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Wound healing requires well-coordinated events including hemostasis, inflammation, proliferation, and remodeling. Delays in any of these stages leads to chronic wounds, infections, and hypertrophic scarring. Burn wounds are particularly problematic, and may require intervention to ensure timely progression to reduce morbidity and mortality. To accelerate burn wound healing, Platelet-Rich Plasma (PRP)1 can be of value, since platelets release growth factor proteins and inorganic polyphosphates (polyP) that may be integral to wound healing. We used polyP-depleted keratinocyte (HaCaT) and fibroblast cell culture models to determine cell proliferation and scratch-wound repair to determine if polyP, platelet lysate, or combined treatment could accelerate wound healing. While polyP and PRP significantly reduced the open scratch-wound area in fibroblasts and keratinocytes, polyP had no effect on keratinocyte or fibroblast proliferation. PRP was also evaluated as a treatment in a murine model of full thickness wound healing in vivo, including a treatment in which PRP was supplemented with purified polyP. PRP induced significantly more rapid re-epithelialization by Day 3. Pure polyP enhanced the effects of PRP on epithelial tongues, which were significantly elongated in the PRP + high-dose polyP treatment groups compared to PRP alone. Thus, PRP and polyP may serve as an effective therapeutic combination for treating wounds.

Background & Aims Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19). Methods We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD. Results Of the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29–4.55), decompensated cirrhosis (HR 2.91 [1.70–5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53–7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47–3.70]) and decompensated cirrhosis (OR 2.50 [1.20–5.21]) were independently associated with risk for severe COVID-19. Conclusions The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. Clinicaltrials.gov number NCT04439084

Stem cells are adherent cells whose multipotency and differentiation can be regulated by numerous microenvironmental signals including soluble growth factors and surface topography. This study describes a simple method for creating distinct micropatterns via microphase separation resulting from polymer demixing of poly(desaminotyrosyl-tyrosine carbonate) (PDTEC) and polystyrene (PS). Substrates with co-continuous (ribbons) or discontinuous (islands and pits) PDTEC regions were obtained by varying the ratio of PDTEC and sacrificial PS. Human mesenchymal stem cells (MSCs) cultured on co-continuous PDTEC substrates for 3 days in bipotential adipogenic/osteogenic (AD/OS) induction medium showed no change in cell morphology but exhibited increased anisotropic cytoskeletal organization and larger focal adhesions when compared to MSCs cultured on discontinuous micropatterns. After 14 days in bipotential AD/OS induction medium, MSCs cultured on co-continuous micropatterns exhibited increased expression of osteogenic markers, whereas MSCs on discontinuous PDTEC substrates showed a low expression of adipogenic and osteogenic differentiation markers. Substrates with graded micropatterns were able to reproduce the influence of local underlying topography on MSC differentiation, thus demonstrating their potential for high throughput analysis. This work presents polymer demixing as a simple, non-lithographic technique to produce a wide range of micropatterns on surfaces with complex geometries to influence cellular and tissue regenerative responses. Statement of Significance A better understanding of how engineered microenvironments influence stem cell differentiation is integral to increasing the use of stem cells and materials in a wide range of tissue engineering applications. In this study, we show the range of topography obtained by polymer demixing is sufficient for investigating how surface topography affects stem cell morphology and differentiation. Our findings show that co-continuous topographies favor early (3-day) cytoskeletal anisotropy and focal adhesion maturation as well as long-term (14-day) expression of osteogenic differentiation markers. Taken together, this study presents a simple approach to pattern topographies that induce divergent responses in stem cell morphology and differentiation.

Truxene (10,15-dihydro-5H-diindeno[ 1,2-a; 1', 2'-c] fluorene) derived blue emitting materials were designed and developed utilizing Suzuki and Buchwald-Hartwig type cross-coupling reactions. The target molecules T-1, T-2 and T-3 bearing N-carbazolyl, 1-pyrenyl and N-phenyl-N-(pyren-1-yl) substituents, respectively at 2,7,12-positions, were synthesized under mild conditions by palladium-catalyzed reactions in good yields. To improve the solution processability of the material, n-hexyl chains were used as substituents at 5,5'-, 10,10'-, 15,15'-positions. From UV-vis measurements, the absorption maxima were found to be at 330 nm for T-1, 356 nm for T-2 and 412 nm for T-3. The materials were found to be blue emitting with their emission maxima at 385 nm, 425 nm and 490 nm for T-1, T-2 and T-3, respectively. The excited state lifetimes were investigated using time correlated single photon counting and were found to be 10 ns, 1.4 ns and 5.4 ns for T-1, T-2 and T-3, respectively. The highest photoluminescence quantum yield was observed in the case of T-2 corresponding to a value of 0.97. The compounds T-2 and T-3 were used as active materials for the fabrication of solution processed, single layer blue light emitting diodes, with low turn-on voltage (2-3.3 V) and Commission Internationale de l'eclairage (CIE) coordinates corresponding to (0.16, 0.23) and (0.17, 0.36) for T-2 and T-3, respectively.

Latex-containing cells called laticifers are present in at least 41 flowering plant families and are thought to have convergently evolved at least 12 times. These cells are known to function in defense, but little is known about the molecular genetic mechanisms of their development. The expansion of laticifers into their distinctive tube shape can occur through two distinct mechanisms, cell fusion and intrusive growth. The mechanism and extent of intrusive laticifer growth are still being investigated. Hormonal regulation by jasmonic acid and ethylene is important for both laticifer differentiation and latex biosynthesis. Current evidence suggests that laticifers can be specified independently of latex production, but extensive latex production requires specified laticifers. Laticifers are an emerging system for studying the intersection of cell identity specification and specialized metabolism.

The leaching potential of heavy metals from Coal Fly Ash (CFA), Coal Fly Ash Bricks (CFAB) and Clay Brick (CB) were assessed through four laboratory batch leaching procedures. The concentration of 12 heavy metals were analyzed to study heavy metal leaching from CFA, CFAB and CB in surrounding environment. The heavy metal concentrations of CFA, CFAB and CB through various leaching studies conducted were compared with those estimated through acid extraction/digestion including physico-chemical, mineralogical and morphological characterization. The comparative assessment between CFAB and CB were also undertaken to study the leaching of heavy metals vis-a-via laboratory batch leaching procedures. The major compounds present in collected samples were SiO 2 , Al 2 O 3 and Fe 2 O 3 while minor compounds include such as K 2 O, TiO 2 , CaO, MgO, P 2 O 5 and SO 3 . The most abundant heavy metals leached out during laboratory batch leaching studies were Al>Fe>Mn>Zn followed by other heavy metals. The study also emphasized the use of CFAB compared to CB in and around thermal power stations due to environmental suitability in the terms of leaching behavior.

Stem and progenitor cells that exhibit significant regenerative potential and critical roles in cancer initiation and progression remain difficult to characterize. Cell fates are determined by reciprocal signaling between the cell microenvironment and the nucleus; hence parameters derived from nuclear remodeling are ideal candidates for stem/progenitor cell characterization. Here we applied high-content, single cell analysis of nuclear shape and organization to examine stem and progenitor cells destined to distinct differentiation endpoints, yet undistinguishable by conventional methods. Nuclear descriptors defined through image informatics classified mesenchymal stem cells poised to either adipogenic or osteogenic differentiation, and oligodendrocyte precursors isolated from different regions of the brain and destined to distinct astrocyte subtypes. Nuclear descriptors also revealed early changes in stem cells after chemical oncogenesis, allowing the identification of a class of cancer-mitigating biomaterials. To capture the metrology of nuclear changes, we developed a simple and quantitative "imaging-derived" parsing index, which reflects the dynamic evolution of the high-dimensional space of nuclear organizational features. A comparative analysis of parsing outcomes via either nuclear shape or textural metrics of the nuclear structural protein NuMA indicates the nuclear shape alone is a weak phenotypic predictor. In contrast, variations in the NuMA organization parsed emergent cell phenotypes and discerned emergent stages of stem cell transformation, supporting a prognosticating role for this protein in the outcomes of nuclear functions.

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is a strong AHR agonist, causes significant suppression of human B cell activation and differentiation. The current studies describe the identification of Src homology phosphatase 1 (SHP-1) encoded by the gene PTPN6 as a putative regulator of TCDD-mediated suppression of B cell activation. Shp-1 was initially identified through a genome-wide analysis of AHR binding in mouse B cells in the presence of TCDD. The binding of AHR to the PTPN6 promoter was further confirmed using electrophoretic mobility shift assays in which, specific binding of AHR was detected at four putative DRE sites within PTPN6 promoter. Time-course measurements performed in human B cells highlighted a significant increase in SHP-1 mRNA and protein levels in the presence of TCDD. The changes in the protein levels of SHP-1 were also observed in a TCDD concentration-dependent manner. The increase in SHP-1 levels was also seen to occur due to a change in early signaling events in the presence of TCDD. We have shown that BCL-6 regulates B cell activation by repressing activation marker CD80 in the presence of TCDD. TCDD-treatment led to a significant increase in the double positive (SHP-1hi BCL-6hi) population. Interestingly, treatment of naive human B cells with SHP-1 inhibitor decreased BCL-6 protein levels suggesting possible regulation of BCL-6 by SHP-1 for the first time. Collectively, these results suggest that SHP-1 is regulated by AHR in the presence of TCDD and may, in part through BCL-6, regulate TCDD-mediated suppression of human B cell activation.

We demonstrate all thermal vapor-deposited CsSnBr 3 perovskite solar cells. The cell architecture consists of a planar CsSnBr 3 heterojunction where the perovskite layer is grown by thin sequential deposition of SnBr 2 and CsBr allowing for immediate reaction. While other halides of CsSnX 3 (e.g. X=Cl, I) are extremely air sensitive and change color within seconds, illumination tests performed on unencapsulated CsSnBr 3 devices in ambient air show no change over the span of hours. Further, we evaluate the impact of low-temperature annealing and incorporation of various fluoride passivating dopant profiles via vapor deposition. Our results demonstrate an exciting alternative pathway to develop all-inorganic lead-free perovskite photovoltaics.

While the development of second- and third-generation drug-eluting stents (DES) have significantly improved patient outcomes by reducing smooth muscle cell (SMC) proliferation, DES have also been associated with an increased risk of late-stent thrombosis due to delayed re-endothelialization and hypersensitivity reactions from the drug-polymer coating. Furthermore, DES anti-proliferative agents do not counteract the upstream oxidative stress that triggers the SMC proliferation cascade. In this study, we investigate biocompatible amphiphilic macromolecules (AMs) that address high oxidative lipoprotein microenvironments by competitively binding oxidized lipid receptors and suppressing SMC proliferation with minimal cytotoxicity. To determine the influence of nanoscale assembly on proliferation, micelles and nanoparticles were fabricated from AM unimers containing a phosphonate or carboxylate end-group, a sugar-based hydrophobic domain, and a hydrophilic poly(ethylene glycol) domain. The results indicate that when SMCs are exposed to high levels of oxidized lipid stimuli, nanotherapeutics inhibit lipid uptake, downregulate scavenger receptor expression, and attenuate scavenger receptor gene transcription in SMCs, and thus significantly suppress proliferation. Although both functional end-groups were similarly efficacious, nanoparticles suppressed oxidized lipid uptake and scavenger receptor expression more effectively compared to micelles, indicating the relative importance of formulation characteristics (e.g., higher localized AM concentrations and nanotherapeutic stability) in scavenger receptor binding as compared to AM end-group functionality. Furthermore, AM coatings significantly prevented platelet adhesion to metal, demonstrating its potential as an anti-platelet therapy to treat thrombosis. Thus, AM micelles and NPs can effectively repress early stage SMC proliferation and thrombosis through non-cytotoxic mechanisms, highlighting the promise of nanomedicine for next-generation cardiovascular therapeutics.

Cyber security and fraud identification are gaining priority with the rise in cyber crime. Any computer on a network is vulnerable to unauthorized access or cyber attacks (bruteforce, DoS, etc.). To deal with these threats of frauds, cyber attacks or unauthorized access, it is important to track the activities of user on any application or website. Logging of user activities and events performed along with the time of access can help the developer to find out the bugs in code as well as the clandestine moves of any user. This paper deals with the significance of the important aspects of logging the details of user activity for secure and easy access of an application. For this, it uses logging framework tools like log4j provided by Apache, to track all the user activities which can be later used for maintenance as well as security purposes.