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Gastroschisis mortality in sub-Saharan Africa (SSA) remains high at 59-100%. Silo inaccessibility contributes to this disparity. Standard of care (SOC) silos cost $240, while median monthly incomes in SSA are $200. Our multidisciplinary American and Ugandan team designed and bench-tested a low-cost (LC) silo that costs $2 and is constructed from locally available materials. Here we describe in vivo LC silo testing.A piglet gastroschisis model was achieved by eviscerating intestines through a midline incision. Eight piglets were randomized to LC or SOC silos. Bowel was placed into the LC or SOC silo, maintained for 1-h, and reduced. Procedure times for placement, intestinal reduction, and silo removal were recorded. Tissue injury of the abdominal wall and intestine was assessed. Bacterial and fungal growth on silos was also compared.There were no gross injuries to abdominal wall or intestine in either group or difference in minor bleeding. Times for silo application, bowel reduction, and silo removal between groups were not statistically or clinically different, indicating similar ease of use. Microbiologic analysis revealed growth on all samples, but density was below the standard peritoneal inoculum of 10LC silos designed for manufacturing and clinical use in SSA demonstrated similar ease of use, absence of tissue injury, and acceptable microbiology profile, similar to SOC silos. The findings will allow our team to proceed with a pilot study in Uganda.

The recent development of solvent- and polymer-based brain clearing techniques has greatly advanced our ability to visualize the mammalian nervous system in 3D. However, it remains challenging to image the mammalian body en bloc as existing methods can be prohibitively expensive or difficult in practice. Here, we developed HYBRiD (HYdrogel-Based Reinforcement of DISCO), by strategically recombining components of organic- and polymer-based clearing pipelines and achieved superb simplicity, transparency, protein retention, and compatibility with direct fluorescent imaging as well as immunostaining in cleared mammalian bodies. Using parvalbumin- and somatostatin-Cre models, we demonstrated the utility of HYBRiD for whole-body imaging of genetically encoded fluorescent reporters without antibody enhancement of signals in newborn and juvenile mice. Using K18-hACE2 transgenic mice, HYBRiD enabled perfusion-free clearing and visualization of SARS-CoV-2 infection in a whole mouse chest, revealing macroscopic and microscopic features of viral pathology in the same sample. HYBRiD offers a simple, affordable, and universal solution to visualize large heterogeneous body parts or entire animals for basic and translational research.

The structural, electronic, and transport properties of zigzag boron nitride nanoribbons (ZBNNRs) with nitrogen-vacancy (N-vacancy) at the center (N-V@C), at the edge (N-V@E), and at the center as well as edge (N-V@CE) are investigated. This work deploys density functional theory (DFT) along with non-equilibrium Green's function (NEGF) formalism. Present DFT-based calculations reveal that a metallic/semiconducting nature can be obtained in N-vacancy ZBNNRs via selective H-passivation. The most structurally stable structure in N-vacancy ZBNNRs is observed for HBN-NV $$_{E}$$ irrespective of ribbon width. The current–voltage characteristics of pristine, bare, and N-vacancy ZBNNRs devices demonstrated that the bare ZBNNRs exhibit maximum current as compared to the N-vacancy ZBNNRs device under low bias. This is because the vacancy defect breaks the edge states and produces some localized defect-induced states, which suppress the electron transmission and reduces current to get a better $$I_{\mathrm{P}}/I_{\mathrm{V}}$$ (peak to valley current ratio PVCR) ratio. It is worth mentioning here that even negative differential resistance (NDR) with a sufficiently high $$I_{\mathrm{P}}/I_{\mathrm{V}}$$ ratio has also been observed for BNH-NV $$_{E}$$ of the order of 10 $$^{10}$$ in both positive and negative biasing. The observed NDR effect suggests that selective H-passivation in N-vacancy ZBNNRs has immense potential applications for nanoscale NDR devices.

A first-principles investigation is carried out on palladium (Pd)-doped armchair graphene nanoribbons (AGNRs) to investigate their structural, electronic and transport properties. The structural analysis of the considered Pd-doped nanoribbons reveals that single Pd doping at the edges of AGNRs results in the most stable configuration. The present findings reveal that the electronic transport properties are strongly dependent on the number of dopant atoms and their positions. Furthermore, it is noted that the proposed two-probe devices exhibit peculiar nonlinear I–V characteristics indicating potential for rectification behavior. Excellent high rectification ratio (RR) and reverse rectification ratio (RRR) are on the order of $$1.8\times 10^{5}$$ and $$9.7\times 10^{4}$$ , respectively, are found for center-Pd-doped 7-AGNRs. The interesting rectifying I–V behavior can be explained by the localization/delocalization effect of frontier orbitals along with the variation of the transmission spectra with the applied bias voltage. These findings indicate that Pd-doped armchair GNRs are a potential candidate for use in next-generation ultralow-power nanoscale switching devices.

Human microbiome studies have shown diversity to exist among different ethnic populations. However, studies pertaining to the microbial composition of CRC among the Indian population have not been well explored. We aimed to decipher the microbial signature in tumor tissues from North Indian CRC patients. Next-generation sequencing of tumor and adjacent tissue derived bacterial 16s rRNA V3-V4 hypevariable regions was performed to investigate the abundance of specific microbes. The expression profile analysis deciphered a decreased diversity among the tumor-associated microbial communities, and at the phyla level, Proteobacteria was differentially expressed in CRC tissues than adjacent normal. Further, DESeq2 normalization identified 4 out of 79 distinct species (pBacteroides massiliensis, Alistipes onderdonkii, Bifidobacterium pseudocatenulatum, and Corynebacterium appendicis. Thus, our findings suggest the use of these microbial signatures as putative biomarkers that can distinguish CRC tissues from their adjacent normal, which may shed light on the pathogenesis of CRC.

The most popular method for production of metallic uranium is by magnesiothermic reduction of UF4. Efficient production of good quality uranium metal chunk in the reaction vessel requires multiple parameter constraints. To theoretically optimize these process parameters, many basic properties, i.e. particle size, heat dissipation, packing density, heating rate, kinetic parameters of reaction, etc., are required. There was lack of information on kinetic parameters of this reaction; therefore, kinetic triplets of UF4 and magnesium metal reaction were determined by non-isothermal DTA method, at 5–20 K min−1 heating rates. The analysis of data was done by model-less methods and model-fitting methods. It was found that the reaction takes place through two parallel competitive mechanisms, bulk diffusion and first-order nucleation and growth of reaction sites, and the corresponding kinetic parameters, frequency factors and activation energies, were 440 min−1, 43.9 kJ mol−1, 420 min−1 and 49.03 kJ mol−1, respectively.

The thin-layer chromatographic (TLC) analysis of extracts/compounds has several applications in the field of food, cosmetics, phytochemistry, and pharmaceutical industry. Mangiferin is a bioactive and natural antioxidant polyphenolic xanthone obtained from different dietary plants and recently gaining remarkable attention due to its high pharmacological significance evident in current scientific validations. This review contains various TLC methods reported so far for the qualitative and quantitative assessments of mangiferin after collating selected research papers from online scientific databases as PubMed, Web of Science, and Scopus. In particular, confirmation of mangiferin from dietary plant, herbal formulations, and biological and bioautographic samples through TLC are discussed in detail and comparison is also established in terms of selectivity, sensitivity, and validity. Ultimately, critical evaluation was done with the aim to deliver useful suggestions for the selection of suitable mobile phase, sample preparation, and detection methods for the analysis of mangiferin.

Electromagnetic safeguards are key factors for electronic devices. Lightweight and highly flexible polymer composite films with high electrical conductivity are considered to be efficient electromagnetic interference (EMI) shielding materials. Polymer composites offer alternative to metal-based composites which have poor flexibility, corrodibility, and are difficult to process. Here, highly flexible polyvinyl alcohol/poly (3, 4-ethylenedioxythiophene):polystyrene sulfonate/multiwalled carbon nanotube (PVA/PEDOT:PSS/MWCNT) free-standing composite films were fabricated by a solution mixing process followed by a simple solvent casting technique. PVA/PEDOT:PSS/MWCNT composite films of thickness around 20 microns showed high EMI shielding effectiveness (SE) in the X-band over the frequency range of 8–12 GHz. Incorporation of MWCNT into the polymer matrix considerably increased the mechanical strength of the PVA/PEDOT:PSS/MWCNT composite free-standing film. This investigation revealed that PVA/PEDOT:PSS/MWCNT composite film with 0.5 wt.% of MWCNT showed excellent absorption-dominated EMI SE of 60 dB over the frequency range of 8–12 GHz with extensive tensile strength. Our study opens a facile way to design flexible, lightweight and free-standing films as EMI shielding for next-generation flexible electronic devices.

Rhamnolipids (RLs) are surface-active compounds and belong to the class of glycolipid biosurfactants, mainly produced from Pseudomonas aeruginosa. Due to their non-toxicity, high biodegradability, low surface tension and minimum inhibitory concentration values, they have gained attention in various sectors like food, healthcare, pharmaceutical and petrochemicals. The ecofriendly biological properties of rhamnolipids make them potent materials to be used in therapeutic applications. RLs are also known to induce apoptosis and thus, able to inhibit proliferation of cancer cells. RLs can also act as immunomodulators to regulate the humoral and cellular immune systems. Regarding their antimicrobial property, they lower the surface hydrophobicity, destruct the cytoplasmic membrane and lower the critical micelle concentration to kill the bacterial cells either alone or in combination with nisin possibly due to their role in modulating outer membrane protein. RLs are also involved in the synthesis of nanoparticles for in vivo drug delivery. In relation to economic benefits, the post-harvest decay of food can be decreased by RLs because they prevent the mycelium growth, spore germination of fungi and inhibit the emergence of biofilm formation on food. The present review focuses on the potential uses of RLs in cosmetic, pharmaceutical, food and health-care industries as the potent therapeutic agents.

Cancer cells hijack autophagy pathway to evade anti-cancer therapeutics. Many molecular signaling pathways associated with drug-resistance converge on autophagy induction. Honokiol (HNK), a natural phenolic compound purified from Magnolia grandiflora, has recently been shown to impede breast tumorigenesis and, in the present study, we investigated whether breast cancer cells evoke autophagy to modulate therapeutic efficacy and functional networks of HNK. Indeed, breast cancer cells exhibit increased autophagosomes-accumulation, MAP1LC3B-II/LC3B-II-conversion, expression of ATG proteins as well as elevated fusion of autophagosomes and lysosomes upon HNK treatment. Breast cancer cells treated with HNK demonstrate significant growth inhibition and apoptotic induction, and these biological processes are blunted by macroautophagy/autophagy. Consequently, inhibiting autophagosome formation, abrogating autophagosome-lysosome fusion or genetic-knockout of BECN1 and ATG7 effectively increase HNK-mediated apoptotic induction and growth inhibition. Next, we explored the functional impact of tumor suppressor STK11 in autophagy induction in HNK-treated cells. STK11-silencing abrogates LC3B-II-conversion, and blocks autophagosome/lysosome fusion and lysosomal activity as illustrated by LC3B-Rab7 co-staining and DQ-BSA assay. Our results exemplify the cytoprotective nature of autophagy invoked in HNK-treated breast cancer cells and put forth the notion that a combined strategy of autophagy inhibition with HNK would be more effective. Indeed, HNK and chloroquine (CQ) show synergistic inhibition of breast cancer cells and HNK-CQ combination treatment effectively inhibits breast tumorigenesis and metastatic progression. Tumor-dissociated cells from HNK-CQ treated tumors exhibit abrogated invasion and migration potential. Together, these results implicate that breast cancer cells undergo cytoprotective autophagy to circumvent HNK and a combined treatment with HNK and CQ can be a promising therapeutic strategy for breast cancer.

First-principle investigations under the flagship of density functional theory have been performed to analyze the prospects of antimonene nanoribbons (SbNR) for carbon mono-oxide (CO) and nitric oxide (NO) sensing applications. We have explored various adsorption configurations of gas molecules on the edges of bare and silicon-doped SbNR with zigzag and armchair edge states. Based on adsorption energy ( $$E_{\text{ads}}$$ ) calculations, it is revealed that CO and NO molecules tend to physisorbed on SbNRs substrate. However, upon the introduction of silicon impurity, gas molecules prefer to chemisorb on SbNRs. The electronic properties’ calculations based on band structures and density of states (DOS) profile predict substantial modification in the band structures of the SbNRs after CO and NO adsorption. Charge transfer analysis indicates that gas molecules act as an acceptor on undoped SbNRs whereas act as a donor on a substitutionally doped substrate. To explore deep into the interaction between the gas molecule and SbNRs’ substrate, charge difference density and projected DOS have been plotted and examined. Furthermore, to determine the feasibility, I–V characteristics have been calculated using a standard two-probe model. It is evident from I–V characteristics that gas adsorption has a prominent impact on the current-carrying capability of SbNR. Finally, the recovery time is calculated to analyze the desorption performance of CO/NO adsorbed on bare and Si-doped SbNRs, henceforth projecting the potential of SbNRs for CO and NO sensor applications.

Single crystal x-ray diffraction measurements on both as-grown as well as oxygenated single crystals of an aluminium doped high temperature superconductor YBa2Cu3−xAlxO6+δ revealed the crystal structure to be orthorhombic with space group Pmmm, in contrast to, tetragonal crystal structures corresponding to space group P4/mmm, previously reported for as-grown YBa2Cu3−xAlxO6+δ, and conflicting structures on oxygenated YBa2Cu3−xAlxO6+δ. The orthorhombic crystal structure was confirmed by powder x-ray diffraction that showed the presence of two peaks corresponding to (020) and (200) reflections associated with orthorhombic structures of space group Pmmm, instead of a single (200) reflection corresponding to tetragonal crystal structures with space group P4/mmm. All the as-grown crystals were found to be superconducting. An oxygen-vacancy cluster distribution model is proposed to explain the differences in the obtained magnetisation hysteresis loop and the broad superconducting transition temperature. The model proposes the existence of two oxygen deficient clusters of (Al-..-Cu-O-Cu)n and (Cu-O-Cu-..)n juxtaposed with each other whose number and size vary as the as-grown single crystals of YBa2Cu3−xAlxO6+δ are subjected to oxygenation. X-ray photoelectron spectroscopy measurements showed the existence of two distinct peaks in each of the spectrum of O, Cu, Y and Ba in YBa2Cu3−xAlxO6+δ crystals corresponding to the two different types of clusters. The relative intensities of each XPS peak was found to decrease in the oxygenated crystals as compared to the as-grown ones confirming the change in the number and size of clusters in the as-grown crystals after oxygenation.

Tumor suppressor and upstream master kinase Liver kinase B1 (LKB1) plays a significant role in suppressing cancer growth and metastatic progression. We show that low-LKB1 expression significantly correlates with poor survival outcome in breast cancer. In line with this observation, loss-of-LKB1 rendered breast cancer cells highly migratory and invasive, attaining cancer stem cell-like phenotype. Accordingly, LKB1-null breast cancer cells exhibited an increased ability to form mammospheres and elevated expression of pluripotency-factors (Oct4, Nanog and Sox2), properties also observed in spontaneous tumors in Lkb1−/− mice. Conversely, LKB1-overexpression in LKB1-null cells abrogated invasion, migration and mammosphere-formation. Honokiol (HNK), a bioactive molecule from Magnolia grandiflora increased LKB1 expression, inhibited individual cell-motility and abrogated the stem-like phenotype of breast cancer cells by reducing the formation of mammosphere, expression of pluripotency-factors and aldehyde dehydrogenase activity. LKB1, and its substrate, AMP-dependent protein kinase (AMPK) are important for HNK-mediated inhibition of pluripotency factors since LKB1-silencing and AMPK-inhibition abrogated, while LKB1-overexpression and AMPK-activation potentiated HNK’s effects. Mechanistic studies showed that HNK inhibited Stat3-phosphorylation/activation in an LKB1-dependent manner, preventing its recruitment to canonical binding-sites in the promoters of Nanog, Oct4 and Sox2. Thus, inhibition of the coactivation-function of Stat3 resulted in suppression of expression of pluripotency factors. Further, we showed that HNK inhibited breast tumorigenesis in mice in an LKB1-dependent manner. Molecular analyses of HNK-treated xenografts corroborated our in vitro mechanistic findings. Collectively, these results present the first in vitro and in vivo evidence to support crosstalk between LKB1, Stat3 and pluripotency factors in breast cancer and effective anticancer modulation of this axis with HNK treatment.

Labeling of proteins with fluorinated amino acids and using fluorine-19 NMR greatly simplifies the NMR spectrum. Changes in the spectrum on interaction with ligands makes protein-observed fragment-based drug screening possible. NMR spectroscopy can be used to quantify the binding affinity between proteins and low-complexity molecules, termed 'fragments'; this versatile screening approach allows researchers to assess the druggability of new protein targets. Protein-observed 19F-NMR (PrOF NMR) using 19F-labeled amino acids generates relatively simple spectra that are able to provide dynamic structural information toward understanding protein folding and function. Changes in these spectra upon the addition of fragment molecules can be observed and quantified. This protocol describes the sequence-selective labeling of three proteins (the first bromodomains of Brd4 and BrdT, and the KIX domain of the CREB-binding protein) using commercially available fluorinated aromatic amino acids and fluorinated precursors as example applications of the method developed by our research group. Fragment-screening approaches are discussed, as well as Kd determination, ligand-efficiency calculations and druggability assessment, i.e., the ability to target these proteins using small-molecule ligands. Experiment times on the order of a few minutes and the simplicity of the NMR spectra obtained make this approach well-suited to the investigation of small- to medium-sized proteins, as well as the screening of multiple proteins in the same experiment.

The isothermal oxidation behavior of UZr2.3 and U2Ti alloys in dry air was studied by thermogravimetric technique in the temperature ranges of 773–848 and 548–623 K, respectively. The oxidation products were found to be U3O8 and ZrO2 for UZr2.3 and U3O8 and TiO2 for U2Ti by X-ray diffraction analysis. The oxidation kinetics were found to best fit into linear rate law for both the alloys in the temperature range of investigation and the lowest value of α (0.11 for UZr2.3 and 0.12 for U2Ti), which corresponds to the fraction of completed reaction. The linear rate constants (k) were evaluated from the oxidation data. The activation energies of oxidation reactions were calculated using the Arrhenius equation and found to be 161 kJ mol−1 for UZr2.3 and 88 kJ mol−1 for U2Ti.

The demonstrated benefits of information seeking for cancer patients, coupled with increases in information availability, underscore the importance of monitoring patient information seeking experiences over time. We compared information seeking among cancer survivors to those with a family history of cancer and those with no history of cancer. We identified characteristics associated with greater information seeking among cancer survivors, key sources of cancer-related information, and changes in information source use over time. Data from five iterations of the Health Information National Trends Survey (HINTS) spanning 2003 to 2013 were merged and analyzed. Frequencies, cross-tabulations, multivariate logistic regression, and multinomial regression analyses were conducted. All data were weighted to provide representative estimates of the adult US population. Cancer information seeking was reported most frequently by cancer survivors (69.8 %). The percentage of cancer survivors who reported information seeking increased from 66.8 % in 2003 to 80.8 % in 2013. Cancer information seeking was independently associated with age, education, and income; seeking was less likely among older adults, those with less education, and those with lower incomes. Compared to respondents in 2003, those in 2005 (odds ratio (OR) = 0.40, 95 % confidence interval (CI) = 0.24-0.65) and 2008 (OR = .43, 95 % CI = 0.26-0.70) were about half as likely to use the Internet as the first source of cancer information compared to a healthcare provider. Despite overall increases in cancer information seeking and access to health information from a variety of sources, healthcare providers remain a key source of health information for cancer survivors.

Hepatocellular carcinoma (HCC) has the second lowest 5-year survival rate (~16%) of all tumor types partly owing to the lack of effective therapeutic agents. Withaferin A (WA) is a bioactive molecule derived from Withania somnifera and the present study is designed to systemically investigate the anti-HCC efficacy of WA. WA inhibited growth, migration and invasion of HCC cells. Using a phospho-kinase screening array, we discovered that WA increased phosphorylation of ERK and p38 in HCC. Further analyses revealed a key role of ERK leading to increased phosphorylation of p90-ribosomal S6 kinase (RSK) and a concomitant activation of ETS-like transcription factor-1(ELK1) and Death Receptor protein-5 (DR5) in HCC. Importantly, oral administration of WA effectively inhibited HepG2-xenografts and DEN-induced-HCC in C57BL/6 mice. Analyses of WA-treated HepG2-xenografts and DEN-induced-HCC tumors showed elevated levels of ERK, RSK, ELK1 and DR5 along with decreased expression of Ki67. In silico analyses of HCC, utilizing published profiling studies showed an inverse correlation between DR5 and Ki67. These data showed the efficacy of WA as an effective agent for HCC inhibition and provided first in vitro and in vivo evidence supporting the key role of a novel crosstalk between WA, ERK/RSK, ELK1, and DR5 in HCC inhibition.

Introduction Honokiol, a small-molecule polyphenol isolated from magnolia species, is widely known for its therapeutic potential as an antiinflammatory, antithrombosis, and antioxidant agent, and more recently, for its protective function in the pathogenesis of carcinogenesis. In the present study, we sought to examine the effectiveness of honokiol in inhibiting migration and invasion of breast cancer cells and to elucidate the underlying molecular mechanisms. Methods Clonogenicity and three-dimensional colony-formation assays were used to examine breast cancer cell growth with honokiol treatment. The effect of honokiol on invasion and migration of breast cancer cells was evaluated by using Matrigel invasion, scratch-migration, spheroid-migration, and electric cell-substrate impedance sensing (ECIS)-based migration assays. Western blot and immunofluorescence analysis were used to examine activation of the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) axis. Isogenic LKB1-knockdown breast cancer cell line pairs were developed. Functional importance of AMPK activation and LKB1 overexpression in the biologic effects of honokiol was examined by using AMPK-null and AMPK-wild type (WT) immortalized mouse embryonic fibroblasts (MEFs) and isogenic LKB1-knockdown cell line pairs. Finally, mouse xenografts, immunohistochemical and Western blot analysis of tumors were used. Results Analysis of the underlying molecular mechanisms revealed that honokiol treatment increases AMP-activated protein kinase (AMPK) phosphorylation and activity, as evidenced by increased phosphorylation of the downstream target of AMPK, acetyl-coenzyme A carboxylase (ACC) and inhibition of phosphorylation of p70S6kinase (pS6K) and eukaryotic translation initiation factor 4E binding protein 1 (4EBP1). By using AMPK-null and AMPK-WT (MEFs), we found that AMPK is required for honokiol-mediated modulation of pACC-pS6K. Intriguingly, we discovered that honokiol treatment increased the expression and cytoplasmic translocation of tumor-suppressor LKB1 in breast cancer cells. LKB1 knockdown inhibited honokiol-mediated activation of AMPK and, more important, inhibition of migration and invasion of breast cancer cells. Furthermore, honokiol treatment resulted in inhibition of breast tumorigenesis in vivo. Analysis of tumors showed significant increases in the levels of cytoplasmic LKB1 and phospho-AMPK in honokiol-treated tumors. Conclusions Taken together, these data provide the first in vitro and in vivo evidence of the integral role of the LKB1-AMPK axis in honokiol-mediated inhibition of the invasion and migration of breast cancer cells. In conclusion, honokiol treatment could potentially be a rational therapeutic strategy for breast carcinoma.