CD248-expressing cancer-associated fibroblasts induce non-small cell lung cancer metastasis via Hippo pathway-mediated extracellular matrix stiffness.

Metastasis is a crucial stage in tumour progression, and cancer-associated fibroblasts (CAFs) support metastasis through their participation in extracellular matrix (ECM) stiffness. CD248 is a possible biomarker for non-small cell lung cancer (NSCLC)-derived CAFs, but its role in mediating ECM stiffness to promote NSCLC metastasis is unknown. We investigated the significance of CD248+ CAFs in activating the Hippo axis and promoting connective tissue growth factor (CTGF) expression, which affects the stromal collagen I environment and improves ECM stiffness, thereby facilitating NSCLC metastasis. In this study, we found that higher levels of CD248 in CAFs induced the formation of collagen I, which in turn increased extracellular matrix stiffness, thereby enabling NSCLC cell infiltration and migration. Hippo axis activation by CD248+ CAFs induces CTGF expression, which facilitates the formation of the collagen I milieu in the stromal matrix. In a tumour lung metastasis model utilizing fibroblast-specific CD248 gene knockout mice, CD248 gene knockout mice showed a significantly reduced ability to develop tumour lung metastasis compared to that of WT mice. Our findings demonstrate that CD248+ CAFs activate the Hippo pathway, thereby inducing CTGF expression, which in turn facilitates the collagen I milieu of the stromal matrix, which promotes NSCLC metastasis.

IL-8 from CD248-expressing cancer-associated fibroblasts generates cisplatin resistance in non-small cell lung cancer.

Chemotherapy-resistant non-small cell lung cancer (NSCLC) presents a substantial barrier to effective care. It is still unclear how cancer-associated fibroblasts (CAFs) contribute to NSCLC resistance to chemotherapy. Here, we found that CD248+ CAFs released IL-8 in NSCLC, which, in turn, enhanced the cisplatin (CDDP) IC50 in A549 and NCI-H460 while decreasing the apoptotic percentage of A549 and NCI-H460 in vitro. The CD248+ CAFs-based IL-8 secretion induced NSCLC chemoresistance by stimulating nuclear factor kappa B (NF-κB) and elevating ATP-binding cassette transporter B1 (ABCB1). We also revealed that the CD248+ CAFs-based IL-8 release enhanced cisplatin chemoresistance in NSCLC mouse models in vivo. Relative to wild-type control mice, the CD248 conditional knockout mice exhibited significant reduction of IL-8 secretion, which, in turn, enhanced the therapeutic efficacy of cisplatin in vivo. In summary, our study identified CD248 activates the NF-κB axis, which, consecutively induces the CAFs-based secretion of IL-8, which promotes NSCLC chemoresistance. This report highlights a potential new approach to enhancing the chemotherapeutic potential of NSCLC-treating cisplatin.

Untargeted metabolic footprinting reveals key differences between fermented brown milk and fermented milk metabolomes.

Fermented brown milk has gained popularity because of its unique taste and flavor. Lactobacillus bulgaricus ND02 is a starter culture that has good milk fermentation characteristics. This study aimed to profile the metabolites produced during Maillard browning and to identify metabolomic differences between fermented brown milk and fermented milk produced by the ND02 strain. This study used liquid chromatography-mass spectrometry to compare the metabolomes of milk, fermented milk, brown milk, and fermented brown milk. Significant differences were observed in the abundances of various groups of metabolites, including peptides, AA, aldehydes, ketones, organic acids, vitamins, and nucleosides. The Maillard browning reaction significantly increased the intensity of a wide spectrum of flavor compounds, including short peptides, organic acids, and compounds of aldehydes, ketones, sulfur, and furan, which might together contribute to the unique flavor of brown milk. However, Maillard browning led to an increase in Nε-(carboxymethyl)lysine, which might cause negative health effects such as diabetes, uremia, or Alzheimer's disease. On the other hand, fermenting brown milk with the ND02 strain effectively countered such an effect. Finally, 5 differentially abundant metabolites were identified between fermented brown milk and fermented milk, including l-lysine, methylglyoxal, glyoxal, 2,3-pentanedione, and 3-hydroxybutanoic acid, which might together contribute to the different nutritional qualities of fermented brown milk and fermented milk. This study has provided novel information about the Maillard reaction and compared the metabolomes of the 4 types of dairy products.

Probiotics as Adjunctive Treatment for Patients Contracted COVID-19: Current Understanding and Future Needs.

The coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which rages all over the world and seriously threatens human life and health. Currently, there is no optimal treatment for COVID-19, and emerging evidence found that COVID-19 infection results in gut microbiota dysbiosis. The intestinal microbial richness of patients of COVID-19 does not return to normal levels even six months after recovery, but probiotic adjunctive treatment has been found to restore gut homeostasis. An updated PubMed search returned four finished clinical trials that supported the use of probiotics as adjunctive treatment for COVID-19, while at least six clinical trials aiming to investigate beneficial effects of probiotic intake in managing COVID-19 are currently in progress worldwide. Here in we tentatively summarized the understanding of the actions and potential mechanisms of probiotics in the management of COVID-19. We also highlighted some future needs for probiotic researchers in the field. The success in using probiotics as adjunctive treatment for COVID-19 has expanded the scope of application of probiotics, meanwhile deepening our knowledge in the physiological function of probiotics in modulating the gut-lung axis.

Coaxial heterogeneous structure of TiO2 nanotube arrays with CdS as a superthin coating synthesized via modified electrochemical atomic layer deposition.

We report the fabrication and characterization of CdS/TiO(2) nanotube-array coaxial heterogeneous structures. Such structures may potentially be applied in various photocatalytic fields, such as water photocatalytic decomposition and toxic pollutant photocatalytic degradation. Thin films of CdS are conformally deposited onto TiO(2) nanotubes using a modified method of electrochemical atomic layer deposition. We propose that such nanostructured electrodes can overcome the poor absorption and high charge-carrier recombination observed with nanoparticulate films. The practical electrochemical deposition technique promotes the deposition of CdS onto the TiO(2) tube walls while minimizing deposition at the tube entrances, thus preventing pore clogging. The coaxial heterogeneous structure prepared by the new electrochemical process significantly enhances CdS/TiO(2) and CdS/electrolyte contact areas and reduces the distance that holes and electrons must travel to reach the electrolyte or underlying conducting substrate. This results in enhanced photon absorption and photocurrent generation. The detailed synthesis process and the surface morphology, structure, elemental analysis, and photoelectrochemical properties of the resulting films with the CdS/TiO(2) nanotube-array coaxial heterogeneous structure are discussed. In comparison with a pure TiO(2) nanotube array, a 5-fold enhancement in photoactivity was observed using the coaxial heterogeneous structure. This methodology may be useful in designing multijunction semiconductor materials for coating of highly structured substrates.

Synthesis and high temperature thermoelectric properties of Yb0.25Co4Sb12-(Ag2Te) x (Sb2Te3)1-x nanocomposites.

Nanocomposites are becoming a new paradigm in thermoelectric study: by incorporating nanophase(s) into a bulk matrix, a nanocomposite often exhibits unusual thermoelectric properties beyond its constituent phases. To date most nanophases are binary, while reports on ternary nanoinclusions are scarce. In this work, we conducted an exploratory study of introducing ternary (Ag2Te)x(Sb2Te3)1-x inclusions in the host matrix of Yb0.25Co4Sb12. Yb0.25Co4Sb12-4wt% (Ag2Te)x(Sb2Te3)1-x nanocomposites were prepared by a melting-milling-hot-pressing process. Microstructural analysis showed that poly-dispersed nanosized Ag-Sb-Te inclusions are distributed on the grain boundaries of Yb0.25Co4Sb12 coarse grains. Compared to the pristine nanoinclusion-free sample, the electrical conductivity, Seebeck coefficient, and thermal conductivity were optimized simultaneously upon nanocompositing, while the carrier mobility was largely remained. A maximum ZT of 1.3 was obtained in Yb0.25Co4Sb12-4wt% (Ag2Te)0.42(Sb2Te3)0.58 at 773 K, a ~ 40% increase compared to the pristine sample. The electron and phonon mean-free-path were estimated to help quantify the observed changes in the carrier mobility and lattice thermal conductivity.