Synthesis and Characterization of Azido-Functionalized 1,2,3-Triazole and Fused 1,2,3-Triazole.

Here, we report the nitration of NH on the 1,2,3-triazole ring and the synthesis of several nitrogen-rich energetic compounds based on key intermediate 4-azido-5-(chlorodinitromethyl)-2-nitro-2H-1,2,3-triazole (5). Starting from 4-amino-1H-1,2,3-triazole-5-carbonitrile (1), we successfully constructed compound 5 through four steps. Subsequently, the dechlorination of compound 5 gave potassium 4-azido-5-(dinitromethyl)-2H-1,2,3-triazole (6) (IS = 1 J, vD = 8802 m s-1). Additionally, diammonium (8) and dihydrazinium (9) salts based on 4-azido-5-(dinitromethyl)-2H-1,2,3-triazole were also successfully synthesized and characterized. A novel fused nitrogen-rich heterocycle, namely, 6H-[1,2,3]triazolo[4,5-d][1,2,3] triazine-6,7-diamine (10), was surprisingly obtained, which has a high nitrogen content of 73.66% and shows good thermal stability (Tdec = 203 °C) and insensitivity to mechanical stimuli, while the detonation velocity (vD) and detonation pressure (P) reach 8421 m s-1 and 26.0 GPa, respectively.

Biomass-Induced Diphasic Carbon Decoration for Carbon Nitride: Band and Electronic Engineering Targeting Efficient N2 Photofixation.

Boosting the replacement of traditional NH3 production (Haber-Bosch process) with photocatalytic technology is of great importance for energy and environment remediation. Herein, to develop a photocatalyst with efficient charge separation and abundant reactive sites for photocatalytic N2 fixation, a biomass-induced diphase-carbon doping strategy is proposed by adding lotus root starch which can be environmentally produced into the preparation of carbon nitride (CN). The adjustment to the CN framework by planar-fused carbon optimizes the band alignment of the catalyst, improving its response to sunlight. In particular, the in-plane-fused carbon in collaboration with the physically piled carbon initiates unique dual electron transfer pathways from different dimensions. The diphasic carbons can both function as qualified reactive sites according to the experimental explorations and further theoretical calculations, which effectively regulate the electron transfer and energy barrier associated with the N2 reduction on catalyst. The bio-carbon-doped catalyst exhibits drastically enhanced photocatalytic N2 fixation performance, and the NH3 yield on the optimized DC-CN0.1 reaches 167.35 µmol g-1 h-1 , which is fivefold of g-C3 N4 and stands far out from the single-phase doped systems. These explorations expand the metal-free skeleton engineering toolbox and provide new guidance for the solar energy utilizations.

The reference ranges and characteristics of lymphocyte parameters and the correlation between lymphocyte parameters and routine health indicators in adults from China.

BACKGROUND: Assessment of immune function is of key importance in recognition of disease or healthy status, which still faces challenge in clinical practice. We conducted a 10-center study to investigate lymphocyte parameters including the number, phenotype and IFN-γ-producing ability, and routine laboratory indicators by using the standard method. RESULTS: Although the heterogeneity of lymphocyte parameters was widely found, we have established the normal ranges of these parameters by using pooled data which showed no significant difference among centers. Cluster analysis of 35 parameters found 3 interesting clusters which represented different immunological status. Cluster 1 (parameters: IFN-γ+CD4+ T cell percentage and IFN-γ+CD8+ T cell percentage) represented current lymphocyte function, which was associated with indicators such as body mass index and red blood cell; Cluster 2 (parameters: NK cell number and CD45RA+CD4+ T cell percentage) represented potential of lymphocytes, which was associated with indicators such as albumin and high-density lipoprotein. Cluster 3 (parameters: HLA-DR+CD8+ T cell percentage) represented inflammatory status, which was associated with indicators such as low-density lipoprotein, globulin and age. Correlation analysis found that nutritional indicator albumin is significantly positively correlated with lymphocyte potential. Triglyceride and body mass index were positively correlated with current lymphocyte function rather than lymphocyte potential. The loss of CD8+ T cells was extremely pronounced with increasing age and was one of the most important factors to cause immunosenescence, which may be associated with increased glucose. CONCLUSIONS: We have established the normal ranges of lymphocyte parameters in different areas. This study elucidates the key indicators used to reflect the current function or potential of lymphocytes, which may provide a valuable clue for how to keep immunity healthy.

COVID-19 pneumonia: CD8+ T and NK cells are decreased in number but compensatory increased in cytotoxic potential.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is posing a huge threat to human health worldwide. We aim to investigate the immune status of CD8+ T and NK cells in COVID-19 patients. METHODS: The count and immune status of lymphocytes were detected by flow cytometry in 32 COVID-19 patients and 18 healthy individuals. RESULTS: As the disease progression in COVID-19 patients, CD8+ T and NK cells were significantly decreased in absolute number but highly activated. After patients' condition improved, the count and immune status of CD8+ T and NK cells restored to some extent. GrA+CD8+ T and perforin+ NK cells had good sensitivity and specificity for assisting diagnosis of COVID-19. CONCLUSIONS: As the disease progression, the declined lymphocytes in COVID-19 patients might lead to compensatory activation of CD8+ T and NK cells. GrA+CD8+ T and perforin+ NK cells might be used as meaningful indicators for assisting diagnosis of COVID-19.

Hyperactivated peripheral invariant natural killer T cells correlate with the progression of HBV-relative liver cirrhosis.

Invariant NKT (iNKT) cells express markers of both T and NK cells and may produce various cytokines to regulate liver immunity. However, the role of iNKT cells in the progression of HBV-relative liver cirrhosis (HBV-LC) is incompletely understood. Here, we investigated the impact of peripheral iNKT cells on a cohort of patients with HBV-LC. The frequency, number, activation status, apoptosis and proliferation ability of peripheral iNKT cells were detected with flow cytometry. The impact of peripheral iNKT cells on the proliferation of hepatocyte cell line (MIHA) and activation of hepatic stellate cell line (LX-2) was detected with flow cytometry and PCR. In HBV-LC patients, the frequency and absolute number of peripheral iNKT cells significantly reduced, but the expression levels of CD25, interleukin (IL)-4, IL-13 and interferon (IFN)-γ increased. No difference was observed in the proliferation and apoptosis of circulating iNKT cells between patients and healthy controls (HCs). CXCR6 (CD186), known to be closely associated with iNKT cells migration from the periphery to the liver, was highly expressed on peripheral iNKT cells in HBV-LC patients. Furthermore, peripheral iNKT cells had a profound impact on MIHA cell proliferation and LX-2 cell activation through IL-4 or IL-13. Our data suggest that in HBV-LC patients, highly activated peripheral iNKT cells may migrate to the liver and affect hepatocyte cell line (MIHA) proliferation and hepatic stellate cell line (LX-2) activation through the expression of type 2 cytokines, which may result in excessive healing and contributing to the progression of fibrosis toward cirrhosis in liver.

lncRNA KRAL reverses 5-fluorouracil resistance in hepatocellular carcinoma cells by acting as a ceRNA against miR-141.

BACKGROUND: 5-Fluorouracil (5-FU) has been widely applied to treat various types of cancers, including hepatocellular carcinoma (HCC). However, primary or acquired 5-FU resistance prevents the clinical application of this drug in cancer therapy. Herein, our study is the first to demonstrate that lower expression of KRAL, a long non-coding RNA (lncRNA), mediates 5-FU resistance in HCC via the miR-141/Keap1 axis. METHODS: Cell proliferation assays, western blot analysis, qRT-PCR, the dual-luciferase reporter assay and RNA immunoprecipitation were performed to investigate the mechanisms by which KRAL mediates 5-fluorouracil resistance in HCC cell lines. RESULTS: The quantitative analysis indicated that KRAL and Keap1 were significantly decreased and that Nrf2 was increased in HepG2/5-FU and SMMC-7721/5-FU cells compared with the corresponding expression levels in the respective parental cells. Overexpression of KRAL increased Keap1 expression, and inactivating the Nrf2-dependent antioxidant pathway could reverse the resistance of HepG2/5-FU and SMMC-7721/5-FU cells to 5-FU. Moreover, KRAL functioned as a competitive endogenous RNA (ceRNA) by effectively binding to the common miR-141 and then restoring Keap1 expression. These findings demonstrated that KRAL is an important regulator of Keap1; furthermore, the ceRNA network involving KRAL may serve as a treatment strategy against 5-FU resistance in hepatocellular carcinoma cells. CONCLUSIONS: KRAL/miR-141/Keap1 axis mediates 5-fluorouracil resistance in HCC cell lines.

Potassium Nitraminofurazan Derivatives: Potential Green Primary Explosives with High Energy and Comparable Low Friction Sensitivities.

Lead-based primary explosives were widely applied in military and civilian ammunition, which have subsequently caused serious environmental and health-related problems. Therefore, the development of green alternatives for the lead-based primary explosives has been one of the major focuses in the field of energetic materials. Four potassium salts based on nitraminofurazan have been easily synthesized and show excellent comprehensive performances. Among them, potassium 3-dinitromethyl-4-nitraminofurazan (K2 DNMNAF, 1) showed better thermal stability (Td : 281.4 °C), higher density (2.174 g cm-3 ), and lower friction sensitivities (72 N) than that of potassium 4,5-bis(dinitromethyl)furoxanate (K2 BDNMF, Td : 218.3 °C, density: 2.130 g cm-3 , FS: 5 N, P: 27.3 GPa, vD : 7759 m s-1 ); furthermore, it displayed comparable detonation performances (P: 27.2 GPa, vD : 7758 m s-1 ). The promising properties of these salts make this kind of material a competitive alternative to lead azide as a primary explosive.

An overview of hedgehog signaling in fibrosis.

The Hedgehog (Hh) signaling pathway plays a key role during embryogenesis and tissue regeneration. Recently, studies revealed that overactivated Hh signaling leads to fibrogenesis in many types of tissues. The activation of Hh signaling is involved in the epithelial-mesenchymal transition and excessive extracellular matrix deposition. Blockade of Hh signaling abolishes the induction of the epithelial-mesenchymal transition and ameliorates tissue fibrosis. Therefore, new therapeutic targets to alleviate fibrosis based on the Hh signaling have attracted a great deal of attention. This is a new strategy for treating fibrosis and other related diseases. In this review, we discuss the crucial role of Hh signaling in fibrogenesis to provide a better understanding of their relationship and to encourage the study of novel targeted therapies.

MiR-141 Activates Nrf2-Dependent Antioxidant Pathway via Down-Regulating the Expression of Keap1 Conferring the Resistance of Hepatocellular Carcinoma Cells to 5-Fluorouracil.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. A major cause for the failure of cancer therapy is the development of chemoresistance. Although progress has been made in the study of the mechanisms underlying cancer cells resistance, little is known about the role of microRNAs (miRNAs) in cancer therapy resistance. METHODS AND RESULTS: Fifteen miRNAs, including 6 up-regulated miRNAs (> 2.0-fold) and 9 down-regulated miRNAs (< 0.5-fold) were differentially expressed in 5-fluorouracil-resistant and their parental cell-lines (HepG2, HepG2/5-FU) by miRNA microarrays. Microarray results were confirmed by validating quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Up-regulation of miR-141 expression resulted in a significant inhibition of 5-FU-mediated cytotoxicity and apoptosis in various hepatocellular carcinoma cells-lines. Mechanically, miR-141 promoted Kelch-like ECH-associated protein 1 (Keap1) mRNA degradation by directly targeting the Keap1 3'untranslated region (3'UTR). Treatment with miR-141 mimics in parental HepG2 cells, restored miR-141 expression and reduced Keap1 levels, thereby resulting in erythroid transcription factor NFE2-L2 (Nrf2) nuclear translocation, activation of Nrf2-dependent HO-1 gene transcription, and subsequent enhancement in 5-FU resistance. Conversely, restoring the expression of Keap1 partly recovered 5-FU sensitivity by counteracting miR-141-mediated 5-FU resistance. CONCLUSION: Our study showed that miR-141 plays a key role in 5-FU resistance by down-regulating Keap1 expression, thereby reactivating the Nrf2-dependent antioxidant pathway, which may serve as a potential target for overcoming 5-FU resistance in hepatocellular carcinoma cells.

Long noncoding RNA PCA3 gene promoter region is related to the risk of prostate cancer on Chinese males.

INTRODUCTION: Long noncoding RNA prostate cancer gene antigen 3 (PCA3) is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 RNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In this study, we investigated a short tandem repeat (STR) polymorphism of TAAA in the promoter region of PCA3 gene found in our previous study in prostate cancer (PCa) patients and benign prostatic hypertrophy (BPH) patients, aiming to evaluate the association between the STR and increased risk for PCa. MATERIAL AND METHODS: 120 PCa cases and 120 benign prostatic hypertrophy (BPH) cases were identified among participants. The region encompassing the TAAA repeat was amplified with a specific primer set we designed and screened by PCR-based cloning and sequencing in paired peripheral blood leukocytes and prostate tissues. Genotype-specific risks were estimated as odds ratios (ORs) associated with 95% confidence intervals (CIs) and adjusted for age by means of unconditional logistic regression. RESULTS: 5 PCA3 TAAA STR polymorphisms and 8 genotypes were found in both peripheral blood leukocytes and prostate tissues, the carriers with more TAAA repeats were associated with increased risk for PCa than individuals having less TAAA repeats. Interestingly, 18 (15.0%) of 120 PCa patients had more (TAAA)n repeats in prostate tissues than that in peripheral blood leukocytes, and 3 (2.5%) of 120 had less (TAAA)n repeats in prostate tissues. CONCLUSIONS: The results of this study suggest that short tandem repeat polymorphism of TAAA in the promoter region of PCA3 gene is a risk-increasing factor for prostate cancer in the Chinese population. In addition to the hereditary factor, the insertion mutation of (TAAA)n in a local tissue maybe another mechanism of the onset of PCa.

Evaluation of the Genotoxicity of Almond Hull: Implications for Its Use as a Novel Food Ingredient.

Almond hull, a substantial byproduct comprising more than half of almond fresh weight, has recently gained attention due to its functionality and sustainability benefits. Despite heightened interest, information regarding its toxicity remains limited. In order to assess its genotoxic potential, we conducted Good Laboratory Practice-compliant in vitro and in vivo studies following Organization for Economic Co-operation and Development (OECD) guidelines. No evidence of toxicity or mutagenicity was observed in a bacterial reverse mutation assay using five tester strains, evaluating almond hull at concentrations up to 5 mg/plate, with or without metabolic activation. Almond hull did not induce chromosome structural damage in a chromosome aberration assay using Chinese hamster ovary cells, nor did it cause any spermatogonial chromosomal aberration in tested male BALB/c mice. To evaluate its ability to induce DNA damage in rodents, a combined micronucleus assay was conducted in KM mice of both sexes. Almond hull was administered at doses of 1250, 2500, and 5000 mg/kg/day via gavage once daily for 2 days. No adverse effects of almond hull were observed in the micronucleus assay. Our results indicate no evidence of the genotoxic potential of almond hull administered up to the maximum concentrations of 5 g/kg, as recommended by OECD guidelines.

STAT3 regulation of Mtb-specific T cell function in active pulmonary tuberculosis patients.

BACKGROUND: Tuberculosis (TB) remains one of the most serious infectious diseases in the world. Our aim was to investigate the regulatory role of STAT3 and pSTAT3 in the regulation of T cell immunophenotype and cell function. METHODS: Twenty-five active pulmonary tuberculosis (APTB) patients, 18 latent tuberculosis infection (LTBI) patients, and 20 healthy controls (HCs) enrolled in this study. T cell phenotype and expression of STAT3 and pSTAT3 were detected by flow cytometry. RESULTS: Compared with HCs, the expression of pSTAT3 in CD4+ T and CD8+ T cells in peripheral blood of APTB patients was increased, and the expression was higher in pleural effusion. Multifunctional T cells that simultaneously secrete IFN-γ, TNF-α and IL-17A have higher pSTAT3 expression levels. Mtb-specific T cells from APTB patients had a higher cell frequency of the STAT3+ pSTAT3+ phenotype and a reduced cell frequency of the STAT3+ pSTAT3- phenotype compared with LTBI patients. Mtb-specific T cells with STAT3+ pSTAT3+ phenotype had higher expression of PD-1 and PD-L1, while cells with STAT3+ pSTAT3- phenotype had higher expression of Bcl-2. CONCLUSIONS: STAT3 and pSTAT3 in T cells of APTB patients feature in the process of anti-apoptosis and cytokine secretion. At the same time, the higher pSTAT3 may be related to the degree of cell functional exhaustion. The pSTAT3 level of T cells is related to the infection status and may indicate the clinical activity of the disease, which provides a new idea for the clinical identification and treatment of active pulmonary tuberculosis.

Reaction Site Designation by Intramolecular Electric Field in Tröger's-Base-Derived Conjugated Microporous Polymer for Near-Unity Selectivity of CO2 Photoconversion.

To facilitate solar-driven overall CO2 and H2 O convsersion into fuels and O2 , a series of covalent microporous polymers derived from Tröger's base are synthesized featuring flexural backbone and unusual charge-transfer properties. The incorporation of rigid structural twist Tröger's base unit grants the polymers enhanced microporosity and CO2 adsorption/activation capacity. Density function theory calculations and photo-electrochemical analyses reveal that an electric dipole moment (from negative to positive) directed to the Tröger's base unit is formed across two obliquely opposed molecular fragments and induces an intramolecular electric field. The Tröger's base unit located at folding point becomes an electron trap to attract photogenerated electrons in the molecular network, which brings about suppression of carrier recombination and designates the reaction site in synergy with the conjugated network. In response to the discrepancy in reaction pathways across the reaction sites, the product allocation in the catalytic reaction is thereby regulated. Optimally, CMP-nTB achieves the highest photocatalytic CO production of 163.53 µmol g-1 h-1 with approximately unity selectivity, along with H2 O oxidation to O2 in the absence of any photosensitizer or co-catalyst. This work provides new insight for developing specialized artificial organic photocatalysts.

Associations of Gut Microbiota and Fatty Metabolism With Immune Thrombocytopenia.

Objective: To determine whether gut microbiota, fatty metabolism and cytokines were associated with immune thrombocytopenia (ITP). Methods: In total, 29 preliminarily diagnosed ITP patients and 33 healthy volunteers were enrolled. Fecal bacterial were analyzed based on 16S rRNA sequencing. Plasma cytokines and motabolites were analyzed using flow cytometry and liquid chromatography-mass spectrometry (LC-MS), respectively. Results: Bacteroides, Phascolarctobacterium, and Lactobacillus were enriched at the genus level in ITP patients, while Ruminococcaceae UCG-002, Eubacterium coprostanoligeues, Megamonas, and Lachnospiraceae NC2004 were depleted. At the phylum level, the relative abundance of Proteobacteria and Chloroflexi increased in ITP patients, while Firmicutes, Actinobacteria, and the Firmicutes/Bacteroidetes ratio decreased. Plasma levels of 5-hydroxyeicosatetraenoic acid (5-HETE), 6-trans-12-epi-leukotriene B4 (6t,12e-LTB4), and resolvin D2 (RvD2) were upregulated, and stachydrine, dowicide A, dodecanoylcarnitine were downregulated in ITP patients. Furthermore, RvD2 is positively correlated with order Bacteroidetes VC2.1 Bac22, 5-HETE is positively correlated with genus Azospirillum, and 6t,12e-LTB4 is positively correlated with genus Cupriavidus. In addition, stachydrine is positively correlated with family Planococcaceae, dowicide A is positively correlated with class MVP-15, and dodecanoylcarnitine is positively correlated with order WCHB1-41. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were upregulated in ITP patients. Conclusion: Our study revealed a relationship between microbiota and fatty metabolism in ITP. Gut microbiota may participate in the pathogenesis of ITP through affecting cytokine secretion, interfering with fatty metabolism.

Dynamic monitoring of circulating CD8+ T and NK cell function in patients with septic shock.

BACKGROUND: Septic shock is a great threat to human life. Our aim is to explore the immune status and dynamic changes of circulating cytotoxic cells in septic shock patients. METHODS: Forty-eight septic shock patients (9 non-survivors and 39 survivors) and 30 healthy controls (HCs) were enroled in our study. The function of cytotoxic cells was dynamically monitored by flow cytometry. RESULTS: The number of circulating CD8+ T and NK cells decreased significantly in septic shock patients, while the number of CD8+ T cells rose in survivors 5 days after admission. The frequency of HLA-DR+CD8+ T/ NK cells increased in both groups after admission but decreased in non-survivors on day 3. Moreover, the frequency of GrA+/GrB+/perforin+NK and GrB+CD8+ T cells decreased to varying degrees in both groups, and the frequency of GrB+/perforin+CD8+ T cells on the second day of non-survivors was significantly lower than that of survival patients. Besides, the frequency of CXCR3+CD8+ T/ NK cells was decreased in both groups and remained low in non-survivors, but remarkably increased in survivors after day 3. And the concentrations of cytokines IL-6, IL-10, TNF-α and IFN-γ were significantly increased in septic shock patients. CONCLUSIONS: Circulating CD8+ T and NK cells reduced but activation function was compensatory enhanced in septic shock patients. The frequency of GrB+/PFP+CD8+ T and CXCR3+CD8+ T/NK cells may predict the progression of septic shock patients 2-3 days after admission.

Dynamic changes in monocytes subsets in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is affecting the whole world and threatening human health. We aim to investigate the immunological characteristics of monocytes in critical patients with COVID-19. METHODS: The number and immune status of monocytes were detected by flow cytometry in 32 COVID-19 patients and 18 healthy individuals. RESULTS: In critical patients with COVID-19, the absolute number of total monocytes and CD16- monocytes was significantly decreased but CD16+ pro-inflammatory monocytes was increased compared to healthy controls. Antigen presentation potential of monocytes, as measured by HLA-DR expression, was suppressed, while their inflammatory phenotype (CD38 expression) was enhanced. Cytokine levels showed sustained increases in critical patients. And the levels of IL-6 were positively correlated with CD16+ monocytes number. IL-6 and IL-10 levels were negatively correlated with HLA-DR expression of monocytes. During the recovery of COVID-19 patients, the count and immune status of monocyte subsets were restored by degrees. HLA-DR+ monocytes possessed good sensitivity and specificity for predicting the incidence of critical patients with COVID-19. CONCLUSIONS: In critical patients with COVID-19, decline in number and HLA-DR expression of monocytes might lead to decreased antigen presentation potential and thus immunosuppression, while increased CD16+ pro-inflammatory monocytes might mediate hyperinflammation. HLA-DR+ monocytes might be a meaningful assisted indicator to predict the incidence of critical patients with COVID-19.

The isoflavone puerarin exerts anti-tumor activity in pancreatic ductal adenocarcinoma by suppressing mTOR-mediated glucose metabolism.

Puerarin (8-(ß-D-glucopyranosyl)-4', 7-dihydroxyisoflavone), a natural flavonoid compound isolated from the traditional Chinese herb Radix puerariae, have been demonstrated has potential anti-tumor effects via induction of apoptosis and inhibition of proliferation. However, the effect and molecular mechanism of puerarin in pancreatic ductal adenocarcinoma (PDAC) remains unknown. In this study, the tumor-suppressive effects of puerarin were determined by both in-vitro and in-vivo assays. The effects of puerarin on the proliferation, apoptosis, migration and invasion of pancreatic cancer cells (PCCs), and tumor growth and metastasis in PDAC xenograft mouse model were performed. Puerarin treatment significantly repressed PCC proliferation. Puerarin induced the mitochondrial-dependent apoptosis of PCCs by causing a Bcl-2/Bax imbalance. Moreover, puerarin inhibited PCC migration and invasion by antagonizing epithelial-mesenchymal transition (EMT). In nude mouse model, PDAC growth and metastasis were reduced by puerarin administration. Mechanistically, puerarin exerted its therapeutic effects on PDAC by suppressing Akt/mTOR signaling. Importantly, puerarin bound to the kinase domain of mTOR protein, affecting the activity of the surrounding amino acid residues associated with the binding of the ATP-Mg2+ complex. Further studies showed that the inhibitory effects of puerarin on PCCs were abolished by a mTOR activator, indicating a crucial role of mTOR in anti-tumor effects of puerarin in PDAC. As a result, puerarin hindered glucose uptake and metabolism by downregulating the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) dependent upon HIF-1α and glucose transporter GLUT1. Therefore, these findings indicated that puerarin has therapeutic potential for the treatment of PDAC by suppressing glucose uptake and metabolism via Akt/mTOR activity.

Multifunctional T cell response in active pulmonary tuberculosis patients.

BACKGROUND: Tuberculosis still threatens human health. We aimed to investigate the T cell immune status and the role of multifunctional T cells in pulmonary tuberculosis patients. METHODS: Thirty active pulmonary tuberculosis (APTB) patients, 30 latent tuberculosis infection (LTBI) patients, 25 cured pulmonary tuberculosis (CPTB) patients and 25 healthy controls (HCs) enrolled in this study. Flow cytometer for detecting T cell phenotype and function. CBA Flex Set was used to measure chemokine. RESULTS: Compared with HCs and LTBI patients, APTB patients had fewer CD4+ T and CD8+ T cells, but the expression of granzyme A, granzyme B and perforin on CD8+ T cells increased. Compared to LTBI and CPTB patients, Mycobacterium tuberculosis-specific CD8+ T cells in APTB patients appeared to be more differentiated CD45RA-CCR7- cells, and there were more multifunctional CD4+ T and CD8+ T cells. Importantly, the frequency of multifunctional CD4+ T cells in the pleural fluid of APTB patients was higher than that of peripheral blood. And the proportion of multifunctional CD4+ T cells expressing the migration receptor CXCR3 in the peripheral blood of APTB patients decreased, while the concentrations of its ligands, chemokine MIG, IP-10 and I-TAC increased significantly in plasma, especially in pleural fluid. CONCLUSIONS: Decreased T lymphocytes in APTB patients may cause compensatory activation of CD8+ T cells. Multifunctional CD4+ T cells in peripheral blood could migrate to the lungs under the action of CXCR3 and associated chemokine. Multifunctional CD4+ T cells and Multifunctional CD8+ T cells were of great significance in monitoring disease treatment.

Dynamic Distribution and Clinical Value of Peripheral Lymphocyte Subsets in Children with Infectious Mononucleosis.

OBJECTIVE: To study the dynamic change of peripheral lymphocyte subsets and its clinical value in children with infectious mononucleosis (IM). METHODS: Thirty-six pediatric patients with IM, 19 children with IM-like symptoms but lacking the serological pattern compatible with EB virus infection, and 33 healthy children were enrolled. The changes of peripheral lymphocyte subsets were detected by flow cytometry on admission and on the fifth day of antiviral treatment, respectively. Indicators of liver function and routine blood count were also detected. Besides, the receiver operating characteristic (ROC) curve and the correlation of related indicators was analyzed. RESULTS: When IM patients were admitted, the frequency and absolute number of T, CD4-CD8+T, and CD4+CD8+T (DPT) cells were significantly increased while B cells were decreased; the frequency of CD4+CD8-T cells were decreased, but its absolute number did not change significantly; the frequency of NK cells decreased, but its absolute number increased. The absolute number of CD4-CD8+T most significantly positively correlated with serum lactate dehydrogenase (LDH) concentration which could reflect the severity of IM patients. After short-term treatment with acyclovir, elevated lymphocytes decreased, but only DPT-cell frequency and NK-cell absolute number were recovering towards normal. The ROC curve suggested that the frequency of B cells has better diagnostic value for IM in pediatric patients compared to other lymphocyte subsets. CONCLUSIONS: Peripheral lymphocyte subsets are closely related to the condition of children with IM, and each subset plays a relatively different role in the diagnosis and evaluation of IM.

Highly activated TRAIL+ CD56bright NK cells are associated with the liver damage in HBV-LC patients.

BACKGROUND: Chronic hepatitis B-related liver cirrhosis(HBV-LC)is the most common cirrhosis in China, which is characterized as liver damage and high mortality. We aim to investigate the characteristics of TRAIL+NK cells in patients with HBV-LC and their relationship with liver damage in patients with HBV-LC. METHODS: Thirty cases each of chronic hepatitis B (CHB), HBV-related compensated liver cirrhosis (HBV-CLC) and HBV-related decompensated liver cirrhosis (HBV-DLC) patients were recruited in this study. Thirty age-and sex-matched healthy individuals were recruited as healthy controls (HCs). NK cell phenotypes were determined using flow cytometry. Serum chemokine concentrations were ascertained using the CBA Flex set. Cell apoptosis was analyzed using the Annexin V-PE/7-AAD apoptosis Kit. RESULTS: CD56bright NK cells increased, but CD56dim NK cells reduced in HBV-LC patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was mainly expressed on CD56bright NK cells. As the degree of liver damage increased, the frequency and activation of total TRAIL+NK cells and TRAIL+NK cell subsets continued to increase, especially in the HBV-LC patients. Furthermore, the difference in frequency and activation of total TRAIL+NK cells between the HBV-CLC and HBV-DLC groups was mainly due to the highly activation and increase of TRAIL+CD56bright NK cells. With the increasing degree of liver damage, CXCR3-associated chemokines (including CXCL9, CXCL10 and CXCL11) were constantly increased, particularly in the HBV-DLC group. The expression of CXCR3 on CD56bright NK cells was almost 100 % in all enrolled cohorts. CXCR3-associated chemokines were negatively correlated with liver function and positively correlated with fibrosis degree. TRAIL+CD56bright NK cells were negatively correlated with liver function, and positively correlated with fibrosis degree and CXCR3-associated chemokines. The apoptosis of K562 cells and hepatocytes was suppressed partially by the TRAIL-neutralizing antibodies. CONCLUSIONS: The increase of CXCR3-related chemokines (including CXCL9, CXCL10 and CXCL11) might be related to the migration of TRAIL+ CD56bright NK cells to the liver. Highly activated TRAIL+ CD56bright NK cells were associated with the liver damage in HBV-LC patients. These findings may provide new perspectives and theoretical basis for future immunotherapy of HBV-LC patients.