Versican Promotes Cardiomyocyte Proliferation and Cardiac Repair.

BACKGROUND: The adult mammalian heart is incapable of regeneration, whereas a transient regenerative capacity is maintained in the neonatal heart, primarily through the proliferation of preexisting cardiomyocytes. Neonatal heart regeneration after myocardial injury is accompanied by an expansion of cardiac fibroblasts and compositional changes in the extracellular matrix. Whether and how these changes influence cardiomyocyte proliferation and heart regeneration remains to be investigated. METHODS: We used apical resection and myocardial infarction surgical models in neonatal and adult mice to investigate extracellular matrix components involved in heart regeneration after injury. Single-cell RNA sequencing and liquid chromatography-mass spectrometry analyses were used for versican identification. Cardiac fibroblast-specific Vcan deletion was achieved using the mouse strains Col1a2-2A-CreER and Vcanfl/fl. Molecular signaling pathways related to the effects of versican were assessed through Western blot, immunostaining, and quantitative reverse transcription polymerase chain reaction. Cardiac fibrosis and heart function were evaluated by Masson trichrome staining and echocardiography, respectively. RESULTS: Versican, a cardiac fibroblast-derived extracellular matrix component, was upregulated after neonatal myocardial injury and promoted cardiomyocyte proliferation. Conditional knockout of Vcan in cardiac fibroblasts decreased cardiomyocyte proliferation and impaired neonatal heart regeneration. In adult mice, intramyocardial injection of versican after myocardial infarction enhanced cardiomyocyte proliferation, reduced fibrosis, and improved cardiac function. Furthermore, versican augmented the proliferation of human induced pluripotent stem cell-derived cardiomyocytes. Mechanistically, versican activated integrin ß1 and downstream signaling molecules, including ERK1/2 and Akt, thereby promoting cardiomyocyte proliferation and cardiac repair. CONCLUSIONS: Our study identifies versican as a cardiac fibroblast-derived pro-proliferative proteoglycan and clarifies the role of versican in promoting adult cardiac repair. These findings highlight its potential as a therapeutic factor for ischemic heart diseases.

Oteseconazole versus fluconazole for the treatment of severe vulvovaginal candidiasis: a multicenter, randomized, double-blinded, phase 3 trial.

Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of ≥7 and positive Candida infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of Candida species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%; P = 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%; P < 0.0001) and clinical cure (71.25% vs 55.97%; P = 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.

4.3†µm high-power amplified spontaneous emission fiber source based on CO2-filled nested hollow-core anti-resonant fiber.

We report a 4.3 µm mid-infrared (mid-IR) high-power amplified spontaneous emission (ASE) fiber source based on CO2-filled nested hollow-core anti-resonant fiber (Nested HC-ARF). The pump source is a homemade hundred-watt-level wavelength-tunable 2 µm single-frequency fiber laser. A 5.7 m long 8-tube Nested HC-ARF is used as the gas cell, with a core diameter of 110 µm and cladding diameter of 400 µm, which exhibits transmission loss of 0.1 dB/m at 2 µm and 0.24 dB/m at 4.3 µm respectively. To improve the coupling efficiency of the high-power pump laser and reduce the influence of the thermal effect at the input end of the hollow-core fiber, the fiber is designed for multimode transmission at the pump wavelength. A continuous wave output power of 6.6 W at 4.3 µm is achieved, and the slope efficiency is 17.05%. To the best of our knowledge, it is the highest output power for such gas-filled HC-ARF ASE sources in 4∼5 µm. This work demonstrates the great potential of gas-filled HC-ARF generating high-power mid-IR emission.

21.8†W acetylene-filled hollow-core anti-resonant fiberamplified spontaneous emission source at 3.1†µm.

We report a 20-W-level acetylene-filled nested hollow-core anti-resonant fiber (nested HC-ARF) amplified spontaneous emission (ASE) source at 3.1 µm. A 1535 nm hundred-watt wavelength tunable single-frequency fiber laser with a high signal-to-noise ratio and narrow linewidth is built for pumping acetylene molecules. Simultaneously, a homemade 120 µm core diameter eight-tube nested HC-ARF is used as a gas chamber to obtain high pump laser coupling efficiency. The mid-infrared (mid-IR) ASE source output power of 21.8 W is achieved at 3.1 µm through the low-pressure acetylene gas-filled nested HC-ARF, and the slope efficiency is 25.1%. In addition, the ASE source features an excellent beam quality of Mx 2 = 1.16 and My 2 = 1.13. To the best of our knowledge, for the first time, it is a record output power for such mid-infrared ASE sources while maintaining excellent beam quality. This work provides a new way to achieve high-power mid-infrared emission.

High-power hollow-core fiber gas laser at 3.1†µm with a linear-cavity structure.

Mid-infrared hollow-core fiber (HCF) gas lasers based on a population inversion regime of gas molecules have made advanced development in recent years, but mostly with single-pass cavity-free structures. Here, we demonstrated a 3.1 µm high-power acetylene-filled HCF continuous wave (CW) laser and a self-Q-switched pulse laser with a linear-cavity structure. This configuration not only facilitates the transformation of amplified spontaneous emission into the laser output but also enhances the coherence of the light source and imparts distinct cavity mode characteristics. Harnessing a homemade high-power 1535 nm single-frequency fiber laser that served as the pump source, a CW laser output of 8.23 W at 3.1 µm was achieved, which is over three orders of magnitude higher than those in reported works so far. The corresponding slope efficiency of 31.8% and beam quality of Mx 2 = 1.18 and My 2 = 1.15 were characterized. When the gas pressure was up to 50 mbar, the laser generated a 3.1 µm self-Q-switched pulse with an output power of 1.98 W as well as a pulse width of 45 ns under the repetition rate of 4.59 MHz. To the best of our knowledge, this is the first time that an HCF gas laser achieves a self-Q-switched pulse. Future studies will aim to further optimize the experimental setup, potentially enabling the direct generation of picosecond pulses in the mid-infrared wavelength band.

Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study.

PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.

Development of a Five-Chemical-Probe Method to Determine Multiple Radicals Simultaneously in Hydroxyl and Sulfate Radical-Mediated Advanced Oxidation Processes.

Advanced oxidation processes (AOPs), such as hydroxyl radical (HO•)- and sulfate radical (SO4•-)-mediated oxidation, are attractive technologies used in water and wastewater treatments. To evaluate the treatment efficiencies of AOPs, monitoring the primary radicals (HO• and SO4•-) as well as the secondary radicals generated from the reaction of HO•/SO4•- with water matrices is necessary. Therefore, we developed a novel chemical probe method to examine five key radicals simultaneously, including HO•, SO4•-, Cl•, Cl2•-, and CO3•-. Five probes, including nitrobenzene, para-chlorobenzoic acid, benzoic acid, 2,4,6-trimethylbenzoic acid, and 2,4,6-trimethylphenol, were selected in this study. Their bimolecular reaction rate constants with diverse radicals were first calibrated under the same conditions to minimize systematic errors. Three typical AOPs (UV/H2O2, UV/S2O82-, and UV/HSO5-) were tested to obtain the radical steady-state concentrations. The effects of dissolved organic matter, Br-, and the probe concentration were inspected. Our results suggest that the five-probe method can accurately measure radicals in the HO•- and SO4•--mediated AOPs when the concentration of Br- and DOM are less than 4.0 µM and 15 mgC L-1, respectively. Overall, the five-probe method is a practical and easily accessible method to determine multiple radicals simultaneously.

Mechanistic and Kinetic Consideration of the Photochemically Generated Oxidative Organic Radicals in Dissolved Black Carbon Solutions under Simulated Solar Irradiation.

The photochemically generated oxidative organic radicals (POORs) in dissolved black carbon (DBC) was investigated and compared with that in dissolved organic matter (DOM). POORs generated in DBC solutions exhibited higher one-electron reduction potential values (1.38-1.56 V) than those in DOM solutions (1.22-1.38 V). We found that the photogeneration of POORs from DBC is enhanced with dissolved oxygen (DO) increasing, while the inhibition of POORs is observed in reference to DOM solution. The behavior of the one-electron reducing species (DBC•-/DOM•-) was employed to explain this phenomenon. The experimental results revealed that the DO concentration had a greater effect on DBC•- than on DOM•-. Low DO levels led to a substantial increase in the steady-state concentration of DBC•-, which quenched the POORs via back-electron reactions. Moreover, the contribution of POORs to the degradation of 19 emerging organic contaminants (EOCs) in sunlight-exposed DBC and DOM solutions was estimated. The findings indicate that POORs play an important role in the photodegradation of EOCs previously known to react with triplets, especially in DBC solutions. Compared to DOM solutions, POOR exhibits a lower but considerable contribution to EOC attenuation. This study enhances the understanding of pollutant fate in aquatic environments by highlighting the role of DBC in photochemical pollutant degradation and providing insights into pollutant transformation mechanisms involving POORs.

Large-scale separation of alkaloids from Corydalis decumbens by pH-zone-refining centrifugal partition chromatography and their anticomplement activity.

Centrifugal partition chromatography in the pH-zone-refining mode was successfully applied to the separation of alkaloids from the crude extract of Corydalis decumbens. The experiment was performed with a two-phase solvent system composed of petroleum ether-ethyl acetate-ethanol-water (5:5:3:7, v/v/v/v) where triethylamine (10 mM) was added to the stationary phase and hydrochloric acid (10 mM) to the mobile phase. From 1.6 g of the crude extract, 43 mg protopine, 189 mg (+)-egenine, and 158 mg tetrahydropalmatine were obtained with a purity of 98.2%, 94.6%, and 96.7%, respectively. Tetrahydropalmatine showed an interesting anticomplement effect with CH50 0.11 and AP50 0.25 mg/mL, respectively. In a mechanistic study, tetrahydropalmatine interacted with C1, C3, C4, and C5 components in the complement activation cascade.

The impact of fasting stress hyperglycemia ratio, fasting plasma glucose and hemoglobin A1c on in-hospital mortality in patients with and without diabetes: findings from the China acute myocardial infarction registry.

BACKGROUND: Stress hyperglycemia was positively associated with poor prognosis in individuals with acute myocardial infarction (AMI). However, admission glucose and stress hyperglycemia ratio (SHR) may not be the best indicator of stress hyperglycemia. We performed this study to evaluate the comparative prognostic value of different measures of hyperglycemia (fasting SHR, fasting plasma glucose [FPG], and hemoglobin A1c [HbA1c]) for in-hospital mortality in AMI patients with or without diabetes. METHODS: In this prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) registry, 5,308 AMI patients including 2081 with diabetes and 3227 without diabetes were evaluated. Fasting SHR was calculated using the formula [(first FPG (mmol/l))/(1.59×HbA1c (%)-2.59)]. According to the quartiles of fasting SHR, FPG and HbA1c, diabetic and non-diabetic patients were divided into four groups, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 225 (4.2%) patients died during hospitalization. Individuals in quartile 4 had a significantly higher rate of in-hospital mortality compared with those in quartile 1 in diabetic cohort (9.7% vs. 2.0%; adjusted odds ratio [OR] 4.070, 95% CI 2.014-8.228) and nondiabetic cohort (8.8% vs. 2.2%; adjusted OR 2.976, 95% CI 1.695-5.224). Fasting SHR was also correlated with higher in-hospital mortality when treated as a continuous variable in diabetic and nondiabetic patients. Similar results were observed for FPG either as a continuous variable or a categorical variable. In addition, fasting SHR and FPG, rather than HbA1c, had a moderate predictive value for in-hospital mortality in patients with diabetes (areas under the curve [AUC] for fasting SHR: 0.702; FPG: 0.689) and without diabetes (AUC for fasting SHR: 0.690; FPG: 0.693). The AUC for fasting SHR was not significantly different from that of FPG in diabetic and nondiabetic patients. Moreover, adding fasting SHR or FPG to the original model led to a significant improvement in C-statistic regardless of diabetic status. CONCLUSIONS: This study indicated that, in individuals with AMI, fasting SHR as well as FPG was strongly associated with in-hospital mortality regardless of glucose metabolism status. Fasting SHR and FPG might be considered as a useful marker for risk stratification in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT01874691.

Impacts of Diabetes Mellitus on Cardiovascular Outcomes and Differential Effects of Direct Oral Anticoagulants in Patients with Left Ventricular Thrombus.

Background: The focus of this investigation into the impact of type 2 diabetes mellitus (T2DM) on left ventricular thrombus (LVT) is (a) the differences in LVT characteristics, (b) long-term clinical outcomes, and (c) differential effects of direct oral anticoagulants (DOAC) among patients with T2DM and without diabetes. Methods: Patients with confirmed LVT from 2009 to 2021 were included. The primary endpoints were major adverse cardiac and cerebrovascular events (MACCE), composite of cardiovascular death, ischemic stroke, and acute myocardial infarction (AMI). The secondary endpoints were all-cause death and cardiovascular death. Multivariable competing-risk regression and cumulative incidence functions (CIF) were used to evaluate the adverse consequences. Results: In total, 1675 patients were assessed initially. Follow-up data were available for 91.1% of the participants. Median follow-up was 3.8 years. This retrospective study ultimately comprised 1068 participants, of which 429 had T2DM. Significantly higher proportions of comorbidities were observed in the T2DM group. The location, morphology, and size of LVT were similar in the two groups. Multivariable analysis suggested a higher risk of MACCE among patients with T2DM. The difference in risk between the two groups after matching and weighting was not statistically significant. Among the whole sample (n = 638) or the just the non-diabetic patients with LVT and anticoagulation (n = 382), the incidence of MACCE did not differ between DOAC treatment and warfarin treatment. In the diabetic LVT population with anticoagulation (n = 256), DOAC treatment was associated with a significantly higher risk of MACCE than was warfarin treatment. Conclusions: The location and morphology of LVT are similar in T2DM and non-diabetic patients. A higher risk of MACCE was found among patients with diabetes.

Time Trends of Etiology, Treatment, and Long-Term Outcomes Among Patients with Left Ventricular Thrombus.

Background: Recommendations for drug treatment of left ventricular thrombus (LVT) are based on the ST-segment elevation myocardial infarction (STEMI) guidelines; however, the etiology of LVT has changed. Due to the lack of evidence regarding LVT treatment in the heart failure population, current heart failure guidelines do not cover LVT treatment. We sought to review the etiology of LVT and changes in antithrombotic therapy over the previous 12 years and explore the impact of anticoagulation treatment from a single center's experience. Methods: From January 2009 to June 2021, we studied 1675 patients with a discharge diagnosis of LVT at a single center to investigate the clinical characteristics, incidence of all-cause death, cardiovascular death, ischemic stroke, major adverse cardiac and cerebrovascular events (MACCE), systemic embolism (SE), and major bleeding events. Patients were divided into an anticoagulant group and a non-anticoagulant group according to whether they received oral anticoagulant therapy at discharge. Results: The study included 909 patients (anticoagulation, 510; no anticoagulation, 399). While overall antiplatelet therapy dramatically decreased, more patients with LVT received oral anticoagulation in 2021 (74.0%) than in 2009 (29.6%). In addition, more than half of the patients had heart failure with reduced ejection fraction (HFrEF) each year. The all-cause mortality was 17.3% during 3.8 years of follow-up. The incidences of cardiovascular death, stroke, MACCE, SE, and major bleeding were 16.0%, 3.3%, 19.8%, 5.1%, and 1.7%, respectively. The anticoagulation group had a significantly higher proportion of dilated cardiomyopathy than the non-anticoagulation group (24.7% vs. 5.5%, p < 0.001), and a lower LVEF (34.0 vs. 41.0, p < 0.001). The anticoagulation group also had a higher probability of adverse events on long-term follow-up (p > 0.05). A multivariable competing risk regression model found no significant difference in all six endpoints between the groups (all p > 0.05). Similar results were found by matched and weighted data analysis. Diabetes mellitus (hazard ratio (HR), 1.42; 95% confidence interval (CI), 1.04-1.93; p = 0.027), renal insufficiency (HR, 2.36; 95% CI, 1.60-3.50; p < 0.001), history of previous stroke (HR, 1.60; 95% CI, 1.13-2.29; p = 0.009), and HFrEF (HR, 2.54; 95% CI, 1.78-3.64; p < 0.001) were predictors of increased risk of MACCE. Conclusions: Heart failure, rather than acute myocardial infarction, is currently the primary cause of LVT. A trend towards better prognosis in the no anticoagulation group was noted. Multivariable, matching and weighting analysis showed no improvement in prognosis with anticoagulant therapy. Our study does not negate the efficacy of anticoagulation but suggests the need to strengthen the management of anticoagulation in order to achieve better efficacy.

YAP/TAZ deficiency reprograms macrophage phenotype and improves infarct healing and cardiac function after myocardial infarction.

Adverse cardiac remodeling after myocardial infarction (MI) causes structural and functional changes in the heart leading to heart failure. The initial post-MI pro-inflammatory response followed by reparative or anti-inflammatory response is essential for minimizing the myocardial damage, healing, and scar formation. Bone marrow-derived macrophages (BMDMs) are recruited to the injured myocardium and are essential for cardiac repair as they can adopt both pro-inflammatory or reparative phenotypes to modulate inflammatory and reparative responses, respectively. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the key mediators of the Hippo signaling pathway and are essential for cardiac regeneration and repair. However, their functions in macrophage polarization and post-MI inflammation, remodeling, and healing are not well established. Here, we demonstrate that expression of YAP and TAZ is increased in macrophages undergoing pro-inflammatory or reparative phenotype changes. Genetic deletion of YAP/TAZ leads to impaired pro-inflammatory and enhanced reparative response. Consistently, YAP activation enhanced pro-inflammatory and impaired reparative response. We show that YAP/TAZ promote pro-inflammatory response by increasing interleukin 6 (IL6) expression and impede reparative response by decreasing Arginase-I (Arg1) expression through interaction with the histone deacetylase 3 (HDAC3)-nuclear receptor corepressor 1 (NCoR1) repressor complex. These changes in macrophages polarization due to YAP/TAZ deletion results in reduced fibrosis, hypertrophy, and increased angiogenesis, leading to improved cardiac function after MI. Also, YAP activation augmented MI-induced cardiac fibrosis and remodeling. In summary, we identify YAP/TAZ as important regulators of macrophage-mediated pro-inflammatory or reparative responses post-MI.

Kinetic and Mechanistic Considerations of the Photosensitized Transformation of Chlorine in Chromophoric Dissolved Organic Matter Solutions under Simulated Solar Irradiation.

Chlorination is one of the most common disinfection methods for water treatments. Although the direct photolysis of free available chlorine (FAC) induced by solar irradiation has been extensively investigated, the photosensitized transformation of FAC caused by chromophoric dissolved organic matter (CDOM) has not previously been examined. Our results suggest that the photosensitized transformation of FAC can occur in sunlit CDOM-enriched solutions. Interestingly, the photosensitized decay of FAC can be fitted using a combined zero- and first-order kinetic model. The photogenerated O2•- from CDOM contributes to the zero-order kinetic component. The reductive triplet CDOM (3CDOM*) contributes to the pseudo-first-order decay kinetic component. The bimolecular reaction rate constants of the model triplet (3-methoxyacetophenone) with HOCl and OCl- were (3.6 ± 0.2) × 109 and (2.7 ± 0.3) × 109 M-1 s-1, respectively. Under simulated solar irradiation, the quantum yield coefficient of the reductive 3CDOM* toward FAC attenuation (fFAC = 840 ± 40 M-1) was 13 times greater than that of the oxidative 3CDOM* toward trimethylphenol (TMP) attenuation (fTMP = 64 ± 4 M-1). This study provides new insights into the photochemical transformation of FAC in sunlit surface waters, and the results are applicable when sunlight/FAC system is employed as an advanced oxidation process.

Organism type of infection is associated with prognosis in sepsis: an analysis from the MIMIC-IV database.

BACKGROUND: Sepsis has a high mortality rate, which is expensive to treat, and is a major drain on healthcare resources; it seriously impacts the quality of human life. The clinical features of positive or non-positive blood cultures have been reported, but the clinical features of sepsis with different microbial infections and how they contribute to clinical outcomes have not been adequately described. METHODS: We extracted clinical data of septic patients with a single pathogen from the online Medical Information Mart for Intensive Care(MIMIC)-IV database. Based on microbial cultures, patients were classified into Gram-negative, Gram-positive, and fungal groups. Then, we analyzed the clinical characteristics of sepsis patients with Gram-negative, Gram-positive, and fungal infections. The primary outcome was 28-day mortality. The secondary outcomes were in-hospital mortality, the length of hospital stay, the length of ICU stay, and the ventilation duration. In addition, Kaplan-Meier analysis was used for the 28-day cumulative survival rate of patients with sepsis. Finally, we performed further univariate and multivariate regression analyses for 28-day mortality and created a nomogram for predicting 28-day mortality. RESULTS: The analysis showed that bloodstream infections showed a statistically significant difference in survival between Gram-positive and fungal organisms; drug resistance only reached statistical significance for Gram-positive bacteria. Through univariate and multivariate analysis, it was found that both the Gram-negative bacteria and fungi were independent risk factors for the short-term prognosis of sepsis patients. The multivariate regression model showed good discrimination, with a C-index of 0.788. We developed and validated a nomogram for the individualized prediction of 28-day mortality in patients with sepsis. Application of the nomogram still gave good calibration. CONCLUSIONS: Organism type of infection is associated with mortality of sepsis, and early identification of the microbiological type of a patient with sepsis will provide an understanding of the patient's condition and guide treatment.

WITHDRAWN: Novel subgroups of patients with left ventricular thrombus and their differential effects with anticoagulation: a data-driven cluster analysis.

UNSTRUCTURED: Ahead of Print article withdrawn by the publisher.

An Interleukin-17 Isoform from Thick Shell Mussel Mytilus coruscus Serves as a Mediator of Inflammatory Response.

The inflammatory cytokine interleukin-17 (IL17) plays an important role in innate immunity by binding to its receptors (IL17Rs) to activate immune defense signals. To date, information on members of the IL17 family is still very limited in molluscan species. Here, a novel member of the IL17 family was identified and characterized from thick shell mussel Mytilus coruscus, and this gene was designated as McIL17-1 by predicting structural domains and phylogenetic analysis. McIL17-1 transcripts existed in all examined tissues with high expression levels in gills, hemocytes and digestive glands. After the stimuli of different pathogen associated molecular patterns (PAMPs) for 72 h, transcriptional expression of McIL17-1 was significantly upregulated, except for poly I:C stimulation. Cytoplasm localization of McIL17-1 was shown in HEK293T cells by fluorescence microscopy. Further, in vivo and in vitro assays were performed to evaluate the potential function of McIL17-1 played in immune response. McIL17-1 was either knocked down or overexpressed in vivo through RNA inference (RNAi) and recombinant protein injection, respectively. With the infection of living Vibrio alginolyticus, a high mortality rate was exhibited in the McIL17-1 overexpressed group compared to the control group, while a lower mortality rate was observed in the McIL17-1 knocked down group than control group. In vitro, the flow cytometric analysis showed that the apoptosis rate of McIL17-1 inhibited hemocytes was significantly lower than that of the control group after lipopolysaccharide stimulation. These results collectively suggested that the newly identified IL17 isoform is involved in the inflammatory response to bacterial infection in M. coruscus.

Effect of type 2 diabetes on coronary artery ectasia: smaller lesion diameter and shorter lesion length but similar adverse cardiovascular events.

BACKGROUND: Coronary artery ectasia (CAE) is a rare finding in coronary angiography and associated with poor clinical outcomes. Unlike atherosclerosis, diabetes mellitus (DM) is not commonly associated with CAE. This study aims to investigate the effect of type 2 diabetes mellitus (DM2) on coronary artery ectasia, especially the differences in angiographic characteristics and clinical outcomes. METHODS: Patients with angiographically confirmed CAE from 2009 to 2015 were included. Quantitative coronary angiography (QCA) was performed to measure the diameter and length of the dilated lesion. The primary endpoint was the maximum diameter and maximum length of the dilated lesion at baseline coronary angiography. The secondary endpoint was 5-year major adverse cardiovascular events (MACE), which was a component of cardiovascular death and nonfatal myocardial infarction (MI). Propensity score weighting (PSW) and propensity score matching (PSM) were used to balance covariates. Kaplan-Meier method and Cox regression were performed to assess the clinical outcomes. RESULTS: A total of 1128 patients were included and 258 were combined with DM2. In the DM2 group, the maximum diameter of dilated lesion was significantly lower (5.26 mm vs. 5.47 mm, P = 0.004) and the maximum length of the dilated lesion was significantly shorter (25.20 mm vs. 31.34 mm, P = 0.002). This reduction in dilated lesion diameter (5.26 mm vs. 5.41 mm, P = 0.050 in PSW; 5.26 mm vs. 5.46 mm, P = 0.007 in PSM, respectively) and length (25.17 mm vs. 30.17 mm, P = 0.010 in PSW; 25.20 mm vs. 30.81 mm, P = 0.012 in PSM, respectively) was consistently observed in the propensity score analysis. A total of 27 cardiovascular deaths and 41 myocardial infarctions occurred at 5-year follow-up. Compared with non-DM group, there were similar risks of MACE (6.02% vs. 6.27%; HR 0.96, 95% CI 0.54-1.71, P = 0.894), cardiovascular death (2.05% vs. 2.61%; HR 0.78, 95% CI 0.29-2.05, P = 0.605) and MI (4.07% vs. 3.72%; HR 1.11, 95% CI 0.54-2.26, P = 0.782) in patients with DM2. Consistent result was observed in multivariable regression. CONCLUSIONS: Compared to non-DM patients, patients with CAE and type 2 diabetes were associated with a smaller diameter and shorter length of dilated vessels, suggesting the important effect of DM2 on the pathophysiological process of CAE. Similar risks of MACE were found during 5-year follow up among diabetic and non-DM patients.

Effect of Thin-Walled Radial Sheath for Large-Bore Access On Reducing Periprocedural Radial Artery Occlusion Following Complex PCI: The REDUCE-RAO Randomized Trial.

Background: Transradial artery (TRA) access for percutaneous coronary intervention (PCI) was associated with lower risks of major bleeding and vascular complications compared to transfemoral artery access. Use of large-bore ( ≥ 7-Fr) guiding catheters through TRA approach increased the likelihood of radial artery occlusion (RAO). This study aimed to investigate whether use of the thin-walled 7-Fr Glidesheath Slender, allowing PCI with large-caliber guiding catheters, is superior to standard 7-Fr Cordis sheath with respect to periprocedural RAO within 24 hours after transradial coronary intervention (TRI) in complex lesions. Methods: A prospective randomized, controlled, single-blinded (patient-blinded) trial was conducted, randomizing 504 patients with TRI for complex lesions to either 7-Fr Glidesheath Slender or conventional 7-Fr Cordis sheath. The primary outcome was defined as the incidence of periprocedural RAO with Doppler ultrasound during the first 24 hours after TRI. Results: The incidence of early RAO was 10.3% for 7-Fr Glidesheath Slender and 13.5% for conventional 7-Fr sheath (p = 0.271). The procedural success rate for Glidesheath Slender was 92.9% and for Cordis sheath was 93.7% (p = 0.722). There was no signficiant difference between treatment arms in terms of local hematoma and radial spasm, whereas use of the Glidesheath Slender was associated with significantly less pain during the procedure (numeric rating scale [NRS], 2.27 ± 0.75 vs. 2.45 ± 0.95, p = 0.017). The assessment of radial artery in ultrasound parameters after complex TRI was improved with Glidesheath Slender. Conclusions: Among patients with complex coronary lesions undergoing TRI, 7-Fr Glidesheath Slender was not superior to conventional 7-Fr in the prevention of periprocedural RAO within 24 hours following complex PCI, without reducing RAO occurrence. Clinical Trial Registration: NCT04748068.

Low loss nested hollow-core anti-resonant fiber at 2 µm spectral range.

We report the fabrication and characterization of a five-tube nested hollow-core anti-resonant fiber (Nested HC-ARF), which exhibits outstanding optical performance in terms of a record attenuation value of 0.85 dB/km at 2 µm wavelength range with a 200 nm bandwidth below 2 dB/km and excellent modal purity. The power handling capability of the Nested HC-ARF is also demonstrated in this work. Pulses of 75 W, 160 ps from the thulium-doped fiber laser are delivered using a 6-m-long fabricated Nested HC-ARF. The tested fiber is coiled into a 20 cm bending radius and achieves a coupling efficiency of 86.7%. The maximum average power of 60.5 W is transmitted through our Nested HC-ARF in a robust single-mode fashion without introducing any damage to the input and output fiber end-faces, which demonstrates the superior ability of such a fiber for high-power laser delivery.