Unveiling Low Temperature Assembly of Dense Fe-N4 Active Sites via Hydrogenation in Advanced Oxygen Reduction Catalysts.

The single-atom Fe-N-C is a prominent material with exceptional reactivity in areas of sustainable energy and catalysis research. It is challenging to obtain the dense Fe-N4 site without the Fe nanoparticles (NPs) sintering during the Fe-N-C synthesis via high-temperature pyrolysis. Thus, a novel approach is devised for the Fe-N-C synthesis at low temperatures. Taking FeCl2 as Fe source, a hydrogen environment can facilitate oxygen removal and dichlorination processes in the synthesis, efficiently favouring Fe-N4 site formation without Fe NPs clustering at as low as 360 °C. We shed light on the reaction mechanism about hydrogen promoting Fe-N4 formation in the synthesis. By adjusting the temperature and duration, the Fe-N4 structural evolution and site density can be precisely tuned to directly influence the catalytic behaviour of the Fe-N-C material. The FeNC-H2-360 catalyst demonstrates a remarkable Fe dispersion (8.3 wt %) and superior acid ORR activity with a half-wave potential of 0.85 V and a peak power density of 1.21 W cm-2 in fuel cell. This method also generally facilitates the synthesis of various high-performance M-N-C materials (M=Fe, Co, Mn, Ni, Zn, Ru) with elevated single-atom loadings.

Confinement-Induced Indium Oxide Nanolayers Formed on Oxide Support for Enhanced CO2 Hydrogenation Reaction.

An enclosed nanospace often shows a significant confinement effect on chemistry within its inner cavity, while whether an open space can have this effect remains elusive. Here, we show that the open surface of TiO2 creates a confined environment for In2O3 which drives spontaneous transformation of free In2O3 nanoparticles in physical contact with TiO2 nanoparticles into In oxide (InOx) nanolayers covering onto the TiO2 surface during CO2 hydrogenation to CO. The formed InOx nanolayers are easy to create surface oxygen vacancies but are against over-reduction to metallic In in the H2-rich atmospheres, which thus show significantly enhanced activity and stability in comparison with the pure In2O3 catalyst. The formation of interfacial In-O-Ti bonding is identified to drive the In2O3 dispersion and stabilize the metastable InOx layers. The InOx overlayers with distinct chemistry from their free counterpart can be confined on various oxide surfaces, demonstrating the important confinement effect at oxide/oxide interfaces.

Asymmetric Hydrogenation of α-Alkyl-Substituted ß-Keto Esters and Amides through Dynamic Kinetic Resolution.

Asymmetric hydrogenation of α-alkyl-substituted ß-keto esters and amides with the DIPSkewphos/3-AMIQ-Ru(II) catalyst system through dynamic kinetic resolution was examined. A series of ß-keto esters and amides with a simple or functionalized α-alkyl group were applicable to this reaction, affording the α-substituted ß-hydroxy esters and amides in ≥99% ee (anti/syn ≥ 99:1) in many cases. The 5 g scale reaction was readily achieved. The mode of enantio- and diastereoselection in the transition state model was proposed.

Why can poorly conductive Bi@UiO-MOF catalyze CO2 electroreduction?

Metal NP @ metal-organic frameworks (MOFs) are widely used in electrocatalysis. However, many of the MOFs are poorly conductive. Here, we loaded bismuth (Bi) into a Zr-based MOF of the UiO structure that is active for CO2 reduction to formate and found that a moderate conductivity of the nanosized MOFs is sufficient to support a reasonably high catalytic current density. This finding allows simpler catalyst design and quantitative rationalization of MOF electrocatalysis.

Silica exposure activates non-canonical inflammasome complex in intratracheal instilled rat model.

Background: Inhalation of silica crystals in occupational settings is a main cause of silicosis, a chronic irreversible pulmonary disorder. Our prior studies demonstrated the activation of inflammasome sensors AIM2 and NLRP3, effector protein caspase-1, and significant increase in IL-1ß in silica exposed rats, suggesting that the canonical inflammasome activation may be associated with silica-induced tissue damage and inflammation. Aims and Methods: In our current study using the same animal model system, we further evaluated the components of non-canonical inflammasome, including NEK7, caspase-11, and GSDMD following silica exposure. Results: We demonstrated sustained NEK7 elevation in the rat lung epithelial cells and macrophages following 1- and 3-day exposure. Enhanced NEK7 expression was also detected in lung homogenate by western blot. Similarly, caspase-11 expression was induced by silica exposure in lung sections and homogenate. Elevated GSDMD was observed both in lung sections by immunohistochemical staining and in lung tissue homogenate by western blot. Conclusion: In summary, our current study demonstrated increase in NEK7, caspase-11, and GSDMD in silica exposed rats, indicating activation of non-canonical inflammasome complex, thereby providing a broad inflammasome activation pathway caused by silica exposure.

Label-free single-particle imaging approach for ultra-rapid detection of pathogenic bacteria in clinical samples.

Rapid detection of pathogenic bacteria within a few minutes is the key to control infectious disease. However, rapid detection of pathogenic bacteria in clinical samples is quite a challenging task due to the complex matrix, as well as the low abundance of bacteria in real samples. Herein, we employ a label-free single-particle imaging approach to address this challenge. By tracking the scattering intensity variation of single particles in free solution, the morphological heterogeneity can be well identified with particle size smaller than the diffraction limit, facilitating the morphological identification of single bacteria from a complex matrix in a label-free manner. Furthermore, the manipulation of convection in free solution enables the rapid screening of low-abundance bacteria in a small field of view, which significantly improves the sensitivity of single-particle detection. As a proof of concept demonstration, we are able to differentiate the group B streptococci (GBS)-positive samples within 10 min from vaginal swabs without using any biological reagents. This is the most rapid and low-cost method to the best of our knowledge. We believe that such a single-particle imaging approach will find wider applications in clinical diagnosis and disease control due to its high sensitivity, rapidity, simplicity, and low cost.

Small airway dysfunction in pneumoconiosis: a cross-sectional study.

BACKGROUND: Although several histological studies have documented airway inflammation and remodelling in the small airways of dust-exposed workers, little is known regarding the prevalence and risk factors of small airway dysfunction (SAD) in pneumoconiosis. The present study investigated the prevalence and characteristics of spirometry-defined SAD in pneumoconiosis and assessed the risk factors for associated with SAD. METHODS: A total of 1255 patients with pneumoconiosis were invited to participate, of whom 1115 patients were eligible for final analysis. Spirometry was performed to assess SAD using the following three indicators: maximal mid-expiratory flow and forced expiratory flow 50% and 75%. SAD was defined as at least two of these three indicators being less than 65% of predicted value. Logistic regression analyses were used to analyse the relationships between clinical variables and SAD. RESULTS: Overall, 66.3% of patients with pneumoconiosis had SAD, among never-smokers the prevalence of SAD was 66.7%. The proportion of SAD did not differ among the subtypes of pneumoconiosis. In addition, SAD was present across the patients with all stages of pneumoconiosis. Even among those with forced expiratory volume in 1 s (FEV1) ≥ 80% and FEV1/forced vital capacity ratio ≥ 70%, 40.8% of patients had SAD. Patients with SAD were older than patients without SAD, more likely to be women and heavy smokers. Importantly, patients with SAD had more severe airflow obstruction, air trapping, and diffusion dysfunction. All patients with both pneumoconiosis and chronic obstructive pulmonary disease had SAD. Based on multivariate analysis, overall, aged 40 years and older, female sex, heavy smoking, body mass index ≥ 25.0 kg/m2 and pneumoconiosis stage III were significantly associated with increased risk of SAD. Among the never smokers, risk factors for SAD included female sex, BMI ≥ 25.0 kg/m2, pneumoconiosis stage II and stage III CONCLUSION: Spirometry-defined SAD is one of the common functional abnormalities caused by occupational dust exposure and should be taken into account when monitoring respiratory health of workers to guide the early precautions and management in pneumoconiosis.

Activation of canonical inflammasome complex by acute silica exposure in experimental rat model.

Silicosis is a chronic irreversible pulmonary disease caused by the inhalation of silica crystals in occupational settings in most cases. Persistent inflammation in the alveolar space is considered to be the major reason for tissue damage and lung fibrogenesis. The mechanisms by which silica exposure activates immune cells are not well understood. Here, we employed an in vivo silicosis disease model by intratracheal instillation of a large dose of silica suspension in rats and explored the involvement of inflammasome activation. Marked leukocyte infiltration and edema were observed 3 days following silica exposure in treated animals compared to controls. Using this model, we compared the expression of inflammasome sensors (AIM2 and NLRP3) and effector protein (caspase-1) by western blot and immunohistochemical staining using the lung homogenates and lung tissue sections. Our results demonstrated that following acute silica exposure, AIM2, NLRP3 and caspase-1 expressions were increased in macrophages or/and lung epithelial cells compared to control animals. We also analyzed interleukin 1ß expression using lung homogenates, and significant increase in interleukin 1ß was observed in 3-day silica-exposed rats. The activation of inflammasome sensors AIM2 and NLRP3 suggested to us that blocking these activators may attenuate silica-associated tissue damage and inflammation.

Fast and Ultrasensitive Visual Detection of Exosomes in Body Fluids for Point-of-Care Disease Diagnosis.

Fast detection of low-concentration exosomes in body fluids is of great significance in understanding the pathogenesis and disease diagnosis but is quite a challenging work due to the complex matrix, tedious pretreatment, and relatively poor sensitivity without the aid of instruments. In this work, by simply using a filter membrane to enrich the exosomes at low concentrations and the use of CuS nanoparticles as labels, we were able to detect exosomes at concentrations as low as 2 × 103 particles/µL in a complex matrix by the naked eye. Due to its high sensitivity, specificity, and simplicity, it can be used for the diagnosis of direct prostate cancer via a 5 mL urine sample within 2 h without the use of any instrument. This method can also be applicable for the detection of other biological nanoparticles, such as viruses, at low concentrations in a complex matrix, offering a promising candidate for point-of-care disease diagnosis with low cost.

Machine-Learning-Guided Discovery and Optimization of Additives in Preparing Cu Catalysts for CO2 Reduction.

Discovery and optimization of new catalysts can be potentially accelerated by efficient data analysis using machine-learning (ML). In this paper, we record the process of searching for additives in the electrochemical deposition of Cu catalysts for CO2 reduction (CO2RR) using ML, which includes three iterative cycles: "experimental test; ML analysis; prediction and redesign". Cu catalysts are known for CO2RR to obtain a range of products including C1 (CO, HCOOH, CH4, CH3OH) and C2+ (C2H4, C2H6, C2H5OH, C3H7OH). Subtle changes in morphology and surface structure of the catalysts caused by additives in catalyst preparation can lead to dramatic shifts in CO2RR selectivity. After several ML cycles, we obtained catalysts selective for CO, HCOOH, and C2+ products. This catalyst discovery process highlights the potential of ML to accelerate material development by efficiently extracting information from a limited number of experimental data.

Engineering BiVO4@Bi2S3 heterojunction by cosharing bismuth atoms toward boosted photocatalytic Cr(VI) reduction.

The photocatalytic efficiency is limited by poor charge separation efficiency and high carrier transport activation energy (CTAE) of photogenerated electron/hole pairs than traditional semiconductor. Hybridizing nanostructure with two staggered alignment band structure is proved as an effective strategy to mitigate these two challenges but still suffers a strong coulomb electrostatic repulsive force between two heterogeneous semiconductors. Here, we steer a friendly sulfurization process to construct BiVO4@Bi2S3 heterojunction with a scenario of cosharing Bi atoms. The intimate atomic-level contact between BiVO4 and Bi2S3 not only enhances the visible-light absorption and lowers CTAE, but also accelerate carrier's separation efficiency, which enables it to deliver the best photocatalytic performance toward reduction of Cr(VI). BiVO4@Bi2S3 only needs less than 40 min to completely reduce 50 ppm Cr(VI) solution. The type II heterojunction photocatalytic mechanism is systematically studied to decipher the carriers' transfer track between BiVO4 and Bi2S3. Our new finding of engineering inorganic heterojunction by cosharing atoms opens a new avenue to other similar materials for potential applications.

Corrigendum: Dapagliflozin Attenuates Hyperglycemia Related Osteoporosis in ZDF Rats by Alleviating Hypercalciuria.

[This corrects the article DOI: 10.3389/fendo.2019.00700.].

Glucagon-like peptide-1 alleviates diabetic kidney disease through activation of autophagy by regulating AMP-activated protein kinase-mammalian target of rapamycin pathway.

Glucagon-like peptide-1 (GLP-1) is a novel antidiabetic agent used in clinical practice. Recently, it was reported to exert a renoprotective effect in the human kidney-2 cells and kidneys of diabetic rats, which was induced by one type of GLP-1 analog, liraglutide, in the presence of high glucose. However, most of the previous findings mainly focused on its indirect effect in inhibiting the advanced glycation end products. Here, besides glycemic control, we also demonstrated a stimulatory role of liraglutide in promoting autophagy and relieving oxidative stress in Zucker diabetic fatty rats. The renoprotective effect of liraglutide has been demonstrated by significantly decreasing urinary albumin (P < 0.01) and ameliorating renal pathological changes (P < 0.001) in vivo. Besides that, proliferation of human epithelial kidney cell line HKC-8 and human embryonic kidney-293 cells has increased after treating with exendin-4, a GLP-1 receptor (GLP-1R) agonist. Moreover, GLP-1 could positively improve the progression of autophagy in vivo and in vitro through regulating the autophagy-related protein light chain 3 and p62 via AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling pathway. Simultaneously, it could reverse NF-erythroid 2-related factor 2 (NRF2) translocation into the nuclei and suppress oxidative stress. In terms of mechanism, the renoprotective effect of GLP-1 would be exerted via the GLP-1R-AMPK-mTOR-autophagy-reactive oxygen species signaling axis. The present study not only illustrates the renoprotective effect of GLP-1 in diabetic kidney disease (DKD) rats, but also for the first time elucidates the underlying mechanism that is independent of controlling glucose, which implies that GLP-1 might be a novel therapeutic strategy for the prevention and treatment of DKD.

Dapagliflozin Attenuates Hyperglycemia Related Osteoporosis in ZDF Rats by Alleviating Hypercalciuria.

Recent studies showed that in patients with type 2 diabetes mellitus (T2DM), Sodium-dependent glucose transporters 2 inhibitor (SGLT2I) may cause potential adverse effects on the skeleton such as increasing the risk of fracture. This risk is possibly mediated by effects induced by all SGLT2I class drugs, but whether Dapagliflozin aggravates osteoporosis in patients with T2DM remains controversial. Therefore, we designed this study to explore how Dapagliflozin affects the metabolism and the quality of bone in T2DM animal models. The effect of Dapagliflozin on the skeleton was evaluated on male ZDF (Zucker Diabetic Fatty) rats-a rat model of diet induced spontaneous T2DM. Dapagliflozin was administrated via gavage at the dosage of 10 mg/kg/day. Bone tissue mineral density and the microarchitecture of tibiae were measured with micro-CT and biomechanics characteristic of the femora were tested using a three-point bending test. Serum bone biomarkers and other metabolic parameters were also tested via ELISA or other assays. Our results found that diabetic rats demonstrated symptoms of osteoporosis and Dapagliflozin could help to alleviate these defections caused by diabetes. Compared to the negative controls, the serum CT (calcitonin) level in ZDF rats as well as the uric calcium and phosphate levels were elevated, and these symptoms were alleviated by Dapagliflozin. Tibiae of Dapagliflozin treated rats demonstrated decreased cortical tissue mineral density while trabecular tissue mineral density and mean bone mineral density received a rise when compared to the matched controls. ZDF rats also showed defections in femora stiffness which could be relieved by Dapagliflozin administration. The mechanism of Dapagliflozin affecting bone quality is possibly connected to the suppression of serum calcitonin and excretion of calcium via urine rose by hyperglycemia. In conclusion, Dapagliflozin can prevent osteoporosis in ZDF rats by alleviating hypercalciuria.

Irbesartan attenuates advanced glycation end products-mediated damage in diabetes-associated osteoporosis through the AGEs/RAGE pathway.

AIMS: Diabetes-associated osteoporosis is mainly caused by the formation and accumulation of advanced glycation end products (AGEs). Angiotensin II type 1 receptor blocker (ARB) has anabolic bone effects on the physicochemical properties of the bone in diabetes. We hypothesized that ARB could inhibit AGEs-induced deleterious effects. MAIN METHODS: In this study, we chose seven-week-old Leprdb/Lepr+ (db/+) and Leprdb/Leprdb (db/db) mice. After 12 week intervention by irbesartan, the microarchitecture and mechanical strength of the bone of seven-week-old db/db mice were investigated systematically. Meanwhile, the molecular mechanisms of the osteoblasts were analyzed, after AGEs or irbesartan were added to the culture. Also, intracellular formation of reactive oxygen species (ROS) was measured with DCF fluorescence. KEY FOUNDINGS: Results showed that 12-week irbesartan treatment could dramatically improve trabecular bone microarchitecture through increasing BV/TV (p = 0.003, +46.7%), Tb.N (p = 0.020, +52.0%), and decreasing that of Tb.Sp (p = 0.005, -21.2%) and SMI (p = 0.007, -26.4%), comparing with the db/db group. Irbesartan could also substantially raise biomechanical parameters including max load (p = 0.013, +20.7%), fracture load (p = 0.014, +70.5%), energy absorption (p = 0.019, +99.4%). Besides, it could inhibit AGEs-induced damage of cell proliferation and osteogenic differentiation of osteoblasts, as well as suppressing the activation of apoptosis caused by AGEs. Moreover, co-incubation with irbesartan could prevent the AGEs-induced increase of intracellular oxidative stress and RAGE expression in osteoblasts. SIGNIFICANCE: In conclusion, this study suggested that irbesartan might play a protective role in diabetes-related bone damages by blocking the deleterious effects of AGEs/RAGE-mediated oxidative stress. This may provide a revolutionary benefits to therapy with irbesartan on diabetic osteoporosis.

Liraglutide relieves myocardial damage by promoting autophagy via AMPK-mTOR signaling pathway in zucker diabetic fatty rat.

Liraglutide, a glucose-lowering agent used to treat type 2 diabetic mellitus is reported to exert cardioprotective effects in clinical trials and animal experiments. However, the cardioprotective mechanism of liraglutide on diabetic cardiomyopathy has not been fully illustrated. The present study was performed to investigate whether liraglutide alleviates diabetic myocardium injury by promoting autophagy and its underlying mechanisms. Our results show that liraglutide significantly reduced the levels of creatine kinase (CK) and lactate dehydrogenase (LDH), improved left ventricular functional status and alleviated myocardial fibrosis in the Zucker diabetic fatty (ZDF) rat model. Liraglutide also mitigated high glucose-induced injury in NRCs. However these effects were partly reversed by the autophagic inhibitor chloroquine (CQ). Liraglutide promoted myocardial autophagy in the vivo and in the vitro models. Furthermore, liraglutide-induced enhancement of autophagy was related to increased AMPK phosphorylation and decreased mTOR phosphorylation, which was partially abolished by the AMPK inhibitor compound C (Comp C). Collectively, our data provide evidence that liraglutide mediated diabetic myocardium injury by promoting AMPK-dependent autophagy.

Interleukin-22 Alleviated Palmitate-Induced Endoplasmic Reticulum Stress in INS-1 Cells through Activation of Autophagy.

OBJECTIVE: Stimulation with saturated fatty acids has been shown to induce oxidative stress and endoplasmic reticulum (ER) stress in ß cells and has been recognized as an important component of the pathogenesis of type 2 diabetes (T2D). Interleukin-22 (IL-22) plays a critical role in preventing ß cells from oxidative and ER stress, and autophagy is associated with the survival and function of ß cells. However, whether IL-22 alleviates cellular stress through activation of autophagy is unclear. In this study, we investigated the effects of IL-22 on rat insulin-secreting cells and the mechanisms underlying IL-22 and lipotoxicity-induced oxidative and ER stress in vitro. METHODS: The levels of reactive oxygen species (ROS) were detected by flow cytometry and fluorescence microscopy. The protein expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), microtubule-associated protein light chain 3B (LC3B) and Bcl-2-interacting myosin-like coiled-coil protein (Beclin-1) were evaluated by western blot. Transmission electron microscopy was utilized to observe the process of autophagy. RESULTS: Palmitate induced increased levels of ROS and the overexpression of GRP78 and CHOP, whereas these effects were partly reversed by treatment with IL-22. Furthermore, IL-22 upregulated the protein expression of Beclin-1 and the conversion of LC3B-I to LC3B-II. Moreover, the aforementioned effects were partly suppressed by treating cells with 3-methyladenine (3-MA), an autophagy inhibitor. CONCLUSIONS: Our results suggest that IL-22 alleviated the oxidative and ER stress induced by palmitate, which was likely mediated by autophagy. These findings could facilitate the development of novel therapeutic strategies to suppress the progression of T2D.

Pneumocystis pneumonia in HIV-infected and immunocompromised non-HIV infected patients: a retrospective study of two centers in China.

BACKGROUND: Pneumocystis pneumonia (PCP) is an emerging infectious disease in immunocompromised hosts. However, the clinical characteristics of these patients are poorly understood in mainland China. METHODS: We performed a retrospective study of PCP from 2008 to 2012. Information was collected regarding clinical manifestations, hospitalization, and outcome. A prognostic analysis was performed using a Cox regression model. RESULTS: 151 cases of PCP were included; 46 non-HIV and 105 HIV cases. All-cause mortality (15.2% vs. 12.4%, p = 0.64) and the results of time-to-event analysis (log-rank test, p = 0.62) were similar between non-HIV and HIV infected cases, respectively. From 2008 to 2012, time from admission to initial treatment in non-HIV infected PCP patients showed declining trend [median (range) 20 (9-44) vs. 12 (4-24) vs. 9 (2-23) vs. 7 (2-22) vs. 7 (1-14) days]. A similar trend was observed for all-cause mortality (33.3% vs. 20.0% vs.14.3% vs. 14.3% vs. 6.7%). Patients with four or more of the following clinical manifestations (cough, dyspnea, fever, chest pain, and weight loss) [adjusted HR (AHR) 29.06, 95% CI 2.13-396.36, P = 0.01] and admission to intensive care unit (ICU) [AHR 22.55, 95% CI 1.36-375.06, P = 0.03] were independently associated with all-cause mortality in non-HIV infected PCP patients. Variables associated with mortality in HIV infected PCP patients were admission to ICU (AHR 72.26, 95% CI 11.76-443.87, P<0.001) and albumin ≤ 30 g/L (AHR 9.93 95% CI 1.69-58.30, P = 0.01). CONCLUSIONS: Upon admission comprehensive clinical assessment including assessment of four or more clinical manifestations (cough, dyspnea, fever, chest pain, and weight loss) in non-HIV infected PCP patients and albumin ≤ 30 g/L in HIV infected patients might improve prognosis.