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Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols  95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols

BACKGROUND: Segmentation of retinal fragments like blood vessels, Optic Disc (OD), and Optic Cup (OC) enables the early detection of different retinal pathologies like Diabetic Retinopathy (DR), Glaucoma, etc. OBJECTIVE: Accurate segmentation of OD remains challenging due to blurred boundaries, vessel occlusion, and other distractions and limitations. These days, deep learning is rapidly progressing in the segmentation of image pixels, and a number of network models have been proposed for end-to-end image segmentation. However, there are still certain limitations, such as limited ability to represent context, inadequate feature processing, limited receptive field, etc., which lead to the loss of local details and blurred boundaries. METHODS: A multi-dimensional dense attention network, or MDDA-Net, is proposed for pixel-wise segmentation of OD in retinal images in order to address the aforementioned issues and produce more thorough and accurate segmentation results. In order to acquire powerful contexts when faced with limited context representation capabilities, a dense attention block is recommended. A triple-attention (TA) block is introduced in order to better extract the relationship between pixels and obtain more comprehensive information, with the goal of addressing the insufficient feature processing. In the meantime, a multi-scale context fusion (MCF) is suggested for acquiring the multi-scale contexts through context improvement. RESULTS: Specifically, we provide a thorough assessment of the suggested approach on three difficult datasets. In the MESSIDOR and ORIGA data sets, the suggested MDDA-NET approach obtains accuracy levels of 99.28% and 98.95%, respectively. CONCLUSION: The experimental results show that the MDDA-Net can obtain better performance than state-of-the-art deep learning models under the same environmental conditions. [ABSTRACT FROM AUTHOR]

Retinal vascular status in fundus images is a reliable biomarker for diabetes, hypertension and many ophthalmic diseases. Therefore, accurate segmentation of retinal vessels is of great significance for the diagnosis of many diseases. However, due to the inherent complexity of the retina itself and the lack of data, it is difficult to obtain the ideal accuracy of the segmentation results of the vascular end. To solve this problem, we propose an innovative two stage cascades convolutional Neural network (TCCNNet) to segment the retinal vessels in fundus images. In stage 1, an entire down sampled fundus images is sent to a probability-anatomical-prior-guided shallow-layer-enhanced location net to perform rough segmentation. In addition, a novel circular inference module and parameter Dice loss are proposed to reduce the uncertain probabilities and false positive points of the boundary. In stage 2, high-resolution 2D image slices are reconstructed to offset the detailed information lost during downsampling, further refining the contours. Moreover, a multi-view 2.5D net composed of three 2D refinement subnetworks is applied to deeply explore the morphological features, compensating for the mistakes and missing spatial information of a single view. The proposed method is evaluated on different evaluation metrics such as sensitivity, specificity and accuracy. The experimental results show that this method shows the most competitive performance compared to other state of the art methods. [ABSTRACT FROM AUTHOR]

Molecular docking (Mol.Doc) approach of an azo-ester based fluorophore (AEF) with widely studied proteins like Human serum Albumin (HSA), Bovine serum Albumin (BSA), Beta lactoglobin (βLG) and Ovalbumin (OVA) were carried out. The binding affinity and strength of AEF-HSA complex is due to hydrogen-bonding (h-bonding) and hydrophobic interactions (predominantly attributed to pi-alkyl). AEF and HSA acts as h-bonding acceptor as well as donor. The energetically favored conformers of AEF-HSA complex are governed and stabilized by polar as well as non-polar amino acids. On the contrary, the pattern observed in all the conformers of AEF-BSA, AEF- βLG and AEF-OVA are energetically least favored (+ve ∆G) compared to that of HSA. The least binding affinity of AEF is towards OVA (Binding energy (BE) +581.15 Kcalmol−1 followed by βLG (+55.11) and BSA (+12.12) . Though BSA and HSA are structurally similar to each other, they vary in the binding stability with AEF. This is attributed to several unfavorable interactions that destabilize AEF-BSA complex which was not resulted in the complex existing between AEF-HSA. The energetically least stable complexes (AEF-BSA, AEF-βLG and AEF-OVA) are predominantly governed by hydrophobic interactions. However, several h-bonding interactions along with pi-sigma/pi-pi/pi-alkyl interactions result in destabilization of the above complexes. Interestingly, AEF-HSA complex stability is attributed to fewer number of hydrophobic interactions along with h-bonding interactions. The h-bonding interaction governs the stability of the complex which is the driving force. Docking studies illustrates that the binding of amino acids (AAs) in various subdomains play a significant role on the binding nature. The stability of AEF-HSA over other protein complexes in terms of BE is emphasized in the study. The energetically stable sites and sub-domains of AEF with HSA and BSA establish the site selective and site-specific nature of AEF with proteins. In silico studies provide an excellent and easier approach in establishing the molecular interactions existing between AEF with globular proteins. ADMET parameters of the guest molecule calculated exemplifies that AEF compound is less toxic and possesses high oral bioavailability. Based on the binding efficiency of AEF with albumins, the ADMET properties and drug likeliness approach of AEF provides an information on the application towards proteins in the concept of medicine and chemistry.

Akyl urea derivatives, either symmetrical or unsymmetrical in nature possessing a free N-H or N-alkyl moieties in the molecular framework of urea governs the excited state properties of acridinedione dye (ADR1) which is a resorcinol-based derivative. Fluorescence enhancement (FE) of ADR1 dye is observed on the addition of unsymmetrical urea derivatives, whereas a decrease in the fluorescence intensity resulted upon the addition of symmetrical urea derivatives. The nature of the urea derivatives controls the suppression of photoinduced electron transfer (PET) via space, which is the cause of the FE. FQ results from the donor and acceptor moieties of ADR1 dye promoting the PET process. Urea (U), symmetrical and unsymmetrical urea derivatives (except Tetramethyl urea (TMU)) results no significant shift of the localized excited (LE) state emission of ADR1 dye. Studies of the ADR1 dye’s fluorescence lifetime in the presence of urea compounds show a significant increase in lifetime. This phenomenon is explained by a significant difference in the hydrogen-bonding (HB) pattern, which causes variation in the microenvironment created by the solute molecules in the aqueous phase. Both the hydrophobic effects of the alkyl group substituents in the urea molecular framework and the HB interactions between the solute and solvent influence the excited state features of ADR1 dye. Further, the role of urea derivatives and ADR1 dye (both are considered as competitive guest molecules) energetics and molecular interactions were studied in the presence of host molecule, Human Serum Albumin (HSA). The binding energy (BE) and several bimolecular interactions driven by urea derivatives in the presence of ADR1-HSA complex in comparison with that of urea derivatives-HSA complex were investigated by molecular docking (Mol.Doc) methodology. Incorporating theoretical research along with steady state and time-resolved fluorescence investigations proved to be an effective method to evaluate the interactions of competing solutes comprising both hydrophobic and HB functional groups.

β2-glycoprotein I (β2-Gp1) is a cardiolipin-binding plasma glycoprotein. It is evolutionarily conserved from invertebrates, and cardiolipin-bound β2-Gp1 is a major target of antiphospholipid antibodies seen in autoimmune disorders. Cardiolipin is almost exclusively present in mitochondria, and mitochondria are present in circulating blood. We show that β2-Gp1 binds to cell-free mitochondria (CFM) in the circulation and promotes its phagocytosis by macrophages at physiological plasma concentrations. Exogenous CFM had a short circulation time of less than 10 minutes in mice. Following infusion of CFM, β2-Gp1-deficient mice had significantly higher levels of transfused mitochondria at 5 minutes (9.9 ± 6.4 pg/ml versus 4.0 ± 2.3 pg/ml in wildtype, p = 0.01) and at 10 minutes (3.0 ± 3.6 pg/ml versus 1.0 ± 0.06 pg/ml in wild-type, p = 0.033, n = 10). In addition, the splenic macrophages had less phagocytosed CFM in β2-Gp1-deficient mice (24.4 ± 2.72% versus 35.6 ± 3.5 in wild-type, p = 0.001, n = 5). A patient with abnormal β2-Gp1, unable to bind cardiolipin, has increased CFM in blood (5.09 pg/ml versus 1.26 ± 1.35 in normal) and his plasma induced less phagocytosis of CFM by macrophages (47.3 ± 1.6% versus 54.3 ± 1.3, p = 0.01) compared to normal plasma. These results show the evolutionarily conserved β2-Gp1 is one of the mediators of the clearance of CFM in circulation.

Palmyrah young shoot is rich in starch and fiber and provides good glycemic control. Unfortunately, the consumption rate is limited by the presence of bitter and toxic compounds. Reported literatures reveal that thermal treatment especially dry heat processes like milling the flour at more than 80 °C had an impact on toxicity reduction rather than wet heat processes like boiling. As a result, the current study was aimed to investigate the combined effect of wet (boiling) and dry (radio frequency) heat processing on the debittering of young shoot flour in comparison with tray drying. In the study the flour obtained by a combination of boiling and drying was considered as treated flour and without boiling and drying was considered as untreated flour. The combined effect of wet and dry heat processing had an impact on the nutrients but had no effect on bitterness reduction. The study found tray dried untreated flour favored the feasibility of bitterness reduction as compared to other samples. The compounds (FlabelliferinsB, Flabelliferins–II, isomers of flabelliferins, and vitamin C) responsible for bitterness and its intensity were identified by FTMS. Furthermore, the study revealed that debittering process improved the functional properties of young shoot flour compared to raw flour.

Combined methylmalonic acidemia (MMA) and hyperhomocysteinemias are inborn errors of vitamin B12 metabolism, and mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) underlie some forms of these disorders. Here the authors generated mouse models of a human syndrome due to mutations in RONIN (THAP11) and HCFC1, and show that this syndrome is both an inborn error of vitamin B12 metabolism and displays some features of ribosomopathy.

Most studies on the language use of Malaysian Tamils focus on the upkeep of the Tamil language. There is, however, a dearth of investigations into language use in a multilingual context among the younger generation of speakers. The present study aims to fill this gap by using Fishman’s (1972) domain model to examine the language used by Tamil youth in intra-group communication in seven domains. Data were collected from 109 questionnaires, 42 audio-recordings of natural conversations and 40 interviews. The findings revealed that in four domains, which were the family, friendship, religion, and neighbourhood, Tamil is used more frequently. The highest usage of the language is predominantly among friends. However, there was a decreasing use of Tamil in the family domain among the younger generations with many married participants claiming to use English rather than Tamil as the home language. This does not bode well for the maintenance of Tamil as a first language in the future. The findings show how participants’ use of Tamil, English and Malay is linked to concepts of identity, solidarity, and their perceptions of these languages. The findings also point to the development of a localised variety of Tamil reflective of the Malaysian cultural landscape.

Sugarcane (Saccharum spp.) is one of the most valuable food and industrial crops. Its production is constrained due to major biotic (fungi, bacteria, viruses and insect pests) and abiotic (drought, salt, cold/heat, water logging and heavy metals) stresses. The ever-increasing demand for sugar and biofuel and the rise of new pest and disease variants call for the use of innovative technologies to speed up the sugarcane genetic improvement process. Developing new cultivars through conventional breeding techniques requires much time and resources. The advent of CRISPR/Cas genome editing technology enables the creation of new cultivars with improved resistance/tolerance to various biotic and abiotic stresses. The presence of genome editing cassette inside the genome of genome-edited plants hinders commercial exploitation due to regulatory issues. However, this limitation can be overcome by using transgene-free genome editing techniques. Transgene-free genome editing approaches, such as delivery of the RNPs through biolistics or protoplast fusion, virus-induced genome editing (VIGE), transient expression of CRISPR/Cas reagents through Agrobacterium-mediated transformation and other approaches, are discussed. A well-established PCR-based assay and advanced screening systems such as visual marker system and Transgene killer CRISPR system (TKC) rapidly identify transgene-free genome edits. These advancements in CRISPR/Cas technology speed up the creation of genome-edited climate-smart cultivars that combat various biotic and abiotic stresses and produce good yields under ever-changing conditions.

Medicated chewing gum, a soft, cohesive enjoyable confectionery product loaded with bioactive compounds are chewed to release the bioactives for healing targeted parts. Currently, the production of chewing gum in the global chewing gum market is rapidly increasing from USD 25 billion to an estimated USD 37 billion by the year 2023. The application of chewing gum in drug delivery system has increased compared to pharmaceutical pre-dosage form. However, gum bases are thrown away after chewing which generates non-biodegradable waste causing harmful effects to the environment as well as living organisms. The review confers adequate information to increase the scale of production of biodegradable chewing gum for delivering of bioactive compounds as well as zero-waste technology which reduces environmental pollution in a sustainable manner. Processing of medicated chewing gums could contribute to the future food industry in developing nutraceutical products by using degradable gum bases.

Normal human red blood cells have an average life span of about 120 days in the circulation after which they are engulfed by macrophages. This is an extremely efficient process as macrophages phagocytose about 5 million erythrocytes every second without any significant release of hemoglobin in the circulation. Despite large number of investigations, the precise molecular mechanism by which macrophages recognize senescent red blood cells for clearance remains elusive. Red cells undergo several physicochemical changes as they age in the circulation. Several of these changes have been proposed as a recognition tag for macrophages. Most prevalent hypotheses for red cell clearance mechanism(s) are expression of neoantigens on red cell surface, exposure phosphatidylserine and decreased deformability. While there is some correlation between these changes with aging their causal role for red cell clearance has not been established. Despite plethora of investigations, we still have incomplete understanding of the molecular details of red cell clearance. In this review, we have reviewed the recent data on clearance of senescent red cells. We anticipate recent progresses in in vivo red cell labeling and the explosion of modern proteomic techniques will, in near future, facilitate our understanding of red cell senescence and their destruction.

Coagulopathy often develops soon after acute traumatic brain injury and its cause remains poorly understood. We have shown that injured brains release cellular microvesicles that disrupt the endothelial barrier and induce consumptive coagulopathy. Morphologically intact extracellular mitochondria accounted for 55.2% of these microvesicles, leading to the hypothesis that these extracellular mitochondria are metabolically active and serve as a source of oxidative stress that activates platelets and renders them procoagulant. In testing this hypothesis experimentally, we found that the extracellular mitochondria purified from brain trauma mice and those released from brains subjected to freeze-thaw injury remained metabolically active and produced reactive oxygen species. These extracellular mitochondria bound platelets through the phospholipid-CD36 interaction and induced α-granule secretion, microvesiculation, and procoagulant activity in an oxidant-dependent manner, but failed to induce aggregation. These results define an extracellular mitochondria-induced and redox-dependent intermediate phenotype of platelets that contribute to the pathogenesis of traumatic brain injury-induced coagulopathy and inflammation.

Angiotensin-converting enzyme (ACE) inhibitors are extensively prescribed to treat patients with hypertension, congestive heart failure, and diabetic nephropathy. A small fraction of these patients (approximately 0.7%) develop angioedema, manifested by swelling of the lips and oropharynx. Angioedema of oropharynx is a medical emergency that can lead to asphyxiation and death. The angioedema is due to bradykinin generated from high molecular weight kininogen by kallikrein, which is derived from plasma prekallikrein by action of the factor XIIa, factor Xia, or prolylcarboxypeptidase. Bradykinin induces vasodilation and increased vascular permeability. ACE is the major degrading enzyme of bradykinin in the intravascular department. ACE inhibitors inhibit the proteolytic inactivation of bradykinin. We report a patient with oropharyngeal angioedema associated with an ACE inhibitor with complete absence of plasma prekallikrein due to homozygous mutation (Ser97PhefsTer173).

Abstract Treatment with dasatinib, a tyrosine kinase inhibitor, is associated with edema, pleural effusion, and pulmonary edema. We investigated the effect of dasatinib on the barrier function of human microvascular endothelial cells‐1 (HMEC‐1) in vitro and in vivo. The permeability of HMEC‐1 to fluorescein isothiocyante (FITC)‐dextran increased in Transwell chambers within 5 min following the addition of therapeutic concentrations of dasatinib. The change in permeability was associated with increased activation of RhoA GTPase and its effector Rho‐associated coiled‐coil kinase 1(ROCK1). RhoA inhibitor C3 transferase almost completely inhibited dasatinib‐induced increase in permeability. Under similar conditions, imatinib had no effect on permeability or activation of RhoA. Since integrin‐induced cell spreading suppresses RhoA activation, we examined the effect of dasatinib on cell spreading on fibronectin substrate. Dasatinib impaired endothelial cell spreading in a concentration‐dependent manner and induced disorganization of actin fibers. Tyrosine kinases play an essential role in transmitting signals from integrins to RhoA and we examined tyrosine phosphorylation of several cytoskeletal proteins. Dasatinib markedly inhibited tyrosine phosphorylation of p130 Crk‐associated substrate (p130cas), paxillin and vinculin. These results suggest that the inhibition of tyrosine phosphorylation of the focal adhesion plaque components by dasatinib may alter the assembly of actin fibers resulting in the activation of RhoA/ROCK pathway. Consistent with these findings, dasatinib‐induced increase in the permeability was blocked by ROCK inhibitor y27632. In vivo administration of y27632, significantly inhibited the dasatinib‐induced extravasation of Evans blue in mice and dasatinib‐induced increase in microvascular permeability was attenuated in ROCK1‐deficient mice. These findings suggest that ROCK inhibitors could serve as therapeutic modalities to ameliorate the dasatinib‐induced pulmonary changes.

Cyclooxygenase (COX) is the rate-limiting enzyme in conversion of arachidonic acid to prostanoids, and has two isoforms, COX1 and COX2, which share ~65% amino acid homology. COX1 is universally expressed in many cell types including platelets; however, expression of COX2 is known to be more limited. We examined expression of COX2 mRNA and protein in platelets and platelet-derived microparticles (MPs); using quantitative RT-PCR, immunostaining, and Western blotting. We have detected a significant amount of COX2 in platelets, both at mRNA and protein levels. We found that COX1/COX2 mRNA and protein ratios in platelets were 370:1 and 17:1, respectively. Expression level of COX2 in platelets was less than COX1, but comparable to the expression of COX2 in malignant epithelial cells. Considering the important role of COX2 in tumorigenesis and thrombosis, and the large number of circulating platelets, we propose that platelet COX2 may play an important role in physiologic and pathologic conditions.

Ticagrelor (TIC), a P2Y purinoceptor 12 (P2Y12)-receptor antagonist, has been widely used to treat patients with acute coronary syndrome. Although animal studies suggest that TIC protects against atherosclerosis, it remains unknown whether it does so through its potent platelet inhibition or through other pathways. Here, we placed hypercholesterolemic Ldlr-/-Apobec1-/- mice on a high-fat diet and treated them with either 25 mg/kg/day of clopidogrel (CLO) or 180 mg/kg/day of TIC for 16 weeks and evaluated the extent of atherosclerosis. Both treatments equally inhibited platelets as determined by ex vivo platelet aggregation assays. The extent of atherosclerosis, however, was significantly less in the TIC group than in the CLO group. Immunohistochemical staining and ELISA showed that TIC treatment was associated with less macrophage infiltration to the atherosclerotic intima and lower serum levels of CCL4, CXCL10, and TNFα, respectively, than CLO treatment. Treatment with TIC, but not CLO, was associated with higher serum activity and tissue level of paraoxonase-1 (PON1), an anti-atherosclerotic molecule, suggesting that TIC might exert greater anti-atherosclerotic activity, compared with CLO, through its unique ability to induce PON1. Although further studies are needed, TIC may prove to be a viable strategy in the prevention and treatment of chronic stable human atherosclerosis.

Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS) who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD) and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA) therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E) in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS.

In resting platelets, the integrin αIIbβ3 is present in a low-affinity "bent" state. During platelet aggregation, intracytoplasmic signals induce conformational changes (inside-out signaling) that result in a "swung-out" conformation competent to bind ligands such as fibrinogen. The cytoskeleton plays an essential role in αIIbβ3 activation. We investigated the role of the actin interacting protein Wdr1 in αIIbβ3 activation. Wdr1-hypomorphic mice had a prolonged bleeding time (> 10 minutes) compared to that of wild-type mice (2.1 ± 0.7 minutes). Their platelets had impaired aggregation to collagen and thrombin. In a FeCl3 induced carotid artery thrombosis model, vessel occlusion in Wdr1-hypomorphic mice was prolonged significantly compared to wild-type mice (9.0 ± 10.5 minutes versus 5.8 ± 12.6 minutes (p = 0.041). Activation-induced binding of JON/A (a conformation-specific antibody to activated αIIbβ3) was significantly less in Wdr1-hypomorphic platelets at various concentrations of collagen, indicating impaired inside-out activation of αIIbβ3, despite a normal calcium response. Actin turnover, assessed by measuring F-actin and G-actin ratios during collagen- and thrombin-induced platelet aggregation, was highly impaired in Wdr1-hypomorphic platelets. Furthermore, talin failed to redistribute and translocate to the cytoskeleton following activation in Wdr1-hypomorphic platelets. These studies show that Wdr1 is essential for talin-induced activation of αIIbβ3 during platelet activation.