C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

Ligand modulation of active center to promote lead-free Cs_(2)AgInCl_(6)photocatalytic CO_(2)reduction

Metal halide perovskites(MHP)are potential candidates for the photocatalytic reduction of CO_(2)due to their long photogenerated carrier lifetime and charge diffusion length.However,the conventional long-chain ligand impedes the adsorption and activation of CO_(2)molecules in practical applications.Here,a ligand modulation technology is employed to enhance the photocatalytic CO_(2)reduction activity of lead-free Cs_(2)AgInCl_(6)microcrystals(MCs).The Cs_(2)AgInCl_(6)MCs passivated by Oleic acid(OLA)and Octanoic acid(OCA)are used for photocatalytic CO_(2)reduction.The results show that the surface defects and electronic properties of Cs_(2)AgInCl_(6)MCs can be adjusted through ligand modulation.Compared with the OLA-Cs_(2)AgInCl_(6),the OCA-Cs_(2)AgInCl_(6)catalyst demonstrated a significant improvement in the catalytic yield of CO and CH_(4).The CO and CH_(4)catalytic yields of OCA-Cs_(2)AgInCl_(6)reached 171.88 and34.15μmol g^(-1)h^(-1)which were 2.03 and 12.98 times higher than those of OLA-Cs_(2)AgInCl_(6),and the total electron consumption rate of OCA-Cs_(2)AgInCl_(6)was 615.2μmol g^(-1)h^(-1)which was 3.25 times higher than that of OLA-Cs_(2)AgInCl_(6).Furthermore,in situ diffuse reflectance infrared Fourier transform spectra revealed the enhancement of photocatalytic activity in Cs_(2)AgInCl_(6)MCs induced by ligand modulation.This study illustrates the potential of lead-free Cs_(2)AgInCl_(6)MCs for efficient photocatalytic CO_(2)reduction and provides a ligand modulation strategy for the active promotion of MHP photocatalysts.

Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma

BACKGROUND The exact regulation network of programmed death 1(PD-1), programmed death ligand 1(PD-L1), and programmed death ligand 2(PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene expression profiles related to PD-1 as well as its ligands PD-L1 and PD-L2, thus deciphering their possible biological processes in hepatocellular carcinoma(HCC).AIM To find the possible mechanism of function of PD-1, PD-L1, and PD-L2 in HCC.METHODS Based on the expression data of HCC from The Cancer Genome Atlas, the PD-1/PD-L1/PD-L2 related genes were screened by weighted correlation network analysis method and the biological processes of certain genes were enriched. Relation of PD1/PD-L1/PD-L2 with immune infiltration and checkpoints was investigated by co-expression analysis. The roles of PD-1/PD-L1/PD-L2 in determination of clinical outcome were also analyzed.RESULTS Mutations of calcium voltage-gated channel subunit alpha1 E, catenin beta 1, ryanodine receptor 2, tumor suppressor protein p53, and Titin altered PD-1/PDL1/PD-L2 expression profiles in HCC. PD-1, PD-L1, and PD-L2 related genes were mainly enriched in biological procedures of T cell activation, cell adhesion, and other important lymphocyte effects. In addition, PD-1/PD-L1/PD-L2 was related with immune infiltration of CD8 T cells, cytotoxic lymphocytes,fibroblasts, and myeloid dendritic cells. Immune checkpoints of CTLA4, CD27, CD80, CD86, and CD28 were significantly related to the PD-1/PD-L1/PD-L2 axis. Clinically, PD-1 and PD-L2 expression was correlated with recurrence(P = 0.005 for both), but there was no significant correlation between their expression and HCC patient survival.CONCLUSION Mutations of key genes influence PD-1, PD-L1, and PD-L2 expression. PD-1, PDL1, and PD-L2 related genes participate in T cell activation, cell adhesion, and other important lymphocyte effects. The finding that PD-1/PD-L1/PD-L2 is related to immune infiltration and other immune checkpoints would expand our understanding of promising anti-PD-1 immunotherapy.

Role of TNF-related apoptosis-inducing ligand （TRAIL） in the pathogenesis of varicocele-induced testicular dysfunction

The higher frequency of varicocele in men with infertility has drawn attention and resulted in increased research at the molecular level towards treatments. The aim of this study was to investigate the role of tumor necrosis factor （TNF）-related apoptosis-inducing ligand （TRAIL） and its receptors in varicocele-induced testicular dysfunction in an experimental rat model. The rats were divided into three groups： control, sham and varicocele. Varicoceles in rats were induced by partial ligation of the left renal vein and left testes. The rats were analyzed 13 weeks after surgery. The degree of DNA fragmentation within cells in the testis was determined using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling （TUNEL） assay. Tubule degeneration was evaluated using the Johnsen score. The expression of TRAIL and its receptors was detected by immunohistochemical and Western blotting techniques. The apoptotic index, Johnsen score and the expression of TRAIL and TRAIL receptors were examined. The data are presented as the mean-.＋s.d, and were analyzed using computer software. The KruskaI-Wallis and Dunn＇s multiple comparison tests were used in the statistical analyses. The germ cell apoptotic index was increased in rats with varicoceles when compared with the sham and control groups （P=0.0031）. The Johnsen score was significantly decreased in the varicocele group when compared with the sham and control groups （P〈O.O001）. Immunohistochemical and Western blotting analyses showed that after varicocele induction, the expression of TRAIL-R1 and TRAIL-R4 in germ cells was increased and the expression of TRAIL-R2 was decreased. There are no significant differences among the groups in terms of TRAIL and TRAIL-R3 receptor expression. The results of this study indicate that TRAIL and its receptors may have a potential role in the pathogenesis of varicocele-induced testicular dysfunction.

Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas Ligand

It was suggested that chronic ethanol exposure could result in testicular germ cell apoptosis, but the mechanism is still unclear. In the present study, we use a model of transgenic mice ubiquitously overexpressing human FasL to investigate whether Fas ligand plays a role in ethanol-induced testicular germ cell apoptosis. Both wild-type (WT)mice and transgenic (TG) mice were treated with acute ethanol (20% v/v) by introperitoneal injection for five times.After ethanol injection, WT mice displayed up-regulation of Fas ligand in the testes, which was shown by FITCconjugated flow cytometry and western blotting. Moreover, TG mice exhibited significantly more apoptotic germ cells than WT mice did after ethanol injection, which was demonstrated by DNA fragmentation, PI staining flow cytometry and TUNEL staining. In addition, histopathological examination revealed that degenerative changes of epithelial component of the tubules occurred in FasL overexpressing transgenic mice while testicular morphology was normal in wild-type mice after acute ethanol exposure, suggesting FasL expression determines the sensitivity of testes to ethanol in mice. In summary, we provide the direct evidences that Fas ligand mediates the apoptosis of testicular germ cells induced by acute ethanol using FasL transgenic mice.

EXPRESSION OF MATRIX METALLOPROTEINASE-7 AND FAS LIGAND: THEIR APOPTOSIS-INDUCING EFFECT ON GASTRIC CANCER CELLS

Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and embedded tissues of primary gastric cancer and adjacent non-tumor mucosa from 113 cases were evaluated for MMP-7, FasL and Capase-3 expression by streptavidin-peroxidase (S-P) immunohistochemistry. The expression of the first two proteins in cancer cells of primary foci was compared with clinicopathological parameters of tumors. We also observed the correlation of MMP-7 and FasL expression with Caspase-3 expression in cancer cells of primary foci. Results: MMP-7 positive immunostaining was less frequently detected in adjacent epithelial cells than in cancer cells of primary foci of gastric cancer (P<0.05, 29.2% vs 69.0%), and so was FasL (P<0.05, 34.5% vs 54.0%). MMP-7 expression was associated with tumor size, Borrmann抯 classification, invasive depth, metastasis and TNM staging (P<0.05), but not with growth pattern, Lauren抯 classification, or histological classification (P>0.05). FasL expression was correlated with tumor size, invasive depth, metastasis, Lauren抯 classification, histological classification (P<0.05), while not with Borrmann抯 classification, TNM staging or growth pattern (P>0.05). Cancer cells of primary foci expressed less Caspase-3 than their adjacent epithelial cells (P<0.05, 32.7% vs 50.4%). There was an obvious correlation between FasL, MMP-7 and Caspase-3 expression in cancer cells of primary foci (P<0.05). Co-expression of MMP-7 and FasL paralleled with Caspase-3 expression in cancer cells of primary foci (P<0.05). Conclusion: MMP-7 and FasL expression was up-regulated in gastric carcinogenesis and was principally involved in progression of gastric cancer. FasL expression could reflect the differentiation of gastric cancer cells and underlie the molecular mechanisms of different pathways of gastric tumorigenesis. Co-expression of MMP-7 and FasL could have apoptosis-inducing effect on gastric cancer cells.

Utility of adenovirus-mediated Fas ligand and bcl-2 gene transfer to modulate rat liver allograft survival

BACKGROUND: Expression of Fas ligand (FasL) on the graft by gene transduction is expected to introduce apoptosis to lymphocytes to protect rejection, but the FasL-expressing graft cells may also induce apoptosis as the graft usually expresses Fas antigens. In this study, a strong antiapoptotic gene, bcl-2, was cotransfected with the FasL gene in rat liver graft to protect against Fas- mediated cell death and to prolong recipient survival. METHODS: Orthotopic liver transplantation was done in a strain combination of DA to LEW rats. After donor vascular isolation, adenovirus-mediated FasL and bcl-2 genes were cotransfected in the liver graft. RESULTS: Intragraft expression of FasL mRNA was constitutively expressed after adenovirus-mediated transduction, although expression of FasL increased mildly in control grafts. Bcl-2 mRNA was highly expressed at 2 days after reperfusion. In contrast, lower expression of bcl-2 was observed in the control group. The average survival of the gene transferred allografts increased from (9.8+1.3) days to (18.5+8.7) days compared with the control group. CONCLUSION: Our results indicate that rat liver allografts can be protected against host immune responses by adenovirus-mediated FasL and bcl-2 transfection, and that bcl-2 expression prevents the graft from Fas-mediated apoptosis.

A 2D Wavy Parquet Architecture Based on the Biphenyl-3,3',4,4'-tetracarboxylic Acid and Bis(2-benzimidazole)alkanes Ligands

A double-T-shaped ligand （H4BPTC） and bis（2-benzimidazole）alkanes as the spacers have been firstly used to direct the assembly of a 2D coordination polymer with wavy parquet network topology, [Zn（BPTC）0.5（H2C2EIm）（H2O）]n （1, C24H18ZnN4O5, Mr = 507.79, H4BPTC = biphenyl-3,3＇,4,4＇-tetracarboxylic acid, H2C2EIm = 2,2＇-（1,2-ethanediyl）-bis（1H-benzi- midazole）, which was determined by single-crystal X-ray diffraction analysis. The crystal belongs to the monoclinic system, space group P21/n with a = 1.1844（5）, b = 1.4019（5）, c = 1.4026（5） nm, β = 108.359（5）°, V = 2.2104（15） nm3, Z = 4, Dc = 1.526 g/cm3, μ（MoKα） = 1.156 mm-1, F（000） = 1040, S = 1.038, the final R = 0.0427 and wR = 0.0793 for 3834 reflections with I 2σ（I）. The compound units are linked through BPTC ligands into a wavilness parquet 2D layer and further connected into a 3D framework via π-π packing interactions between the adjacent H2C2EIm ligands and weak N-H…O hydrogen bonding between uncoordinated carboxylate and the nitrogen atoms of H2C2EIm as well as the free water molecules.

Association between Up-regulation of Fas Ligand Expression and Apoptosis of Tumor-infiltrating Lymphocytes in Human Breast Cancer

In order to study the significance of FasL expression in immune escape of breast cancer, FasL protein expression and the number of tumor-infiltrating lymphocytes （TILs） in 40 specimens of breast cancer were detected by immunohistochemitry. The expression of FasL mRNA was measured by in situ hybridization in the consecutive tissue slices of 40 breast cancers respectively. By using terminal deoxynucleotidyl transferase-mediaed dUTP nick end labeling （TUNEL）, apoptotic cells were detected in 40 specimens of breast cancer. The expression of FasL was detected in all 40 specimens to varying degrees. In the consecutive tissue slices, the location of expression of FasL protein corresponded with that of FasL mRNA. In those with FasL extensive expression, the number of TILs was less （P〈0.05）, the apoptotic index （AI） of TILs was higher and the AI of tumor cells was lower （P〈0.01） than those with FasL weak expression respectively. The AI of TILs was correlated with that of tumor cells （r=-0.629, P〈0.01）. In conclusion, breast cancer cells can induce the apoptosis of TILs through the expression of FasL, which can counterattack the immune system. This may be a mechanism of immune evasion in breast cancer.

Peroxisome Proliferator-Activated Receptor-γActivated by Ligands Can Inhibit Human Lung Cancer Cell Growth through Induction of Apoptosis

To study the expression of peroxisome proliferator-activated receptor-7(PPAR-γ) in lung cancer cells, and to testify if the PPAR-γ agonists can inhibit human lung cancer cell growth through induction of apoptosis, PPAR-γ was detected in two lung cancer cell lines by RT-PCR and immuno-histochemistry, the inhibition of human lung cancer cell growth was investigated by MTT and cell counts, and the apoptosis was assessed by TUNEL. The results showed that: (1) PPAR-γ expressed on two lung cancer cell lines; (2) PPAR-γ activated by ligands could inhibit human lung cancer cell growth remarkably; (3) PPAR-γ agonists could induce apoptosis to inhibit lung cancer cell growth. It was concluded that PPAR-γ expressed in lung cancer cell can be activated by ligands and can inhibit lung cancer cell growth through induction of apoptosis.

Science Letters:A synthetic Toll-like receptor 2 ligand decreases allergic immune responses in a mouse rhinitis model sensitized to mite allergen

It has been proposed that activation of Toll-like receptors （TLRs） plays crucial roles in the polarization of adaptive immune responses. A synthetic Toll-like receptor 2 （TLR2） ligand, Pam3CSK4, has been reported to modulate the balance of Th1/Th2 responses. We evaluated the modulation effect of Pam3CSK4 on allergic immune response in a mouse rhinitis model sensitized to house dust mite allergen （HDM）. Mice were sensitized and challenged with Dermatophagoidesfarinae allergen （Der f）, and then the allergic mice were treated by Pam3CSK4. Nasal allergic symptoms and eosinophils were scored. Der f-specific cytokine responses were examined in the splenocytes and bronchoalveolar lavage fluid （BALF）. Serum level of total IgE was also detected. After establishing a mouse allergic rhinitis model with HDM, we have showed that Pam3CSK4 treatment not only ameliorated the nasal allergic symptoms remarkably but also decreased the eosinophils and total inflammation cells in BALF significantly. Analysis of cytokine profile found that IFN-7 released from either BALF or stimulated splenocytes increased markedly in Pam3CSK4-treated mice, while IL-13 decreased significantly. Moreover, serum level of total IgE was significantly lower in Pam3CSK4-treated mice than in the untreated. Thus, in an allergic rhinitis mouse model developed with HDM, Pam3CSK4 was shown to exhibit an antiallergic effect, indicating its potential application in allergic diseases.

Controlled Self-assembly of Two Coordination Polymers via subtly Varying Bis(2-methyl imidazole) Ligands:from 3-Connected(6,3) Net to 4-Connected sql Net

Two coordination polymers constructed from 3,4-thiophenedicarboxylic acid and bis（2-methyl imidazole） ligands, namely, {[Cd2（tdc）2（bip）2]·7H20}n （1） and [Cd（tdc）（bib）]n （2） （Hgtdc = 3,4-thiophenedicarboxylic acid, bip = 1,3-bis-（imidazol-2-methyl）propane and bib = 1,4-bis（imidazol-2-methyl）butane）, have been synthesized and structurally characterized by single-crystal X-ray diffraction. Structural analyses reveal that 1 exhibits a two-dimensional （2D） layered network with 3-connected （6,3） topology, which is further connected into a three- dimensional （3D） supramolecular structure by intermolecular hydrogen bonds. However, 2 features a 2D network which can be rationalized as a 4-connected sql net. The results indicate the subtle difference of auxiliary bis（imidazol-2-methyl） ligands may lead to diverse architectures. Moreover, they exhibit luminescence emission in the solid state at room temperature.

TNF related apoptosis-inducing ligand and its receptors in ocular tumors

Most of the ocular tumors have poor prognosis, and they remain a difficult problem in the area of ophthalmology. With the rapid development of molecular biology and immunologic techniques and the deep research on ocular tumor related genes, it becomes possible to diagnose and treat malignant tumors from the molecular level. The tumor necrosis factor related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor (TNF) super family, is a promising candidate, either alone or in combination with established cancer therapies, since it can initiate apoptosis through the activation of their death receptors. The ability of TRAIL to selectively induce apoptosis of transformed, virus-infected or tumor cells but not normal cells promotes the development of TRAIL-based cancer therapy. Here, we will review TRAIL and its receptors' structure, function, mechanism of action and application in ocular tumors therapy.

Synthesis,Crystal Structure and Antitumor Activity of a Novel Zn(Ⅱ)Complex with 2-(Nicotinoyloxy)acetic Acid Ligand

A novel Zn（Ⅱ） complex, [ZnL2（H2O）4]·H2O（1, HL = 2-（nicotinoyloxy）acetic acid）, was synthesized using Zn（OAc）2·2H2O and 2-（nicotinoyloxy）acetic acid as raw materials. Its structure has been elucidated by elemental analysis, IR and single-crystal X-ray diffraction. The structural analysis revealed that complex 1 crystallizes in triclinic, space group P1 and the Zn（Ⅱ） atom is six-coordinated with two N atoms from two different 2-（nicotinoyloxy）acetate anion ligands and four O atoms from coordinated water molecules. Complex 1 forms a 3D network structure by O–H···O hydrogen bonds. The antitumor activities of 2-（nicotinoyloxy）acetic acid ligand and its Zn（Ⅱ） complex were evaluated against human lung adenocarcinoma A549 cells, human hepatoma SMMC-7721 cells and human colon carcinoma Wi Dr cells.

Two Cobalt(II) Complexes Derived from the Hydrolysis Product of Di-Schiff Base Ligand N,N'-Bis-(1-benzimidazo-2-yl-ethylidene)-ethane-1,2-diamine:Preparation,Characterization and Crystal Structure of the 6-Coordinate Species [CoL_2]X·H_2O (X = ClO_4^-, N

The reactions of Co（C1O4）2·6H2O and Co（NO3）2.6H2O with the di-Schiff base ligand N,N＇-bis-（1-benzimidazo-2-yl-ethylidene）-ethane-1,2-diamine （LA） in ethanol have been investigated. The reactions of LA with excess amount of cobalt salts yield the six-coordinate complexes [CoL2]（ClO4）E·H2O 1 and [CoL2]（NO3）E·H2O 2 as isolatable products （L= N-（1- benzimidazo-2-yl-ethylidene）-ethane-1,2-diamine）, where L is a tri-dentate mono-Schiff base ligand, resulting from the hydrolysis of the precursor di-Schiff base LA. Both complexes were characterized by X-ray crystallography. Crystal data for complex 1： monoclinic, space group P21/c, a = 11.9214（10）, b = 23.5828（17）, c = 14.0387（12）A, β = 135.219（4）°, C22H30Cl2CoN8O9, Mr = 680.37, V = 2780.1（4） A^3 ,Z = 4, Dc = 1.625 g/cm^3,μ（MoKa） = 0.876 mm^-1, F（000） = 1404, the final R = 0.0725 and wR = 0.1530 for 5726 observed reflections （I 〉 2σ（I））. Crystal data for complex 2： monoclinic, space group P21/c, a = 18.2162（16）, b = 10.0610（6）, c = 18.593（2）A, β = 130.099（3）°, C22H30CoN10O7, Mr = 605.49, V = 2606.5（4） A3 Z = 4, Dc = 1.543 g/cm^3,μ（MoKa） = 0.722 mm^-1, F（000） = 1260, the final R = 0.0619 and wR = 0.1429 for 5194 observed reflections （I 〉 2σ（I））. X-ray diffraction analysis reveals that each cobalt atom in the two complexes is chelated by six nitrogen atoms from two tridentate iigands L, exhibiting a slightly distorted octahedral coordination sphere. In both complexes, the strong hydrogen-bonding interactions between the lattice waters and N-H groups of the ligands result in 1D chains which are further connected by ClO4^- （or NO3^-） groups to form a 3D framework. In complex 2, the strong π-π interactions increase the stability of the structure.

Controllably partial removal of thiolate ligands from unsupported Au_(25) nanoclusters by rapid thermal treatments for electrochemical CO_(2)reduction

Colloidal synthesis of metal nanoclusters will inevitably lead to the blockage of catalytically active sites by organic ligands.Here,taking[Au_(25)(PET)_(18)]-(PET=2-phenylethanethiol)nanocluster as a model catalyst,this work reports a feasible procedure to achieve the controllably partial removal of thiolate ligands from unsupported[Au_(25)(PET)_(18)]-nanoclusters with the preservation of the core structure.This procedure shortens the processing duration by rapid heating and cooling on the basis of traditional annealing treatment,avoiding the reconfiguration or agglomeration of Au_(25)nanoclusters,where the degree of dethiolation can be regulated by the control of duration.This work finds that a moderate degree of dethiolation can expose the Au active sites while maintaining the suppression of the competing hydrogen evolution reaction.Consequently,the activity and selectivity towards CO formation in electrochemical CO_(2)reduction reaction of Au_(25)nanoclusters can be promoted.This work provides a new approach for the removal of thiolate ligands from atomically precise gold nanoclusters.

Prognostic value of programmed death.1, programmed death-ligand 1, programmed death-ligand 2 expression, and CD8(+) T cell density in primary tumors and metastatic lymph nodes from patients with stage T1.4N+M0 gastric adenocarcinoma

Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.

Synergistic Effect of Metal Doping and Tethered Ligand Promoted High-Selectivity Conversion of CO_(2)to C_(2)Oxygenates at Ultra-Low Potential

Effectively controlling the selectivity of C_(2) oxygenates is desirable for electrocatalytic CO_(2) reduction.Copper catalyst has been considered as the most potential for reducing CO_(2) to C_(2) products,but it still suffers from low C_(2) selectivity,high overpotential,and competitive hydrogen evolution reaction(HER).Here,we propose a design strategy to introduce a second metal that weakly binds to H and a functional ligand that provides hydrogen bonds and protons to achieve high selectivity of C_(2)oxygenates and effective suppression of HER on the Cu(100)surface simultaneously.Seven metals and eleven ligands are screened using first-principles calculations,which shows that Sn is the most efficient for inhibiting HER and cysteamine(CYS)ligand is the most significant in reducing the limiting potential of^(*)CO hydrogenation to^(*)CHO.In the post C-C coupling steps,a so-called“pulling effect”that transfers H in the CYS ligand as a viable proton donor to the C_(2)intermediate to form an H bond,can further stabilize the OH group and facilitate the selection of C_(2)products toward oxygenates.Therefore,this heterogeneous electrocatalyst can effectively reduce CO_(2)to ethanol and ethylene glycol with an ultra-low limiting potential of-0.43 V.This study provides a new strategy for effectively improving the selectivity of C_(2)oxygenates and inhibiting HER to achieve advanced electrocatalytic CO_(2)reduction.

FasLigand转染人肝癌细胞株HepG2细胞后的生物学效应

目的:将FasLpcDNA3.1hisB转染至人肝癌细胞株HepG2并检测其生物学效应。方法:转染采用脂质体转染方法,HepG2细胞FasL的表达采用免疫组化检测,培养液上清sFasL的检测采用EIA,细胞凋亡采用AnnexinV/PI双染后双变量流式细胞仪检测及荧光显微镜和共聚焦激光扫描显微镜观察。结果:转染后HepG2细胞FasL表达呈阳性,培养液上清检测出微量sFasL,转染后HepG2细胞与HepG2.2.15共同培养后,细胞凋亡率为36.30%,未转染FasL的对照组细胞凋亡率11.53%。结论:将FasLcDNA转染入肝癌细胞系HepG2,可使肝癌细胞发生细胞毒性T细胞(CTL)非依赖FasFasL介导的细胞凋亡。

Synthesis and Crystal Structure of a Three-dimensional Mn(Ⅱ) Coordination Polymer with 3-(Pyrazin-2-yloxy)-pyridine and Azide Anion as Mixed Bridge Ligand

A three-dimensional coordination polymer [Mn2（μ1.3-N3）4（μ-PP）2]n （PP = 3-（pyrazin-2-yloxy）-pyridine） has been synthesized with 3-（pyrazin-2-yloxy）-pyridine and azide anion as mixed bridge ligand, and its crystal structure was determined by X-ray crystallography. The crystal data： triclinic system, space group P1, with a = 6.794（4）, b = 9.885（6）, c = 9.947（6） A, α = 64.170（6）, β= 84.190（8）, γ= 85.319（8）°, V = 597.7（6）A^3, Z = 1, C18H14Mn2N18O2, Mr = 624.35, Dc = 1.735 g/cm^3, F（000） = 314 and μ = 1.117 mm^-1. In the crystal, the azide anion acts as a bridge ligand and makes adjacent Mn（Ⅱ） ions connect into a two-dimensional sheet on the ab plane, then 3-（pyrazin-2-yloxy）-pyridine serves as a bidentate bridge ligand to connect neighboring sheets along