Gametogenesis, Embryogenesis, and Fertilization Ecology of Platygyra acuta

Understanding the reproductive biology of dominant coral species in subtropical nonreefal coral communities is critical in providing important information on the processes underlying the distribution limits of coral species and communities. This is the first study that investigates the reproduction cycle, gametogenesis, and fertilization ecology of Platygyra acuta. Results indicated that P. acuta is hermaphroditic and exhibits a single annual gametogenic cycle. Oogenic and spermatogenic cycle occurs for 6-7 months and for 2 months, respectively, prior to annual mass spawning event in May to June in Hong Kong. It took 18 hours for P. acuta to complete embryonic development, develop cilia, and start to rotate. High (>70%) fertilization success can be achieved under a broad range of sperm concentrations from 104 to 107 sperms mL−1. Fertilization success remained consistently high 6 h after spawning, indicating a prolonged viability of its gametes that is much longer than that recorded for other coral species. Significantly higher percentage of fertilization success was recorded in the first of the two consecutive nights of spawning, suggesting differences in the quality of the eggs and/or sperms between days of spawning. These results serve as important baseline information for better understanding of corals in marginal communities

Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils

IL-1 family regulatory cytokine IL-37b can suppress innate immunity and inflammatory activity in inflammatory diseases. In this study, IL-37b showed remarkable in vitro suppression of inflammatory tumor necrosis factor-α, IL-1β, IL-6, CCL2, and CXCL8 production in the coculture of human primary eosinophils and human bronchial epithelial BEAS-2B cells with the stimulation of bacterial toll-like receptor-2 ligand peptidoglycan, while antagonizing the activation of intracellular nuclear factor-κB, PI3K–Akt, extracellular signal-regulated kinase 1/2, and suppressing the gene transcription of allergic inflammation-related PYCARD, S100A9, and CAMP as demonstrated by flow cytometry, RNA-sequencing, and bioinformatics. Results therefore elucidated the novel anti-inflammation-related molecular mechanisms mediated by IL-37b. Using the house dust mite (HDM)-induced humanized asthmatic NOD/SCID mice for preclinical study, intravenous administration of IL-37b restored the normal plasma levels of eosinophil activators CCL11 and IL-5, suppressed the elevated concentrations of Th2 and asthma-related cytokines IL-4, IL-6, and IL-13 and inflammatory IL-17, CCL5, and CCL11 in lung homogenate of asthmatic mice. Histopathological results of lung tissue illustrated that IL-37b could mitigate the enhanced mucus, eosinophil infiltration, thickened airway wall, and goblet cells. Together with similar findings using the ovalbumin- and HDM-induced allergic asthmatic mice further validated the therapeutic potential of IL-37b in allergic asthma. The above results illustrate the novel IL-37-mediated regulation of intracellular inflammation mechanism linking bacterial infection and the activation of human eosinophils and confirm the in vivo anti-inflammatory activity of IL-37b on human allergic asthma

A Method for Rapid Screening of Anilide-Containing AMPK Modulators Based on Computational Docking and Biological Validation

Adenosine 5′-monophsphate-activated protein kinase (AMPK) is a crucial energy sensor for maintaining cellular homeostasis. Targeting AMPK may provide an alternative approach in treatment of various diseases like cancer, diabetes, and neurodegenerations. Accordingly, novel AMPK activators are frequently identified from natural products in recent years. However, most of such AMPK activators are interacting with AMPK in an indirect manner, which may cause off-target effects. Therefore, the search of novel direct AMPK modulators is inevitable and effective screening methods are needed. In this report, a rapid and straightforward method combining the use of in silico and in vitro techniques was established for selecting and categorizing huge amount of compounds from chemical library for targeting AMPK modulators. A new class of direct AMPK modulator have been discovered which are anilides or anilide-like compounds. In total 1,360,000 compounds were virtually screened and 17 compounds were selected after biological assays. Lipinski’s rule of five assessment suggested that, 13 out of the 17 compounds are demonstrating optimal bioavailability. Proton acceptors constituting the structure of these compounds and hydrogen bonds with AMPK in the binding site appeared to be the important factors determining the efficacy of these compounds

Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study

BACKGROUND: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. METHODS: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. RESULTS: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. CONCLUSION: This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Sensitivity of ventricular systolic function to afterload during veno‐arterial extracorporeal membrane oxygenation

Abstract Aims Veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) increases afterload to the injured heart and may hinder myocardial recovery. We aimed to compare the sensitivity of left ventricular (LV) systolic function to the afterload effects of peripheral V‐A ECMO during the acute and delayed stages of acute myocardial dysfunction. Methods and results A total of 46 adult patients who were supported by peripheral V‐A ECMO between April 2019 and June 2021 were analysed. Serial cardiac performance parameters were measured by transthoracic echocardiography (TTE) on mean day 1 ± 1 of V‐A ECMO initiation (n = 45, ‘acute phase’) and mean day 4 ± 2 of V‐A ECMO initiation (n = 36, ‘delayed phase’). Measurements were obtained at 100%, 120%, and 50% of ECMO target blood flow (TBF). LV global longitudinal strain (GLS) significantly improved from −6.1 (−8.9 to −4.0)% during 120% TBF to −8.8 (−11.5 to −6.0)% during 50% TBF (P < 0.001). The sensitivity of LV GLS to changes in ECMO flow was significantly greater in the acute phase of myocardial injury compared with the delayed phase [median (IQR) percentage change: 72.7 (26.8–100.0)% vs. 22.5 (14.9–43.8)%, P < 0.001]. Findings from other echocardiographic parameters including LV ejection fraction [43.0 (29.1–56.8)% vs. 22.8 (9.2–42.2)%, P = 0.012] and LV outflow tract velocity‐time integral [45.8 (18.6–58.7)% vs. 24.2 (12.6–34.0)%, P = 0.001] were similar. A total of 24 (52.2%) patients were weaned off ECMO successfully. Conclusions We demonstrated that LV systolic function was significantly more sensitive to the afterload effects of V‐A ECMO during the acute stage of myocardial dysfunction compared with the delayed phase. Understanding the evolution of the heart–ECMO interaction over the course of acute myocardial dysfunction informs the clinical utility of echocardiographic assessment in patients on V‐A ECMO

What Predicts Threat Perceptions Toward People Opposing to the Government? A Population-Based Study Following Umbrella Movement, Hong Kong

We examined the incidence and predictors of threat perceptions toward people who oppose government action (i.e., protestors) following the Umbrella Movement in Hong Kong (September 28th to December 15th, 2014). A population-representative sample of 1,208 citizens (mean age = 46.89 years; 52.4% female) was recruited two months after the conclusion of the Movement using random digit dialing. Upon giving their informed consent, respondents reported sociodemographics, perceived threats of protestors to the prospects of democracy, ways of life, and the economy, anxiety symptoms (STAI), and depressive symptoms (PHQ-9). More than half disagreed that protestors threatened the prospects of democracy (54.7%, 95% CI = .52, .57), ways of life (52.2%, 95% CI = .49, .55), and the economy (51.4%, 95% CI = .49, .54). Regression analyses revealed that male sex was associated with lower odds of perceiving threats to the prospects of democracy and ways of life. Being unmarried was associated with lower odds of perceiving threats to the economy. Secondary education level and depressive symptoms were associated with higher odds of perceiving threats to ways of life and the economy, respectively. This is one of the first population-based studies that measured socioeconomic and mental health correlates of political attitudes immediately following pro-democracy movements

Molecular Characterization of Quinolone-Resistant Neisseria gonorrhoeae in Hong Kong

In Hong Kong, ParC changes among high-level quinolone-resistant Neisseria gonorrhoeae (QRNG) isolates at Ser-87→Arg were associated with a higher level of resistance than a Ser-87→Ile alteration. Two previously undescribed mutations in clinical isolates occurring in gyrA, conferring Ala-92→Pro and Asp-95→Tyr changes, were detected. Nine different outer membrane lipoprotein (Lip) repeat classes—11 to 19 repeats—were identified, with repeat lengths of 16 and 17 the most common, indicating considerable strain diversity

Ultralow-Power Alcohol Vapor Sensors Using Chemically Functionalized Multiwalled Carbon Nanotubes

Alcohol sensors, batch fabricated by forming bundles of chemically functionalized multiwalled carbon nanotubes (f-CNTs) across Au electrodes on SiO2/Si substrates using an AC electrophoretic technique, were developed for alcohol vapor detection using an ultralow input power of ∼ 0.01-1 μW, which is lower than the power required for most commercially available alcohol sensors by more than four orders of magnitude. The multiwalled carbon nanotubes (MWCNTs) have been chemically functionalized with the COOH groups by oxidation. We found that the sensors are selective with respect to flow from air, water vapor, and alcohol vapor. The sensor response is linear for alcohol vapor concentrations from 1 to 21 ppm with a detection limit of 0.9 ppm. The transient response of these sensors is experimentally shown to be ∼1 s and the variation of the responses at each concentration is within 10% for all of the tested sensors. The sensors could also easily be reset to their initial states by annealing the f-CNTs sensing elements at a current of 100-200 μA within ∼ 100-200 s. We demonstrated that the response of the sensors can be increased by one order of magnitude after adding the functional group COOH onto the nanotubes, i.e., from ∼0.9% of a bare MWCNTs sensor to ∼9.6% of an f-CNTs sensor with a dose of 21 ppm alcohol vapor. © 2007 IEEE