The Applications of Ferulic-Acid-Loaded Fibrous Films for Fruit Preservation

The aim of this study was to develop a novel ultrathin fibrous membrane with a core–sheath structure as an antioxidant food packaging membrane. The core–sheath structure was prepared by coaxial electrospinning, and the release of active substances was regulated by its special structure. Ferulic acid (FA) was incorporated into the electrospun zein/polyethylene oxide ultrathin fibers to ensure their synergistic antioxidant properties. We found that the prepared ultrathin fibers had a good morphology and smooth surface. The internal structure of the fibers was stable, and the three materials that we used were compatible. For the different loading positions, it was observed that the core layer ferulic-acid-loaded fibers had a sustained action, while the sheath layer ferulic-acid-loaded fibers had a pre-burst action. Finally, apples were selected for packaging using fibrous membranes to simulate practical applications. The fibrous membrane was effective in reducing water loss and apple quality loss, as well as extending the shelf life. According to these experiments, the FA-loaded zein/PEO coaxial electrospinning fiber can be used as antioxidant food packaging and will also undergo more improvements in the future

Effects of Prone Positioning for Patients with Acute Respiratory Distress Syndrome Caused by Pulmonary Contusion: A Single-Center Retrospective Study

Background. The effects of prone positioning (PP) on patients with acute respiratory distress syndrome (ARDS) caused by pulmonary contusion (PC) are unclear. We sought to determine the efficacy of PP among patients whose ARDS was caused by PC. Methods. A retrospective observational study was performed at an intensive care unit (ICU) from January 2017 to June 2021. ARDS patients with PaO2/FiO2 (P/F) 0.05), more 28-day ventilator-free days (21.6 ± 5.2 vs. 16.2 ± 7.2 days, P<0.05), and lower mortality (4.4% vs. 13.3%, P<0.05). Conclusions. Among PC cases with moderate to severe ARDS, PP can correct hypoxemia more quickly, improve Crs, reduce atelectasis, increase the extubation rate, shorten mechanical ventilation time and length of ICU stay, and reduce mortality

Production of cultured meat from pig muscle stem cells

Cultured meat is meat for consumption produced in a more sustainable way. It involves cell harvesting and expansion, differentiation into myotubes, construction into muscle fibres and meat structuring. We isolated 5.3 × 104 porcine muscle stem cells from 1 g of neonatal pig muscle tissue. According to calculations, we need to expand muscle stem cells 106-107 times to produce 100 g or 1 kg of cultured meat. However, the cells gradually lost the ability to express stemness and mature muscle cell markers (PAX7, MyHC). To tackle this critical issue and maintain cell function during cell expansion, we found that long-term culture with (100 μM) l-Ascorbic acid 2-phosphate (Asc-2P) accelerated cell proliferation while preserving the muscle cell differentiation. We further optimized a scalable PDMS mold. Porcine muscle stem cells formed structurally-organized myotubes similar to muscle fibres in the mold. Asc-2P enhanced porcine muscle cells grown as 3D tissue networks that can produce a relatively large 3D tissue networks as cultured meat building blocks, which showed improved texture and amino acid content. These results established a realistic workflow for the production of cultured meat that mimics the pork meat structurally and is potentially scalable for industry

Repression of human γ-globin gene expression by a short isoform of the NF-E4 protein is associated with loss of NF-E2 and RNA polymerase II recruitment to the promoter

Binding of the stage selector protein (SSP) to the stage selector element (SSE) in the human γ-globin promoter contributes to the preferential expression of the γ-gene in fetal erythroid cells. The SSP contains the transcription factor CP2 and an erythroid-specific partner, NF-E4. The NF-E4 gene encodes a 22-kDa polypeptide employing a non-AUG initiation codon. Antisera specific to NF-E4 detects this species and an additional 14 kDa protein, which initiates from an internal methionine. Enforced expression of p14 NF-E4 in the K562 fetal/erythroid cell line, and in primary erythroid cord blood progenitors, results in repression of γ-gene expression. Biochemical studies reveal that p14 NF-E4 interacts with CP2, resulting in diminished association of CP2 with the SSE in chromatin immunoprecipitation assays. p45 NF-E2 recruitment to the γ-promoter is also lost, resulting in a reduction in RNA polymerase II and TBP binding and a fall in promoter transcriptional activity. This effect is specific, as enforced expression of a mutant form of p14 NF-E4, which fails to interact with CP2, also fails to repress γ-gene expression in K562 cells. These findings provide one potential mechanism that could contribute to the autonomous silencing of the human γ-genes in adult erythroid cells

An F876l mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (Enzalutamide)

Castration-resistant prostate cancer (CRPC) is the most aggressive, incurable form of prostate cancer. MDV3100 (enzalutamide), an antagonist of the androgen receptor (AR), was approved for clinical use in men with metastatic CRPC. Although this compound showed clinical efficacy, many initial responders later developed resistance. To uncover relevant resistant mechanisms, we developed a model of spontaneous resistance to MDV3100 in LNCaP prostate cancer cells. Detailed characterization revealed that emergence of an F876L mutation in AR correlated with blunted AR response to MDV3100 and sustained proliferation during treatment. Functional studies confirmed that ARF876L confers an antagonist-to-agonist switch that drives phenotypic resistance. Finally, treatment with distinct antiandrogens orcyclin-dependent kinase (CDK)4/6 inhibitors effectively antagonized ARF876L function. Together, these findings suggest that emergence of F876L may (i) serve as a novel biomarker for prediction of drug sensitivity, (ii) predict a "withdrawal" response to MDV3100, and (iii) be suitably targeted with other antiandrogens or CDK4/6 inhibitors. SIGNIFICANCE: We uncovered an F876L agonist-switch mutation in AR that confers genetic and phenotypic resistance to the antiandrogen drug MDV3100. On the basis of this finding, we propose new therapeutic strategies to treat patients with prostate cancer presenting with this AR mutation. © 2013 American Association for Cancer Research

Shearo-caloric effect enhances elastocaloric responses in polymer composites for solid-state cooling

Abstract Room-temperature elastocaloric cooling is considered as a zero-global-warming-potential alternative to conventional vapor-compression refrigeration technology. However, the limited entropy and large-deformation features of elastocaloric polymers hinder the creation of the breakthrough in their caloric responses and device development. Herein, we report that the addition of a small amount of inorganic nanofillers into the polymer induces the aggregate of the effective elastic chains via shearing the interlaminar molecular chains, which provides an additional contribution to the entropy in elastocaloric polymers. Consequently, the adiabatic temperature change of −18.0 K and the isothermal entropy change of 187.4 J kg−1 K−1 achieved in the polymer nanocomposites outperform those of current elastocaloric polymers. Moreover, a large-deformation cooling system with a work recovery efficiency of 56.3% is demonstrated. This work opens a new avenue for the development of high-performance elastocaloric polymers and prototypes for solid-state cooling applications

Targeting HSF1 sensitizes cancer cells to HSP90 inhibitor

The molecular chaperone heat shock protein 90 (HSP90) facilitates the appropriate folding of oncoprotein and is hence thought to be necessary for the survival of certain oncogene-driven cancer cells. This specific hypothesis is being tested in clinical trials involving a number of distinct LWM HSP90 inhibitors including NVP-AUY922 and NVP-HSP990. Signs of clinical activity have been observed, most notably in trastuzumab-refractory, HER2-positive breast cancer, in EGFR-driven lung adenocarcinoma and in ALK-driven lung cancer. Through a pooled RNA interference screen, we showed that heat shock factor 1 (HSF1) is the top sensitizer of HSP90 inhibitor and knockdown of HSF1 specifically enhanced cell death induced by the HSP90 inhibitor. A striking combinational effect was observed when HSF1 knockdown plus with HSP90 inhibitors treatment in a various cell lines and tumor mouse models. In particularly, HSF1 is highly expressed in hepatocellular carcinoma (HCC) patient samples and knockdown of HSF1 sensitizes HSP90 inhibitor in liver cancer model, which might be a new indication for the combinational treatment. To understand the mechanism of the combinational effect, we identified a novel HSF1-target gene DEDD2, which is also involved in attenuation of the activity of HSP90 inhibitors. Interestingly, high expression of DEDD2 is associated with poor prognosis of breast cancer. Thus, the transcriptional activities of HSF1 induced by HSP90 inhibitors suggest a feedback mechanism to attenuate the HSP90 inhibitor activity and targeting HSF1 may provide a new avenue to enhance HSP90 inhibitor efficacy in human cancer, such as HCC

Phosphoglycerate dehydrogenase is dispensable for breast tumor maintenance and growth

Cancer cells have the ability to use aerobic glycolysis to maintain cell growth and proliferation via the Warburg effect. Phosphoglycerate dehydrogenase (PHDGH) catalyzes the first step of the serine biosynthetic pathway, which is a metabolic gatekeeper both for macromolecular biosynthesis and serine-dependent DNA synthesis. PHGDH is amplified or overexpressed in a subset of breast cancer and melanoma, and critical for the viability of those cells. Here, we report that PHDGH is overexpressed in many ER-negative human breast cancer cell lines and PHGDH knockdown in these cells leads to a decrease in the levels of serine production and impairment of cancer cell proliferation. However, PHGDH knockdown does not affect tumor maintenance and growth in established xenograft tumor mouse models, suggesting that PHGDH-dependent cell growth is only observed in the in vitro context. Our finding indicates that PHGDH is dispensable for tumor maintenance and growth in vivo, which suggests that other mechanisms or pathways may bypass the function of PHGDH in human breast cancer cells