The search of multifunctional epoxy nanocomposites with both strength and toughness combined with smart features such as electrical conductivity is essential in design of advanced materials. In this ...work, by utilizing a binary nanofiller strategy, both strength and toughness as well as high electrical conductivity are obtained in epoxy with trace nanopolystyrene grafted with epichlorohydrin (nano g-PS) to facilitate the dispersion of multi-walled carbon nanotubes (MWCNTs). The increased tensile strength (37.6%) and flexural strength (34.4%) are acquired in nano g-PS (0.0677 vol%)/MWCNTs (0.0335 vol%)/epoxy in contrast to pure epoxy. A remarkably improved tensile toughness up to 379.2% and an increased elongation at break up to 208.3% are obtained in this epoxy nanohybrid. The synergistic interactions among nano g-PS, MWCNTs and epoxy matrix as well as the state transition of nano g-PS from glassy state to fluid state provide an improved dispersion of nanofillers which is responsible for the increased electrical conductivity and enhanced mechanical properties. The decreased surface resistivity allows these nanohybrids to sufficiently dissipate surface charges as an antistatic material. This work provides an effective way to disperse carbon nanotubes with small amount of thermoplastic PS to simultaneously strengthen and toughen the thermosetting epoxy while introducing highly conductive function.
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Herein, we report the preparation of polyaniline (PANI) crystalline nanostructures and their dependent negative permittivity. By controlling the types of doped acids and the doping levels, PANI ...nanostructures with different crystallinity degrees are synthesized and composed of alternating metallic islands and amorphous regions confirmed by high resolution transmission electron microscopy (HRTEM). It's found that 0.15 mol L−1 of p-toluenesulfonic acid (PTSA) as doped acid is the optimal concentration to achieve a proper molecular weight (226,904 g mol−1) and higher degree of crystallinity (33.4%) from X-ray diffraction (XRD) for PANI. With further increasing the concentration of PTSA to 0.30 mol L−1, the degree of crystallinity (37%) of PANI has little change, but its molecular weight is quickly decreased to 35,102 g mol−1. As a consequence, the electrical conductivity of PANI increases from 1.1 × 10−3 S cm−1 for poly (2-acrylamido-2-methyl-1-propanesulfonic acid) (p-AMPS) to 6.9 S cm−1 for PTSA and the PANI crystalline nanostructures doped with PTSA and hydrochloric acid possess a negative permittivity within the measured frequency range of 20 Hz to 2 MHz, whereas the permittivity for PANI doped with perchloric acid, phosphoric acid, camphorsulfonic acid, and p-AMPS switches from negative at low frequency to positive at high frequency. By calculation from AC conductivity, the charge carrier transport in these PANI systems follows the polaron hopping transport mechanism.
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•Negative permittivity of polyaniline (PANI) could be tuned via PANI nanostructures.•The influences of the doped acid types and doping degrees on the structure of PAN were studied.•The PANI nanostructures were composed of alternating metallic island and amorphous regions.•The charge carrier transport in these PANI systems followed the polaron hopping transport mechanism.
Nicotinamide adenine dinucleotide (NAD), a cofactor for hundreds of metabolic reactions in all cell types, plays an essential role in metabolism, DNA repair, and aging. However, how NAD metabolism is ...impacted by the environment remains unclear. Here, we report an unexpected trans-kingdom cooperation between bacteria and mammalian cells wherein bacteria contribute to host NAD biosynthesis. Bacteria confer resistance to inhibitors of NAMPT, the rate-limiting enzyme in the amidated NAD salvage pathway, in cancer cells and xenograft tumors. Mechanistically, a microbial nicotinamidase (PncA) that converts nicotinamide to nicotinic acid, a precursor in the alternative deamidated NAD salvage pathway, is necessary and sufficient for this protective effect. Using stable isotope tracing and microbiota-depleted mice, we demonstrate that this bacteria-mediated deamidation contributes substantially to the NAD-boosting effect of oral nicotinamide and nicotinamide riboside supplementation in several tissues. Collectively, our findings reveal an important role of bacteria-enabled deamidated pathway in host NAD metabolism.
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•Bacteria confer host cells with resistance to NAMPT inhibitors (NAMPTis)•Bacteria produce deamidated NAD precursors and prevent NAD depletion•Bacteria rescue NAMPTi-induced toxicity through nicotinamidase PncA•Oral NAM and NR boost in vivo NAD largely via microbiota-dependent deamidated pathway
Shats et al. describe an unexpected trans-kingdom interaction between bacteria and mammals, wherein bacteria contribute to mammalian host NAD biosynthesis through a microbial nicotinamidase (PncA). This bacteria/gut microbiota-mediated facilitation of the deamidated NAD biosynthesis is important for the efficacy of commercial oral NAD-boosting supplements in mice.
Glucocorticoids (GCs) are master regulators of systemic metabolism. Intriguingly, Cushing’s syndrome, a disorder of excessive GCs, phenocopies several menopause-induced metabolic pathologies. Here, ...we show that the glucocorticoid receptor (GR) drives steatosis in hypogonadal female mice because hepatocyte-specific GR knockout mice are refractory to developing ovariectomy-induced steatosis. Intriguingly, transcriptional profiling revealed that ovariectomy elicits hepatic GC hypersensitivity globally. Hypogonadism-induced GC hypersensitivity results from a loss of systemic but not hepatic estrogen (E2) signaling, given that hepatocyte-specific E2 receptor deletion does not confer GC hypersensitivity. Mechanistically, enhanced chromatin recruitment and ligand-dependent hyperphosphorylation of GR underlie ovariectomy-induced glucocorticoid hypersensitivity. The dysregulated glucocorticoid-mediated signaling present in hypogonadal females is a product of increased follicle-stimulating hormone (FSH) production because FSH treatment in ovary-intact mice recapitulates glucocorticoid hypersensitivity similar to hypogonadal female mice. Our findings uncover a regulatory axis between estradiol, FSH, and hepatic glucocorticoid receptor signaling that, when disrupted, as in menopause, promotes hepatic steatosis.
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•Hypogonadal female mice develop Cushing-like syndrome•The hepatic GR transcriptome is reprogrammed in the absence of estrogen•Ovariectomy promotes GC hypersensitivity•FSH potentiates hepatic GR signaling
Menopause is well known to promote metabolic dysfunction in females. Loss of systemic estrogen has long been thought to be the primary mediator of these metabolic defects in post-menopausal women. Quinn et al. reveal that stress hormones are, in fact, the primary contributor to metabolic disturbances following ovariectomy in mice.
Spermatogonial stem cells (SSCs) have the dual capacity to self-renew and differentiate into progenitor spermatogonia that develop into mature spermatozoa. Here, we document that preferentially ...expressed antigen of melanoma family member 12 (PRAMEF12) plays a key role in maintenance of the spermatogenic lineage. In male mice, genetic ablation of Pramef12 arrests spermatogenesis and results in sterility which can be rescued by transgenic expression of Pramef12. Pramef12 deficiency globally decreases expression of spermatogenic-related genes, and single-cell transcriptional analysis of post-natal male germline cells identifies four spermatogonial states. In the absence of Pramef12 expression, there are fewer spermatogonial stem cells which exhibit lower expression of SSC maintenance-related genes and are defective in their ability to differentiate. The disruption of the first wave of spermatogenesis in juvenile mice results in agametic seminiferous tubules. These observations mimic a Sertoli cell-only syndrome in humans and may have translational implications for reproductive medicine.
For decades, the Wind Chill Temperature Index (WCT) and its various iterations have been used to assess the risk of frostbite on unclothed body parts. This paper presents an innovative ...knowledge-based Cold Weather Ensemble Decision Aid (CoWEDA) that can be used to guide the selection of the most appropriate cold weather ensemble(s) relative to anticipated mission physical activities and environmental conditions. CoWEDA consists of a validated six-cylinder thermoregulatory model, a database of clothing properties, algorithms for calculating the whole ensemble properties from individual garments and a graphical user interface. The user-friendly CoWEDA allows users to select from an inventory of clothing items to build an ensemble suitable for their needs. CoWEDA predicts the risks of both frostbite and hypothermia and ensures that a selected clothing ensemble will provide adequate protection to prevent cold injury. CoWEDA predictions provide not only estimates of frostbite risk similar to WCT tables but also hypothermia times and clothing required to prevent cold injuries. In addition, a CoWEDA model variant can predict survivability and clothing requirements during cold water immersion. Thus, CoWEDA represents a significant enhancement of the WCT-based guidance for cold weather safety and survival by providing greater individual fidelity in cold injury predictions.
Body ventilation systems (BVS) are effective in reducing heat strain, but the amount of heat that a BVS removes from a human body is unclear. The purpose of this study was to propose a method for ...quantifying BVS cooling capacity using manikin evaluation and modeling. Cooling capacity was calculated as the product of maximum cooling potential and cooling efficiency. The maximum cooling potential is calculated as the difference in enthalpy between the air entering and exiting the BVS where the outlet air temperature is equal to skin temperature with a relative humidity of 100%. The cooling efficiency, defined as a ratio of the cooling capacity to the maximum cooling potential, can be determined through measurements on sweating thermal manikins. A BVS system was evaluated on a manikin with the ventilation fan ON (flow rate 4.7 L/s) or OFF under eleven ambient conditions. The measured cooling efficiencies were 0.31 ± 0.02 and almost constant. Using this cooling efficiency, the BVS cooling capacities at various skin temperature and ambient conditions were estimated. This two-step approach can be used to quantify BVS cooling effectiveness during physiology studies. First, the cooling efficiency is determined on sweating thermal manikins. Second, the cooling capacity is calculated from the skin temperature, ambient temperature and relative humidity. However, various factors may reduce the actual cooling provided by the BVS, and the calculated cooling capacity should be considered the upper limit for cooling.
In preparation for embryo implantation and pregnancy, the uterine epithelium undergoes a genomic and biological transition that mediates adhesion and invasion of the blastocyst. These events resemble ...an inflammatory response, and the immune system likely takes an active role in the establishment and maintenance of pregnancy. Although glucocorticoids are primary mediators of the immune system, the functional role of glucocorticoid signaling in the uterine epithelium is not well defined. To investigate the dynamic relationship between glucocorticoids and reproductive hormones, we performed whole-genome microarray analysis in a human uterine endometrial cancer cell line (ECC1 cells) treated with the synthetic glucocorticoid dexamethasone (Dex) alone or in combination with estradiol (E₂). Over 10,000 genes were significantly regulated in the presence of Dex and/or E₂. Surprisingly, unique targets of Dex and E₂ together represented the largest group of regulated genes. Ingenuity pathway analysis found both overlapping and independent regulated networks for each hormone. Several hundred genes were found to be coregulated by Dex and E₂, including several that were antagonistically regulated. The effects of glucocorticoids and E₂ are mediated primarily through the glucocorticoid receptor (NR3C1) and estrogen receptor (ESR1), respectively. In silico promoter analysis revealed that NR3C1 and ESR1 response elements are enriched in antagonistically regulated genes, and signaling through these receptors was required for antagonism. Glucocorticoid and E₂ antagonism of target genes may represent a critical junction between the immune system and female reproductive system. Moreover, identification and ontology analysis of glucocorticoid-regulated genes in a uterine epithelial-like cell line suggests that glucocorticoid signaling regulates important biological functions, including immune cell trafficking and embryonic development.
A significant number of healthcare workers have responded to aid in the relief and containment of the 2013 Ebola virus disease (EVD) outbreak in West Africa. Healthcare workers are required to wear ...personal protective clothing (PPC) to impede the transmission of the virus; however, the impermeable design and the hot humid environment lead to risk of heat stress.
Provide healthcare workers quantitative modeling and analysis to aid in the prevention of heat stress while wearing PPC in West Africa.
A sweating thermal manikin was used to measure the thermal (Rct) and evaporative resistance (Ret) of the five currently used levels of PPC for healthcare workers in the West Africa EVD response. Mathematical methods of predicting the rise in core body temperature (Tc) in response to clothing, activity, and environment was used to simulate different responses to PPC levels, individual body sizes, and two hot humid conditions: morning/evening (air temperature: 25°C, relative humidity: 40%, mean radiant temperature: 35°C, wind velocity: 1 m/s) and mid-day (30°C, 60%, 70°C, 1 m/s).
Nearly still air (0.4 m/s) measures of Rct ranged from 0.18 to 0.26 m2 K/W and Ret ranged from 25.53 to 340.26 m2 Pa/W.
Biophysical assessments and modeling in this study provide quantitative guidance for prevention of heat stress of healthcare workers wearing PPC responding to the EVD outbreak in West Africa.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The current pathological and molecular classification of pancreatic ductal adenocarcinoma (PDAC) provides limited guidance for treatment options, especially for immunotherapy. Cancer-associated ...fibroblasts (CAFs) are major players of desmoplastic stroma in PDAC, modulating tumor progression and therapeutic response. Using single-cell RNA sequencing, we explored the intertumoral heterogeneity among PDAC patients with different degrees of desmoplasia. We found substantial intertumoral heterogeneity in CAFs, ductal cancer cells, and immune cells between the extremely dense and loose types of PDACs (dense-type, high desmoplasia; loose-type, low desmoplasia). Notably, no difference in CAF abundance was detected, but a novel subtype of CAFs with a highly activated metabolic state (meCAFs) was found in loose-type PDAC compared to dense-type PDAC. MeCAFs had highly active glycolysis, whereas the corresponding cancer cells used oxidative phosphorylation as a major metabolic mode rather than glycolysis. We found that the proportion and activity of immune cells were much higher in loose-type PDAC than in dense-type PDAC. Then, the clinical significance of the CAF subtypes was further validated in our PDAC cohort and a public database. PDAC patients with abundant meCAFs had a higher risk of metastasis and a poor prognosis but showed a dramatically better response to immunotherapy (64.71% objective response rate, one complete response). We characterized the intertumoral heterogeneity of cellular components, immune activity, and metabolic status between dense- and loose-type PDACs and identified meCAFs as a novel CAF subtype critical for PDAC progression and the susceptibility to immunotherapy.
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