-induced grain boundary migration.The evolution of α globularization,driven by a solute concentration gradient,starts from the sub-boundary until the formation of equiaxed primary α.Simultaneous strengthening and toughening are achieved,which means an increase in yield strength,ultimate tensile strength,fracture elongation,and work hardening rate.The formation of α recrystallization leads to more fine grain boundaries to strengthen the yield strength,and the improvement of ductility is due to the better-coordinated deformation ability of discontinuous intergranular α and equiaxed primary α.As a result,the fracture mode in micro-rolling changes from intergranular type to transgranular type.

CK5/6-positive,P63-positive lymphoepithelioma-like hepatocellular carcinoma:A case report and literature review

BACKGROUND Lymphoepithelioma-like carcinoma(LELC),a rare and unique variant of liver cancer,can be divided into lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like intrahepatic cholangiocarcinoma.Dense lymphocytic infiltration is its characteristic pathological feature.In recent years,the number of reported cases of this type has increased each year.Studies have shown that lymphoepithelioma-like cholangiocarcinoma occurs more frequently in Asian women;LELC is associated with Epstein–Barr virus infection of liver cells of epithelial origin.Existing research shows that the prognosis of this tumour is good.CASE SUMMARY A 38-year-old female patient was hospitalized after 3 mo of abdominal pain and nausea.She had been infected with hepatitis B virus more than 10 years prior.The patient was hospitalized on January 21,2022.Magnetic resonance imaging showed a 36 mm×28 mm mass under the envelope of the left inner lobe of the liver.No metastasis of lymph nodes or other organs was observed.After left hemihepatectomy,biopsy and immunohistochemistry yielded a final diagnosis of lymphoepithelial hepatocellular carcinoma.After 12 mo of outpatient follow-up and chemotherapy,no tumour metastases were found on the latest computed tomography examination.CONCLUSION Herein,the patient was treated surgically and then followed up as an outpatient for 12 mo.This case will further expand our overall knowledge of the diagnosis and treatment of this rare tumor.

The role of LOX-1 on innate immunity against Aspergillus keratitis in mice

AIM:To explore the effects of lectin-like ox-LDL receptor(LOX-1) on innate immunity against Aspergillus fumigatus(A.fumigatus) in mice cornea.METHODS:The mRNA levels of LOX-1 were tested in normal and A.fumigatus infected corneas of C57BL/6and BALB/c mice.The expression of LOX-1,pro-inflammatory cytokines TNF-α,CXCL1 and IL-6,antiinflammatory cytokines IL-10,and matrix metalloproteinase 9(MMP9) were tested with treatment with LOX-1 neutralizing antibody or control IgG in A.fum/gatus infected corneas of C57BL/6.Macrophages and neutrophils were extracted from susceptible C57BL/6mice,and pretreated with LOX-1 neutralizing antibody or IgG,then stimulated with A.fum/gatus.The mRNA levels of LOX-1,TNF-α,CXCL1,IL-6,IL-10 and MMP9 were evaluated by polymerase chain reaction.RESULTS:The expression of LOX-1 was significantly increased in C57BL/6 mice corneas after A.fum/gatus infection compared with BABL/c mice.After treatment with LOX-1 neutralizing antibody,the expression of LOX-1,TNF-α,CXCL1,IL-6,MMP9 and IL-10 in C57BL/6corneas were significantly decreased compared with treatment with control IgG;the expression of LOX-1,CXCL1,IL-6 and IL-10 were significantly decreased in macrophages,while TNF-α and MMP9 expressions had no change;LOX-1,TNF-α,CXCL1,IL-6,MMP9 and IL-10 expressions were significantly decreased in neutrophils.CONCLUSION:The expression of LOX-1 can affect the expression of pro-inflammatory and anti-inflammatory cytokines in fungal infected corneas,macrophages and neutrophils of C57BL/6.LOX-1 inhibition rebalances the inflammatory response of fungal keratitis in mice.

Mincle in the innate immune response of mice fungal keratitis

AIM: To investigate how macrophage inducible C-type lectin(Mincle) influences inflammation in mice fungal keratitis induced by Aspergillus fumigatus(A. fumigatus).METHODS: C57 BL/6 mice were infected with A. fumigatus after pretreated with Mincle agonist TDB or Mincle neutralizing antibody(MincleAb), taking DMSO or IgG as control group respectively. The cornea lesions were monitored with slit-lamp microscope and evaluated by clinical score. Mincle expression was assessed using reverse transcriptionploymerase chain reaction(RT-PCR) and immunostaining. The expression of cytokines(IL-1β, TNF-α and IL-6) chemokines(CXCL-1 and MIP-2) was determined by RTPCR and ELISA. Neutrophil infiltration was observed by immunostaining. The levels of nitric oxide(NO) generated by corneas were tested by Griess reaction. RESULTS: Mincle mRNA and protein levels were higher in infected corneas than normal corneas of C57 BL/6 mice, saving clinical scores revealed differences. When pretreated with Mincle agonist TDB, the mRNA and protein levels of IL-1β, TNF-α and IL-6 in infected corneas were significantly increased compared with the control group(P<0.01). Results of the counterpart in corneas pretreated with Mincle neutralizing antibody was decreased consistently(P<0.01). Expression of CXCL1 and MIP-2 mRNA levels were upregulated in TDB group and down-regulated in Mincle Ab group(P<0.01), coincide with neutrophil aggregation degree in corneas showed by immunostaining. As for the concentration of NO, it was promoted in TDB group compared with DMSO control group, and decreased in Mincle Ab group compared with Ig G control group.CONCLUSION: Mincle plays a dual role in mice fungal keratitis. It participates in the innate immune system by enhancing inflammation. What's more, Mincle can mediate cytotoxic effects by regulating the formation of NO.

Effects of U-ore on the chemical and isotopic composition of products of hydrous pyrolysis of organic matter

In order to investigate the impact of U-ore on organic matter maturation and isotopic fractionation,we designed hydrous pyrolysis experiments on Type-II kerogen samples,supposing that the water and water–mineral interaction play a role.U-ore was set as the variable for comparison.Meanwhile,anhydrous pyrolysis under the same conditions was carried out as the control experiments.The determination of liquid products indicates that the presence of water and minerals obviously enhanced the yields of C_(15+) and the amounts of hydrocarbon and nonhydrocarbon gases.Such results may be attributed to waterorganic matter reaction in the high-temperature system,which can provide additional hydrogen and oxygen for the generation of gas and liquid products from organic matter.It is found that δD values of hydrocarbon gases generated in both hydrous pyrolysis experiments are much lower than those in anhydrous pyrolysis.What is more,δD values are lower in the hydrous pyrolysis with uranium ore.Therefore,we can infer that water-derived hydrogen played a significant role during the kerogen thermal evolution and the hydrocarbon generation in our experiments.Isotopic exchange was facilitated by the reversible equilibration between reaction intermediaries with hydrogen under hydrothermal conditions with uranium ore.Carbon isotopic fractionations of hydrocarbon gases were somehow affected by the presence of water and the uranium ore.The increased level of i-C_4/n-C_4ratios for gas products in hydrous pyrolysis implied the carbocation mechanism for water-kerogen reactions.

Impact of formation water on the generation of H2S in condensate reservoirs： a case study from the deep Ordovician in the Tazhong Uplift of the Tarim Basin, NW China

A number of condensate reservoirs with high concentrations of H_2S have been discovered in the deep dolomite reservoirs of the lower Ordovician Yingshan Formation(O_1y) in the Tazhong Uplift, where the formation water has a high p H value. In the O_1y reservoir, the concentrations of Mg^(2+)and SO_4^(2-)in the formation water are higher than those in the upper Ordovician formation.The concentration of H2 S in the condensate reservoirs and the concentration of Mg^(2+)in the formation water correlate well in the O_1y reservoirs of the Tazhong Uplift, which indicates a presumed thermochemical sulfate reduction(TSR) origin of H_2S according to the oxidation theory of contact ion-pairs(CIPs). Besides, the p H values of the formation water are positively correlated with the concentration of H_2S in the condensate reservoirs, which may indicate that high p H might be another factor to promote and maintain TSR. Oil–source correlation of biomarkers in the sulfuretted condensates indicates the Cambrian source rocks could be the origin of condensates. The formation water in the condensate reservoirs of O_1y is similar to that in the Cambrian; therefore, the TSR of sulfate-CIPs likelyoccurred in the Cambrian. High H_2S-bearing condensates are mainly located near the No. 1 Fault and NE-SW strikeslip faults, which are the major migration pathway of deep fluids in the Tazhong Uplift. The redox between sulfateCIPs and hydrocarbons is the generation mechanism of H_2S in the deep dolomite condensate reservoirs of the Tazhong Uplift. This finding should be helpful to predict the fluid properties of deep dolomite reservoirs.

Profiles and Source Apportionment of Nonmethane Volatile Organic Compounds in Winter and Summer in Xi’an, China, based on the Hybrid Environmental Receptor Model

Summer and winter campaigns for the chemical compositions and sources of nonmethane hydrocarbons(NMHCs)and oxygenated volatile organic compounds(OVOCs)were conducted in Xi’an.Data from 57 photochemical assessment monitoring stations for NMHCs and 20 OVOC species were analyzed.Significant seasonal differences were noted for total VOC(TVOC,NMHCs and OVOCs)concentrations and compositions.The campaign-average TVOC concentrations in winter(85.3±60.6 ppbv)were almost twice those in summer(47.2±31.6 ppbv).Alkanes and OVOCs were the most abundant category in winter and summer,respectively.NMHCs,but not OVOCs,had significantly higher levels on weekends than on weekdays.Total ozone formation potential was higher in summer than in winter(by 50%)because of the high concentrations of alkenes(particularly isoprene),high temperature,and high solar radiation levels in summer.The Hybrid Environmental Receptor Model(HERM)was used to conduct source apportionment for atmospheric TVOCs in winter and summer,with excellent accuracy.HERM demonstrated its suitability in a situation where only partial source profile data were available.The HERM results indicated significantly different seasonal source contributions to TVOCs in Xi’an.In particular,coal and biomass burning had contributions greater than half in winter(53.4%),whereas traffic sources were prevalent in summer(53.1%).This study’s results highlight the need for targeted and adjustable VOC control measures that account for seasonal differences in Xi’an;such measures should target not only the severe problem with VOC pollution but also the problem of consequent secondary pollution(e.g.,from ozone and secondary organic aerosols).

Graded 2D/3D(CF_(3)-PEA)_(2)FA_(0.85)MA_(0.15)Pb_(2)I_(7)/FA_(0.85)MA_(0.15)PbI_(3) heterojunction for stable perovskite solar cell with an efficiency over 23.0%

The replacement of small cations with bulkier organic cations containing long alkyl chains or benzene rings to form a thin two-dimensional(2D)perovskite passivation layer on three-dimensional(3D)perovskite(2D/3D)has become a promising strategy for improving both the efficiency and stability of perovskite solar cells(PSCs).The 2 D layer defines the interfacial chemistry and physics at the 2D/3D bilayer and endows the 2D/3D structure with better chemical and thermal stability.Herein,2D/3D(CF_(3)-PEA)_(2) FA_(0.85)MA_(0.15)Pb_(2)I_(7)/FA_(0.85)MA_(0.15)PbI_(3) planar heterojunction perovskite was produced using a facile interfacial ion exchange process.The 2 D(CF_(3)-PEA)_(2) FA_(0.85)MA_(0.15)Pb_(2)I_(7) capping layer can not only passivate the FA_(0.85)MA_(0.15)PbI_(3) film but also act as super-hydrophobic layer to inhibit water diffusion and significantly enhance the stability.The 2D capping layer can also establish a unique graded band structure at the perovskite/Spiro-OMeTAD interface and lead to p-type doping for Spiro-OMeTAD layer which is beneficial for efficient charge transport.Optimized PSCs based on this 2D/3D heterojunction yield a champion power conversion efficiency(PCE)of 23.1%and improved stability.The device maintains 84%output for 2400 h aging under ambient environmental conditions without encapsulation,and maintains 81%for 200 h under illumination with encapsulation.This work will inspire the design of more fluorinated 2D perovskite interfaces for advanced photovoltaics and beyond.

生物羊膜覆盖联合角膜绷带镜治疗眼表化学性烧伤

目的:探讨生物羊膜覆盖联合角膜绷带镜治疗眼表化学性烧伤患者的临床效果及生物羊膜的稳定性。方法:回顾性研究。选取2018-12/2021-08在我院治疗的眼表化学性烧伤患者49例49眼的临床资料,按照手术方式分为单纯羊膜覆盖组25眼和羊膜覆盖术后配戴角膜绷带镜组24眼。比较两组患者的羊膜脱落时间、术后疼痛评分、眼表修复率及修复时间、术后视力和并发症情况。结果:单纯羊膜覆盖组和羊膜覆盖术后配戴角膜绷带镜组患者术后1d眼部疼痛评分为2.208±0.758和2.063±0.800分(P>0.05),术后3d为1.844±0.762和1.150±0.582分,术后7d为1.684±0.820和0.750±0.514分(均P<0.05)。羊膜覆盖术后配戴角膜绷带镜组羊膜脱落时间为10.75±2.63d,比单纯羊膜覆盖组(7.60±2.22d)更长(P<0.05),且角膜修复效果较单纯羊膜覆盖组更好。术后6mo,两组患者视力分别为0.30(0.10,0.55)和0.30(0.20,0.58)(P>0.05),两组患者并发症发生情况无差异(P>0.05)。结论:生物羊膜覆盖可以有效地治疗眼表化学性烧伤,联合角膜绷带镜治疗可以延缓其脱落时间,提高角膜修复率,降低患者术后不适程度。

Risk factors of gastroparesis syndrome after abdominal nongastroduodenal operation and its prevention

Objective:To investigate risk factors of gastroparesis syndrome(PGS) after abdominal nongastroduodenal operation and its prevention.Methods:Clinical data of 22 patients with PGS after abdominal non-gastroduodenal operation was analyzed retrospectively,and compared with the patients of non-PGS after abdominal non-gastroduodenal operation during the same time.The possible influencing factors of PCS were analyzed by single factor analysis and logistic regression analysis.Results:All t3 selected factors related with PGS,including age,disease category (benign and malignant),operation time,intraoperative blood loss,postoperative analgesic pump, postoperative enteral nutrition time,postoperative parenteral nutrition time,perioperative blood glucose level,perioperative nutrition status(anaemia or lower proleinemia),pylorus obstruction before surgery,intra-abdominal infection after surgery,and spiritual factor were related with PGS.The statistical analysis showed that the difference was statistical significant(P【0.05),and gender had no correlation with PCS(P】0.05);non-conditional multivariate analysis showed that malignant tumor,perioperative nutrition status,pylorus obstruction,operation time,blood loss, intra-abdominal infection after surgery,and mental factor were significant related with PGS as dependent variable and related risk factors in single factor analysis as independent variables (P 【0.05).Conclusions:PGS is a result of multiple factors,and among these factors,malignant tumor,poor nutrition status,pylorus obstruction before surgery,longer operation—time,more blood loss,intra-abdominal infection after surgery,and mental factor are major risk factors of PGS.

N/S co-doped 3D carbon framework prepared by a facile morphology-controlled solid-state pyrolysis method for oxygen reduction reaction in both acidic and alkaline media

Developing high-performance non-precious metal electrocatalysts for oxygen reduction reaction(ORR)is crucial for the commercialization of fuel cells and metal-air batteries.However,doped carbon-based materials only show good ORR activity in alkaline medium,and become less effective in acidic environment.We believe that an appropriate combination of both ionic and electronic transport path,and well dopant distribution of doped carbon-based materials would help to realize high ORR performance un-der both acidic and alkaline cond让ions.Accordingly,a nitrogen and sulfur co-doped carbon framework with hierarchical through-hole structure is fabricated by morphology-controlled solid-state pyrolysis of poly(aniline-co-2-ami no thiophenol)foam.The uniform high concentrations of nitrogen and sulfur,high intrinsic conductivity,and integrated three dimensional ionic and electronic transfer passageways of the 3D porous structure lead to synergistic effects in catalyzing ORR.As a result,the limiting current density of the carbonized poly(aniline-co-2-aminothiophenol)foam is equivalent to commercial Pt/C in acidic environment,and twice the latter in alkaline medium.

Association of level of leisure-time physical activity with risks of all-cause mortality and cardiovascular disease in an elderly Chinese population: a prospective cohort study

Background Implementing the current guidelines for leisure-time physical activity(LTPA)provides significant health benefits,especially for middle-aged adults,but it is unclear whether LTPA also translates into cardiovascular health benefits among elderly people.Therefore,we aimed to assess the association of LTPA with the risks of cardiovascular disease(CVD),including coronary heart disease(CHD)and stroke,and all-cause mortality in an elderly population.Methods In this prospective cohort study,32,942 participants aged 60 years or older who participated in a health check-up programme in China between 2010 and 2018 were included.We evaluated the morbidity and mortality risks through the Cox regression model,competing risk model and restricted cubic spline model.Results During a median of 6.84 years of follow-up,there were 6,857 elderly people with incident CVD;a total of 6,324 deaths occurred due to all causes and 2,060 deaths occurred due to CVD.Compared with the inactive group,reductions in CVD morbidity and mortality were observed,with hazard ratios(HRs)of 0.89(95%CI:0.83–0.96)and 0.81(95%CI:0.71–0.92)in the insufficiently active group,0.86(95%CI:0.80–0.92)and 0.79(95%CI:0.69–0.90)in the sufficiently active group,and 0.79(95%CI:0.70–0.89)and 0.58(95%CI:0.45–0.76)in the highly active group,respectively;but no significant reductions were observed in the very highly active group,with HRs of 0.87(95%CI:0.71–1.06)and 0.99(95%CI:0.70–1.40),respectively.Compared with the inactive group,reductions in all-cause mortality were also observed,with a HR of 0.90(95%CI:0.84–0.97)in the insufficiently active group,0.82(95%CI:0.77–0.89)in the sufficiently active group,0.77(95%CI:0.67–0.87)in the highly active group,and 0.80(95%CI:0.64–0.98)in the very highly active group.A restricted cubic spline diagram showed that there was an L-shaped association between LTPA and the risk of all-cause mortality but a U-shaped or reverse J-shaped relationship between LTPA and the risk of CVD morbidity and mortality,especially stroke.In addition,a subgroup analysis showed that elderly population who consistently performed LTPA for ten years or more had a lower risk of morbidity and mortality.Conclusions In an elderly population,even insufficient activity is associated with a decreased risk of all-cause mortality and CVD,and moderate levels of LTPA may be optimal for CVD prevention.In addition,elderly people who consistently perform LTPA over several years may experience greater health benefits.

A Special Additive Enables All Cations and Anions Passivation for Stable Perovskite Solar Cells with Efficiency over 23%

Passivating undercoordinated ions is an effective way to reduce the defect densities at the surface and grain boundaries(GBs)of perovskite materials for enhanced photovoltaic performance and stability of perovskite solar cells(PSCs).Here,(BBF)complex is chosen as a multifunctional additive,which contains both C7H9N and BF3 groups working as Lewis base and Lewis acid,respectively,can bond with Pb^(2+)/I^(−) and FA+on the surface and in the GBs in the perovskite film,affording passivation of both cation and anion defects.The synergistic effect of the C7H9N and BF3 complex slows the crystallization during the perovskite film deposition to improve the crystalline quality,which reduces the trap density and the recombination in the perovskite film to suppress nonradiative recombination loss and minimizes moisture permeation to improve the stability of the perovskite material.Meanwhile,such an additive improves the energy-level alignment between the valence band of the perovskite and the highest occupied molecular orbital of the hole-transporting material,Spiro-OMeTAD.Consequently,our work achieves power conversion efficiency of 23.24%,accompanied by enhanced stability under ambient conditions and light illumination and opens a new avenue for improving the performance of PSCs through the use of a multifunctional complex.

High-mobility group box1 as an amplifier of immune response and target for treatment in Aspergillus fumigatus keratitis

AIM:To determine the roles of high-mobility group box1(HMGB1)in pro-inflammation,host immune response and its potential target for treatment in Aspergillus fumigatus(A.fumigatus)keratitis.METHODS:Expression of HMGB1 was tested in C57 BL/6 normal and infected corneas.Dual immunostaining tested coexpression of HMGB1 with TLR4 or LOX-1.C57 BL/6 mice were pretreated with Box A or PBS and then infected.Clinical scores,polymerase chain reaction,ELISA,and MPO assay were used to assess the disease response.Flow cytometry were used to test the effect of Box A on reactive oxygen species(ROS)expression after A.fumigatus stimulation in polymorphonuclear neutrophilic leukocytes(PMN).C57 BL/6 peritoneal macrophages were pretreated with Box B before A.fumigatus stimulation,and MIP-2,IL-1β,TNF-α,HMGB1 and LOX-1 were measured.Macrophages were pretreated with Box B or Box B combined with Poly(I)(an inhibitor of LOX-1)before stimulating with A.fumigatus,and MIP-2,IL-1β,TNF-α,LOX-1,p38-MAPK,p-p38-MAPK were measured.RESULTS:HMGB1 levels were elevated in C57 BL/6 mice after infection.HMGB1 co-expressed with TLR4,and LOX-1 in infiltrated cells.Box A vs PBS treated C57 BL/6 mice had lower clinical scores and down-regulated corneal HMGB1,MIP-2,IL-1βexpression and neutrophil influx.Box B treatment amplified expression of MIP-2,IL-1β,TNF-α,HMGB1 and LOX-1 that induced by A.fumigatus in macrophage.Compared to the treatment of Box B only,the protein expression of IL-1β,TNF-αshowed inhibition of Box B combined with Poly(I),which also reduced the A.fumigatusevoked protein level of LOX-1 and phosphorylation level of p38-MAPK.The production of A.fumigatus-stimulated ROS was significantly declined after Box A pretreatment in PMN.CONCLUSION:Blocking HMGB1 reduces the disease response in C57 BL/6 mice.HMGB1 can amplify the host immune response through p38-MAPK,and is a target for treatment of A.fumigatus keratitis.

Role of vasoactive intestinal peptide in Aspergillus fumigatus-infected cornea

AIM: To investigate the anti-inflammatory role of vasoactive intestinal peptide(VIP) in Aspergillus fumigatus(A. fumigatus) ketatitis.METHODS: Expression of VIP was tested by polymerase chain reaction(PCR) in C57BL/6 and BALB/c normal and A. fumigatus infected corneas. C57BL/6 mice were pretreated with recombinant(r) VIP, while BALB/c mice were pretreated with VIP antagonist, and then infected with A. fumigatus. Clinical score was recorded. Expression of pro-and anti-inflammatory cytokines, toll-like receptor 4(TLR4), lectin-like oxidized low-density lipoprotein receptor 1(LOX-1), and neutrophil infiltration were tested by PCR, enzyme-linked immunosorbent assay(ELISA), and myeloperoxidase(MPO) assay.RESULTS: VIP mR NA expression in BALB/c cornea was higher than C57BL/6 cornea at 1 and 3 d post infection(p.i.). rV IP treatment of C57BL/6 mice showed alleviated disease and down-regulated expression of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α), while IL-10 expression was up-regulated. Neutrophil infiltration and TLR4, IL-17 expression were decreased after rVIP treatment, while LOX-1 expression was up-regulated in C57BL/6. VIP antagonist pretreatment showed increased disease and higher IL-1β, TNF-α, TLR4, IL-17 and MPO levels, while IL-10 and LOX-1 levels were down-regulated in BALB/c mice.CONCLUSION: rVIP alleviate disease response of C57BL/6 mice. VIP antagonist resulted in worsened disease of BALB/c mice. VIP proposed anti-inflammatory role in A. fumigatus keratitis.

Better Visual Image Super-Resolution with Laplacian Pyramid of Generative Adversarial Networks

Although there has been a great breakthrough in the accuracy and speed of super-resolution(SR)reconstruction of a single image by using a convolutional neural network,an important problem remains unresolved:how to restore finer texture details during image super-resolution reconstruction?This paper proposes an Enhanced Laplacian Pyramid Generative Adversarial Network(ELSRGAN),based on the Laplacian pyramid to capture the high-frequency details of the image.By combining Laplacian pyramids and generative adversarial networks,progressive reconstruction of super-resolution images can be made,making model applications more flexible.In order to solve the problem of gradient disappearance,we introduce the Residual-in-Residual Dense Block(RRDB)as the basic network unit.Network capacity benefits more from dense connections,is able to capture more visual features with better reconstruction effects,and removes BN layers to increase calculation speed and reduce calculation complexity.In addition,a loss of content driven by perceived similarity is used instead of content loss driven by spatial similarity,thereby enhancing the visual effect of the super-resolution image,making it more consistent with human visual perception.Extensive qualitative and quantitative evaluation of the baseline datasets shows that the proposed algorithm has higher mean-sort-score(MSS)than any state-of-the-art method and has better visual perception.

Elevated neutrophil extracellular traps by HBV-mediated S100A9-TLR4/RAGE-ROS cascade facilitate the growth and metastasis of hepatocellular carcinoma

Background:Neutrophil extracellular traps(NETs)are considered significant contributors to cancer progression,especially metastasis.However,it is still unclear whether NETs are involved in hepatitis B virus(HBV)-related hepatocarcinogenesis and have potential clinical significance during evaluation and management for hepatocellular carcinoma(HCC).In this study,we aimed to investigate the functional mechanism of NETs in HBV-related hepatocarcinogenesis and their clinical significance.Methods:A total of 175 HCC patients with and without HBV infection and 58 healthy controls were enrolled in this study.NETs weremeasured in tissue specimens,freshly isolated neutrophils and blood serum from these patients,and the correlation of circulating serum NETs levels with malignancy was evaluated.The mechanism by which HBV modulates NETs formation was explored using cell-based studies.In addition,in vitro and in vivo experiments were further performed to clarify the functional mechanism of NETs on the growth and metastasis of HCC.Results:We observed an elevated level of NETs in blood serum and tissue specimens from HCC patients,especially those infected with HBV.NETs facilitated the growth and metastasis of HCC both in vitro and in vivo,which were mainly dominated by increased angiogenesis,epithelial-mesenchymal transition(EMT)-related cell migration,matrix metalloproteinases(MMPs)-induced extracellular matrix(ECM)degradation and NETs-mediated cell trapping.Inhibition of NETs generation by DNase 1 effectively abrogated the NETs-aroused HCC growth and metastasis.In addition,HBV-induced S100A9 accelerated the generation of NETs,which was mediated by activation of toll-like receptor(TLR4)/receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)signaling.Further,circulatory NETs were found to correlate with viral load,TNM stage and metastasis status in HBV-related HCC,and the identified NETs could predict extrahepatic metastasis,with an area under the ROC curve(AUC)of 0.83 and 90.3%sensitivity and 62.8%specificity at a cutoff value of 0.32.Conclusions:Our findings indicated that activation of RAGE/TLR4-ROS signaling by HBV-induced S100A9 resulted in abundant NETs formation,which subsequently facilitated the growth and metastasis of HCC cells.More importantly,the identified circulatory NETs exhibited potential as an alternative biomarker for predicting extrahepatic metastasis in HBV-related HCC.