Screening and Stability Evaluation of Angiotensin Converting Enzyme Inhibitory Peptides from Bangia fusco-purpurea

In this study, peptide fractions (F1-F4) with different molecular masses were obtained from Bangia fusco-purpurea through enzymatic hydrolysis and ultrafiltration. F2, with molecular masses of 800–2 000 Da, exhibited the highest in vitro angiotensin-converting enzyme (ACE) inhibitory activity as determined by high performance liquid chromatography (HPLC). The amino acid sequence of F2 was identified through liquid chromatography-tandem mass spectrometry (LC-MS/MS) and de novo sequencing using PEAKS Studio software. Six ACE inhibitory peptides that stably bind to ACE were selected through molecular docking. The predicted peptides were synthesized by solid-phase synthesis and their in vitro ACE inhibitory activity was verified. Among them, L1 (LVLLFLFGE) showed the highest ACE inhibitory activity with a half maximal inhibitory concentration (IC50) value of 14.22 μg/mL. Molecular docking results indicated that the inhibition of ACE by L1 was mainly attributed to its ability to form hydrogen bond interactions with the active site of ACE. Finally, the effects of temperature, pH, metal ions, light exposure, and simulated gastrointestinal digestion on the stability of L1 were investigated. The results revealed that L1 was highly stable to heat and ionic strength. However, its activity gradually decreased at pH > 2, and was affected by ultraviolet treatment. The ACE inhibitory activity of L1 decreased after simulated gastric and intestinal digestion, but was still significant

Incidence and risk factors of anti-tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients

Background and Aims: Anti-tuberculosis drugs remain as an important cause of drug-induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti-tuberculosis DILI (ATDILI). Methods: Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis. Results: In the derivation cohort (n=3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR=1.014, 95% CI: 1.005-1.023), baseline ALT (HR=1.014, 95% CI: 1.003-1.024), haemoglobin (HR=1.011, 95% CI: 1.002-1.020) and HBsAg positivity (HR=1.516, 95% CI: 1.004-2.290) were independent risk factors for DILI. In the second cohort (n=1497) of which 85 (5.7%) developed ATDILI. Age (HR=1.029, 95% CI: 1.003-1.056), baseline AST (HR=1.036, 95% CI: 1.010-1.062), previous TB treatment (HR=3.894, 95% CI: 1.304-11.625) and active drinking (HR=3.624, 95% CI: 1.147-11.454) were risk factors for developing jaundice. Conclusion: Elevation of ALT of ≥3×ULN during anti-TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients

Role of drugs used for chronic disease management on susceptibility and severity of COVID-19: A large case-control study

The study aimed to investigate whether specific medications used in the treatment chronic diseases affected either the development and/ or severity of COVID-19 in a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zheijang, China. Using a cohort of 578 COVID-19 cases and 48,667 population-based controls from Zheijang, China we tested the role of usage of cardiovascular, antidiabetic and other medications on risk and severity of COVID 19. Analyses were adjusted for age, sex and BMI and for presence of relevant comorbidities. Individuals with hypertension taking calcium channel blockers had significantly increased risk [odds ratio (OR)= 1.73 (95% CI 1.2-2.3)] of manifesting symptoms of COVID-19 whereas those taking angiotensin receptor blockers and diuretics had significantly lower disease risk (OR=0.22; 95%CI 0.15-0.30 and OR=0.30; 95%CI 0.19-0.58 respectively). Among those with type 2 diabetes, dipeptidyl peptidase-4 inhibitors (OR= 6.02; 95% CI 2.3- 15.5) and insulin (OR= 2.71; 95% CI 1.6-5.5) were more and glucosidase inhibitors were less prevalent (OR= 0.11; 95% CI 0.1-0.3) among with COVID-19 patients. Drugs used in the treatment of hypertension and diabetes influence the risk of development of COVID-19, but, not its severity

Meeting Report: Aging Research and Drug Discovery

Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year's 8th Annual Aging Research and Drug Discovery ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community

Highly Efficient 2.84-mu m Emission in Ho3+/Yb3+ Co-Doped Tellurite-Germanate Glass for Mid-Infrared Laser Materials

International audienceThe use of Yb3+ co-doping with Ho3+ to enhance the Ho3+: I-5(6) -> I-5(7) similar to 2.84-mu m emissions is investigated in the tellurite-germanate glasses. An intense similar to 2.84-mu m emission with a full width at half maximum (FWHM) of 132 nm is achieved in the Ho3+/Yb3+ co-doped tellurite-germanate glass upon excitation at 980 nm. The glass not only possesses considerably low OH-absorption coefficient (0.206 cm(-1)), but also exhibits 2.84-mu m large emission cross section (14.6 x 10(-21) cm(2)). Moreover, the measured lifetime of Ho3+: I-5(6) level is as high as 0.283 ms. Results reveal that Ho3+/Yb3+ co-doped Tellurite-germanate glass is an attractive host for developing a mid-infrared 3-mu m solid-state laser

A transient production prediction method for tight condensate gas wells with multiphase flow

Considering the phase behaviors in condensate gas reservoirs and the oil-gas two-phase linear flow and boundary-dominated flow in the reservoir, a method for predicting the relationship between oil saturation and pressure in the full-path of tight condensate gas well is proposed, and a model for predicting the transient production from tight condensate gas wells with multiphase flow is established. The research indicates that the relationship curve between condensate oil saturation and pressure is crucial for calculating the pseudo-pressure. In the early stage of production or in areas far from the wellbore with high reservoir pressure, the condensate oil saturation can be calculated using early-stage production dynamic data through material balance models. In the late stage of production or in areas close to the wellbore with low reservoir pressure, the condensate oil saturation can be calculated using the data of constant composition expansion test. In the middle stages of production or when reservoir pressure is at an intermediate level, the data obtained from the previous two stages can be interpolated to form a complete full-path relationship curve between oil saturation and pressure. Through simulation and field application, the new method is verified to be reliable and practical. It can be applied for prediction of middle-stage and late-stage production of tight condensate gas wells and assessment of single-well recoverable reserves

Cut-Price Fabrication of Free-standing Porous Carbon Nanofibers Film Electrode for Lithium-ion Batteries

Freestanding thin film electrodes are competitive candidate materials for high-performance energy stockpile equipment due to their self-supporting structure and because they lack any polymer binder or conductive additive. In our work, a porous carbon nanofiber film (PCNF) electrode has been synthesized via a convenient and low-cost electrospinning approach and the following carbonization and air etching process. The obtained PCNF electrode sample shows a high reversible capacity (1138 mAh g−1 at 0.1 C), remarkable rate capacity (101.2 mAh g−1 at 15 C), and superior cycling stability with a lower capacity decay rate of ~0.013% each cycle upon 1000 cycles (278 mAh g−1 at 5 C). The prominent electrochemical performance of PCNF can be put down to the stable self-supporting conductive structure and the porous feature in each carbon nanofiber, which will significantly promote the transfer tempo of Li-ion and electron and relieve the large volume change during inserting lithium ion. More interestingly, this work exhibits a low-cost and primitive strategy to fabricate thin film anode for lithium-ion batteries

Novel ultra-wideband fluorescence material: Defect state control based on nickel-doped semiconductor QDs embedded in inorganic glasses

In recent years, the development of an environmentally friendly quantum dots (QDs) embedded luminous solid by a simple method has attracted considerable attention. In this study, semiconductor ZnS QDs were successfully prepared in an inorganic matrix of amorphous glass, which yielded beneficial broad-band emission in the long-wavelength region of the visible range. The strong red emission belonged to the defect state energy level of the ZnS QDs, which could be enhanced by incorporation of nickel ions into the fixed matrix to regulate the defects state. The novel material had a small self-absorption, wide excitation and emission ranges, and thus potential applications in light-conversion devices, luminescent solar concentrators, and solar cell cover glasses

Enhanced luminescence of manganese in singly doped white light zinc phosphate glass

International audienceOn the basis of a kind of zinc phosphate oxynitride glass matrix with a broadband blue light, a series of manganese single-doped glasses were obtained. A broader red emission with the higher intensity belonging to the Mn2+ ion was observed in this glass matrix. The mechanism of the emission from Mn2+ ions was clarified through Mn3+ as an "energy acquisition probe" to replace complex dynamic luminescence discussion, which was a fit explanation for the differences in luminescence behavior of Mn ions in prepared glasses at different degrees of redox. The research results indicated that the prepared manganese-doped glass was a potential candidate as phosphor-converted white-light-emitting diodes. An encapsulated white-light-emitting diode device based on this glass with 276 nm ultraviolet chip was achieved. It showed the CIE values of (0.33, 0.35), high CRI (Ra = 86), and low color temperature (5228 K)

Targeting NOX4 alleviates sepsis-induced acute lung injury via attenuation of redox-sensitive activation of CaMKII/ERK1/2/MLCK and endothelial cell barrier dysfunction.

Increased pulmonary vascular permeability due to endothelial cell (EC) barrier dysfunction is a major pathological feature of acute respiratory distress syndrome/acute lung injury (ARDS/ALI), which is a devastating critical illness with high incidence and excessive mortality. Activation of NADPH oxidase (NOX) induces EC dysfunction via production of reactive oxygen species (ROS). However, the role(s) of NOX isoform(s), and their downstream signaling events, in the development of ARDS/ALI have remained unclear. Cecal Ligation Puncture (CLP) was used to induce preclinical septic ALI in wild-type mice and mice deficient in NOX2 or p47phox, or mice transfected of control siRNA, NOX1 or NOX4 siRNA in vivo. The survival rate of the CLP group at 24 h (26.6%, control siRNA treated) was substantially improved by NOX4 knockdown (52.9%). Mice lacking NOX2 or p47phox, however, had worse outcomes after CLP (survival rates at 0% and 8.3% respectively), whereas NOX1-silenced mice had similar survival rate (30%). NOX4 knockdown attenuated lung ROS production in septic mice, whereas NOX1 knockdown, NOX2 knockout, or p47phox knockout in mice had no effects. In addition, NOX4 knockdown attenuated redox-sensitive activation of the CaMKII/ERK1/2/MLCK pathway, and restored expression of EC tight junction proteins ZO-1 and Occludin to maintain EC barrier integrity. Correspondingly, NOX4 knockdown in cultured human lung microvascular ECs also reduced LPS-induced ROS production, CaMKII/ERK1/2/MLCK activation and EC barrier dysfunction. Scavenging superoxide in vitro and in vivo with TEMPO, or inhibiting CaMKII activation with KN93, had similar effects as NOX4 knockdown in preserving EC barrier dysfunction. In summary, we have identified a novel, selective and causal role of NOX4 (versus other NOX isoforms) in inducing lung EC barrier dysfunction and injury/mortality in a preclinical CLP-induced septic model, which involves redox-sensitive activation of CaMKII/ERK1/2/MLCK pathway. Targeting NOX4 may therefore prove to an innovative therapeutic option that is markedly effective in treating ALI/ARDS