Photocatalytic reduction of molecular oxygen is a promising route toward sustainable production of hydrogen peroxide (H2O2). This challenging process requires photoactive semiconductors enabling ...solar energy driven generation and separation of electrons and holes with high charge transfer kinetics. Covalent organic frameworks (COFs) are an emerging class of photoactive semiconductors, tunable at a molecular level for high charge carrier generation and transfer. Herein, we report two newly designed two-dimensional COFs based on a (diarylamino)benzene linker that form a Kagome (kgm) lattice and show strong visible light absorption. Their high crystallinity and large surface areas (up to 1165 m2·g–1) allow efficient charge transfer and diffusion. The diarylamine (donor) unit promotes strong reduction properties, enabling these COFs to efficiently reduce oxygen to form H2O2. Overall, the use of a metal-free, recyclable photocatalytic system allows efficient photocatalytic solar transformations.
A tonically high level of brain arousal and its hyperstable regulation is supposed to be a pathogenic factor in major depression. Preclinical studies indicate that most antidepressants may counteract ...this dysregulation. Therefore, it was hypothesized that responders to antidepressants show a) a high level of EEG-vigilance (an indicator of brain arousal) and b) a more stable EEG-vigilance regulation than non-responders. In 65 unmedicated depressed patients 15-min resting-state EEGs were recorded off medication (baseline). In 57 patients an additional EEG was recorded 14 ± 1 days following onset of antidepressant treatment (T1). Response was defined as a ≥50% HAMD-17-improvement after 28 ± 1 days of treatment (T2), resulting in 29 responders and 36 non-responders. Brain arousal was assessed using the Vigilance Algorithm Leipzig (VIGALL 2.1). At baseline responders and non-responders differed in distribution of overall EEG-vigilance stages (F
= 4.780, p = 0.009), with responders showing significantly more high vigilance stage A and less low vigilance stage B. The 15-minutes Time-course of EEG-vigilance did not differ significantly between groups. Exploratory analyses revealed that responders showed a stronger decline in EEG-vigilance levels from baseline to T1 than non-responders (F
= 4.978, p = 0.005). Higher brain arousal level in responders to antidepressants supports the concept that dysregulation of brain arousal is a possible predictor of treatment response in affective disorders.
Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the use of V-V ECMO in septic shock ...remains controversial. The effect of ECMO-induced inflammation on the microcirculation of the intestine, liver, and critically damaged lungs is unknown. Therefore, the aim of this study was to measure the hepatic and intestinal microcirculation and pulmonary inflammatory response in a model of V-V ECMO and septic shock in the rat. Twenty male Lewis rats were randomly assigned to receive V-V ECMO therapy or a sham procedure. Hemodynamic data were measured by a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by the intravenous infusion of lipopolysaccharide (1 mg/kg). During V-V ECMO therapy, rats received lung-protective ventilation. The hepatic and intestinal microcirculation was assessed by micro-lightguide spectrophotometry after median laparotomy for 2 h. Systemic and pulmonary inflammation was measured by enzyme-linked immunosorbent assays of plasma and bronchoalveolar lavage (BAL), respectively, which included tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-10, C-X-C motif ligand 2 (CXCL2), and CXCL5. Reduced oxygen saturation and relative hemoglobin concentration were measured in the hepatic and intestinal microcirculation during treatment with V-V ECMO. These animals also showed increased systolic, mean, and diastolic blood pressures. While no differences in left ventricular ejection fraction were observed, animals in the V-V ECMO group presented an increased heart rate, stroke volume, and cardiac output. Blood gas analysis showed dilutional anemia during V-V ECMO, whereas plasma analysis revealed a decreased concentration of IL-10 during V-V ECMO therapy, and BAL measurements showed increased concentrations of TNF-α, CXCL2, and CXCL5. Rats treated with V-V ECMO showed impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Despite lung-protective ventilation, increased pulmonary inflammation was recognized during V-V ECMO therapy in septic shock.
Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, ...we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome.
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•Elevated IFN-α plasma levels characteristic for early severe COVID-19 (sCOVID-19)•Differential IFN-α vs. TNF signaling discriminates severe vs. moderate COVID-19•NK cells exert anti-SARS-CoV-2 activity but are functionally impaired in sCOVID-19•Persistent NK cell dysfunction may promote fibrotic lung disease in sCOVID-19
The importance of NK cells in the innate response to viral infection provides rationale for deeper understanding of their role in COVID-19. Here, Krämer et al. utilize longitudinal analysis of NK cells to show early TNF and IFN-α signatures associated with moderate and severe COVID-19, respectively, and NK cell functional impairment in severe disease.
Background:
Platelet-rich plasma (PRP) is widely used in sports medicine. Available PRP preparations differ in white blood cell, platelet, and growth factor concentrations, making standardized ...research and clinical application challenging.
Purpose:
To characterize a newly standardized procedure for pooled PRP that provides defined growth factor concentrations.
Study Design:
Controlled laboratory study.
Methods:
A standardized growth factor preparation (lyophilized PRP powder) was prepared using 12 pooled platelet concentrates (PCs) derived from different donors via apheresis. Blood samples and commercially available PRP (SmartPrep-2) served as controls (n = 5). Baseline blood counts were analyzed. Additionally, single PCs (n = 5) were produced by standard platelet apheresis. The concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor AB (PDGF-AB), transforming growth factor β1 (TGF-β1), insulin-like growth factor 1 (IGF-1), interleukin (IL)–1α, IL-1β, and IL-1 receptor agonist (IL-1RA) were analyzed by enzyme-linked immunosorbent assay, and statistical analyses were performed using descriptive statistics, mean differences, 95% CIs, and P values (analysis of variance).
Results:
All growth factor preparation methods showed elevated concentrations of the growth factors VEGF, bFGF, PDGF-AB, and TGF-β1 compared with those of whole blood. Large interindividual differences were found in VEGF and bFGF concentrations. Respective values (mean ± SD in pg/mL) for whole blood, SmartPrep-2, PC, and PRP powder were as follows: VEGF (574 ± 147, 528 ± 233, 1087 ± 535, and 1722), bFGF (198 ± 164, 410 ± 259, 151 ± 99, and 542), PDGF-AB (2394 ± 451, 17,846 ± 3087, 18,461 ± 4455, and 23,023), and TGF-β1 (14,356 ± 4527, 77,533 ± 13,918, 68,582 ± 7388, and 87,495). IGF-1 was found in SmartPrep-2 (1539 ± 348 pg/mL). For PC (2266 ± 485 pg/mL), IGF-1 was measured at the same levels of whole blood (2317 ± 711 pg/mL) but was not detectable in PRP powder. IL-1α was detectable in whole blood (111 ± 35 pg/mL) and SmartPrep-2 (119 ± 44 pg/mL).
Conclusion:
Problems with PRP such as absent standardization, lack of consistency among studies, and black box dosage could be solved by using characterized PRP powder made by pooling and lyophilizing multiple PCs. The new PRP powder opens up new possibilities for PRP research as well as for the treatment of patients.
Clinical Relevance:
The preparation of pooled PRP by means of lyophilization may allow physicians to apply a defined amount of growth factors by using a defined amount of PRP powder. Moreover, PRP powder as a dry substance with no need for centrifugation could become ubiquitously available, thus saving time and staff resources in clinical practice. However, before transferring the results of this basic science study to clinical application, regulatory issues have to be cleared.
The angle-dependent scattering effect of aerosols in the atmosphere not only influences climate through radiative forcing effects but also impacts trace gas remote sensing by modifying the path of ...radiation through the atmosphere. The aerosol phase function, which characterizes the angular signature of scattering, has been continuously monitored from ground-based and space-borne observations. However, the range of scattering angles these instruments can sample is very limited. Here, we report multi-year measurements from a mountain-top remote sensing instrument: the California Laboratory for Atmospheric Remote Sensing Fourier Transform Spectrometer (CLARS-FTS), which overlooks the Los Angeles megacity. The observational geometries of CLARS-FTS provide a wide range of scattering angles, from about 20° (forward) to about 140° (backward), which is larger than the range provided by any existing aerosol remote sensing instrument. We then quantify the aerosol angular scattering effect using the O2 ratio, which is the ratio of retrieved O2 Slant Column Density (SCD) to geometric O2 SCD. The O2 ratio quantifies the light path modification due to aerosol scattering, with a value of 1 representing an aerosol-free scenario. The lower the O2 ratio value than 1, the stronger the aerosol loading. CLARS-FTS measurements are highly sensitive to the angular scattering effect of aerosols in the Los Angeles (LA) urban atmosphere, due to the long light path going through the boundary layer and the wide range of observational angles. The differences in aerosol scattering between different surface reflection points targeted by CLARS-FTS can be explained by differences in their angular scattering geometries. The correlation between measurements at different targets can be used to quantify the strength of the angular dependence of the aerosol phase function. Applying the correlation technique to CLARS-FTS measurements, we find that, from 2011 to 2018, there is no significant trend in the aerosol phase function in the LA megacity. Overall, this study provides a practical observing strategy for quantifying the angular dependence of aerosol scattering in urban atmospheres that could potentially contribute towards improved greenhouse gas remote sensing in megacities.
•A mountain-top observatory for monitoring aerosols in megacities is introduced.•The observatory makes measurements at a wide range of scattering angles.•Aerosol scattering is quantified based on retrieved oxygen slant column.•The aerosol scattering pattern can be explained by variations in scattering angle.•No significant change in aerosol phase function in LA from 2011 to 2018.
HIV pre-exposure prophylaxis (PrEP) has likely contributed to large decreases in HIV incidence among men who have sex with men (MSM) in several major cities. Berlin has seen a smaller decline, and ...affordable PrEP has been accessible through formal channels in Germany only since autumn 2017. We aimed to investigate knowledge and use of PrEP among MSM in Berlin, and factors predictive of a desire to use PrEP and history of PrEP use.
Multicentre, paper-based, self-administered survey of adult MSM whose HIV status was negative or unknown at time of participation. Data were collected from 1 October 2017 to 2 April 2018.
473 of 875 questionnaires were returned (response rate 54.1%; mean age 37.4 years, range 18-79). 90.0% of participants were aware of PrEP and, of these, 48.2% felt well informed about it. Among the 17.2% of participants reporting PrEP use, 59.3% indicated obtaining some or all of it from informal sources. 23.7% of those with no history of PrEP use reported having condomless anal intercourse (CAI) with two or more partners over the past six months. Worries about side effects, cost, not having a doctor who prescribes it, and a lack of information were the most frequently reported barriers to PrEP use. A desire to use PrEP and history of PrEP use were associated in our multivariable model with having multiple CAI partners. A history of PrEP use was associated with having a university degree, one or two parents born outside Germany, or friends living with HIV.
We found high awareness of PrEP among MSM in Berlin, but also a strong need for more education on its pros, cons and proper use. The frequency of informal PrEP use was also high, raising urgent individual and public health concerns. Policy makers need to consider recent calls to improve access to PrEP and PrEP education through regular health services.
Several animal models of atrial fibrillation (AF) have been developed that demonstrate either atrial structural remodeling or atrial electrical remodeling, but the characteristics and spatiotemporal ...organization of the AF between the models have not been compared. Thirty-nine dogs were divided into five groups: rapid atrial pacing (RAP), chronic mitral regurgitation (MR), congestive heart failure (CHF), methylcholine (Meth), and control. Right and left atria (RA and LA, respectively) were simultaneously mapped during episodes of AF in each animal using high-density (240 electrodes) epicardial arrays. Multiple 30-s AF epochs were recorded in each dog. Fast Fourier transform was calculated every 1 s over a sliding 2-s window, and dominant frequency (DF) was determined. Stable, discrete, high-frequency areas were seen in none of the RAP or control dogs, four of nine MR dogs, four of six CHF dogs, and seven of nine Meth dogs in either the RA or LA or both. Average DFs in the Meth model were significantly greater than in all other models in both LA and RA except LA DFs in the RAP model. The RAP model was the only one with a consistent LA-to-RA DF gradient (9.5 +/- 0.2 vs. 8.3 +/- 0.3 Hz, P < 0.00005). The Meth model had a higher spatial and temporal variance of DFs and lower measured organization levels compared with the other AF models, and it was the only model to show a linear relationship between the highest DF and dispersion (R(2) = 0.86). These data indicate that structural remodeling of atria (models known to have predominantly altered conduction) leads to an AF characterized by a stable high-frequency area, whereas electrical remodeling of atria (models known to have predominantly shortened refractoriness without significant conduction abnormalities) leads to an AF characterized by multiple high-frequency areas and multiple wavelets.
Epidermal melanin synthesis determines an individual's skin color. In humans, melanin is formed by melanocytes within the epidermis. The process of melanin synthesis strongly depends on a range of ...cellular factors, including the fine-tuned interplay with reactive oxygen species (ROS). In this context, a role of cold atmospheric plasma (CAP) on melanin synthesis was proposed due to its tunable ROS generation. Herein, the argon-driven plasma jet kINPen
MED was employed, and its impact on melanin synthesis was evaluated by comparison with known stimulants such as the phosphodiesterase inhibitor IBMX and UV radiation. Different available model systems were employed, and the melanin content of both cultured human melanocytes (in vitro) and full-thickness human skin biopsies (in situ) were analyzed. A histochemical method detected melanin in skin tissue. Cellular melanin was measured by NIR autofluorescence using flow cytometry, and a highly sensitive HPLC-MS method was applied, which enabled the differentiation of eu- and pheomelanin by their degradation products. The melanin content in full-thickness human skin biopsies increased after repeated CAP exposure, while there were only minor effects in cultured melanocytes compared to UV radiation and IBMX treatment. Based on these findings, CAP does not appear to be a useful option for treating skin pigmentation disorders. On the other hand, the risk of hyperpigmentation as an adverse effect of CAP application for wound healing or other dermatological diseases seems to be neglectable.
We quantify the impact of atmospheric transport and limited marine boundary layer sampling on changes in global and regional methane burdens estimate using tracer transport model simulations with ...annually repeating methane emissions and sinks but varying atmospheric transport patterns. We find the 1σ error due to this transport and sampling effect on annual global methane increases to be 1.11 ppb/year and on zonal growth rates to be 3.8 ppb/year, indicating that it becomes more critical at smaller spatiotemporal scales. We also find that the trends in inter‐hemispheric and inter‐polar difference of methane are significantly influenced by the effect. Contrary to a negligible trend in the inter‐hemispheric difference of measurements, we find, after adjusting for the transport and sampling, a trend of 0.37 ± 0.06 ppb/year. This is consistent with the emission trend from a 3‐D inversion of the measurements, suggesting a faster increase in emissions in the Northern Hemisphere than in the Southern Hemisphere.
Plain Language Summary
Changes in global and regional atmospheric burdens of methane are determined by the net effect of sources and sinks and atmospheric transport. Many studies approximate the burdens based on measurements from a network of globally distributed surface air sampling sites. Here we quantify the impact of atmospheric transport and limited marine boundary layer sampling (transport and sampling) on changes in global and regional methane burden estimates using tracer transport model simulation with annually repeating methane emissions and sinks but varying atmospheric transport patterns. We find that for assessing the annual global methane increases, a measurement‐only approach is fairly accurate. However, extending the measurement‐only analysis to hemispheric or latitudinal variations is more problematic as transport influences quickly become significant or even dominant. We find a large impact of transport and sampling effect on the inter‐hemispheric and inter‐polar difference.
Key Points
Transport gives rise to CH4 variations in the spatiotemporal gradients, which are not caused by source or sink changes
We find the transport and sampling error on annual global CH4 increases to be 1.11 ppb/year and on zonal growth rates to be 3.8 ppb/year
The transport‐adjusted inter‐hemispheric difference has a trend of 0.37 ppb/year, consistent with the emission trend from a 3‐D inversion
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