CircHAT1 regulates the proliferation and phenotype switch of vascular smooth muscle cells in lower extremity arteriosclerosis obliterans through targeting SFRS1.

This study aimed to decipher the mechanism of circular ribonucleic acids (circRNAs) in lower extremity arteriosclerosis obliterans (LEASO). First, bioinformatics analysis was performed for screening significantly down-regulated cardiac specific circRNA-circHAT1 in LEASO. The expression of circHAT1 in LEASO clinical samples was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of splicing factor arginine/serine-rich 1 (SFRS1), α-smooth muscle actin (α-SMA), Calponin (CNN1), cyclin D1 (CNND1) and smooth muscle myosin heavy chain 11 (SMHC) in vascular smooth muscle cells (VSMCs) was detected by Western blotting. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and Transwell assays were used to evaluate cell proliferation and migration, respectively. RNA immunoprecipitation (RNA-IP) and RNA pulldown verified the interaction between SFRS1 and circHAT1. By reanalyzing the dataset GSE77278, circHAT1 related to VSMC phenotype conversion was screened, and circHAT1 was found to be significantly reduced in peripheral blood mononuclear cells (PBMCs) of LEASO patients compared with healthy controls. Knockdown of circHAT1 significantly promoted the proliferation and migration of VSMC cells and decreased the expression levels of contractile markers. However, overexpression of circHAT1 induced the opposite cell phenotype and promoted the transformation of VSMCs from synthetic to contractile. Besides, overexpression of circHAT1 inhibited platelet-derived growth factor-BB (PDGF-BB)-induced phenotype switch of VSMC cells. Mechanistically, SFRS1 is a direct target of circHAT1 to mediate phenotype switch, proliferation and migration of VSMCs. Overall, circHAT1 regulates SFRS1 to inhibit the cell proliferation, migration and phenotype switch of VSMCs, suggesting that it may be a potential therapeutic target for LEASO.

Elastic Fluorescent Protein-Based Down-Converting Optical Films for Flexible Display.

Protein-based material design provides great advantages to developing smart biomaterials with tunable structures and desired functions. They have been widely used in many biomedical applications including tissue engineering and drug delivery. However, protein-based materials are not yet widely used in optoelectronic materials despite their excellent optical and tunable mechanical properties. Here, we synthesized engineered fluorescent proteins (FPs) fused with elastic protein for the development of optoelectrical down-converting optical filters for flexible display materials. We synthesized sequence-specific FPs to tune blue, green, yellow, and red colors and fused them with elastic protein to tune mechanical properties. We fabricated flexible self-supporting film materials and characterized mechanical properties and down-converting optical properties. We also fabricated a hybrid light-emitting diode (LED) to down convert blue to desired green, red, and white colors. Furthermore, we constructed a flexible white LED using organic LED as a flexible substrate. Our modular synthesis approach of tunable bio-optoelectrical material approaches will be useful to design future biocompatible and flexible display materials and technologies.

SPAG5 promotes the proliferation, migration, invasion, and epithelial-mesenchymal transformation of colorectal cancer cells by activating the PI3K/AKT signaling pathway.

Colorectal cancer (CRC) is a cancer that occurs in the rectum or colon with a high incidence. Sperm-associated antigen 5 (SPAG5), a gene that regulates cell division, has been observed highly expressed in a variety of cancers, but its role in CRC is unclear. This study aimed to investigate the regulatory role of SPAG5 in CRC. The expression of SPAG5 in multiple cancers and normal tissues was predicted by The Cancer Genome Atlas and Tumor Immune Estimation Resource, and the expression of SPAG5 in human normal intestinal epithelial cells NCM460 and human CRC cell lines Caco2, HT29, SW480, and LOVO was verified by western blotting (WB). The effects of silencing SPAG5 on cell viability, proliferation, and apoptosis were then investigated by cell counting kit-8, WB, and flow cytometry. The effects of silencing SPAG5 on cell migration and invasion were investigated by scratch assay and transwell assay. Finally, the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and AKT in cells were detected by WB. The results showed that SPAG5 was highly expressed in CRC and was verified by WB. Silencing of SPAG5 inhibited cell viability and proliferation and increased the cell apoptosis rate. Furthermore, both cell invasion and migration abilities were suppressed by the low expression of SPAG5. Finally, WB results found that the phosphorylation levels of PI3K and AKT were reduced after SPAG5 silencing. In summary, the results showed that SPAG5 can promote the proliferation and invasion of CRC cells by targeting the PI3K/AKT signaling pathway.

Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors.

Alterations in histone modification have been linked to cancer development and progression. Celastrol, a Chinese herbal compound, shows potent anti-tumor effects through multiple signaling pathways. However, the involvement of histone modifications in this process has not yet been illustrated. In this study, barcode sequencing of a eukaryotic genome-wide deletion library revealed that histone modifications, especially histone acetylation associated with the NuA4 histone acetyltransferase complex, were involved in the anti-proliferation actions of celastrol. The essential roles of histone modification were verified by celastrol sensitivity tests in cells lacking specific genes, such as genes encoding the subunits of the NuA4 and Swr1 complex. The combination of celastrol and histone deacetylase inhibitors (HDACi), rather than the combination of celastrol and histone acetyltransferase inhibitors, synergistically suppressed cancer cell proliferation. In addition to upregulating H4K16 acetylation (H4K16ac), celastrol regulates H3K4 tri-methylation and H3S10 phosphorylation. Celastrol treatment significantly enhanced the suppressive effects of HDACi on lung cancer cell allografts in mice, with significant H4K16ac upregulation, indicating that a combination of celastrol and HDACi is a potential novel therapeutic approach for patients with lung cancer.

A two-stage design enhanced biodegradation of high concentrations of a C16-alkyl quaternary ammonium compound in oxygen-based membrane biofilm reactors.

Quaternary ammonia compounds (QAC), such as hexadecyltrimethyl-ammonium (CTAB), are widely used as disinfectants and in personal-care products. Their use as disinfectants grew during the SARS-CoV-2 (COVID-19) pandemic, leading to increased loads to wastewater treatment systems and the environment. Though low concentrations of CTAB are biodegradable, high concentrations are toxic to bacteria. Sufficient O2 delivery is a key to achieve high CTAB removal, and the O2-based Membrane Biofilm Reactor (O2-MBfR) is a proven means to biodegrade CTAB in a bubble-free, non-foaming manner. A strategy for achieving complete biodegradation of high-concentrations of CTAB is a two-stage O2-MBfR, in which partial CTAB removal in the Lead reactor relieves inhibition in the Lag reactor. Here, more than 98 % removal of 728 mg/L CTAB could be achieved in the two-stage MBfR, and the CTAB-removal rate was 70 % higher than for a one-stage MBfR with the same O2-delivery capacity. CTAB exposure shifted the bacterial community toward Pseudomonas and Stenotrophomonas as the dominant genera. In particular, P. alcaligenes and P. aeruginosa were enriched in the Lag reactor, as they were capable of biodegrading the metabolites of initial CTAB monooxygenation. Metagenomic analysis also revealed that the Lag reactor was enriched in genes for CTAB and metabolite oxygenation, due to reduced CTAB inhibition.

Berberine synergises with ferroptosis inducer sensitizing NSCLC to ferroptosis in p53-dependent SLC7A11-GPX4 pathway.

Berberine (BBR) is a compound derived from Chinese herbal medicine, known for its anticancer properties through multiple signaling pathways. However, whether BBR can inhibit tumor growth by participating in ferroptosis remains unconfirmed. In this study, we demonstrated that berberine synergistically inhibited NSCLC in combination with multiple ferroptosis inducers, and this combination synergistically down-regulated the mRNA and protein expression of SLC7A11, GPX4, and NRF2, resulting in ferroptosis accompanied by significant depletion of GSH, and aberrant accumulation of reactive oxygen species and malondialdehyde. In a lung cancer allograft model, the combination treatment exhibited enhanced anticancer effects compared to using either drug alone. Notably, p53 is critical in determining the ferroptosis sensitivity. We found that the combination treatment did not elicit a synergistic anticancer effect in cells with a p53 mutation or with exogenous expression of mutant p53. These findings provide insight into the mechanism by which combination induces ferroptosis and the regulatory role of p53 in this process. It may guide the development of new strategies for treating NSCLC, offering great medical potential for personal diagnosis and treatment.

Exploring the core functional microbiota related with flavor compounds in fermented soy sauce from different sources.

Flavor, the most important quality index of soy sauce, is mostly influenced by the microbiota in fermented food ecosystem, however, the association between microorganisms and soy sauce flavor is still poorly understood. Therefore, the bacterial and fungal profiles, physicochemical parameters, and flavor compounds (9 organic acids, 17 free amino acids and 97 volatile flavor compounds) of 5 different source soy sauce were investigated using high-throughput sequencing, HPLC, amino acid analyzer and SPME/LLE-GC-MS, and their correlations were explored. A total of 3 fungal genera and 12 bacterial genera were identified as potential flavor-producing microorganisms by multivariate data and correlation analysis. Notably, Lactobacillus and Tetragenococcus were strongly positively correlated with succinic acid and lactic acid, respectively. Moreover, not only fungi, but also bacteria were found to be closely correlated with volatiles. Finally, 5 screened potential flavor-producing microorganisms were validated using a rapid fermentation model, with multiple strains showing the potential to improve the soy sauce flavor, with Lactobacillus fermentum being the most significant. Our research will provide a theoretical basis for the regulation and enhancement of soy sauce flavor.

Comparison of nomogram for Primary Nonfunctional Pancreatic Neuroendocrine Tumors based on the 7th vs 8th edition of the AJCC cancer staging manual.

BACKGROUND: Our study aimed to construct and validate prognostic nomograms for predicting survival for patients with Nonfunctional Pancreatic neuroendocrine tumor (NF-pNET). METHODS: This retrospective study included 1824 patients diagnosed with NF-pNET in the Surveillance, Epidemiology and End Results database between 2004 and 2016. Randomization divided the patients into training (n = 1278) and validation (n = 546) cohorts. Prognostic factors were determined using Cox regression analyses, nomograms based on AJCC 7th and 8th staging system were constructed separately. The prediction models were validated using internal validation and external validation. RESULTS: Age, year of diagnosis, primary tumor site, grade, 7th or 8th TNM stage, surgery, tumor size were determined as prognostic indicator to construct two nomograms. Harrell's concordance index (C-index) of two nomograms exhibited a clinical predictive ability of 0.828 (95%CI, 0.808~0.849) vs 0.828 (95% CI, 0.808~0.849) in the internal verification. The c-index in the external validation was 0.812 (95%CI, 0.778~0.864) vs 0.814 (95% CI, 0.779~0.848). The predictive power of the two nomograms is comparable. CONCLUSIONS: Our nomogram may be a effective tool for predicting overall survival in patients with NF-pNET. The AJCC 8th-edition system provides discrimination similar to that of the 7th-edition system.

Formosanin C inhibits non-small-cell lung cancer progression by blocking MCT4/CD147-mediated lactate export.

BACKGROUND: Tumor cells reprogram their metabolic network to maintain their uncontrolled proliferation, metastasis, and resistance to cancer therapy. Treatments targeting abnormal cellular metabolism may have promising therapeutic effects. Formosanin C (FC), a diosgenin derived from the rhizoma of Paris polyphylla var. yunnanensis, has shown potent anti-cancer activities against various cancer types. However, the effect of FC on cancer metabolism remains to be elucidated. PURPOSE: In this research, we aimed to elucidate FC's effect and potential mechanisms on metabolism in lung cancer. METHODS: Colony formation, transwell cell migration, and apoptosis were detected in multiple NSCLC cell lines to assess the cytotoxicity of FC. 1H NMR metabolomics approach was applied to screen the differential metabolites in H1299 cells and the culture medium. Western blotting, flow cytometry, and other molecular biological techniques were performed to verify the latent mechanism involved in metabolites. An allograft tumor model was employed to investigate the anti-tumor effects of FC in vivo. RESULTS: FC significantly inhibited monoclonal formation and migration and induced cell cycle arrest and apoptosis in NSCLC cells. FC altered the abundances of 12 metabolites in lung cancer cells and 3 metabolites in the medium. These differential metabolites are primarily involved in glycolysis, citric acid cycle, and glutathione pathways. Notably, there was a remarkable increase in intracellular lactate and a reduction in extracellular lactate after FC treatment. Mechanically, FC downregulated the expression of MCT4 and CD147, blocking the export of lactate. Furthermore, FC also evoked mitochondrial dysfunction coupled with excessive oxidative stress, decreased mitochondrial membrane potential, ATP production reduction, glutathione depletion, and Ca2+ overload. Moreover, FC suppressed tumor progression in vivo with reduced protein levels of the MCT4 and CD147 in tumor tissues. CONCLUSION: FC inhibits lung cancer growth by the novel mechanism in which MCT4/CD147-mediated inhibition of lactate transport and disruption of mitochondrial functions are involved.

Cross-camera Performance of Deep Learning Algorithms to Diagnose Common Ophthalmic Diseases: A Comparative Study Highlighting Feasibility to Portable Fundus Camera Use.

PURPOSE: To compare the inter-camera performance and consistency of various deep learning (DL) diagnostic algorithms applied to fundus images taken from desktop Topcon and portable Optain cameras. METHODS: Participants over 18 years of age were enrolled between November 2021 and April 2022. Pair-wise fundus photographs from each patient were collected in a single visit; once by Topcon (used as the reference camera) and once by a portable Optain camera (the new target camera). These were analyzed by three previously validated DL models for the detection of diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucomatous optic neuropathy (GON). Ophthalmologists manually analyzed all fundus photos for the presence of DR and these were referred to as the ground truth. Sensitivity, specificity, the area under the curve (AUC) and agreement between cameras (estimated by Cohen's weighted kappa, K) were the primary outcomes of this study. RESULTS: A total of 504 patients were recruited. After excluding 12 photographs with matching errors and 59 photographs with low quality, 906 pairs of Topcon-Optain fundus photos were available for algorithm assessment. Topcon and Optain cameras had excellent consistency (Κ=0.80) when applied to the referable DR algorithm, while AMD had moderate consistency (Κ=0.41) and GON had poor consistency (Κ=0.32). For the DR model, Topcon and Optain achieved a sensitivity of 97.70% and 97.67% and a specificity of 97.92% and 97.93%, respectively. There was no significant difference between the two camera models (McNemar's test: x2=0.08, p = .78). CONCLUSION: Topcon and Optain cameras had excellent consistency for detecting referable DR, albeit performances for detecting AMD and GON models were unsatisfactory. This study highlights the methods of using pair-wise images to evaluate DL models between reference and new fundus cameras.

Application of nursing based on the authorization theory in asthmatic children aged 7 to 14 years.

OBJECTIVE: To investigate the effect of a nursing model based on the authorization theory of asthma in children aged 7 to 14 years. METHODS: In total, 200 children who were 7 to 14 years with asthma in remission were recruited in this study. These children were admitted to our hospital and were randomly divided into the control group (n=100) and the experimental group (n=100). Patients in the control group received routine nursing, while those in the experimental group received routine nursing and nursing based on the authorization theory. Treatment compliance, the time of disappearance of symptoms (like sputum, cough, wheeze, and wet rales), the length of hospitalization, lung function, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC, general self-efficacy scale (GSES) score, MOS 36-item short form health survey (SF-36) score, and parents' satisfaction with nursing were compared between the two groups. RESULTS: FEV1, FVC, FEV1/FVC, GSES score, and SF-36 scores in all aspects in the two groups after intervention were increased when compared with before intervention; in addition, FEV1, FVC, FEV1/FVC, GSES score, and SF-36 scores in all aspects in the experimental group after intervention were significantly higher than those in the control group (all P<0.05). The time of disappearance of symptoms (like sputum, cough, wheeze, and wet rales) and length of hospitalization in the experimental group were shorter than those in the control group (all P<0.05). Compared with the control group, treatment compliance and satisfaction in nursing in the experimental group were increased (both P<0.05). CONCLUSION: Nursing based on the authorization theory can effectively improve treatment compliance, lung function, SF-36 scores, and satisfaction in nursing, and shorten the length of hospitalization.

Comprehensive analysis of lncRNAs N6-methyladenosine modification in colorectal cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) and their N6-methyladenosine (M6A) modifications are involved in cancer occurrence and development. METHODS: lncRNA M6A modification in colorectal cancer (CRC) was comprehensively analyzed for the first time. RESULTS: M6A levels of lnRNAs in CRC tissues were higher than those in tumor-adjacent normal tissues. A total of 8,332 M6A peaks were detected in 6,690 lncRNAs in CRC tissues. Approximately 91% of the modified lncRNAs had unique M6A modification peaks. A total of 383 lncRNAs were differentially methylated in CRC, of which 48.24% had a length of 1-1,000 bp. Most of these were located on chromosomes 1, 2, 7, 11, 16 and 19; 42.3% were within a sense-overlapping exon. RNA sequencing identified 163 differentially expressed lncRNAs in CRC. GO and KEGG analyses revealed that genes near differentially-methylated or -expressed lncRNAs were associated with CRC occurrence and development. Methylation was positively correlated with lncRNA expression levels in CRC and tumor-adjacent normal tissues. More unmethylated than M6A methylated lncRNA molecules were detected. A competing endogenous RNA (ceRNA) and lncRNA-mRNA expression-regulation network revealed a regulatory relationship between lncRNAs, microRNAs (miRNAs), and mRNAs. CONCLUSIONS: The findings may help improve our understanding of lncRNA function in colorectal cancer.