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.

Genomic Insights into the Pathogenicity and Drug-Resistance of a Bacillus cereus Isolated from Human Teeth.

Background: Bacillus cereus is a common bacterium found in the environment. Some strains can cause food poisoning, and very few can cause clinically severe infections, leading to death. Here, we characterized the genome sequence of B. cereus LIN78 isolated from teeth with deep caries and compared it with those of 25 other related species. Methods: Third-generation sequencing technology, bacteriological analyses, biochemistry, and mass spectrometry were applied to characterize the drug-resistance genes and virulence factors of B. cereus LIN78. Results: The complete genome sequence of B. cereus Lin78 consists of 5647 genes distributed on a circular chromosome, a 393 kbp plasmid, and 928 pseudogenes (37.4% of whole-genome DNA). The LIN78 genome contains 14 sets of 16s, 23s, and 5s ribosomal RNA operons; 106 tRNA genes, one tmRNA, 12 genomic islands, six prophases, 64 repeats; 37 antibiotic-resistant genes; and 1119 putative virulence genes, including enterotoxins and cytolysins. The B. cereus LIN78 genome carries multiple copies of non-ribosomal polypeptide synthetase (NRPS) and post-translationally modified peptides (RiPPs). Phylogenetic analysis of the 26 B. cereus strains showed that B. cereus LIN78 is evolutionarily closely related to B. thuringiensis ATCC 10792 and B. cereus ATCC 14579. Conclusion: The newly isolated B. cereus carries many virulence genes, including enterotoxins and hemolysins, similar to B. anthracis, and multiple antibiotic resistance genes. These findings suggest that the strain has a potential risk of causing disease. Our studies are vital for further exploration of the evolution of B. cereus, its pathogenic mechanisms, and the control and treatment of bacterial infections.

Luoshi Neiyi Prescription inhibits estradiol synthesis and inflammation in endometriosis through the HIF1A/EZH2/SF-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Endometriosis (EMS) is a common gynecological disease that causes dysmenorrhea, chronic pelvic pain and infertility. Luoshi Neiyi Prescription (LSNYP), a traditional Chinese medicine (TCM) formula, is used to relieve EMS in the clinic. AIMS: This study aimed to examine the active components of LSNYP and the possible mechanism involved in its treatment of EMS. MATERIALS AND METHODS: Ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to identify the chemical components of LSNYP. Human primary ectopic endometrial stromal cells (ecESCs) and eutopic endometrial stromal cells (euESCs) were isolated, and the expression levels of hypoxia inducible factor 1A (HIF1A), enhancer of zeste homolog 2 (EZH2) and steroidogenic factor 1 (SF-1) were detected by immunofluorescence and qPCR. Cobalt chloride (CoCl2) was utilized to construct an in vitro hypoxic environment, and lentiviruses were engineered to downregulate HIF1A and EZH2 and upregulate EZH2. Subsequently, the expression levels of HIF1A, EZH2, and SF-1 were measured using qPCR or western blotting. The binding of EZH2 to the SF-1 locus in ESCs was examined via ChIP. Furthermore, the effects of LSNYP on the HIF1A/EZH2/SF-1 pathway were evaluated both in vitro and in vivo. RESULTS: A total of 185 components were identified in LSNYP. The protein and gene expression levels of HIF1A and SF-1 were increased, whereas those of EZH2 were decreased in ecESCs. After treating euESCs with 50 µmol L-1 CoCl2 for 24 h, cell viability and estradiol (E2) production were enhanced. Hypoxia decreased EZH2 protein expression, while si-HIF1A increased it. SF-1 was increased when EZH2 was downregulated in normal and hypoxic environments, whereas the overexpression of EZH2 led to a decrease in SF-1 expression. ChIP revealed that hypoxia reduced EZH2 binding to the SF-1 locus in euESCs. In vitro, LSNYP-containing serum decreased E2 and prostaglandin E2 (PGE2) production, inhibited cell proliferation and invasion, and reduced the expression of HIF1A, SF-1, steroidogenic acute regulatory protein (StAR), and aromatase cytochrome P450 (P450arom). In vivo, LSNYP suppressed inflammation and adhesion and inhibited the HIF1A/EZH2/SF-1 pathway in endometriotic tissues. CONCLUSIONS: LSNYP may exert pharmacological effects on EMS by inhibiting E2 synthesis and inflammation through regulation of the HIF1A/EZH2/SF-1 pathway. These results suggest that LSNYP may be a promising candidate for the treatment of EMS.

Solving patient referral problems by using bat algorithm.

BACKGROUND: A two-hospital patient referral problem intends to calculate an optimal value of referral patients between two hospitals and to evaluate whether or not the current number of referral patients is too low. OBJECTIVE: The goal of this study is to develop a simulation-based optimization algorithm to find the optimal referral between two hospitals with the unfixed daily patient referral policy. METHODS: This study applied system simulation and a bat algorithm (BA) to build a simulation model in accordance with the status of the two hospitals case and to calculate an optimal value of daily referral patients. RESULTS: Based on the 20 test instances, we verified the stability of this algorithm. The results show that the average magnetic resonance imaging (MRI) patient wait time reduced from 16 days to eight days. The hospital should increase the average total monthly MRI referral patients to 370 under the limitation of the daily referral patients to 25. CONCLUSIONS: This research investigated the two-hospital patient referral problems. We conducted and analyzed a simulation model and improved the case hospital's conditions, enhancing the quality of its medical care. The findings of this study can extend to other departments or hospitals.

A bio-inspired optical system with a polymer membrane and integrated structure.

A bio-inspired optical imaging system with a polymer membrane and integrated structure is proposed. Similar to the human eye, the presented system has a biomimetic multilayered optical structure and utilizes a solid-liquid mixed tunable lens as the variable-focus unit. The focal length of the imaging system can be adjusted flexibly through the deformation of the tunable lens when it is compressed. A detailed description of the design principle, materials and fabrication process of the system is presented. The deformation property, adjustable range and surface roughness of the tunable lens are measured. Images under different displacement loads are captured, and the relationships among the back focal length (BFL) and effective focal length (EFL) of the system and the change in radius of the tunable lens are analyzed. A 7.6 times variation of the BFL is achieved through a tiny alteration in radius of 1.2 mm. All the measured resolutions during the deformation stage are larger than 40 line pairs mm-1, and the imaging system shows good optical quality and stability. The proposed optical system is of interest for the development of compact and stable imaging systems with a large zooming range.

Investigation on wind energy-compressed air power system.

Wind energy is a pollution free and renewable resource widely distributed over China. Aimed at protecting the environment and enlarging application of wind energy, a new approach to application of wind energy by using compressed air power to some extent instead of electricity put forward. This includes: explaining the working principles and characteristics of the wind energy-compressed air power system; discussing the compatibility of wind energy and compressor capacity; presenting the theoretical model and computational simulation of the system. The obtained compressor capacity vs wind power relationship in certain wind velocity range can be helpful in the designing of the wind power-compressed air system. Results of investigations on the application of high-pressure compressed air for pressure reduction led to conclusion that pressure reduction with expander is better than the throttle regulator in energy saving.