Boron-Doped Ti3C2Tx MXene for Effective and Durable High-Current-Density Ammonia Synthesis.

Ammonia (NH3) synthesis via the nitrate reduction reaction (NO3RR) offers a competitive strategy for nitrogen cycling and carbon neutrality; however, this is hindered by the poor NO3RR performance under high current density. Herein, it is shown that boron-doped Ti3C2Tx MXene nanosheets can highly efficiently catalyze the conversion of NO3RR-to-NH3 at ambient conditions, showing a maximal NH3 Faradic efficiency of 91% with a peak yield rate of 26.2 mgh-1 mgcat. -1, and robust durability over ten consecutive cycles, all of them are comparable to the best-reported results and exceed those of pristine Ti3C2Tx MXene. More importantly, when tested in a flow cell, the designed catalyst delivers a current density of ‒1000 mA cm-2 at a low potential of ‒1.18 V versus the reversible hydrogen electrode and maintains a high NH3 selectivity over a wide current density range. Besides, a Zn-nitrate battery with the catalyst as the cathode is assembled, which achieves a power density of 5.24 mW cm-2 and a yield rate of 1.15 mgh-1 mgcat. -1. Theoretical simulations further demonstrate that the boron dopants can optimize the adsorption and activation of NO3RR intermediates, and reduce the potential-determining step barrier, thus leading to an enhanced NH3 selectivity.

Spermidine regulates wheat grain weight at high planting density by promoting the synthesis of sucrose and starch in inferior grains.

Increasing density is an effective way to enhance wheat (Triticum aestivum L.) yield under limited cultivated areas. However, the physiological mechanisms underlying the reduction in grain weight when density increased are still unclear. Three field experiments were conducted during the 2014-2019 growing seasons to explore the physiological mechanisms by which polyamines affect grain weight formation. The results showed that when wheat planting density exceeded 450 × 104 seedlings ha-1 and 525 × 104 seedlings ha-1, wheat yield tended to decrease. Compared to moderate density (DM, 450 × 104 seedlings ha-1), the filling rate of inferior grains was reduced before 25 days after anthesis (DAA) and the active filling period was shortened by 6.4%-7.4% under high density (DH, 600 × 104 seedlings ha-1), resulting in a loss of 1000-grain weight by 5.4%-8.1%. DH significantly reduced sucrose and starch content in inferior grains at the filling stage. Meanwhile, DH inhibited the activity of key enzymes involved in polyamine synthesis [SAMDC (EC 4.1.1.50) and SpdSy (EC 2.5.1.16)] and induced the activity of ethylene (ETH) precursor synthase, resulting in a significant decrease in endogenous spermidine (Spd) content in inferior grains, but a significant increase in ETH release rate. Post-flowering application of exogenous Spd increased the accumulation of sucrose and starch in the inferior grains and positively regulated the filling and grain weight of the inferior grains, whereas exogenous ETH had a negative effect. Overall, Spd may affect wheat grain weight at high planting density by promoting the synthesis of sucrose and starch in inferior grains.

Virtual bronchoscopic navigation with intraoperative cone-beam CT for the diagnosis of peripheral pulmonary nodules.

OBJECTIVE: Transbronchial biopsy is a safe manner with fewer complications than percutaneous transthoracic needle biopsy; however, the current diagnostic yield is still necessitating further improvement. We aimed to evaluate the diagnostic yield of using virtual bronchoscopic navigation (VBN) and cone-beam CT (CBCT) for transbronchial biopsy and to investigate the factors that affected the diagnostic sensitivity. METHODS: We retrospectively investigated 255 patients who underwent VBN-CBCT-guided transbronchial biopsy at our two centers from May 2021 to April 2022. A total of 228 patients with final diagnoses were studied. Patient characteristics including lesion size, lesion location, presence of bronchus sign, lesion type and imaging tool used were collected and analyzed. Diagnostic yield was reported overall and in groups using different imaging tools. RESULTS: The median size of lesion was 21 mm (range of 15.5-29 mm) with 46.1% less than 2 cm in diameter. Bronchus sign was present in 87.7% of the patients. The overall diagnostic yield was 82.1%, and sensitivity for malignancy was 66.3%. Patients with lesion > 2 cm or with bronchus sign were shown to have a significantly higher diagnostic yield. Four patients had bleeding and no pneumothorax occurred. CONCLUSION: Guided bronchoscopy with VBN and CBCT was an effective diagnostic method and was associated with a high diagnostic yield in a safe manner. In addition, the multivariant analysis suggested that lesion size and presence of bronchus sign could be a predictive factor for successful bronchoscopic diagnosis.

Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.

Gastric cancer is one of the most prevalent cancers worldwide, and human epidermal growth factor receptor 2 (HER2)-positive cases account for approximately 20% of the total cases. Currently, trastuzumab + chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer, and the combination has exhibited definite efficacy in HER2-targeted therapy. However, the emergence of drug resistance during treatment considerably reduces its effectiveness; thus, it is imperative to investigate the potential mechanisms underlying resistance. In the present review article, we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases, aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.

Physiologically-based pharmacokinetic modeling-guided rational combination of tacrolimus and voriconazole in patients with different CYP3A5 and CYP2C19 alleles.

The drug-drug interactions (DDIs) between tacrolimus and voriconazole are highly variable among individuals. We aimed to develop a physiologically based pharmacokinetic (PBPK) model to predict the DDIs in people with different CYP3A5 and CYP2C19 alleles. First, pharmacokinetic data of humans receiving tacrolimus with or without voriconazole from the literature were used to construct and validate the PBPK model. Thereafter, we developed a model incorporating the metabolism of voriconazole mediated by CYP2C19 and the inhibitory effect of voriconazole on CYP3A4/5. Finally, the model was used to evaluate the dose adjustment of tacrolimus in people with different CYP3A5 and CYP2C19 alleles. When tacrolimus was administered alone (3 mg PO, single dose), the predicted AUC0-∞ of tacrolimus in CYP3A5 nonexpressers (19.22) was 3.5-fold higher than that in expressers (5.48). Following voriconazole (200 mg PO, bid) administration in human with different CYP2C19 genotypes, the AUC0-∞ of tacrolimus increased by 5.1- to 8.3-fold in CYP3A5 expressers and by 5.3- to 10.2-fold in CYP3A5 nonexpressers. The lower the gene expression level of CYP2C19 in the population, the higher the exposure to tacrolimus. When tacrolimus was combined with voriconazole (200 mg, bid; 400 mg, bid, on Day 1), the final model simulations suggested that the dose regimen of tacrolimus should be regulated to 0.15 mg/kg/day (qd) in CYP3A5 expressers with different CYP2C19 genotypes. For CYP3A5 nonexpressers, the dosing schedule of tacrolimus should be modified to 0.05 mg/kg/24 h for patients with 2C19 EM, 0.05 mg/kg/48 h for 2C19 IM and 0.05 mg/kg/72 h for 2C19 PM. In conclusion, a PBPK model with CYP3A5 and CYP2C19 polymorphisms was successfully established, providing more insights regarding the DDIs between tacrolimus and voriconazole to guide the clinical use of tacrolimus.

Peripheral PD-1 and Tim-3 percentages are associated with primary sites and pathological types of peritoneal neoplasms.

PURPOSE: Programmed death-1 (PD-1) and T cell immunoglobulin and mucin-domain-containing molecule 3(Tim-3) may be used as the biomarkers for the therapy in patients with peritoneal neoplasms. In the current study, the differential percentages of peripheral PD-1 and Tim-3 are explored to investigate whether to associate with primary sites and pathological types of patients with peritoneal neoplasms or not. We also investigated the frequencies of PD-1 and Tim-3 on circulating Lymphocytes, CD3 + T cells, CD3 + CD4 + T cells and CD3 + CD8 + T cells if would correlate with the progression-free survival of peritoneal neoplasms patients. METHODS: 115 patients with peritoneal neoplasms were recruited, subjected to multicolor flow cytometric analyses of the percentages of PD-1 and Tim-3 receptors of circulating Lymphocytes, CD3 + T cells, CD3 + CD4 + T cells and CD3 + CD8 + T cells. The peritoneal neoplasms patients were divided into primary group and secondary group depending on whether the tumor had primary focus and limited to peritoneal tumor or not. Then all the patients were regrouped by the pathological types of neoplasms (adenocarcinoma, mesothelioma, and pseudomyxoma). The secondary peritoneal neoplasms group was divided into the different primary site groups (colon, gastric, gynecology). This study also enrolled 38 cases of normal volunteers. The above markers were explored by flow cytometer, to find the differential levels in peritoneal neoplasms patients compared with normal group in peripheral blood. RESULTS: Higher levels of CD4 + T lymphocytes, CD8 + T lymphocytes, CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells, CD3 + CD4 + PD-1 + T cells, CD3 + CD8 + PD-1 + T cells and CD45 + Tim-3 + lymphocytes were found in peritoneal neoplasms group than normal control (the p value was respectively 0.004, 0.047, 0.046, 0.044, 0.014, 0.038 and 0.017). Compared with primary peritoneal neoplasms group, the percentages of CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells, and CD3 + CD4 + PD-1 + T cells were increased in the secondary peritoneal neoplasms group (the p value was respectively 0.010, 0.044, and 0.040), while PD-1 did not correlate with the primary sites in secondary group (P > 0.05). Tim-3 had no statistical differences in primary peritoneal neoplasms group compared with secondary group (p > 0.05), but CD45 + Tim-3+% lymphocytes, CD3 + Tim-3+%T cells, and CD3 + CD4 + Tim-3 + T cells were associated with different secondary sites of peritoneal neoplasms (p < 0.05). In the different pathological type groups, the percentages of CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells presented the higher levels in adenocarcinoma group compared with mesothelioma group (p = 0.048, p = 0.045). The frequencies of CD45 + PD-1 + lymphocytes and CD3 + PD-1 + T cells in peripheral blood were associated with progression-free survival (PFS). CONCLUSIONS: Our work uncovers peripheral PD-1 and Tim-3 percentages are associated with primary sites and pathological types of peritoneal neoplasms. Those findings might provide important assessment to predict peritoneal neoplasms patients' immunotherapy responses.

Why Ligand Doping Increases the Fluorescence of an Anthracene-Based Metal-Organic Framework.

Metal-organic frameworks (MOFs) built from fluorescent ligands frequently exhibit enhanced fluorescence when doped with inert ligands. This study focuses on a MOF of the UiO-68 structure, which is built from a fluorescent dibenzoate-anthracene ligand doped with a dibenzoate-benzene ligand. Our investigation aims to understand the mechanism behind the doping-enhanced emission of this MOF. We rule out several possible mechanisms, including exciton coupling, electron transfer between ligand and metal center, and ligand intersystem crossing induced by the metal center. Inhibition of the interligand charge transfer is considered a possible way to enhance emission. Furthermore, we propose that the conformational change of the anthracene-based ligand in the MOF cavity is also a way for enhancement. Our molecular dynamics simulations of the MOF structure filled with solvents reveal that the steric crowding in the cavity induces a conformational change at different doping levels, affecting the rate of intersystem crossing of the ligand.

Dexrazoxane Alleviated Doxorubicin-Induced Nephropathy in Rats.

INTRODUCTION: Doxorubicin (DOX), an anthracycline antitumor agent, has been widely used against various solid tumors and hematological malignancies. However, the clinical application of DOX is restricted by its multiple organ toxicity including nephrotoxicity. This study investigated the protective effects and mechanisms of dexrazoxane (DZR) against DOX-induced nephropathy in rats. METHODS: Male Sprague Dawley rats received 2.5 mg/kg DOX once a week for 5 consecutive weeks. 24-h urinary protein and renal function injury biomarkers were determined to evaluate the renal function. Histopathological changes and glomerulosclerosis were examined by hematoxylin and eosin and periodic acid-Schiff staining. The change of renal ultrastructure in the DOX-induced rats was observed by the electron microscopy. The renal apoptosis was detected by TUNEL staining and measured the protein expression of Caspase-3, Bcl-2, and Bax. Renal interstitial fibrosis was determined by Masson staining and immunohistochemistry examination. The levels of vimentin, alpha-smooth muscle actin (α-SMA), and transforming growth factor ß (TGF-ß) in kidney tissue were detected by Western blot. RESULTS: DZR pretreatment markedly raised the survival rate and improved the renal dysfunction in DOX-treated rats. DZR ameliorated DOX-induced histopathological lesion of glomerular and tubular and apoptosis. DZR restored the oxidant/antioxidant balance via regulating the levels of MDA, SOD, and TAC. DZR reduced DOX-induced collagen IV deposition and renal interstitial fibrosis and downregulated the fibrosis-related protein expressions of vimentin, α-SMA, and TGF-ß1. CONCLUSION: Our results suggest DZR exerted its protective effects against DOX-induced nephropathy through inhibition of lipid peroxidation, apoptosis, and fibrosis.

[Risk factors for acute kidney injury after hematopoietic stem cell transplantation in children: a retrospective study]. / å„¿ç«¥é€ è¡€å¹²ç»†èƒžç§»æ¤åŽæ€¥æ€§è‚¾æŸä¼¤ç›¸å ³å±é™©å› ç´ çš„å›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the risk factors for acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) in children. METHODS: A retrospective analysis was performed on the medical data of 111 children who underwent HSCT from January 2018 to January 2020. A multivariate logistic regression analysis was used to identify the risk factors for AKI. The Kaplan-Meier survival analysis was used to compare the prognosis in children with different grades of AKI. RESULTS: Graft-versus-host disease (grade Ⅱ-Ⅳ) (OR=4.406, 95%CI: 1.501-12.933, P=0.007), hepatic veno-occlusive disease (OR=4.190, 95%CI: 1.191-14.740, P=0.026), and thrombotic microangiopathy (OR=10.441, 95%CI: 1.148-94.995, P=0.037) were closely associated with the development of AKI after HSCT. The children with stage Ⅲ AKI had a lower 1-year survival rate than those without AKI or with stage Ⅰ AKI or stage Ⅱ AKI (28.6%±12.1% vs 82.8%±5.2%/81.7%±7.4%/68.8%±11.6%; P<0.05). CONCLUSIONS: Children with stage Ⅲ AKI after HSCT have a higher mortality rate. Graft-versus-host disease, hepatic veno-occlusive disease, and thrombotic microangiopathy are closely associated with the development of AKI after HSCT.

Immunohistochemical Assessment of Transthyretin Association with Colorectal Adenocarcinoma.

BACKGROUND: To explore the association of transthyretin (TRR) with colorectal cancer (CRC) development and progression. METHODS: This study was conducted on 12 normal colorectal tissue samples, 15 colorectal adenomas, and 39 colorectal adenocarcinoma tissue specimens. TTR expression was assessed by immunohistochemistry, and the results were correlated to clinicopathological characteristics of CRC patients. RESULTS: TTR staining was detected in 16.7% (2/12) of normal colon tissues, 46.7% (7/15) of colorectal adenomas, and 89.7% (35/39) of colorectal adenocarcinoma tissues. TTR staining scores in normal colon tissues, adenoma, and adenocarcinoma were 0.58, 2.27, and 5.40, respectively. G3 grade adenocarcinoma had a higher TTR staining score compared with G2 and G1 grades (8.40, p = 0.0009). Lower TTR expression was significantly associated with metastasis (p = 0.043). CONCLUSIONS: TTR expression is positively correlated with adenoma to CRC progression. Thus, TTR has the potential to serve as a predictive marker in CRC.

Innovative method for Amplatzer device implantation in patients with bronchopleural fistulas.

BACKGROUND: Bronchopleural fistula (BPF) is a relatively rare complication after various types of pulmonary resection. The double-sided mushroom-shaped occluder (Amplatzer device, AD) has been gradually used for BPF blocking due to its reliable blocking effect. We have improved the existing AD implantation methods to facilitate clinical use and named the new approach Sheath-free method (SFM). The aim of the present report was to explore the reliability and advantages of the SFM in AD implantation. METHODS: We improved the existing implantation methods by abandoning the sheath of the AD and using the working channel of the bronchoscope to directly store or release the AD without general anesthesia, rigid bronchoscopy, fluoroscopy, or bronchography. A total of 6 patients (5 men and 1 woman, aged 66.67 ± 6.19 years [mean ± SD]) had BPF blocking and underwent the SFM in AD implantation. RESULTS: AD implantation was successfully performed in all 6 patients with the SFM, 4 persons had a successful closure of the fistula, one person died after few days and one person did not have a successful closure of the fistula. The average duration of operation was 16.17 min (16.17 ± 4.67 min [mean ± SD]). No patients died due to operation complications or BPF recurrence. The average follow-up time was 13.2 months (range 10-17 months). CONCLUSION: We observed that the SFM for AD implantation-with accurate device positioning and a clear field of vision-is efficient and convenient. The AD is effective in BPF blocking, and could contribute to significantly improved symptoms of patients.

Photoactivation of Cu Centers in Metal-Organic Frameworks for Selective CO2 Conversion to Ethanol.

CO2 hydrogenation to ethanol is of practical importance but poses a significant challenge due to the need of forming one C-C bond while keeping one C-O bond intact. CuI centers could selectively catalyze CO2-to-ethanol conversion, but the CuI catalytic sites were unstable under reaction conditions. Here we report the use of low-intensity light to generate CuI species in the cavities of a metal-organic framework (MOF) for catalytic CO2 hydrogenation to ethanol. X-ray photoelectron and transient absorption spectroscopies indicate the generation of CuI species via single-electron transfer from photoexcited [Ru(bpy)3]2+-based ligands on the MOF to CuII centers in the cavities and from Cu0 centers to the photoexcited [Ru(bpy)3]2+-based ligands. Upon light activation, this Cu-Ru-MOF hybrid selectively hydrogenates CO2 to EtOH with an activity of 9650 µmol gCu-1 h-1 under 2 MPa of H2/CO2 = 3:1 at 150 °C. Low-intensity light thus generates and stabilizes CuI species for sustained EtOH production.

R93P Substitution in the PmrB HAMP Domain Contributes to Colistin Heteroresistance in Escherichia coli Isolates from Swine.

Here, the mechanisms of colistin heteroresistance (CHR) were assessed in 12 Escherichia coli isolates from swine in China. CHR was investigated by population analysis profile tests. CHR stability was studied by culturing isolates for five overnight incubation periods in colistin-free medium. Subsequently, the mcr-1 gene and mutations in PmrAB, PhoPQ, and MgrB were screened in parental isolates and resistant subpopulations. Additionally, the expression levels of phoPQ, its target gene pagP, and its negative regulator gene mgrB, as well as pmrAB and its target genes pmrHFIJKLM and pmrC, were determined by real-time relative quantitative PCR. Eleven of the 12 isolates were confirmed to show CHR, with 17 resistant subpopulations. Also, 11 of the 17 subpopulations (64.71%) harbored point mutations in PmrB and/or PhoQ, differing from their parental isolates. However, only one stable resistant subpopulation (EPF42-4) was identified; it harbored an arginine-to-proline substitution at position 93 (R93P) within the PmrB HAMP (histidine kinase, adenylyl cyclase, methyl-binding protein, and phosphatase) domain. Compared to the pmrB expression levels in the parental isolate EPF42 and E. coli K-12 MG1655, remarkable pmrB overexpression was observed in EPF42-4, which showed upregulated pmrA, pmrK, and pmrC expression. Structural analysis demonstrated that the R93P substitution promotes conformational changes in the HAMP domain, leading to an acceleration in its signal transduction ability and the activation of PmrB expression. In conclusion, point mutations in PmrB and/or PhoQ were primarily associated with CHR. The R93P substitution resulted in the establishment of stable resistant subpopulations in E. coli showing CHR.

Size-controllable synthesis of zinc ferrite/reduced graphene oxide aerogels: efficient electrochemical sensing of p-nitrophenol.

In this study, a nonaqueous method for the synthesis of size-controlled highly crystalline zinc ferrite/reduced graphene oxide (ZFO/rGO) aerogel was provided by using benzyl alcohol as the medium. In our findings, benzyl alcohol was introduced not only as the solvent, but the structure-directing agent and strong reducing agent during the nucleation and growth of ZnFe2O4 nanoparticles (NPs). The characterization analysis indicated that ZnFe2O4 NPs were immobilized on the multilayer rGO with a controllable size of 12 nm. Moreover, the 3D ZFO/rGO aerogel shows excellent electrochemical property as a facile electrochemical sensor for the detection of p-nitrophenol (p-NP). The ZFO/rGO electrochemical sensing offers the advantages of wide linear range (1-500 µmol l-1), excellent sensitivity (23.985 mA mM-1 cm-2), good stability and selectivity (<8.8%). In addition, the possible reaction mechanism of 3D ZFO/rGO aerogel was explained during the detection process under acidic condition. Significantly, our results not only provided insight into the possible reaction mechanism of 3D ZFO/rGO nanocomposite, but proposed the way for the synthesis of highly crystalline materials through a benzyl alcohol-mediated method.

Selective ablation of the ligament of Marshall attenuates atrial electrical remodeling in a short-term rapid atrial pacing canine model.

INTRODUCTION: Cardiac sympathetic activation facilitates atrial electrical remodeling during atrial fibrillation (AF). Selective ablation of the distal part of the ligament of Marshall (LOMLSPV ) could decrease cardiac sympathetic innervation. This study aimed to investigate the effects of LOMLSPV ablation on atrial electrical remodeling in a short-term rapid atrial pacing (RAP) model. METHODS: In 16 anesthetized dogs, 6 hours of RAP (20 Hz, 2 × threshold) was delivered before LOMLSPV ablation (group 1, N  =  8) or after (group 2, N  =  8). Heart rate variability (HRV), serum norepinephrine (NE), atrial electrophysiological indices were analyzed. Six times of burst pacing (20 Hz, 2 × threshold, lasting for 5 seconds, were performed to induce AF, the number of episodes and the duration of AF were compared. RESULTS: LOMLSPV ablation decreased sympathetic indices of HRV and serum NE. Atrial effective refractory period (ERP) was shortened during RAP in both groups with higher reduction degrees in group 1. In group 1, the shortening of atrial ERP, elevating of ERP dispersion and sum of window of vulnerability (ΣWOV), facilitating of AF induced by RAP were subsequently reversed by LOMLSPV ablation. In group 2, LOMLSPV ablation prolonged atrial ERP, decreased ΣWOV, eliminated AF induction. The subsequent RAP failed to alter these indices. Histological studies showed abundant sympathetic nerve fibers in LOMLSPV . CONCLUSION: LOMLSPV ablation could inhibit atrial electrical remodeling during short-term RAP by reducing the cardiac sympathetic activity. LOMLSPV may be a potential target in AF ablation, especially in patients with highly cardiac sympathetic activation or atrial electrical remodeling.

Selective adsorption of organic dyes by porous hydrophilic silica aerogels from aqueous system.

Hydrophilic silica aerogel (HSA) was obtained by sol-gel method and dried at ambient conditions and further studied for the removal of organic dyes in water. Silica aerogel was characterized by its morphology, porous structure, specific surface area and particle size distribution by scanning electron microscopy, Brunauer-Emmett-Teller and pore size distribution. The HSA after calcination had a specific surface area of 888.73 m2/g and an average particle size of 2.6341 nm. Moreover, adsorption properties of the HSA toward organic dyes - adsorption conditions, kinetics data, and equilibrium model - were investigated. The removal rate of cationic dyes (rhodamine B (RhB), methylene blue (MB) and crystal violet (CV)) by HSA was up to 90%, while the removal rate of anionic dye (acid orange 7) was not more than 30%. The maximum adsorptions were: RhB 191.217 mg/g, MB 51.1601 mg/g and CV 24.85915 mg/g, respectively. Based on the adsorption mechanism of HSA for cationic/anionic dyes, the conclusion confirmed the prospect of HSA as effective adsorbent to treat cationic dyes wastewater.

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway.

In this study, we investigated the cardioprotective mechanisms of action of DT-010, a novel danshensu-tetramethylpyrazine conjugate. DT-010 significantly preserved cell viability and suppressed cell apoptosis in H9c2 cells injured by tert-butylhydroperoxide (t-BHP), iodoacetic acid (IAA) and hypoxia-reoxygenation. In addition, DT-010 pre-treatment reduced the intracellular level of free radicals including superoxide anion (·O2-), hydroxyl radical (·OH) and peroxynitrite anion (ONOO-) after t-BHP exposure. Moreover, DT-010 up-regulated the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear factor-E2-related factor 2 (Nrf2) as well as mitochondrial transcription factor A (Tfam) and heme oxygenase-1 (HO-1) in H9c2 cells. DT-010 also triggered Nrf2 nuclear translocation. In a rat myocardial ischemia-reperfusion model, DT-010 significantly alleviated myocardial infarction. The results indicated that DT-010 may be a promising candidate for the treatment of cardiovascular diseases, particularly myocardial ischemia and reperfusion injury.

Involvement of CapG in proliferation and apoptosis of pulmonary arterial smooth muscle cells and in hypoxia-induced pulmonary hypertension rat model.

PURPOSE: Actin-binding protein capping protein gelsolin-like (CapG) was preferentially expressed in human pulmonary arterial smooth muscle cells (PASMCs) under hypoxia, and reduced CapG expression was accompanied by impaired migration ability in vitro. We intended to investigate the effects of CapG on rat PASMCs and hypoxia-induced pulmonary hypertension (HPH) rat model. MATERIALS AND METHODS: We investigated the effect of RNA interference-medicated down-regulation of CapG expression in rat PASMCs as well as in HPH rat model. The proliferation, apoptosis and cell cycle of PASMCs were evaluated. The HPH rat model was established by intratracheal instillation of lentiviral vector and subsequent hypoxia exposure for four weeks. Right ventricular systolic pressure, right ventricular hypertrophy and the percentage of medial wall thickness were measured to evaluate the development of HPH. RESULTS: Knock-down CapG in PASMCs resulted in decreased proliferation, increased apoptosis and induced cell cycle inhibition. Down-regulation of CapG expression locally could attenuate pulmonary hypertension, pulmonary vascular remodeling and right ventricular hypertrophy in HPH rat model. CONCLUSIONS: Our study indicated that CapG participated in the pathogenesis of pulmonary vascular remodeling in HPH rats, which was probably mediated by promoting the proliferation and inhibiting the apoptosis of PASMCs. We proposed CapG modulating protective effects of pulmonary hypertension.

[Expression of apolipoprotein A-I in eight histological types of renal neoplasms].

OBJECTIVE: To investigate the expression of apolipoprotein A-I(ApoA-I) in eight histological types of renal neoplasms and to explore a new biomarker for differential diagnosis. METHODS: The immunochemistry was used to detect the expression of ApoA-I in 23 cases of renal tumors, including clear cell carcinoma,papillary cell carcinoma, chromophobe cell carcinoma, oncocytoma,multilocular cystic carcinoma, renal pelvis invasive urothelial carcinoma,metanephric adenoma and collecting ducts carcinoma. Five cases of cancer-adjacent normal tissues were obtained from another five renal tumor patients and were chosen as control group. RESULTS: In the 23 cases of renal tumors, ApoA-I was expressed in 21 cases (positive rate was 91.3%). There were only two in five cases of normal tissues which expressed this protein (positive rate was 40.0%). A significant differentiation was observed between the two groups(Z=-2.829,P=0.003). In renal clear cell carcinoma (RCC), ApoA-I expression level was correlated with the grade and stage of tumor tissues. ApoA-I was stained much more stronger in RCC II-III than in RCC I (Z=-2.070,P=0.038).In various histological types of renal cancer, ApoA-I was all expressed to some degrees. CONCLUSION: ApoA-I can be chosen as a tumor biomarker to differentiate various histological types of renal neoplasms.

Correlation analysis between peripheral blood dendritic cell subsets and PD-1 in patients with peritoneal adenocarcinoma.

The aim of this study was to explore the association between differential percentages of dendritic cell (DC) subsets in peripheral blood and malignancy (grade and lymph node metastasis) of peritoneal adenocarcinoma patients and the frequencies of dendritic cell subsets in the normal controls. The peripheral blood of 30 patients with peritoneal adenocarcinoma and 12 healthy controls were collected for multicolor flow cytometry analysis. Peritoneal adenocarcinoma patients were grouped according to the malignant degree (grade and lymph node metastasis). Percentages of myeloid DCs (mDCs) and its subsets MDC1 and MDC2 in DCs were lower in peripheral blood of patients with peritoneal adenocarcinoma than in normal controls. The percentages of plasmacytoid dendritic cells (pDCs) and CD16+mDCs in DCs were higher than in normal controls. Compared with poor differentiation grade, patients with well/moderate differentiation grade had an increased percentage of CD16+mDCs. Contrary to CD16+mDCs, the percentage of MDC1 was lower in the well/moderate differentiation grade group. In patients with no lymph node metastasis, pDCs and CD16+mDCs levels were higher compared with patients with lymph node metastasis. mDCs and MDC1 levels had opposite results. pDCs were positively correlated with CD16+mDCs in peripheral blood of peritoneal patients, as was mDCs and MDC1. CD16+mDCs were negatively correlated with MDC1. The percentages of pDCs and CD16+mDCs in DCs were positively correlated with CD3+CD8+T cells, and pDCs also positively correlated with CD8+PD-1+T cells. Our results revealed that DCs subsets correlated with peritoneal adenocarcinoma malignancy. Dendritic cells play an independent role in the immune function of peritoneal adenocarcinoma.