TiN as Radical Scavenger in Fe─N─C Aerogel Oxygen Reduction Catalyst for Durable Fuel Cell.

Fe─N─C is the most promising alternative to platinum-based catalysts to lower the cost of proton-exchange-membrane fuel cell (PEMFC). However, the deficient durability of Fe─N─C has hindered their application. Herein, a TiN-doped Fe─N─C (Fe─N─C/TiN) is elaborately synthesized via the sol-gel method for the oxygen-reduction reaction (ORR) in PEMFC. The interpenetrating network composed by Fe─N─C and TiN can simultaneously eliminate the free radical intermediates while maintaining the high ORR activity. As a result, the H2 O2 yields of Fe─N─C/TiN are suppressed below 4%, ≈4 times lower than the Fe─N─C, and the half-wave potential only lost 15 mV after 30 kilo-cycle accelerated durability test (ADT). In a H2 ─O2 fuel cell assembled with Fe─N─C/TiN, it presents 980 mA cm-2 current density at 0.6 V, 880 mW cm-2 peak power density, and only 17 mV voltage loss at 0.80 A cm-2 after 10 kilo-cycle ADT. The experiment and calculation results prove that the TiN has a strong adsorption interaction for the free radical intermediates (such as *OH, *OOH, etc.), and the radicals are scavenged subsequently. The rational integration of Fe single-atom, TiN radical scavenger, and highly porous network adequately utilize the intrinsic advantages of composite structure, enabling a durable and active Pt-metal-free catalyst for PEMFC.

Genetically determined gut microbiota associates with pulmonary arterial hypertension: a Mendelian randomization study.

BACKGROUND: Emerging evidences have demonstrated that gut microbiota composition is associated with pulmonary arterial hypertension (PAH). However, the underlying causality between intestinal dysbiosis and PAH remains unresolved. METHOD: An analysis using the two-sample Mendelian randomization (MR) approach was conducted to examine the potential causal relationship between gut microbiota and PAH. To assess exposure data, genetic variants associated with 196 bacterial traits were extracted from the MiBioGen consortium, which included a sample size of 18,340 individuals. As for the outcomes, summary statistics for PAH were obtained from the NHGRI-EBI GWAS Catalog, which conducted a meta-analysis of four independent studies comprising a total of 11,744 samples. Causal effects were estimated employing various methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weight mode and simple mode, with sensitivity analyses also being implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots. RESULTS: Following false discovery rate (FDR) correction, the genetically predicted genus Eubacterium fissicatena group (odds ratio (OR) 1.471, 95% confidence interval (CI) 1.178-1.837, q = 0.076) exhibited a causal association with PAH. In addition, the genus LachnospiraceaeUCG004 (OR 1.511, 95% CI 1.048-2.177) and genus RuminococcaceaeUCG002 (OR 1.407, 95% CI 1.040-1.905) showed a suggestive increased risk of PAH, while genus Eubacterium eligens group (OR 0.563, 95% CI 0.344-0.922), genus Phascolarctobacterium (OR 0.692, 95% CI 0.487-0.982), genus Erysipelatoclostridium (OR 0.757, 95% CI 0.579-0.989) and genus T-yzzerella3 (OR 0.768, 95% CI 0.624-0.945) were found to have nominal protective effect against PAH. CONCLUSION: The findings from our MR study have revealed a potential causal relationship between gut microbiota and PAH. Specifically, we have identified four types of gut microbiota that exhibit a protective effect on PAH, as well as three types that have a detrimental impact on PAH, thereby offering valuable insights for future mechanistic and clinical investigations in the field of PAH.

Downregulation of G protein-coupled receptor kinase 4 protects against kidney ischemia-reperfusion injury.

Ischemia/reperfusion injury of the kidney is associated with high morbidity and mortality, and treatment of this injury remains a challenge. G protein-coupled receptor kinase 4 (GRK4) plays a vital role in essential hypertension and myocardial infarction, but its function in kidney ischemia/reperfusion injury remains undetermined. Among the GRK subtypes (GRK2-6) expressed in kidneys, the increase in GRK4 expression was much more apparent than that of the other four GRKs 24 hours after injury and was found to accumulate in the nuclei of injured mouse and human renal tubule cells. Gain- and loss-of-function experiments revealed that GRK4 overexpression exacerbated acute kidney ischemia/reperfusion injury, whereas kidney tubule-specific knockout of GRK4 decreased injury-induced kidney dysfunction. Necroptosis was the major type of tubule cell death mediated by GRK4, because GRK4 significantly increased receptor interacting kinase (RIPK)1 expression and phosphorylation, subsequently leading to RIPK3 and mixed lineage kinase domain-like protein (MLKL) phosphorylation after kidney ischemia/reperfusion injury, but was reversed by necrostatin-1 pretreatment (an RIPK1 inhibitor). Using co-immunoprecipitation, mass spectrometry, and siRNA screening studies, we identified signal transducer and activator of transcription (STAT)1 as a GRK4 binding protein, which co-localized with GRK4 in the nuclei of renal tubule cells. Additionally, GRK4 phosphorylated STAT1 at serine 727, whose inactive mutation effectively reversed GRK4-mediated RIPK1 activation and tubule cell death. Kidney-targeted GRK4 silencing with nanoparticle delivery considerably ameliorated kidney ischemia/reperfusion injury. Thus, our findings reveal that GRK4 triggers necroptosis and aggravates kidney ischemia/reperfusion injury, and its downregulation may provide a promising therapeutic strategy for kidney protection.

Effect of body mass index on clinical outcomes after robotic cardiac surgery: is there an obesity paradox?

BACKGROUND: To investigate the effect of body mass index (BMI) on clinical outcomes after robotic cardiac surgery, and to explore the postoperative obesity paradox. METHODS: The data of 146 patients who underwent robotic cardiac surgery under cardiopulmonary bypass (CPB) from July 2016 to June 2022 in Daping Hospital of Army Medical University were retrospectively analyzed, and their demographic data and related clinical data were statistically analyzed. The mean age was (42.88 ± 13.01) years, 55 (37.67%) were male and 91 (62.33%) were female. Patients were divided into 3 groups according to preoperative BMI: lean group (BMI < 18.5 kg/m2; n = 17; 11.64%), normal group (BMI 18.5 kg/m2 to 23.9 kg/m2; n = 81; 55.48%), and overweight and obese group (BMI ≥ 24 kg/m2; n = 48; 32.88%). Multivariate analysis was performed to compare clinical outcomes across BMI groups. RESULTS: Preoperative data in different BMI groups showed that there were statistically significant differences in age, height, weight, body surface area (BSA), diabetes, left atrial anteroposterior diameter (LAD), triglyceride (TG), and high-density lipoprotein (HDL) (all P < 0.05). Postoperative clinical outcomes showed that there was no statistical difference between the lean group and the normal group; the intensive care unit stay and postoperative hospital stay in the overweight and obese group were significantly higher than those in the normal group (P < 0.05), and the risk of postoperative cardiac surgery-related acute kidney injury (CSA-AKI) was significantly increased (P = 0.021); further Multiple Binary Logistic Regression Analysis suggested that preoperative TG (OR = 1.772, 95% CI 1.068-2.942, P = 0.027) and operation time ≥ 300 min (OR = 3.823, 95% CI 1.098-13.308, P = 0.035) were independent risk factors for postoperative CSA-AKI. CONCLUSIONS: Overweight and obese patients had significantly prolonged intensive care unit stay and postoperative hospital stay after robotic cardiac surgery, and significantly increased incidence of postoperative CSA-AKI, which did not support the obesity paradox; preoperative TG and operation time ≥ 300 min were independent risk factors for postoperative CSA-AKI.

G-protein-coupled receptor kinase 4 causes renal angiotensin II type 2 receptor dysfunction by increasing its phosphorylation.

Activation of the angiotensin II type 2 receptor (AT2R) induces diuresis and natriuresis. Increased expression or/and activity of G-protein-coupled receptor kinase 4 (GRK4) or genetic variants (e.g., GRK4γ142V) cause sodium retention and hypertension. Whether GRK4 plays a role in the regulation of AT2R in the kidney remains unknown. In the present study, we found that spontaneously hypertensive rats (SHRs) had increased AT2R phosphorylation and impaired AT2R-mediated diuretic and natriuretic effects, as compared with normotensive Wistar-Kyoto (WKY) rats. The regulation by GRK4 of renal AT2R phosphorylation and function was studied in human (h) GRK4γ transgenic mice. hGRK4γ142V transgenic mice had increased renal AT2R phosphorylation and impaired AT2R-mediated natriuresis, relative to hGRK4γ wild-type (WT) littermates. These were confirmed in vitro; AT2R phosphorylation was increased and AT2R-mediated inhibition of Na+-K+-ATPase activity was decreased in hGRK4γ142V, relative to hGRK4γ WT-transfected renal proximal tubule (RPT) cells. There was a direct physical interaction between renal GRK4 and AT2R that was increased in SHRs, relative to WKY rats. Ultrasound-targeted microbubble destruction of renal GRK4 decreased the renal AT2R phosphorylation and restored the impaired AT2R-mediated diuresis and natriuresis in SHRs. In vitro studies showed that GRK4 siRNA reduced AT2R phosphorylation and reversed the impaired AT2R-mediated inhibition of Na+-K+-ATPase activity in SHR RPT cells. Our present study shows that GRK4, at least in part, impairs renal AT2R-mediated diuresis and natriuresis by increasing its phosphorylation; inhibition of GRK4 expression and/or activity may be a potential strategy to improve the renal function of AT2R.

Association of circulating vaspin levels and patients with metabolic-associated fatty liver disease: a systematic review and meta-analysis.

BACKGROUND: The incidence rate of metabolic-associated fatty liver disease (MAFLD) is increasing annually; however, there are still no effective methods for establishing an early diagnosis and conducting real-time tracing. Vaspin can affect the metabolic processes in the body, and it is closely associated with many metabolic diseases. Many previous studies have speculated on the association between vaspin and MAFLD, but the results of these studies have not been conclusive. This meta-analysis examined the differences in circulating vaspin levels between patients with MAFLD and healthy individuals. METHODS: Six databases and other sources were searched with free terms and Medical Subject Headings terms, and a total of 13 articles were included (900 cases and 669 controls). RevMan 5.3 and Stata 16 were used for analysis. The standardised mean difference (SMD) and 95% confidence interval (CI) were used to assess the overall outcomes. Cohen's kappa coefficient was applied to examine the differences between the two authors in the selection of studies and in the evaluation of the quality of evidence for the studies. RESULTS: The results demonstrated that there was no significant difference in the circulating vaspin levels between the MAFLD group and healthy group (SMD = 0.46, 95% CI: [- 0.12, 1.04]). The subgroup analysis suggested that area and body mass index (BMI) may be the sources of heterogeneity, and the results of univariate meta-regression analysis were consistent with those of the subgroup analysis (P = 0.005 and P < 0.001, respectively). Furthermore, BMI may better explain the source of heterogeneity (P = 0.032) in the multivariate meta-regression analysis. CONCLUSION: In summary, no significant correlation was observed between the circulating vaspin levels and MAFLD. BMI may be an important factor affecting this correlation, which may provide a reference for further studies on mechanism and diagnosis of MAFLD.

Perfluoroalkyl-Promoted Synthesis of Perfluoroalkylated Pyrrolidine-Fused Coumarins with Methyl ß-Perfluoroalkylpropionates.

Employing the methyl ß-perfluoroalkylpropionate as the Michael acceptor, an efficient approach for the synthesis of perfluoroalkylated pyrrolidine-fused coumarins has been achieved. A tandem reaction involving [3 + 2] cycloaddition and intramolecular transesterification was proposed for the mechanism. The enhanced electrophilicity resulting from the strong electron-withdrawing ability of the perfluoroalkyl group was crucial for this tandem reaction.

A Polymeric Bilayer Multi-Legged Soft Millirobot with Dual Actuation and Humidity Sensing.

There are numerous works that report wirelessly controlling the locomotion of soft robots through a single actuation method of light or magnetism. However, coupling multiple driving modes to improve the mobility of robots is still in its infancy. Here, we present a soft multi-legged millirobot that can move, climb a slope, swim and detect a signal by near-infrared irradiation (NIR) light or magnetic field dual actuation. Due to the design of the feet structure, our soft millirobot incorporates the advantages of a single actuation mode of light or magnetism. Furthermore, it can execute a compulsory exercise to sense a signal and analyze the ambience fluctuation in a narrow place. This work provides a novel alternative for soft robots to achieve multimode actuation and signal sensing.

Loss of SMAD3 Promotes Vascular Remodeling in Pulmonary Arterial Hypertension via MRTF Disinhibition.

RATIONALE: Vascular remodeling in pulmonary arterial hypertension (PAH) results from smooth muscle cell hypertrophy and proliferation of vascular cells. Loss of BMPR-II (bone morphogenetic protein receptor 2) signaling and increased signaling via TGF-ß (transforming growth factor ß) and its downstream mediators SMAD (small body size [a C. elegans protein] mothers against decapentaplegic [a Drosophila protein family])-2/3 has been proposed to drive lung vascular remodeling; yet, proteomic analyses indicate a loss of SMAD3 in PAH. OBJECTIVES: We proposed that SMAD3 may be dysregulated in PAH and that loss of SMAD3 may present a pathophysiological master switch by disinhibiting its interaction partner, MRTF (myocardin-related transcription factor), which drives muscle protein expression. METHODS: SMAD3 levels were measured in lungs from PAH patients, rats treated either with Sugen/hypoxia or monocrotaline (MCT), and in mice carrying a BMPR2 mutation. In vitro, effects of SMAD3 or BMPR2 silencing or SMAD3 overexpression on cell proliferation or smooth muscle hypertrophy were assessed. In vivo, the therapeutic and prophylactic potential of CCG1423, an inhibitor of MRTF, was investigated in Sugen/hypoxia rats. MEASUREMENTS AND MAIN RESULTS: SMAD3 was downregulated in lungs of patients with PAH and in pulmonary arteries of three independent PAH animal models. TGF-ß treatment replicated the loss of SMAD3 in human pulmonary artery smooth muscle cells (huPASMCs) and human pulmonary artery endothelial cells. SMAD3 silencing increased proliferation and migration in huPASMCs and human pulmonary artery endothelial cells. Coimmunoprecipitation revealed reduced interaction of MRTF with SMAD3 in TGF-ß-treated huPASMCs and pulmonary arteries of PAH animal models. In huPASMCs, loss of SMAD3 or BMPR-II increased smooth muscle actin expression, which was attenuated by MRTF inhibition. Conversely, SMAD3 overexpression prevented TGF-ß-induced activation of an MRTF reporter and reduced actin stress fibers in BMPR2-silenced huPASMCs. MRTF inhibition attenuated PAH and lung vascular remodeling in Sugen/hypoxia rats. CONCLUSIONS: Loss of SMAD3 presents a novel pathomechanism in PAH that promotes vascular cell proliferation and-via MRTF disinhibition-hypertrophy of huPASMCs, thereby reconciling the parallel induction of a synthetic and contractile huPASMC phenotype.

Left thorax approach to repair doubly committed juxta-arterial ventricular septal defect with Da Vinci robotic system.

Robotic repair of the ventricular septal defect was performed mainly for perimembranous type via right thorax approach. Minimally invasive strategies for doubly committed juxta-arterial ventricular septal defect were limited. Here, for the first time, we successfully repaired a doubly committed juxta-arterial ventricular septal defect with Da Vinci robotic system via left thorax approach. The technique could provide excellent exposure of surgical field and accurate repair, with the advantage of reducing trauma and shortening the overall length of stay.

Bacillamidins A⁻G from a Marine-Derived Bacillus pumilus.

Seven long-chain amides, including five previously undescribed bacillamidins A⁻E (1⁻5) and two previously reported synthetic analogs, bacillamidins F (6) and G (7), were isolated from extracts of the marine-derived Bacillus pumilus strain RJA1515. The structures of the new compounds were established by extensive analysis of 1D and 2D nuclear magnetic resonance (NMR) data as well as high resolution mass spectrometry (HRMS), and the absolute configurations of the stereogenic carbons of 1⁻4 were established by comparison of the calculated and the experimental electronic circular dichroism (ECD) spectra. The cytotoxic and antimicrobial activities of 1⁻7 were evaluated.

The mast cell-B cell axis in lung vascular remodeling and pulmonary hypertension.

Over past years, a critical role for the immune system and, in particular, for mast cells in the pathogenesis of pulmonary hypertension (PH) has emerged. However, the way in which mast cells promote PH is still poorly understood. Here, we investigated the mechanisms by which mast cells may contribute to PH, specifically focusing on the interaction between the innate and adaptive immune response and the role of B cells and autoimmunity. Experiments were performed in Sprague-Dawley rats and B cell-deficient JH-KO rats in the monocrotaline, Sugen/hypoxia, and the aortic banding model of PH. Hemodynamics, cell infiltration, IL-6 expression, and vascular remodeling were analyzed. Gene array analyses revealed constituents of immunoglobulins as most prominently regulated mast cell-dependent genes in the lung in experimental PH. IL-6 was shown to link mast cells to B cells, as 1) IL-6 was upregulated and colocalized with mast cells and was reduced by mast-cell stabilizers and 2) IL-6 or mast cell blockade reduced B cells in lungs of monocrotaline-treated rats. A functional role for B cells in PH was demonstrated in that either blocking B cells by an anti-CD20 antibody or B-cell deficiency in JH-KO rats attenuated right ventricular systolic pressure and vascular remodeling in experimental PH. We here identify a mast cell-B cell axis driven by IL-6 as a critical immune pathway in the pathophysiology of PH. Our results provide novel insights into the role of the immune system in PH, which may be therapeutically exploited by targeted immunotherapy.

Animal models of sarcoidosis.

Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

Profiling of anthocyanins in transgenic purple-fleshed sweet potatoes by HPLC-MS/MS.

BACKGROUND: Anthocyanins in purple-fleshed sweet potato (PSP) are beneficial to human health. The leaf color (Lc) gene is a transcription factor involved in regulating anthocyanin biosynthesis. The anthocyanin profiles of wild-type PSP of Ayamurasaki and its three Lc-transgenic lines were investigated by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). In vitro antioxidant activities of wild-type and Lc-transgenic lines, including reducing power activity, DPPH radical scavenging activity, hydroxyl radical scavenging activity, linoleic acid autoxidation inhibition activity, ABTS free radical scavenging activity and oxygen radical absorbance capacity activity, were measured. RESULTS: The results showed that the total anthocyanin contents increased 1.5-1.9 times in three transgenic lines compared with that in wild-type PSP. Seventeen anthocyanins were found in wild-type PSP, while 19 in Lc-transgenic lines including cyanidin-based, peonidin-based and pelargonidin-based anthocyanins. Three pelargonidin-based anthocyanins were detected in three Lc-transgenic lines. Among them, the relative contents of cyanidin-based and pelargonidin-based anthocyanins increased 1.9-2.0 and 3.4-4.5 times respectively, while peonidin-based anthocyanins decreased 1.8-1.9 times in Lc-transgenic lines, compared with wild-type PSP. PSP from wild-type Ayamurasaki and three Lc-transgenic lines exhibited potent antioxidant activities, whereas there was no distinct difference among them. CONCLUSION: The transgene Lc significantly increased the content of total anthocyanins and remarkably changed the anthocyanin profiles in Ayamurasaki. Such novel and high content of anthocyanins obtained in the Lc-transgenic lines with potent antioxidant activities may provide unique functional products with potential helpful for human health. © 2017 Society of Chemical Industry.

Mixed Supra- and Intracardiac Totally Anomalous Pulmonary Venous Connection in an Adult Female: Pre- and Postoperative Evaluation with Emphasis on MDCT Angiographic Advantages.

All cases with total anomalous pulmonary venous connection (TAPVC) were reported in neonates and children in the previous literature. This report describes the only case in which a mixed supra- and intracardiac TAPVC was discovered in a 25-year-old adult female and multidetector-row computed tomography (MDCT) angiography was used in its pre- and postoperative evaluation. Multidetector-row computed tomography angiography is superior to echocardiography in showing the draining sites and courses of the anomalous connected pulmonary veins, as well as postoperative evaluation in a patient with mixed TAPVC. It indicates that MDCT angiography may be a more suitable diagnostic modality for use in the pre- and postoperative evaluation of the mixed TAPVC.

High takeoff of the right coronary artery associated with ventricular septal defect, right aortic arch, and bridging bronchus.

We report a case of a 14-year-old female with abnormally high takeoff of the right coronary artery (RCA) that was associated with a ventricular septal defect, right aortic arch, and bridging bronchus. During surgery, an exceptionally high takeoff of the RCA was discovered. Postoperative computed tomography confirmed the presence of the associated right aortic arch with anomalous branching pattern, and bridging bronchus.

[Renchangianin E: a new dibenzocyclooctadiene lignan from Kadsura renchangiana].

A new dibenzocyclooctadiene lignan, renchangianin E (1) was isolated from the stems of Kadsura renchangiana. Its structure and stereochemistry were elucidated by spectroscopic methods, including 2D-NMR techniques.

Boosting the Performance of Low-Platinum Fuel Cells via a Hierarchical and Interconnected Porous Carbon Support.

The design of a low-platinum (Pt) proton-exchange-membrane fuel cell (PEMFC) can reduce its high cost. However, the development of a low-Pt PEMFC is severely hindered by the high oxygen transfer resistance in the catalyst layer. Herein, a carbon with interconnected and hierarchical pores is synthesized as a support for the low-Pt catalyst to lower the oxygen transfer resistance. A H2-air fuel cell assembled by Pt/hierarchical porous carbon shows 1610 mW/cm2 peak power density, 2230 mA/cm2 current density at 0.60 V, and only 18.4 S/m local oxygen transfer resistance with 0.10 mgPt/cm2 Pt loading at the cathode, which far exceeds those of various carbon black supports and commercially used Pt/C catalysts. Both the experimental and simulation results have shown the advancement of hierarchical pores toward the high efficiency of oxygen transportation.