LINC00330/CCL2 axis-mediated ESCC TAM reprogramming affects tumor progression.

BACKGROUND: Tumor-associated macrophages (TAMs) significantly influence the progression, metastasis, and recurrence of esophageal squamous cell carcinoma (ESCC). The aberrant expression of long noncoding RNAs (lncRNAs) in ESCC has been established, yet the role of lncRNAs in TAM reprogramming during ESCC progression remains largely unexplored. METHODS: ESCC TAM-related lncRNAs were identified by intersecting differentially expressed lncRNAs with immune-related lncRNAs and performing immune cell infiltration analysis. The expression profile and clinical relevance of LINC00330 were examined using the TCGA database and clinical samples. The LINC00330 overexpression and interference sequences were constructed to evaluate the effect of LINC00330 on ESCC progression. Single-cell sequencing data, CIBERSORTx, and GEPIA were utilized to analyze immune cell infiltration within the ESCC tumor microenvironment and to assess the correlation between LINC00330 and TAM infiltration. ESCC-macrophage coculture experiments were conducted to investigate the influence of LINC00330 on TAM reprogramming and its subsequent effect on ESCC progression. The interaction between LINC00330 and C-C motif ligand 2 (CCL2) was confirmed through transcriptomic sequencing, subcellular localization analysis, RNA pulldown, silver staining, RNA immunoprecipitation, and other experiments. RESULTS: LINC00330 is significantly downregulated in ESCC tissues and strongly associated with poor patient outcomes. Overexpression of LINC00330 inhibits ESCC progression, including proliferation, invasion, epithelial-mesenchymal transition, and tumorigenicity in vivo. LINC00330 promotes TAM reprogramming, and LINC00330-mediated TAM reprogramming inhibits ESCC progression. LINC00330 binds to the CCL2 protein and inhibits the expression of CCL2 and downstream signaling pathways. CCL2 is critical for LINC00330-mediated TAM reprogramming and ESCC progression. CONCLUSIONS: LINC00330 inhibited ESCC progression by disrupting the CCL2/CCR2 axis and its downstream signaling pathways in an autocrine fashion; and by impeding CCL2-mediated TAM reprogramming in a paracrine manner. The new mechanism of TAM reprogramming mediated by the LINC00330/CCL2 axis may provide potential strategies for targeted and immunocombination therapies for patients with ESCC.

Protective effect of vitamin B6 against doxorubicin-induced cardiotoxicity by modulating NHE1 expression.

Doxorubicin (DOX) has been used to treat various types of cancer, but its application is limited due to its heart toxicity as well as other drawbacks. Chronic inhibition of Na+ /H+ exchanger (NHE1) reduces heart failure and reduces the production of reactive oxygen species (ROS); vitamin B6 (VitB6 ) has been demonstrated to have a crucial role in antioxidant mechanism. So, this study was designed to explore the effect of VitB6 supplement on the DOX-induced cardiotoxicity and to imply whether NHE1 is involved. Ultrasonic cardiogram analysis revealed that VitB6 supplement could alleviate DOX-induced cardiotoxicity; hematoxylin and eosin (HE) and Masson's staining further confirmed this effect. Furthermore, VitB6 supplement exhibited significant antioxidative stress and antiapoptosis effect, which was evidenced by decreased serum malondialdehyde (MDA) content and increased serum superoxide dismutase (SOD) content, and decreased Bcl-2-associated X protein/B-cell lymphoma-2 ratio, respectively. Collectively, VitB6 supplement may exert antioxidative and antiapoptosis effects to improve cardiac function by decreasing NHE1 expression and improve DOX-induced cardiotoxicity.

A systematic pan-cancer analysis identifies RIOK3 as an immunological and prognostic biomarker.

OBJECTIVES: Despite recent research highlighting the critical function of RIO kinase 3 (RIOK3) in a variety of malignancies, a comprehensive evaluation of RIOK3 in human tumors is absent. Our study helps to clarify the molecular mechanism of RIOK3 in carcinogenesis from multiple perspectives. METHODS: Our research looked into the potential oncogenic role of RIOK3 in 33 cancers using TCGA (The Cancer Genome Atlas), GTEx (Genotype-Tissue Expression Project), GEO (Gene Expression Omnibus) datasets, and several bioinformatics tools. RESULTS: RIOK3 expression in tumors is disordered compared to normal tissue, and it is highly linked with the level of MMR (Mismatch repair) gene mutations and DNA methyltransferase expression. According to univariate survival analysis, it could be used as an independent prognostic factor. Further investigation demonstrated that RIOK3 expression was correlated with cancer-associated fibroblast, neutrophil, and endothelial infiltration levels in kidney cancer and was positively correlated with the expression of immune checkpoint markers in different cancers. The functional pathways of RIOK3 also included cell-cell adhesion, protein phosphorylation, and innate immune-related functions. CONCLUSIONS: These findings suggest that RIOK3 could be used as an immunological and prognostic biomarker in various malignant tumors.

Sulforaphane regulates the proliferation of leukemia stem-like cells via Sonic Hedgehog signaling pathway.

Sulforaphane (SFN), the main ingredient in broccoli/broccoli sprouts, has a good anticancer effect in a wide variety of tumors, but whether SFN affects acute leukemia is not elucidated. Due to the self-renewal capability for leukemia stem cells, acute leukemia has a high relapse rate. This study explored the effects and related molecular mechanisms of SFN on the proliferation of leukemia stem-like cells in acute myeloid leukemia cells. We found that SFN inhibited the proliferation of leukemia stem-like cells in vitro and in vivo. Meanwhile, we observed that SFN could regulate the stem characteristic of leukemia cells. After SFN treatment, the expression of the key players in the Sonic Hedgehog (Shh) signaling pathway was significantly decreased at the transcriptional and protein levels. To further determine the contribution of the Shh signaling molecular mechanism to SFN-mediated self-renewal capability of LSCs, we then manipulated the Shh gene in the leukemia cells to either overexpress the gene using lentiviral vector transduction or knockdown the gene via siRNA. The results demonstrated that SFN suppressed proliferation in Shh-overexpressed cells more than in Shh-downregulated cells, suggesting that SFN negatively modulates proliferation of leukemia stem-like cells via affecting the Shh signaling pathway. Altogether, these results suggest that SFN is a potent anti-leukemia agent that has inhibitory effects on leukemia stem-like cells' proliferation by regulating the Shh signaling pathway.

Prevalence and distribution of human papillomavirus genotypes among women attending gynecology clinics in northern Henan Province of China.

BACKGROUND: Human papillomavirus (HPV) infection can cause cervical and other cancers, including vulva, vagina, penis, anus, or oropharynx. However, in China's northern Henan Province, data on the prevalence and genotype distribution of HPV among women attending gynecology clinics is limited. This study aimed to investigate the current prevalence and genotype distribution of HPV among women attending gynecology clinics in northern Henan Province. METHODS: This study included 15,616 women aged 16-81 years old who visited the Xinxiang central hospital's gynecology department between January 2018 and December 2019. HPV DNA was detected by a conventional PCR method followed by HPV type-specific hybridization, which was designed to detect 17 high-risk HPV (HR-HPV) genotypes and 20 low-risk HPV (LR-HPV) genotypes. HPV prevalence and corresponding 95% confidence intervals (95% CI) were calculated using SPSS 18.0. RESULTS: The overall HPV prevalence was 19.7% among women in northern Henan Province. Single, double, and multiple HPV infections accounted for 13.7%, 4.3%, and 1.8% of the total cases. Most infections were caused by HR-HPV (71.8%), and single genotype HPV infection (13.7%) was the most common pattern. The most common HR-HPV genotype was HPV16 (4.3%), followed by HPV52 (3.5%) and HPV58 (2.0%). The most common LR-HPV genotype was HPV6 (1.4%), followed by HPV61 (1.1%) and HPV81 (1.1%). CONCLUSIONS: HPV infection is high among women attending gynecology clinics in northern Henan Province. The highest prevalence was found in women less than 20 years old. In northern Henan Province, the 9-valent HPV vaccine is strongly recommended for regular immunization.

Floralozone protects endothelial function in atherosclerosis by ameliorating NHE1.

Endothelial dysfunction is the pathological basis of atherosclerosis. Incomplete understanding of endothelial dysfunction etiology has impeded drug development for this devastating disease despite the currently available therapies. Floralozone, an aroma flavor, specifically exists in rabbit ear grass. Recently, floralozone has been demonstrated to inhibit atherosclerosis, but the underlying mechanisms are undefined. The present study was undertaken to explore whether floralozone pharmacologically targets endothelial dysfunction and therefore exerts therapeutic effects on atherosclerosis. The Na+/H+ exchanger 1 (NHE1), a channel protein, plays a vital role in atherosclerosis. Whether NHE1 is involved in the therapeutic effects of floralozone on endothelial dysfunction has yet to be further answered. By performing oil red staining and hematoxylin-eosin staining, vascular functional study, and oxidative stress monitoring, we found that floralozone not only reduced the size of carotid atherosclerotic plaque but also prevented endothelial dysfunction in atherosclerotic rats. NHE1 expression was upregulated in the inner membrane of carotid arteries and H2O2-induced primary rat aortic endothelial cells. Inspiringly, floralozone prevented the upregulation of NHE1 in vivo and in vitro. Notably, the administration of NHE1 activator LiCl significantly weakened the protective effect of floralozone on endothelial dysfunction in vivo and in vitro. Our study demonstrated that floralozone exerted its protective effect on endothelial dysfunction in atherosclerosis by ameliorating NHE1. NHE1 maybe a drug target for the treatment of atherosclerosis, and floralozone may be an effective drug to meet the urgent needs of atherosclerosis patients by dampening NHE1.

Fe-N-C with Intensified Exposure of Active Sites for Highly Efficient and Stable Direct Methanol Fuel Cells.

Fe-N-C catalysts are promising candidates to replace expensive and scarce Pt-based catalysts for oxygen reduction reaction (ORR) in fuel cell devices. Herein, simultaneous improvement of activity and stability of Fe-N-C is achieved through exposing active sites via a surface modification strategy. Concretely, EDTAFe groups are anchored on the external surface of zeolitic imidazolate framework-8 (ZIF-8) through size limitation, followed by pyrolysis to obtain ZIF@EDTAFe-1%-950, whose surface active site density increases more than 1.7 times as detected by X-ray photoelectron spectroscopy (XPS) and 57Fe Mössbauer spectra. Consequently, 1.7 times improvement of active site utilization efficiency in electrochemical measurements and more than 2 times performance enhancement in direct methanol fuel cells (DMFCs) are achieved due to facilitated mass transport as revealed by oxygen gain voltage and electrochemical impedance spectroscopy (EIS). Furthermore, through engineering robust drainage channels around exposed active sites to alleviate flooding, the assembled DMFC exhibits better stability than that of Pt/C in the first 3 h and remains 83.9% voltage after 24 h at 100 mA cm-2.

Identification of the first Alu-mediated gross deletion involving the BCKDHA gene in a compound heterozygous patient with maple syrup urine disease.

AIMS: To investigate a family with clinical symptoms of maple syrup urine disease and reveal a genetic cause underlying this disease. METHODS: Targeted capture sequencing was used to screen for mutations in the patient. Real-Time PCR was carried out to perform exon 1, 5, 9 CNV analysis of samples from the patient's father, mother and sister. Whole genome sequencing was performed to map the approximate location of the break points of the gross deletion. Long-range PCR and Sanger sequencing were performed to identify the length of the deletion and to locate the break points. RESULTS: The patient is a compound heterozygous mutation including a small deletion mutation (c.1227_1229del chr19: 41930402) and a gross novel deletion including exon1-9 in BCKDHA. The junction site of the gross deletion was localized within a microhomologous sequence in two Alu elements. CONCLUSIONS: This study is the first time report on rearrangement sequences in BCKDHA mediated by Alu element, which resulted in MSUD. Our results may also offer new insights into the formation and pathogenicity of MSUD, and may be useful to genetic counseling and genetic testing.

DNA damage/cGAS-triggered up-regulation of MALAT1 promotes undesirable inflammatory responses in radiotherapy of cancer.

Radiotherapy is the most common strategy for treating cancer. However, the radiation-induced inflammatory responses, acute or chronic, in the normal tissues of the irradiated region may result in undesirable side effects, such as lung injury and atherosclerosis. MALAT1 is believed to function in the onset, development, progression and metastasis of various cancers. Silencing MALAT1 may be a promising treatment for rescuing cancer. Nevertheless, whether MALAT1 promotes the radiation-induced undesirable inflammatory response is still uncovered. The present study reveals that radiation-induced DNA damage triggers cGAS signaling and subsequently increases the expression of MALAT1. Overexpression of MALAT1 inhibits the function of miR146a in the suppression of STAT1, which results in the boost of adhesion molecules and eventually induces acute lung injury and atherosclerosis. Thus, silencing MALAT1 may facilitate the reduction of radiation-induced acute and chronic complications in the radiotherapy of cancer.

Expanded newborn screening for inborn errors of metabolism by tandem mass spectrometry in newborns from Xinxiang city in China.

BACKGROUND: Tandem mass spectrometry is a powerful technology available in China over the last 15 years. The development of tandem mass spectrometry had made it possible to rapidly screen newborns for inborn errors of metabolism. The aim of this study was to determine the birth incidence of inborn errors of metabolism through expanded screening of newborns by tandem mass spectrometry in Xinxiang area. METHODS: Dried blood spots from 50 112 newborns were assessed for inborn errors of metabolism by tandem mass spectrometry. The diagnoses were confirmed based on the clinical features, conventional laboratory tests, and the organic acid levels tested in urine by gas chromatography-mass spectrometry. RESULTS: The study findings revealed that 31 newborns were diagnosed with inborn errors of metabolism. The total incidence rate of inborn errors of metabolism was 1/1617, and these included 16 cases of amino acid disorders (51.6%), nine cases of organic acid disorders (29.0%), and 6 (19.4%) cases of fatty acid beta-oxidation disorders. CONCLUSIONS: The screening for the incidence of inborn errors of metabolism in Xinxiang area showed that the rate was higher than previously reported. This study provides valuable data which may be useful in facilitating improvements in the expansion of screening to enable early diagnosis and treatment of inborn errors of metabolism before the onset of symptoms.

Giant urethral calculus in anterior urethral diverticulum: a case report.

BACKGROUND: In this case report, giant calculus in the urethral diverticulum was found through ureteroscopy investigation, the pneumatic lithotripsy combined with ultrasound lithotripsy (PLCUL) was successfully performed to break down this rare and giant urethral calculus in the diverticulum without open surgery. CASE PRESENTATION: A 82-year-old male presented to the urology department, complaining of frequent urination and dysuria. One giant, dark brown stone (6.5 × 6 × 5.5 cm) was revealed in the diverticulum of the anterior urethra using combination of local ultrasound, pelvic Computer Tomography (CT) and Magnetic Resonance Imaging (MRI). The stone was then successfully broken down via the PLCUL, and the emptied anterior urethral diverticulum was left untreated. In the 18 months' follow-up, no new calculus was found in urethral tract, anterior diverticula became gradually smaller, eventually disappeared. CONCLUSION: In the treatment of giant calculus in the urethral diverticulum, this case report provides an effective method of lithotripsy in the clinical trials.

Efficient Design for a High-Energy and High-Power Capability Hybrid Electric Power Device with Enhanced Electrochemical Interfaces.

Fabrication of novel electrode architectures with tailored electrochemical interfaces (EI) is an effective strategy for enhancing charge and mass transport processes within electrochemical devices. Here, we design and fabricate a well-hybrid electrode based on the coupling of polyaniline (PANI) nanowires and Pt-based electrocatalysts to manufacture a hybrid electric power device (HEPD) combining the advantages of supercapacitors and fuel cells. Because of the boosted charge transfer between PANI nanowires and Pt-based materials via enhanced EIs, the HEPD assembled with hybrid electrodes shows remarkable performance with a peak power density of 222 mW cm-2, a specific power of 3810 W kg-1, and a specific energy of 2100 Wh kg-1, normalized to the mass of membrane electrode assemblies. The in situ Raman spectra and extended electrochemical studies demonstrate the intrinsic mechanism of charge transfer processes within hybrid electrodes, shedding light on the alternative progress of electrochemical energy conversion systems and storage devices.

Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory Responses.

Peptidoglycan (PGN), as the major components of the bacterial cell wall, is known to cause excessive proinflammatory cytokine production. Toll-like receptor 2 (TLR2) is abundantly expressed on immune cells and has been shown to be involved in PGN-induced signaling. Although more and more evidences have indicated that PGN is recognized by TLR2, the role of TLR2 PGN recognition is controversial. Mannan-binding lectin (MBL), a plasma C-type lectin, plays a key role in innate immunity. More and more evidences show that MBL could suppress the amplification of inflammatory signals. Whether MBL can alter PGN-elicited cellular responses through TLR2 in macrophages is still unknown, and possible mechanism underlying it should be investigated. In this study, we found that MBL significantly attenuated PGN-induced inflammatory cytokine production, including TNF-α and IL-6, in PMA-stimulated THP-1 cells at both mRNA and protein levels. The expression of TLR2 was strongly induced by PGN stimulation. Furthermore, the administration of TLR2-neutralized antibody effectively suppressed PGN-induced TNF-α and IL-6 expression. These results supplied the evidence that PGN from Saccharomyces cerevisiae could be recognized by TLR2. In addition, we also found that MBL decreased PGN-induced TLR2 expression and suppressed TLR2-mediated downstream signaling, including the phosphorylation of IκBα, nuclear translocation of NF-κBp65, and phosphorylation of MAPK p38 and ERK1/2. Administration of MBL alone did not have an effect on the expression of TLR2. Finally, our data showed that PGN-mediated immune responses were more severely suppressed by preincubation with MBL and indicated that MBL can combine with both TLR2 and PGN to block the inflammation cytokine expression induced by PGN. All these data suggest that MBL could downregulate inflammation by modulating PGN/TLR2 signaling pathways. This study supports an important role for MBL in immune regulation and signaling pathways involved in inflammatory responses.

MicroRNA-125a suppresses cell migration, invasion, and regulates hyaluronic acid synthase 1 expression by targeting signal transducers and activators of transcription 3 in renal cell carcinoma cells.

Renal cell carcinoma (RCC) is one of the most common cancers in urology. MicroRNA-125a (miR-125a) has been demonstrated to be implicated in various cancers. However, the functional role of miR-125a in RCC remains largely unclear. This study was aimed to investigate the functional role of miR-125a and the expression relevance of signal transducers and activators of transcription 3 (STAT3) with hyaluronic acid synthase 1 (HAS1) in RCC. We revealed that miR-125a was downexpressed in 786-O cells, and examined transfected efficiency. According to functional assay, overexpression of miR-125a inhibited cell migration and cell invasion, but no obvious effect was observed on cell proliferation. The luciferase activity assay showed that miR-125a could directly target STAT3 3'-untranslated regions. Meanwhile, quantitative polymerase chain reaction (qPCR) assay and Western blot analysis demonstrated that miR-125a could inhibit STAT3 expression at both messenger RNA and protein levels. Furthermore, the combination sites between STAT3 and HAS1 were predicted by prediction of transcription factor binding sites database analysis. The expression of STAT3 was correlated with HAS1 expression, exemplified by the same tendency detected by qPCR assay. Taken together, our results preliminarily demonstrate that miR-125a could constrain cell migration, invasion, and regulate HAS1 expression in RCC cells by targeting STAT3. It is likely to facilitate a better understanding of the regulation mechanisms of miR-125a in RCC.

Long noncoding RNA UCA1 promotes the proliferation of hypoxic human pulmonary artery smooth muscle cells.

Our study explored the effects of lncRNA UCA1 on the proliferation and apoptosis in hypoxic human pulmonary artery smooth muscle cells (HPASMCs) and highlighted the endogenous relationship between UCA1, ING5, and hnRNP I in cell proliferation. Hypoxia-induced HPASMCs were used to simulate pulmonary arterial hypertension in vitro. Microarray assay was adopted to screen the dysregulated expressed lncRNAs in HPASMCs to find out the target gene of our study. And RT-qPCR was performed to detect the expression of lncRNA UCA1 under hypoxia and normoxia. After transfection, the relationship between UCA1 and cell proliferation in HPASMCs under hypoxia were determined by cell proliferation assay and relative expression of PCNA. Next, ELISA assays were conducted to measure the protein levels of PCNA and ING5. What's more, flow cytometry was employed to measure the apoptosis rate in differentially UCA1-expressed HPASMCs. RIP assays were conducted to further clarify the endogenous relationship between UCA1 and ING5 in hypoxic HPASMCs. Finally, the effects of ING5 to HPASMCs were detected after transfection of ING5 and UCA1 to figure out the role of ING5 in HPASMCs. Hypoxia was revealed to induce proliferation and inhibited apoptosis in HPASMCs. Besides, UCA1 was confirmed to be highly expressed under hypoxia compared with normoxia. UCA1 boosted cell proliferation under hypoxia in HPASMCs. However, the apoptosis was suppressed in the hypoxic HPASMCs transfected with pcDNA3.1-UCA1. Further, mechanism studies found that UCA1 competed with ING5 for hnRNP I, so that upregulating UCA1 inhibited the protein levels of ING5. And finally we found that ING5 restrained cell viability, but promoted cell apoptosis in hypoxic HPASMCs, which was reversed by UCA1 over-expression. In summary, our findings manifested that UCA1 promoted proliferation and restrained apoptosis by competing with ING5 for hnRNP I in HPASMCs induced by hypoxia, indicating their potential roles for the cure of hypoxic pulmonary hypertension.

Angiotensin II type 1 receptor blockers prevent aortic arterial stiffness in elderly patients with hypertension.

Backgrounds and aims: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blockers (ARBs) are potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of ARBs in aged patients with essential hypertension are not entirely investigated. Methods: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension. Results: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared to patients without essential hypertension. In correlation analysis, PWV was associated positively with age, hypertension duration, and carotid atherosclerosis. However, there was no relationship between PWV and gender in aged patients with essential hypertension. In a perspective study, 6-12 months administration of ARBs (losartan, 50 mg/day; telmisartan, 40 mg/day; valsartan 80 mg/day; irbesartan, 150 mg/day) remarkably reduced PWV in aged patients with essential hypertension. Regression analyses of multiple factors indicated that the effects of ARBs on arterial stiffness were not associated with the reduction of blood pressure. Conclusion: ARB treatment is a negative risk factor of arterial stiffness in aged patients with essential hypertension.

STC1 promotes cell apoptosis via NF-κB phospho-P65 Ser536 in cervical cancer cells.

Stanniocalin-1 (STC1) is a secreted glycoprotein hormone and involved in various types of human malignancies. Our previous studies revealed that STC1 inhibited cell proliferation and invasion of cervical cancer cells through NF-κB P65 activation, but the mechanism is poorly understood. In our studies, we found overexpression of STC1 promoted cell apoptosis while silencing of STC1 promoted cell growth of cervical cancer. Phospho-protein profiling and Western blotting results showed the expression of NF-κB related phosphorylation sites including NF-κB P65 (Ser536), IκBα, IKKß, PI3K, and AKT was altered in STC1-overexpressed cervical cancer cells. Moreover, PI3K inhibitor LY294002, AKT-shRNA and IκBα-shRNA could decrease the protein content of phospho-P65 (Ser536), phospho-IκBα, phospho-AKT and phospho-IKKß while increasing the level of P65 compared to STC1 overexpression groups in cervical cancer cells. Also, PI3K inhibitor LY294002, AKT-shRNA and IκBα-shRNA elevated the percentage of apoptosis and suppressed the G1/S transition in those cells. Additionally, STC1 level was decreased in cervical cancer, especial in stage II and III. The results of immunohistochemistry for the cervical cancer microarray showed that a lower level of STC1, phospho-PI3K and P65 protein expression in tumor tissues than that in normal tissues, and a higher level of phospho-P65 protein expression in tumor tissues, which is consistent with the results of the Western blotting. These data demonstrated that STC1 can promote cell apoptosis via NF-κB phospho-P65 (Ser536) by PI3K/AKT, IκBα and IKK signaling in cervical cancer cells. Our results offer the first mechanism that explains the link between STC1 and cell apoptosis in cervical cancer.

Hybrid Polymer Nanoarrays with Bifunctional Conductance of Ions and Electrons and Enhanced Electrochemical Interfaces.

Ion migration and electron transfer are crucial phenomena in electrochemistry and interfacial sciences, which require effective coupling and integration of separated charge pathways within medium materials. Here, in this work, we fabricated an ordered nanowire material based on hybrid polymers of polypyrrole, with electronic conductance, and perfluorosulfonic acid ionomers, with ionic conductance, via a facile one-step electrochemical route. Because of the nanoconfined effects for the different charge-transfer channels within the nanowire polymer matrix, the electronic and ionic conductivities of the hybrid polymer are surprisingly enhanced, being 26.4 and 0.096 S cm-1, respectively. Such an improvement in the formation of charge pathways also leads to an increased electrochemical capacitance through enlargement of the area of ion/electron transport boundaries, which may show great potential in the applications of supercapacitors, fuel cells, rechargeable batteries, and other electrochemical devices.

Both intrinsic and extrinsic apoptotic pathways are involved in Toll-like receptor 4 (TLR4)-induced cell death in monocytic THP-1 cells.

Our previous study showed that TLR3 induces apoptosis via both death receptors and mitochondial in human endothelial cells. We report here that the activation of TLR4 induced dose- and time-dependent cell death in moncytic THP-1 cells. LPS treatment of THP-1 cells induced the activation of both caspase 8 and 9, suggesting the involvement of intrinsic and extrinsic apoptosis pathways. TNFα was induced by TLR4 activation at both mRNA and protein levels, but its neutralization did not down-regulated TLR4-induced cell death. TLR4 activation also induced the up-regulation of TRAIL and its receptors DR4 and DR5, and the neutralization of TRAIL ameliorated TLR4 induced apoptosis, suggesting the involvement of TRAIL and its receptors DR4 and DR5 in LPS-induced cell death. Meanwhile, LPS treatment down-regulated the expression of FLICE inhibitory protein (FLIP), a suppressor of death receptor-induced cell death. In addition, TLR4 activation down-regulated the anti-apoptotic protein bcl-2, and up-regulated the pro-apoptotic proteins Noxa and Puma, suggesting that mitochondrial apoptotic pathway was also involved in LPS-induced cell death. Furthermore, we found that TAP63α might confer to the activation of intrinsic and extrinsic apoptotic pathways. The treatment of THP-1 cells with LPS induced the translocation of TAP63α from cytoplasm to nucleus. Taken together, our study suggested that both death receptors and mitochondial were involved in TLR4-induced cell death, and TAP63α may be a target for the prevention of LPS-induced cell death.

[Changes in peripheral blood T helper 9 cells and interleukin-9 in children in the acute stage of Kawasaki disease].

OBJECTIVE: To investigate the changes in the expression levels of peripheral blood T helper 9 (Th9) cells and cytokine interleukin-9 (IL-9) in children in the acute stage of Kawasaki disease (KD) and their clinical significance. METHODS: A total of 45 children in the acute stage of KD who were treated from April 2014 to July 2015 were enrolled, and the children were followed up in the recovery stage. Another 45 healthy children who underwent physical examination were enrolled as the control group. Flow cytometry was used to measure the percentage of peripheral blood Th9 cells, and ELISA was used to measure the serum level of IL-9. RESULTS: The children in the acute stage of KD showed a significantly higher percentage of Th9 cells and a significantly higher serum level of IL-9 compared with those in the recovery stage and the control group (P<0.05). The percentage of Th9 cells and serum level of IL-9 showed no significant differences between the children in the recovery stage and those in the control group (P>0.05). In the acute stage, the percentage of Th9 cells was positively correlated with the levels of IL-9, C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), platelet count (PLT), and globulin (r=0.624, 0.324, 0.402, 0.382, 0.467, and 0.386 respectively, all P<0.05), but negatively correlated with serum albumin (r=-0.306, P<0.05). The serum level of IL-9 was positively correlated with the levels of CRP, PCT, ESR, PLT, and globulin (r=0.365, 0.456, 0.403, 0.423, and 0.453 respectively, all P<0.05), but negatively correlated with serum albumin (r=-0.343, P<0.05). CONCLUSIONS: The children in the acute stage of KD show significant increases in the percentage of peripheral Th9 cells and serum cytokine IL-9 level, which return to normal in the recovery stage. In the acute stage of KD, the expression levels of Th9 and IL-9 are closely correlated with laboratory markers. The results suggest that Th9 cells and IL-9 play important roles in the pathogenesis and outcome of KD.