Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Acute Coronary Syndrome.

The evidence for sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of type 2 diabetes or chronic heart failure was sufficient but lacking in acute coronary syndrome (ACS). Our aim was to investigate the effects of SGLT2i on cardiovascular outcomes in ACS patients. Studies of SGLT2i selection in ACS patients were searched and pooled. Outcomes included all-cause death, adverse cardiovascular events, cardiac remodeling as measured by the left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic dimension (LVESD), cardiac function as assessed by the left ventricular ejection fraction (LVEF) and NT-proBNP, and glycemic control. Twenty-four studies with 12,413 patients were identified. Compared to the group without SGLT2i, SGLT2i showed benefits in reducing all-cause death (OR 0.72, 95% CI [0.61, 0.85]), major adverse cardiovascular events (MACE) (OR 0.44, 95% CI [0.30, 0.64]), cardiovascular death (OR 0.66, 95% CI [0.54, 0.81]), heart failure (OR 0.52, 95% CI [0.44, 0.62]), myocardial infarction (OR 0.68, 95% CI [0.56, 0.83]), angina pectoris (OR 0.37, 95% CI [0.17, 0.78]), and stroke (OR 0.48, 95% CI [0.24, 0.96]). Results favored SGLT2i for LVEDD (MD -2.03, 95% CI [-3.29, -0.77]), LVEF (MD 3.22, 95% CI [1.71, 4.72]), and NT-proBNP (MD -171.53, 95% CI [-260.98, -82.08]). Thus, SGLT2i treatment reduces the risk of all-cause death and MACE and improves cardiac remodeling and function in ACS patients.

Dual-Analyte Sensing with a Molecularly Imprinted Polymer Based on Enhancement-Mode Organic Electrochemical Transistors.

Novel enhancement-mode organic electrochemical transistors (OECTs) have been prepared by poly(3, 4-ethylenedioxythiophene)-poly(styrenesulfonate) de-doped polyethylenimine on the multi-walled carbon nanotube-modified viscose yarn. The fabricated devices exhibit low power consumption with a high transconductance of 6.7 mS, rapid response time < 2 s, and excellent cyclic stability. In addition, the device has washing durability and bending and long-term stability suitable for wearable applications. Biosensors based on enhancement-mode OECTs for the selective detection of adrenaline and uric acid (UA) are developed by using molecularly imprinted polymer (MIP)-functionalized gate electrodes. The detection limits of adrenaline and UA analysis are as low as 1 pM, with the linear ranges of 0.5 pM to 10 µM and 1 pM to 1 mM, respectively. Moreover, the sensor based on enhancement-mode transistors can efficiently amplify the current signals according to the modulation of the gate voltage. The MIP-modified biosensor has high selectivity in the presence of interferents and desirable reproducibility. Additionally, due to the wearable nature of the developed biosensor, this sensing tool has the capability of being integrated with fabrics. Therefore, it has successfully been applied in textiles for the determination of adrenaline and UA in artificial urine samples. The excellent recoveries and rsds are 90.22-109.05% and 3.97-6.94%, respectively. Ultimately, these sensitive, low-power, wearable, and dual-analyte sensors help to develop non-laboratory tools for early disease diagnosis and clinical research.

Re-evaluation of dipeptidyl peptidase-4 inhibitors in patients with heart failure and diabetes mellitus.

OBJECTIVES: The question of whether dipeptidyl peptidase-4 inhibitors (DPP-4i) should be preferred as new glucose-lowering agents in heart failure is controversial. This studyaimed to evaluate the effects of DPP-4i treatment on all-cause mortality and cardiovascular outcomes in patients with heart failure. METHODS: We searched for available studies of DPP-4i therapy in heart failure and performed a pooled analysis. Outcomes included all-cause mortality, cardiovascular death, hospitalization for heart failure, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), acute coronary syndrome, and acute myocardial infarction. RESULTS: Treatment with DPP-4i did not reduce the risk of all-cause death, cardiovascular death, or hospitalization for heart failure. Subgroup analyses showed that DPP-4i significantly reduced all-cause mortality in trials with > 40% female patients (OR 0.30, 95% CI [0.16, 0.58], P = 0.0003) and in trials with > 20% patients with heart failure with preserved ejection fraction (HFpEF) (OR 0.34, 95% CI [0.19, 0.60], P = 0.0003). Changes in LVEF and LVEDV showed no statistical differences between the 2 groups. Accordingly, DPP-4i did not alter the risk of acute coronary syndrome and acute myocardial infarction. CONCLUSIONS: DPP-4i may reduce all-cause mortality in heart failure patients in subgroups of women and HFpEF and has a high coronary safety profile.

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention.

Cardiac fibrosis plays an indispensable role in cardiac tissue homeostasis and repair after myocardial infarction (MI). The cardiac fibroblast-to-myofibroblast differentiation and extracellular matrix collagen deposition are the hallmarks of cardiac fibrosis, which are modulated by multiple signaling pathways and various types of cells in time-dependent manners. Our understanding of the development of cardiac fibrosis after MI has evolved in basic and clinical researches, and the regulation of fibrotic remodeling may facilitate novel diagnostic and therapeutic strategies, and finally improve outcomes. Here, we aim to elaborate pathophysiology, examination and intervention of cardiac fibrosis after MI.

Bradykinin-(1-9) mitigates autophagy through upregulating PI3K/Akt in rats with myocardial infarction.

The cardioprotective mechanisms of bradykinin-(1-9) in myocardial infarction were unclear. We investigated the effect of bradykinin-(1-9) on cardiac function, fibrosis, and autophagy induced by myocardial infarction and identified the mechanisms involved. To investigate the cardioprotective effect of bradykinin-(1-9), various doses of bradykinin-(1-9), its B2 receptor blocker HOE140, or their combination were administered to rats via subcutaneous osmotic minipump implantation before myocardial infarction. After 2 days, myocardial infarction was induced by ligation of the left anterior descending coronary artery. After 2 weeks, echocardiographic measurements and euthanasia were performed. Bradykinin-(1-9) treatment attenuated left ventricular dysfunction, fibrosis, and autophagy in rats with myocardial infarction, which was partially reversed by HOE140 administration. Moreover, the downregulatory effect of bradykinin-(1-9) on autophagy was partially reversed by combination with the PI3K inhibitor LY294002. Thus, bradykinin-(1-9) inhibits myocardial infarction-induced cardiomyocyte autophagy by upregulating the PI3K/Akt pathway.

Prognostic value of growth differentiation factor-15 in patients with coronary artery disease: A meta-analysis and systematic review.

Background and aims: The predictive value of growth differentiation factor-15 (GDF-15) for individual cardiovascular outcomes remained controversial in patients with coronary artery disease (CAD). We aimed to investigate the effects of GDF-15 on all-cause death, cardiovascular death, MI and stroke in CAD patients. Methods: We searched PubMed, EMBASE, Cochrane library and Web of Science till 30 December, 2020. Hazard ratios (HRs) were combined with fixed or random effect meta-analyses. Subgroup analyses were performed in different disease types. Sensitivity analyses were used to evaluate the stability of the results. Publication bias was tested using funnel plots. Results: A total of 10 studies with 49,443 patients were included in this meta-analysis. Patients with the highest GDF-15 concentrations had significantly increased risk of all-cause death (HR 2.24; 95% CI: 1.95-2.57), cardiovascular death (HR 2.00; 95% CI: 1.66-2.42), MI (HR 1.42; 95% CI: 1.21-1.66) after adjusting clinical characteristics and prognostic biomarkers (hs-TnT, cystatin C, hs-CRP, and NT-proBNP) but except for stroke (HR 1.43; 95% CI: 1.01-2.03, p = 0.05). For the outcome of all-cause death and cardiovascular death, subgroup analyses revealed consistent results. Sensitivity analyses showed that the results were stable. Funnel plots showed that there was no publication bias. Conclusion: In CAD patients with elevated GDF-15 levels on admission, there were independently significant risks for all-cause death and cardiovascular death. The highest concentrations of GDF-15 had a lower predictive effect on MI than all-cause death and cardiovascular death. The association of GDF-15 with the outcome of stroke needs to be further studied.

Effectiveness and safety of four different beta-blockers in patients with chronic heart failure.

In this study, we evaluated the effectiveness and safety of bisoprolol, metoprolol, carvedilol, and nebivolol in the treatment of chronic heart failure. The results demonstrated that bisoprolol improved the prognosis of chronic heart failure in comparison with carvedilol, and carvedilol exerted similar effects as metoprolol succinate and nebivolol and better effect than metoprolol tartrate (evidence levels: bisoprolol > carvedilol = metoprolol succinate = nebivolol > metoprolol tartrate; " > " means "prior to").

ADAM17 knockdown mitigates while ADAM17 overexpression aggravates cardiac fibrosis and dysfunction via regulating ACE2 shedding and myofibroblast transformation.

A disintegrin and metalloprotease domain family protein 17 (ADAM17) is a new member of renin-angiotensin system (RAS) but its role in the pathogenesis of diabetic cardiomyopathy (DCM) is obscure. To test the hypothesis that ADAM17 knockdown mitigates while ADAM17 overexpression aggravates cardiac fibrosis via regulating ACE2 shedding and myofibroblast transformation in diabetic mice, ADAM17 gene was knocked down and overexpressed by means of adenovirus-mediated short-hairpin RNA (shRNA) and adenovirus vector carrying ADAM17 cDNA, respectively, in a mouse model of DCM. Two-dimensional and Doppler echocardiography, histopathology and immunohistochemistry were performed in all mice and in vitro experiments conducted in primary cardiofibroblasts. The results showed that ADAM17 knockdown ameliorated while ADAM17 overexpression worsened cardiac dysfunction and cardiac fibrosis in diabetic mice. In addition, ADAM17 knockdown increased ACE2 while reduced AT1R expression in diabetic hearts. Mechanistically, ADAM17 knockdown decreased while ADAM17 overexpression increased cardiac fibroblast-to-myofibroblast transformation through regulation of TGF-ß1/Smad3 signaling pathway. In conclusion, ADAM17 knockdown attenuates while ADAM17 overexpression aggravates cardiac fibrosis via regulating ACE2 shedding and myofibroblast transformation through TGF-ß1/Smad3 signaling pathway in diabetic mice. Targeting ADAM17 may provide a promising approach to the prevention and treatment of cardiac fibrosis in DCM.

Cardiomyocyte-specific knockout of ADAM17 ameliorates left ventricular remodeling and function in diabetic cardiomyopathy of mice.

Angiotensin-converting enzyme 2 (ACE2) has proven beneficial in attenuating diabetic cardiomyopathy (DCM) but has been found to be a substrate of a disintegrin and metalloprotease protein-17 (ADAM17). However, whether ADAM17 plays a role in the pathogenesis and intervention of DCM is obscure. In this study, we created cardiomyocyte-specific knockout of ADAM17 (A17α-MHCKO) mice, and left ventricular dimension, function, pathology and molecular biology were assessed in ADAM17fl/fl control, A17α-MHCKO control, ADAM17fl/fl diabetic and A17α-MHCKO diabetic mice. Both differentiated H9c2 cells and neonatal rat cardiomyocytes (NRCMs) were used to explore the molecular mechanisms underlying the effect of ADAM17 on DCM. The results showed that protein expression and activity of ADAM17 were upregulated whereas the protein expression of ACE2 was downregulated in the myocardium of diabetic mice. Cardiomyocyte-specific knockout of ADAM17 mitigated cardiac fibrosis and cardiomyocyte apoptosis and ameliorated cardiac dysfunction in mice with DCM. Bioinformatic analyses detected a number of genes enriched in metabolic pathways, in particular the AMPK signaling pathway, expressed differentially between the hearts of A17α-MHCKO and ADAM17fl/fl diabetic mice. The mechanism may involve activated AMPK pathway, increased autophagosome formation and improved autophagic flux, which reduced the apoptotic response in cardiomyocytes. In addition, hypoxia-inducible factor-1α (HIF-1α) might act as an upstream mediator of upregulated ADAM17 and ADAM17 might affect AMPK signaling via α1 A-adrenergic receptor (ADRA1A). These results indicated that ADAM17 activity and ACE2 shedding were enhanced in DCM, which was reversed by cardiomyocyte-specific ADAM17 knockout. Thus, inhibition of ADAM17 may provide a promising approach to the treatment of DCM.

Serum Metal Ion-Induced Cross-Linking of Photoelectrochemical Peptides and Circulating Proteins for Evaluating Cardiac Ischemia/Reperfusion.

Patients having experienced the ischemia-reperfusion process are particularly vulnerable to subsequent heart attacks because this process can induce myocardial fibrosis, hallmarked by the release of reactive oxygen species and some proteases, such as cathepsin G, into the circulating blood. If these risk indicators can be monitored from the peripheral serum, early diagnosis and intervention may become a reality. For this purpose, we have designed an assay of free copper ions and cathepsin G in serum using only synthetic small molecules as the biosensing elements. No antibodies are needed to recognize the target protein, and no enzymes are needed to generate and amplify the biosensing signal. In this design, a short peptide can target-specifically recognize protease, while the copper ion in the serum can stimulate the photoelectrochemical activity of the probe, resulting in cross-linking of the serum proteins in a target protein-specific manner. Using this method, serum cathepsin G and free copper ion are found to be significantly elevated in the blood samples collected from patients with acute myocardial infarction and successful percutaneous coronary intervention in comparison with healthy controls, indicating a higher risk of subsequent myocardial injury and cardiovascular events. These results may point to the possible application of the proposed assay to evaluate the severity and prognosis of cardiac ischemia/reperfusion in the near future.

The optimal anticoagulation strategy for COVID-19, prophylactic or therapeutic?: a meta-analysis, trial sequential analysis, and meta-regression of more than 27,000 participants.

Background: Anticoagulants are promising regimens for treating coronavirus disease 2019 (COVID-19). However, whether prophylactic or intermediate-to-therapeutic dosage is optimal remains under active discussion. Methods: We comprehensively searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, ClinicalTrials, and MedRxiv databases on April 26, 2022. Two independent researchers conducted literature selection and data extraction separately according to predetermined criteria. Notably, this is the first meta-analysis on COVID-19, taking serious consideration regarding the dosage overlap between the 2 comparison groups of prophylactic anticoagulation (PA) and intermediate-to-therapeutic anticoagulation (I-TA). Results: We included 11 randomized controlled trials (RCTs) and 36 cohort studies with 27,051 COVID-19 patients. By analyzing all the RCTs, there was no significant difference in mortality between the PA and I-TA groups, which was further confirmed by trial sequential analysis (TSA) (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.71-1.22; P = 0.61; TSA adjusted CI: 0.71-1.26). The rate of major bleeding was remarkably higher in the I-TA group than in the PA group, despite adjusting for TSA (OR: 1.73; 95% CI: 1.15-2.60; P = 0.009; TSA adjusted CI: 1.09-2.58). RCTs have supported the beneficial effect of I-TA in reducing thrombotic events. After including all studies, mortality in the I-TA group was significantly higher than in the PA group (OR: 1.38; 95% CI: 1.15-1.66; P = 0.0005). The rate of major bleeding was similar to the analysis from RCTs (OR: 2.24; 95% CI: 1.86-2.69; P < 0.00001). There was no distinct difference in the rate of thrombotic events between the 2 regimen groups. In addition, in both critical and noncritical subgroups, I-TA failed to reduce mortality but increased major bleeding rate compared with PA, as shown in meta-analysis of all studies, as well as RCTs only. Meta-regression of all studies suggested that there was no relationship between the treatment effect and the overall risk of mortality or major bleeding (P = 0.14, P = 0.09, respectively). Conclusion: I-TA is not superior to PA for treating COVID-19 because it fails to lower the mortality rate but increases the major bleeding rate in both critical and noncritical patients.

Angiotensin IV attenuates diabetic cardiomyopathy via suppressing FoxO1-induced excessive autophagy, apoptosis and fibrosis.

Rationale: The rennin-angiotensin-aldosterone system (RAAS) plays a critical role in the pathogenesis of diabetic cardiomyopathy, but the role of a member of RAAS, angiotensin IV (Ang IV), in this disease and its underlying mechanism are unclear. This study was aimed to clarify the effects of Ang IV and its downstream mediator forkhead box protein O1 (FoxO1) on diabetic cardiomyopathy. Methods:In vivo, diabetic mice were treated with low-, medium- and high-dose Ang IV, AT4R antagonist divalinal, FoxO1 inhibitor AS1842856 (AS), or their combinations. In vitro, H9C2 cardiomyocytes and cardiac fibroblasts were treated with different concentrations of glucose, low-, medium- and high-dose Ang IV, divalinal, FoxO1-overexpression plasmid (FoxO1-OE), AS, or their combinations. Results: Ang IV treatment dose-dependently attenuated left ventricular dysfunction, fibrosis, and myocyte apoptosis in diabetic mice. Besides, enhanced autophagy and FoxO1 protein expression by diabetes were dose-dependently suppressed by Ang IV treatment. However, these cardioprotective effects of Ang IV were completely abolished by divalinal administration. Bioinformatics analysis revealed that the differentially expressed genes were enriched in autophagy, apoptosis, and FoxO signaling pathways among control, diabetes, and diabetes+high-dose Ang IV groups. Similar to Ang IV, AS treatment ameliorated diabetic cardiomyopathy in mice. In vitro, high glucose stimulation increased collagen expression, apoptosis, overactive autophagy flux and FoxO1 nuclear translocation in cardiomyocytes, and upregulated collagen and FoxO1 expression in cardiac fibroblasts, which were substantially attenuated by Ang IV treatment. However, these protective effects of Ang IV were completely blocked by the use of divalinal or FoxO1-OE, and these detrimental effects were reversed by the additional administration of AS. Conclusions: Ang IV treatment dose-dependently attenuated left ventricular dysfunction and remodeling in a mouse model of diabetic cardiomyopathy, and the mechanisms involved stimulation of AT4R and suppression of FoxO1-mediated fibrosis, apoptosis, and overactive autophagy.

Erythropoietin promotes abdominal aortic aneurysms in mice through angiogenesis and inflammatory infiltration.

Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disease, but the underlying mechanisms remain unknown. Here, we tested the hypothesis that erythropoietin (EPO) may promote the formation of AAA. We found that EPO dose-dependently promoted the formation of AAA in both Apoe -/- (66.7%) and wild-type (WT) (60%) mice receiving a high dose of EPO. EPO monoclonal antibodies given to Apoe -/- mice receiving angiotensin II (AngII) stimulation resulted in a markedly lower incidence of AAA (from 86.7 to 20%, P < 0.001), and EPO receptor (EPOR) knockdown in Epor +/- Apoe -/- mice substantially reduced the incidence of AAA compared to Apoe -/- mice after AngII stimulation (from 86.7 to 45.5%, P < 0.05), further supporting the finding that EPO is a contributor to AAA formation. EPO-induced AAA resulted in increased microvessels, phagocyte infiltration, and matrix metalloproteinase secretion, as well as reduced collagen and smooth muscle cells (SMCs). Experiments in vitro and ex vivo demonstrated that EPO induced proliferation, migration, and tube formation of endothelial cells via the JAK2/STAT5 signaling pathway. In humans, serum EPO concentrations were higher in patients with AAA than in healthy individuals and correlated with the size of the AAA, suggesting a potential link between EPO and the severity of AAA in humans. In conclusion, we found that EPO promotes the formation of AAA in both Apoe -/- and WT mice by enhancing angiogenesis, inflammation, collagen degradation, and apoptosis of SMCs and that EPO/EPOR signaling is essential for AngII-induced AAA. The association between EPO and AAA in humans warrants further study.

Electrochemical Resonance of Molecular Motion Enabling Label-, Antibody-, and Enzyme-Free Detection of SARS-CoV-2.

In this work, we developed a method to detect two viral marker proteins, the main protease and the spike protein (S protein), of SARS-CoV-2, as well as a host marker, chemokine receptor 5 (CCR5), which is associated with the risk of developing the severe acute respiratory syndrome. This assay can be completed in two steps in a label-free fashion, yielding a "signal-on" signal readout, which usually cannot be attained by electrochemical label-free detection using no labels or markers to tag the target protein. The proposed assay also utilizes no antibodies or enzyme-based reagents. The method achieves this performance by moderating the frequency of electrochemical potential scanning such that the scanning rate keeps pace with, or "resonances" with, the molecular motion of the probe molecule. This method has been successfully applied to detect the three target proteins in serum samples collected from patients infected with SARS-CoV-2, and the results indicate a strong correlation with the risk of deteriorating into severe acute conditions after virus infection. Soon, the clinical application of this method may provide a low-cost but effective method for virus surveillance in the general public.

Prolylcarboxypeptidase Mitigates Myocardial Ischemia/Reperfusion Injury by Stabilizing Mitophagy.

The role of prolylcarboxypeptidase (PRCP) in myocardial ischemia/reperfusion (I/R) injury is unclear. Herein, we aimed to evaluate the protective effect of the PRCP-angiotensin-(1-7) [Ang-(1-7)]/bradykinin-(1-9) [BK-(1-9)] axis on myocardial I/R injury and identify the mechanisms involved. Plasma PRCP level and activity, as well as Ang-(1-7) and BK-(1-9) levels, were compared in healthy subjects, patients with unstable angina, and those with ST-segment-elevated acute myocardial infarction (AMI). Thereafter, the effects of PRCP overexpression and knockdown on left ventricular function, mitophagy, and levels of Ang-(1-7) and BK-(1-9) were examined in rats during myocardial I/R. Finally, the effects of Ang-(1-7) and BK-(1-9) on I/R-induced mitophagy and the signaling pathways involved were investigated in vitro in rat cardiomyocytes. AMI patients showed increased plasma level and activity of PRCP and levels of Ang-(1-7) and BK-(1-9) as compared with healthy subjects and those with unstable angina. PRCP protected against myocardial I/R injury in rats by paradoxical regulation of cardiomyocyte mitophagy during the ischemia and reperfusion phases, which was mediated by downstream Ang-(1-7) and BK-(1-9). We further depicted a possible role of activation of AMPK in mitophagy induction during ischemia and activation of Akt in mitophagy inhibition during reperfusion in the beneficial effects of Ang-(1-7) and BK-(1-9). Thus, the PRCP-Ang-(1-7)/BK-(1-9) axis may protect against myocardial I/R injury by paradoxical regulation of cardiomyocyte mitophagy during ischemia and reperfusion phases.

Surrounded catalysts prepared by ion-exchange inverse loading.

The supported catalyst featuring highly dispersed active phase on support is the most important kind of industrial catalyst. Extensive research has demonstrated the critical role (in catalysis) of the interfacial interaction/perimeter sites between the active phase and support. However, the supported catalyst prepared by traditional methods generally presents low interface density because of limit contact area. Here, an ion-exchange inverse loading (IEIL) method has been developed, in which the precursor of support is controllably deposited onto the precursor of active phase by ion-exchange reaction, leading to an active core surrounded (by support) catalyst with various structures. The unique surrounded structure presents not only high interface density and mutually changed interface but also high stability due to the physical isolation of active phase, revealing superior catalytic performances to the traditional supported catalysts, suggesting the great potential of this new surrounded catalyst as the upgrade of supported catalyst in heterogeneous catalysis.

Personalized application of three different concentrations of iodinated contrast media in coronary computed tomography angiography.

No study has evaluated the impact of different iodinated contrast media on coronary contrast enhancement, using an injection protocol according to body surface area (BSA). Thus, the present study aimed to examine the usefulness and safety of personalized application of different iodine concentrations of contrast media in coronary computed tomographic (CT) angiography with a 2nd dual-source CT scanner in eliminating differences in coronary contrast enhancement based on a BSA-adapted injection protocol of contrast media. A total of 270 enrolled participants were randomly assigned to three groups: ioversol 320, ioversol 350 and iopromide 370 (n = 90 per group). The three groups were administered contrast media at a BSA-adjusted volume and flow rate with a fixed injection time of 15 seconds, and they subsequently received a 30-mL saline flush. All patients were scanned with a prospective electrocardiogram-gated protocol in a craniocaudal direction using a second-generation 128-slice dual-source CT system. The three iodinated contrast media used in coronary CT angiography exhibited similar diagnostic quality and safety. No significant differences were found in the contrast enhancement degrees, image quality scores, radiation doses and incidences of adverse effects among the three groups. The three contrast media used in coronary CT angiography with 320, 350 and 370 mg/mL iodine, respectively, have comparable diagnostic quality and safety. However, more large-scale, multinational, multi-centre and prospective trials are warranted.

Iron Nanoparticles Encapsulated in S,N-Codoped Carbon: Sulfur Doping Enriches Surface Electron Density and Enhances Electrocatalytic Activity toward Oxygen Reduction.

Development of highly efficient nonprecious metal (NPM) catalysts for oxygen reduction reaction (ORR) in acidic media is challenging but of great significance. Herein, an effective ORR catalyst based on Fe nanoparticles encapsulated by S,N-codoped few-layer defective carbon (Fe@S,N-DC) was synthesized via a microwave-assisted strategy. The obtained Fe@S,N-DC nanocomposite showed a remarkable electrocatalytic activity toward ORR in acidic media, with a half-wave potential (E1/2) of +0.785 V versus reversible hydrogen electrode, which was 80 mV more positive than that of the sulfur-free counterpart (Fe@N-DC). Furthermore, due to the protection by the S,N-codoped carbon shell, the Fe@S,N-DC nanocomposite displayed apparent stability with only a 13 mV negative shift of E1/2 after 10,000 cycles and excellent tolerance to methanol. X-ray absorption near-edge spectroscopy measurements confirmed the formation of multiple defective sites on the S,N-codoped carbon surface and strong interfacial electron transfer from the Fe core to the outer carbon surface, as compared to the sulfur-free counterpart. The enriched electron density on the defective carbon surface of Fe@S,N-DC, induced by the interfacial electron transfer, facilitated the reduction of O2 to OOH*, leading to enhanced ORR performance. These results shed light on the significance of S doping in Fe-N-C catalysts in the design of high-performance NPM catalysts for ORR in acidic media.

Factors influencing breath analysis results in patients with diabetes mellitus.

Breath analysis is used to detect the composition of exhaled gas. As a quick and non-invasive detection method, breath analysis provides deep insights into the progression of various kinds of diseases, especially those with metabolism disorders. Abundant information on volatile compounds in diabetic patients has been studied in numerous articles in the literature. However, exhaled gas in diabetic patients can be altered by various complications. So far, little attention has been paid to this alteration. In our paper, we found that under air pollution conditions, diabetic patients exhale more nitric oxide. Diabetic patients with heart failure exhale more acetone than those without heart failure. After 13C-labeled glucose intake, patients infected with Helicobacter pylori exhaled more 13C and less 18O than those without infection. Exhalation with chronic kidney disease changes volatile organic compounds on a large scale. Diabetic patients with ketoacidosis exhale more acetone than those without ketoacidosis. Some specific volatile organic compounds also emanate from diabetic feet. By monitoring breath frequency, diabetic patients with obstructive sleep apnea syndrome exhibit a unique breath pattern and rhythm as compared with other diabetic patients, and sleep apnea is prevalent among diabetic patients. In addition to clinical findings, we analyzed the underlying mechanisms at the levels of molecules, cells and whole bodies, and provided suggestions for further studies.