Search

Supporting information include 3 tables and 3 figures. Table 1 describes the Patients characteristics from which primary cell lines were established. Table 2 the characteristics of ovarian tumor samples from which RNA was extracted. Table 3 the characterization of particle formulations Supplementary figure 1 shows the DNA release in vitro in culture medium. The Supplementary figure 2 the ovarian tumors' uptake of c-CPE-NP in vivo. The Supplementary figure 3 shows the survival curves of the tumor bearing mice treated with vehicle, c-CPE-NP encapsulating the empty plasmid or the p16 DTA c-CPE-NP.

An iron-catalyzed C(sp3)–H cyanoalkylation of glycine derivatives with cyclobutanone oxime esters was established for the incorporation of a cyano group into amino acids and peptides. In this react...

Background aims To investigate the feasibility of using CD4 + T cells genetically modified to express an allo-HLA directed CAR and FOXP3 to suppress T cell proliferation and cytokine secretion in GvHD. Methods: Human CD4+ T cells from A*02:01 negative donors were transduced to express A*02 CAR and FOXP3 and co-cultured in mixed lymphocyte reaction assays to demonstrate T cell suppression. A*02- CAR/FOXP CD4+ T cells were then injected into mice engrafted with allogeneic T cells in a GvHD mouse model. Results CD4+ T cells genetically modified to express allo-HLA-directed CAR and FOXP3 proliferate rapidly, downregulate CD127 and interferon-γ, express high CD25 and Helios and convert to a stable antigen-dependent suppressive phenotype. In mixed lymphocyte reaction assays, these cells potently suppressed T-cell proliferation and secreted IL-10. In a graft-versus-host disease model, A*02-CAR/FOXP3 CD4+ T cells outperformed polyclonal Tregs by reducing liver and lung inflammation, inhibiting pro-inflammatory cytokine production and limiting grafted CD3+ T-cell expansion. Conclusions CD4 + T cells expressing allo-antigen directed HLA-specific CAR and FOXP3 act as potent, specific and stable suppressors of inflammation that out-perform their Treg counterparts both in vitro and in vivo.

Sepsis-related acute liver injury (ALI) is a fatal disease associated with many complications. Recent studies indicate that malvidin, an active flavonoid, has multiple bioactivities including anti-oxidant and anti-inflammation. However, the protective roles of malvidin against LPS-induced ALI are unknown. The purpose of this research is to explore whether malvidin has biological activities on LPS-induced ALI in mice and the underlying mechanisms. Male C57 mice were injected intraperitoneally with malvidin for five days and the mice were euthanized 6 h after LPS (10 mg/kg body weight) intraperitoneal injection. Multiple methods of HE staining, biochemical kits, qRT-PCR assay, western blotting analysis, TUNEL and transmission electron microscope (TEM) were used. Results showed that decreased ALT, AST levels and alleviated histopathological damage of liver tissue were observed in malvidin pretreatment group in mice. Then, malvidin prevented LPS-induced reduction of antioxidant enzyme activities such as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) via up-regulating nuclear factor E2-related factor2 (Nrf2) pathway. In addition, in malvidin pretreatment groups, mRNA levels of pro-inflammatory cytokines (TNF-α，IL-1β, IL-6) and protein levels of NOD-like receptor protein 3 (NLRP3) inflammasome in the liver were significantly down-regulated. We also found that the malvidin could reduce the expression of apoptosis key protein and TUNEL-labeled apoptotic hepatocytes. Furthermore, malvidin inhibited the protein expression of ATG5, p62 and the ratio of LC3-II/LC3-I. In conclusion, our study firstly suggests that malvidin is a potentially protective agent against LPS-induced ALI through up-regulating Nrf2 signaling pathway, suppressing NLRP3 inflammasome and inhibiting apoptosis and autophagy.

Farfarae Flos is a traditional Chinese medicine that has long been used to treat allergies. In this study, we aimed to investigate the effect of a petroleum extract of Farfarae Flos (PEFF) in a mouse model of allergic rhinitis (AR) and to explore the underlying molecular mechanisms of action. An animal model of AR was established by sensitization and challenge of BALB/c mice with ovalbumin (OVA). PEFF was administered intranasally and AR nasal symptoms were assessed on a semi-quantitative scale according to the frequencies of nose rubbing and sneezing and the degree of rhinorrhea. The mechanism of action of PEFF was evaluated by histological analysis of nasal mucosa architecture and inflammatory status; ELISA-based quantification of serum OVA-specific IgE, interferon-γ (IFN-γ), and interleukin-4 (IL-4) concentrations; and immunohistochemical and western blot analysis of T-bet and GATA3 protein expression in nasal mucosa and spleen tissues. The results showed intranasal administration of PEFF alleviated AR symptom scores and reduced both the infiltration of inflammatory cells and tissue damage in the nasal mucosa. PEFF significantly decreased serum concentrations of OVA-specific IgE (P

In recent years, there has been increasing interest in microbial biotechnology for the production of value-added compounds from renewable resources. Pseudomonas species have been proposed as a suitable workhorse for high-value secondary metabolite production because of their unique characteristics for fast growth on sustainable carbon sources, a clear inherited background, versatile intrinsic metabolism with diverse enzymatic capacities, and their robustness in an extreme environment. It has also been demonstrated that metabolically engineered Pseudomonas strains can produce several industrially valuable aromatic chemicals and natural products such as phenazines, polyhydroxyalkanoates, rhamnolipids, and insecticidal proteins from renewable feedstocks with remarkably high yields suitable for commercial application. In this review, we summarize cell factory construction in Pseudomonas for the biosynthesis of native and non-native bioactive compounds in P. putida, P. chlororaphis, P. aeruginosa, as well as pharmaceutical proteins production by P. fluorescens. Additionally, some novel strategies together with metabolic engineering strategies in order to improve the biosynthetic abilities of Pseudomonas as an ideal chassis are discussed. Finally, we proposed emerging opportunities, challenges, and essential strategies to enable the successful development of Pseudomonas as versatile microbial cell factories for the bioproduction of diverse bioactive compounds.

The differences of dietary iron and zinc intakes between patients with nonalcoholic fatty liver disease (NAFLD) and controls remain controversial. The meta-analysis aimed to explore the differences of dietary iron and zinc intakes between NAFLD patients and healthy subjects.A systematic literature search was performed up to July 2021 in databases of PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and Wanfang. Using a randomeffects model, the differences of dietary iron and zinc intakes between cases and controls were calculated as standardized mean differences (SMDs) with 95% confidence intervals (CIs). A total of 21 studies from 19 articles with 6639 cases were included.The pooled estimate showed no difference in dietary iron consumption in the NAFLD groups compared with control groups. The difference became significant in Asia (SMD=0.16; 95% CI: 0.04, 0.28; I2=89.1%; pheterogeneity0.001) as well as in cross-sectional studies (SMD=0.12; 95% CI: 0.07, 0.17; I2=4.7%; pheterogeneity=0.350). The difference in dietary zinc intake between cases and controls was not significant. We noticed a statistically significant increase of dietary zinc intake in NAFLD compared to controls in studies using food-frequency questionnaire (FFQ) to evaluate dietary intake (SMD=0.15; 95% CI: 0.10, 0.20; I2=12.2%; pheterogeneity=0.332).Our findings indicated that dietary iron intake in patients with NAFLD was higher than healthy subjects in Asia.

Autonomic dysfunction can lead to many physical and psychological diseases. The assessment of autonomic regulation plays an important role in the prevention, diagnosis, and treatment of these diseases. A physiopathological mathematical model for cardiopulmonary autonomic regulation, namely Respiratory-Autonomic-Sinus (RSA) regulation Model, is proposed in this study. A series of differential equations are used to simulate the whole process of RSA phenomenon. Based on this model, with respiration signal and ECG signal simultaneously acquired in paced deep breathing scenario, we manage to obtain the cardiopulmonary autonomic regulation parameters (CARP), including the sensitivity of respiratory-sympathetic nerves and respiratory-parasympathetic nerves, the time delay of sympathetic, the sensitivity of norepinephrine and acetylcholine receptor, as well as cardiac remodeling factor by optimization algorithm. An experimental study has been conducted in healthy subjects, along with subjects with hypertension and coronary heart disease. CARP obtained in the experiment have shown their clinical significance.

Over the past few decades, pesticides have been used in large quantities, and they pose potential risks to organisms across various environments. Reducing the use of pesticides and their environmental risks has been an active research focus and difficult issue worldwide. As a class of pesticides with special structures, chiral pesticides generally exhibit enantioselectivity differences in biological activity, ecotoxicity, and environmental behavior. At present, replacing the racemates of chiral pesticides by identifying and developing their individual enantiomers with high efficiency and environmentally friendly characteristics is an effective strategy to reduce the use of pesticides and their environmental risks. In this study, we review the stereoselective behaviors of chiral pesticide, including their environmental behavior, stereoselective biological activity, and ecotoxicity. In addition, we emphasize that the systematic evaluation of chiral pesticides at the enantiomeric level is a promising novel strategy for developing highly effective and less harmful pesticides, which will provide important data support and an empirical basis for reducing pesticide application.

As a diamide insecticide, flubendiamide is widely used and has many adverse effects on environmental organisms. In this study, bioaccumulation and toxicity effects of flubendiamide in zebrafish (Danio rerio) were studied. Specifically, the results showed that the concentrations of flubendiamide increased in the early stage and achieved steady stages at 14 days and the bioconcentration factors (BCFs) of flubendiamide in zebrafish were 1.125 - 2.011. Furthermore, flubendiamide had no significant effects on the growth phenotypes of zebrafish. However, zebrafish hepatic somatic index (HSI) of zebrafish had changed significantly with exposure. Histopathological analysis showed that exposure to flubendiamide could cause structural damage to liver tissue of zebrafish. Further physiological and biochemical analysis showed that flubendiamide could significantly change the activity of CAT and the contents of MDA and GSH in liver of zebrafish. In particular, exposure to flubendiamide could also cause significant changes in the mRNA expression levels of cell apoptosis-related genes involving p53, puma, caspase-3, caspase-9, apaf-1 and bax in liver of zebrafish. In general, these results indicated that exposure to flubendiamide could induce liver damage by inducing oxidative stress and apoptosis in liver of zebrafish. The results of this study will help to further comprehensively evaluate the safety of flubendiamide to aquatic organisms.

To study the effect of silencing LncRNA SNHG7 on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and its targeted regulation on miR-181b-5p.Rat cardiomyocytes H9c2 were cultured in vitro and randomly divided into control group, H/R group, H/R + si-NC group, H/R + si-SNHG7 group, H/R + si-SNHG7 + anti-miR-NC group and H/R + si-SNHG7 + anti-miR-181b-5p group. The content of lactate dehydrogenase (LDH), malondialedhyde (MDA) and the activity of superoxide dismutase (SOD) were detected. Flow cytometry was carried out to detect the rate of apoptosis. qRT-PCR was used to detect the expression of SNHG7 and miR-181b-5p. Dual luciferase report experiment was used to verify the targeting relationship between SNHG7 and miR-181b-5p. Western blotting was used to detect the expression of Bax and Bcl-2.Compared with the control group, the H/R group showed significantly increased SNHG7 expression in cardiomyocytes, reduced miR-181b-5p expression, higher levels of LDH and MDA, reduced activity of SOD, increased cell apoptosis rate, higher level of Bax protein, and reduced level of Bcl-2 protein (all P0.05). Compared with the H/R and H/R + si-NC groups, the H/R + si-SNHG7 group had significantly reduced level of LDH and MDA, increased activity of SOD, reduced apoptosis rate, reduced level of Bax protein, increased level of Bcl-2 protein (all P0.05). The dual luciferase report experiment confirmed that SNHG7 could target miR-181b-5p. Interference with the expression of miR-181b-5p could reduce the effect of silencing SNHG7 on H/R-induced cardiomyocyte oxidative stress and apoptosis.Silencing SNHG7 may inhibit H/R-induced cardiomyocyte oxidative stress and apoptosis by up-regulating the expression of miR-181b-5p, thereby exerting a protective effect on cardiomyocytes.

The cobalt-free material of Bi3+-doped BaFeO3-δ (BBFO) is synthesized and applied as a cathode material for intermediate-temperature solid oxide fuel cells (IT-SOFCs) with proton conducting electrolyte Ba(Zr0·1Ce0·7Y0.2)O3 (BZCY). The as-prepared BBFO demonstrates a tetragonal structure with sufficient chemical compatibility, high thermal stability and low thermal expansion coefficient. BBFO exhibits higher electrical conductivity of 4.1 S cm−1compared to the parent material BaFeO3-δ (BFO) of 3.5 S cm−1. The composite cathode BBFO-BZCY with the mass ratio of 7:3 presents a relatively low Rp of 0.128 Ω cm2 at 700 °C in air. According to the oxygen reduction reaction process, the rate-determining step is transformed from charge transfer to oxygen gas (O2) adsorption-dissociation with the rising temperature. In addition, the performance of the anode-supported cell NiO-BZCY∣BZCY∣BBFO-BZCY is 120 mW cm−2 as the thickness of electrolyte is 150 μm. It thus promises BBFO as a novel cathode for proton-conducting ceramic fuel cells.

Fascin actin-bundling protein 1 (FSCN1) is an evolutionarily conserved actin-bundling protein that plays a critical role in cell migration, motility, adhesion, and cellular interactions. Although multiple clinical studies have implicated the expression of FSCN1 in laryngeal squamous cell carcinoma (LSCC) progression, the precise mechanism of FSCN1 in the process has not been clearly elucidated. To define FSCN1 function, we characterized FSCN1‐interacting proteins in two cell lines by immunoprecipitation followed by mass spectrometry (MS). After data filtering, 119 proteins with expression in both the Hep-2 and TU-177 cell samples were identified as FSCN1-interacting partners. With in-depth bioinformatics analysis, we linked FSCN1 to critical cellular processes including cell adhesion, glycolysis/gluconeogenesis, regulation of protein ubiquitination, ribosomal RNA processing, and small molecule metabolism. We discuss the interactions between FSCN1 and some of the newly validated partners. The identification of these potential partners of FSCN1 expands our knowledge of the FSCN1 interactome and provides a valuable resource for understanding the functions of this protein in LSCC progression.

Reversible solid oxide cells could be energy transfer devices between electrical power and hydrogen energy due to their multi-functions, such as fuel cells and electrolysis cells. However, the traditional configuration of solid oxide cells induces the thermal mismatch among different components during the changing between different operating modes. Herein, we demonstrate that A-site deficient (La0.8Sr0.2)0.9Sc0.2Mn0.8-xRuxO3–δ can be used as an air electrode and a fuel electrode simultaneously in reversible solid oxide cells. Ruthenium nanoparticle catalysts are exsolved on the surface of (La0.8Sr0.2)0.9Sc0.2Mn0.8-xRuxO3–δ in the reducing atmosphere. The electronic conductivity in air and 5% H2/N2 are optimized via the substitution of manganese by ruthenium, which changes the distortion of BO6 octahedron and the integral overlap between d orbitals of B-site atoms and O-p orbitals. The electrochemical activity of air electrode and fuel electrode are significantly improved simultaneously after Ru-doing. In fuel cell mode, the maximum power density of the symmetrical single cell reaches 318 mW cm−2 at 800 °C. In electrolysis cell mode, the electrolysis current density is 0.536 A cm−2 at 750 °C with an applied voltage of 1.5 V at 50% H2O/H2. The synthesized (La0.8Sr0.2)0.9Sc0.2Mn0.8-xRuxO3–δ material is a promising symmetrical electrode for reversible solid oxide cells.

Degradable poly(amine-co-ester) (PACE) terpolymers hold tremendous promise for siRNA delivery because these materials can be formulated into delivery vehicles with highly efficient siRNA encapsulation, providing effective knockdown with low toxicity. Here, we demonstrate that PACE nanoparticles (NPs) provide substantial protein knockdown in human embryonic kidney 293 cells (HEK293) and hard-to-transfect primary human umbilical vein endothelial cells (HUVECs). After intravenous administration, NPs of solid PACE (sPACE)—synthesized with high monomer content of a hydrophobic lactone—accumulated in the liver and, to a lesser extent, in other tissues. Within the liver, a substantial fraction of sPACE NPs were phagocytosed by liver macrophages, while a smaller fraction of NPs accumulated in hepatic stellate cells and liver sinusoidal endothelial cells, suggesting that sPACE NPs could deliver siRNA to diverse cell populations within the liver. To test this hypothesis, we loaded sPACE NPs with siRNA designed to knockdown Nogo-B, a protein that has been implicated in the progression of alcoholic liver disease and liver fibrosis. These sPACE:siRNA NPs produced up to 60% Nogo-B protein suppression in the liver after systemic administration. We demonstrate that sPACE NPs can effectively deliver siRNA therapeutics to the liver to mediate protein knockdown in vivo.

Laryngeal squamous cell carcinoma (LSCC) is a common form of head and neck cancer with poor prognosis. However, the mechanism underlying the pathogenesis of LSCC remains unclear. Here, we demonstrated increased expression of fascin actin-bundling protein 1 (FSCN1) and decreased expression of microRNA-145-5p (miR-145-5p) in a clinical cohort of LSCC. Luciferase assay revealed that miR-145-5p is a negative regulator of FSCN1. Importantly, low miR-145-5p expression was correlated with TNM (tumor, node, metastasis) status and metastasis. Moreover, cases with low miR-145-5p/high FSCN1 expression showed poor prognosis, and these characteristics together served as independent prognostic indicators of survival. Gain- and loss-of-function studies showed that miR-145-5p overexpression or FSCN1 knockdown inhibited LSCC migration, invasion, and growth by suppressing the epithelial-mesenchymal transition along with inducing cell-cycle arrest and apoptosis. Additionally, hypermethylation of the miR-145-5p promoter suggested that repression of miR-145-5p arises through epigenetic inactivation. LSCC tumor growth in vivo could be inhibited by using miR-145-5p agomir or FSCN1 small interfering RNA (siRNA), which highlights the potential for clinical translation. Collectively, our findings indicate that miR-145-5p plays critical roles in inhibiting the progression of LSCC by suppressing FSCN1. Both miR-145-5p and FSCN1 are important potential prognostic markers and therapeutic targets for LSCC., Graphical Abstract, Gao et al. demonstrate that miR-145-5p expression is prognostic for LSCC with low expression associated with poorer outcomes. Underlying this pathology, miR-145-5p suppresses FSCN1 expression, but its inactivation facilitates epithelial-to-mesenchymal transition (EMT), proliferation, and survival. LSCC growth in vivo is inhibited by miR-145-5p agomir, highlighting potential as a biomarker and therapeutic target.