Kidney Bean Protein Prevents High-Fat and High-Fructose Diet-Induced Obesity, Cognitive Impairment, and Disruption of Gut Microbiota Composition.

A long-term intake of a high-fat and high-fructose diet (HFFD), even a high-fat, high-fructose but low-protein diet (HFFD + LP), could cause obesity associated with cognitive impairments. In the present study, rats were subjected to a normal diet (ND), an HFFD diet, an HFFD + LP diet, and an HFFD with kidney bean protein (KP) diet for 8 weeks to evaluate the effect of KP on HFFD- or HFFD + LP-induced obesity and cognitive impairment. The results demonstrated that compared with the HFFD diet, KP administration significantly decreased the body weight by 7.7% and the serum Angiotensin-Converting Enzyme 2 (ACE-2) and Insulin-like Growth Factor 1 (IGF-1) levels by 14.4% and 46.8%, respectively (p < 0.05). In addition, KP suppressed HFFD-induced cognitive impairment, which was evidenced by 8.7% less time required to pass the water maze test. The 16s RNA analysis of the colonic contents showed that the relative abundance of Bifidobacterium, Butyricimonas, and Alloprevotella was increased by KP by 5.9, 44.2, and 79.2 times. Additionally, KP supplementation primarily affected the choline metabolic pathway in the liver, and the synthesis and functional pathway of neurotransmitters in the brain, thereby improving obesity and cognitive function in rats.

Active multi-focus vortex beam terahertz encoding metasurface based on Dirac semimetals.

An electromagnetic wavefront can be flexibly manipulated by discrete phase coding on the coding unit. In this paper, we designed two coding metasurfaces with 1-bit and 3-bit based on active tuning of Dirac semimetals by controlling the Fermi level (E F) with an external polarization voltage. The size and structure of the metasurface remain unchanged with this strategy. Both designs were found to be dynamically tunable. The 1-bit coding metasurface enables beam conversion, single-focus switching, and switching between single-focus and multi-focus. On the other hand, the 3-bit coding metasurface enables the switching between vortex beams and single-beam mirror reflections. These proposed structures have potential applications in terahertz (THz) communications and terahertz-focused imaging, opening up new possibilities for the dynamic modulation of THz waves.

Bisphenol F induced hyperglycemia via activation of oxidative stress-responsive miR-200 family in the pancreas.

Bisphenol F (BPF), BPS and BPAF are gaining popularity as main substitutes to BPA, but there is no clear evidence that these compounds disrupt glycemic homeostasis in the same way. In this study, four bisphenols were administered to C57BL/6 J mice, and showed that the serum insulin was elevated in the BPA and BPS exposed mice, whereas BPF exposed mice exhibited lower serum insulin and higher blood glucose. BPF decreased oxidized glutathione/reduced glutathione ratio (GSSG/GSH) and N6-methyladenosine (m6A) levels, which was responsible for pancreatic apoptosis in mice. Additionally, the downregulation of Nrf2 and the aberrant regulation of the p53-lncRNA H19 signaling pathway further increased miR-200 family in the BPF-exposed pancreas. The miR-200 family directly suppressed Mettl14 and Xiap by targeting their 3' UTR, leading to islet apoptosis. Antioxidant treatment not only elevated m6A levels and insulin contents but also suppressed the miR-200 family in the pancreas, ultimately improving BPF-induced hyperglycemia. Taken together, miR-200 family could serve as a potential oxidative stress-responsive regulator in the pancreas. And moreover, we demonstrated a novel toxicological mechanism in that BPF disrupted the Keap1-Nrf2 redox system to upregulate miR-141/200b/c which controlled pancreatic insulin production and apoptosis via Mettl14 and Xiap, respectively. As the major surrogates of BPA in various applications, BPF was also diabetogenic, which warrants attention in future research.

Parity-time symmetry transition and exceptional points in terahertz metal-graphene hybrid metasurface with switchable transmission and reflection characteristics.

Non-Hermitian metasurfaces provide an excellent platform for the study of parity-time (PT) symmetry transition. The exceptional point (EP) in the transition process exhibits peculiar physical phenomena and enriches the development of metasurfaces. In this study, a terahertz metal-graphene hybrid metasurface that can study PT symmetry transition and EP in transmission and reflection polarization channels is designed by using the phase transition characteristics of VO2. The tunable asymmetric loss and PT symmetry transition can be actively controlled by changing the Fermi energy of the graphene strip. Interestingly, owing to the special chirality of the structure, the original metasurface, and the mirrored metasurface degenerate into a circularly polarized state with opposite rotations at the same Fermi energy. The π-phase mutation at EP is observed following the interaction of circularly polarized waves and the metasurface and is expected to have good application prospects in environmental monitoring and gas sensing.

The Indicative Value of Serum Tumor Markers for Metastasis and Stage of Non-Small Cell Lung Cancer.

Objective: This study aimed to explore the roles of serum tumor markers for metastasis and stage of non-small cell lung cancer (NSCLC). Methods: This study recruited 3272 NSCLC patients admitted to the Tianjin Union Medical Center and the Tianjin Medical University Cancer Institute and Hospital. The predictive abilities of some serum tumor markers (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), total prostate-specific antigen (TPSA) and carbohydrate antigen 199 (CA199)) for NSCLC metastasis (intrapulmonary, lymphatic and distant metastasis) and clinical stage were analyzed. Results: Tumor markers exhibited different numerical and proportional distributions in NSCLC patients. Elevated CEA, CYFRA 21-1 and CA199 levels were indicative of tumor metastasis and stage. Increased CEA and CA199 provided an accurate prediction of intrapulmonary and distant metastasis with the area under the receiver operator characteristic curve (AUC) of 0.69 both (p < 0.001); Increased CEA, CYFRA 21-1 and CA199 provided an accurate prediction of lymphatic metastasis with the AUC of 0.62 (p < 0.001). Conclusion: Combined detection of serum tumor markers can indicate tumor metastasis and stage in NSCLC patients.

The complete chloroplast genome sequence of the medicinal plant Crotalaria albida.

Crotalaria albida (C. albida) is a traditional Chinese medicinal plant that belongs to Fabaceae family. In this study, the complete chloroplast genome sequence of C. albida was sequenced. The genome is 152,743 bp in length and includes two inverted repeat regions of 25,535 bp. It was predicted to contain 127 genes in the chloroplast genome, among which 82 were protein-coding genes, 37 were tRNA genes, and 8 were rRNA genes. The maximum likelihood phylogenetic analysis based on 24 complete chloroplast genome sequences showed that C. albida was closely related to Ormosia semicastrata, Ormosia emarginata, and Ormosia xylocarpa.

Development in Detection Methods for the Expression of Surface-Displayed Proteins.

Directed evolution is a widely-used engineering strategy for improving the stabilities or biochemical functions of proteins by repeated rounds of mutation and selection. A protein of interest is selected as the template and expressed on a molecular display platform such as a bacteriophage for engineering. Initially, the surface-displayed protein template needs to be checked against the desired target via ELISA to examine whether the functions of the displayed template remain intact. The ELISA signal is subject to the protein-target binding affinity. A low-affinity results in a weak ELISA signal which makes it difficult to determine whether the weak signal is because of low affinity or because of poor expression of the protein. Using a methyllysine-binding chromodomain protein Cbx1 that weakly binds to the histone H3K9me3 peptide, we developed and compared three different approaches to increase the signal-to-background ratio of ELISA measurements. We observed that the specific peptide-binding signal was enhanced by increasing the Cbx1 phage concentration on the ELISA plate. The introduction of previously known gain-of-function mutations to the Cbx1 protein significantly increased the ELISA signals. Moreover, we demonstrated that the H3K9me3-specific binding signal was enhanced by fusing Cbx1 with a high-affinity phosphotyrosine-binding protein and by coating the ELISA plate with a mixture of H3K9me3 and phosphotyrosine peptides. This approach also worked with binding to a lower affinity momomethyllysine peptide H3K9me1. These approaches may help improve ELISA experiments when dealing with low-affinity ligand-protein interactions.

Integrated Bioinformatics Analysis Identifies a New Stemness Index-Related Survival Model for Prognostic Prediction in Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most lethal malignancies and is currently lacking in effective biomarkers to assist in diagnosis and therapy. The aim of this study is to investigate hub genes and develop a risk signature for predicting prognosis of LUAD patients. METHODS: RNA-sequencing data and relevant clinical data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to identify hub genes associated with mRNA expression-based stemness indices (mRNAsi) in TCGA. We utilized LASSO Cox regression to assemble our predictive model. To validate our predictive model, me applied it to an external cohort. RESULTS: mRNAsi index was significantly associated with the tissue type of LUAD, and high mRNAsi scores may have a protective influence on survival outcomes seen in LUAD patients. WGCNA indicated that the turquoise module was significantly correlated with the mRNAsi. We identified a 9-gene signature (CENPW, MCM2, STIL, RACGAP1, ASPM, KIF14, ANLN, CDCA8, and PLK1) from the turquoise module that could effectively identify a high-risk subset of these patients. Using the Kaplan-Meier survival curve, as well as the time-dependent receiver operating characteristic (tdROC) analysis, we determined that this gene signature had a strong predictive ability (AUC = 0.716). By combining the 9-gene signature with clinicopathological features, we were able to design a predictive nomogram. Finally, we additionally validated the 9-gene signature using two external cohorts from GEO and the model proved to be of high value. CONCLUSION: Our study shows that the 9-gene mRNAsi-related signature can predict the prognosis of LUAD patient and contribute to decisions in the treatment and prevention of LUAD patients.

Extracellular vesicles promotes liver metastasis of lung cancer by ALAHM increasing hepatocellular secretion of HGF.

Tumor-derived extracellular vesicles (EVs) are involved in tumor metastasis. Highly enriched lncRNA-ALAHM was identified from serum EVs of lung adenocarcinoma (LUAD) patients with liver metastasis by high-throughput sequencing. A mouse model of in situ lung cancer was used to determine the effect of ALAHM in LUAD cell EVs on liver metastasis. The effects of ALAHM on hepatocyte paracrine HGF as well as proliferation, invasion, and migration of LUAD cells were observed in vitro. As results, ALAHM expression in LUAD cell EVs was significantly increased. LUAD-cell-derived EVs overexpressing ALAHM significantly promoted lung cancer liver metastasis in model mice. ALAHM of LUAD cell EVs also promotes hepatocyte parasecretion of HGF by binding with AUF1 and increases the proliferation, invasion, and migration of LUAD cells. Thus, LUAD-cell-derived EVs containing ALAHM causes increasing HGF and promoting liver metastasis of LUAD cells.

MicroRNA as an early diagnostic biomarker for contrast-induced acute kidney injury.

Contrast-induced acute kidney injury (CI-AKI) is a common clinical complication and an important cause of increased mortality, prolonged hospitalization, and increased medical costs. For taking effective interventions in CI-AKI, early diagnosis and active prevention are of key importance. Currently, early CI-AKI detection depends on serum creatinine (Scr) levels, which lags behind the actual time of renal injury and seriously affects early diagnosis and interventions. MicroRNA (miRNA) has been found to be a useful biomarker in early CI-AKI diagnosis. Several studies have reported on tissue and time-specific miRNAs in AKI as effective diagnostic biomarkers and potential therapeutic targets, but there are only a few studies on miRNA in CI-AKI. However, these studies are preliminary exploratory investigations on changes in miRNA expression in CI-AKI, and whether these specific miRNAs can be used as biomarkers for early CI-AKI diagnosis and as clinical therapeutic targets requires systematic and in-depth studies. Therefore, more sensitive and specific miRNAs of CI-AKI could be discovered, providing newer options and development directions for early diagnosis and intervention in clinical CI-AKI practice. This review evaluates the research progress on specific miRNAs in the early diagnosis of CI-AKI with an aim of providing basic data for the clinical application of these molecular markers in CI-AKI.

Insertion of a TRIM-like sequence in MdFLS2-1 promoter is associated with its allele-specific expression in response to Alternaria alternata in apple.

Alternaria blotch disease, caused by Alternaria alternata apple pathotype (AAAP), is one of the major fungal diseases in apple. Early field observations revealed, the anther-derived homozygote Hanfu line (HFTH1) was highly susceptible to AAAP, whereas Hanfu (HF) exhibited resistance to AAAP. To understand the molecular mechanisms underlying the difference in sensitivity of HF and HFTH1 to AAAP, we performed allele-specific expression (ASE) analysis and comparative transcriptomic analysis before and after AAAP inoculation. We reported an important immune gene, namely, MdFLS2, which displayed strong ASE in HF with much lower expression levels of HFTH1-derived alleles. Transient overexpression of the dominant allele of MdFLS2-1 from HF in GL-3 apple leaves could enhance resistance to AAAP and induce expression of genes related to salicylic acid pathway. In addition, MdFLS2-1 was identified with an insertion of an 85-bp terminal-repeat retrotransposon in miniature (TRIM) element-like sequence in the upstream region of the nonreference allele. In contrast, only one terminal direct repeat (TDR) from TRIM-like sequence was present in the upstream region of the HFTH1-derived allele MdFLS2-2. Furthermore, the results of luciferase and ß-glucuronidase reporter assays demonstrated that the intact TRIM-like sequence has enhancer activity. This suggested that insertion of the TRIM-like sequence regulates the expression level of the allele of MdFLS2, in turn, affecting the sensitivity of HF and HFTH1 to AAAP.

High TSPAN8 expression in epithelial cancer cell-derived small extracellular vesicles promote confined diffusion and pronounced uptake.

Small extracellular vesicles (sEVs) play a key role in intercellular communication. Cargo molecules carried by sEVs may affect the phenotype and function of recipient cells. Epithelial cancer cell-derived sEVs, particularly those enriched in CD151 or tetraspanin8 (TSPAN8) and associated integrins, promote tumour progression. The mechanism of binding and modulation of sEVs to recipient cells remains elusive. Here, we used genetically engineered breast cancer cells to derive TSPAN8-enriched sEVs and evaluated the impact of TSPAN8 on target cell membrane's diffusion and transport properties. The single-particle tracking technique showed that TSPAN8 significantly promoted sEV binding via confined diffusion. Functional assays indicated that the transgenic TSPAN8-sEV cargo increased cancer cell motility and epithelial-mesenchymal transition (EMT). In vivo, transgenic TSPAN8-sEV promoted uptake of sEVs in the liver, lung, and spleen. We concluded that TSPAN8 encourages the sEV-target cell interaction via forced confined diffusion and significantly increases cell motility. Therefore, TSPAN8-sEV may serve as an important direct or indirect therapeutic target.

Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms.

As an important medium of intercellular communication, exosomes play an important role in information transmission between tumor cells and their microenvironment. Tumor metastasis is a serious influencing factor for poor treatment effect and shortened survival. Lung cancer is a major malignant tumor that seriously threatens human health. The study of the underlying mechanisms of exosomes in tumor genesis and development may provide new ideas for early and effective diagnosis and treatment of lung cancer metastasis. Many studies have shown that tumor-derived exosomes promote lung cancer development through a number of processes. By promoting epithelial-mesenchymal transition of tumor cells, they induce angiogenesis, establishment of the pretransfer microenvironment, and immune escape. This understanding enables researchers to better understand the mechanism of lung cancer metastasis and explore new treatments for clinical application. In this article, we systematically review current research progress of tumor-derived exosomes in metastasis of lung cancer. Although positive progress has been made toward understanding the mechanism of exosomes in lung cancer metastasis, systematic basic research and clinical translational research remains lacking and are needed to translate our scientific understanding toward applications in the clinical diagnosis and treatment of lung cancer metastasis in the near future.

miR-30e-5p Regulates Autophagy and Apoptosis by Targeting Beclin1 Involved in Contrast-induced Acute Kidney Injury.

AIMS: This study aims to verify if miR-30e-5p targets Beclin1 (BECN1), a key regulator of autophagy, and investigate the function of miR-30e-5p and Beclin1 through mediating autophagy and apoptosis in contrast-induced acute kidney injury (CIAKI). METHODS: Human renal tubular epithelial HK-2 cells were treated with Urografin to construct a cell model of CI-AKI. Real-time reverse transcription-polymerase chain reaction was used to detect gene expression. The dual-luciferase reporting assay and endogenous validation were used to verify targeting and regulating function. The expressions of protein were detected using Western blot. Cell proliferation was detected using methylthiazolyldiphenyl- tetrazolium bromide (MTT) assay. Cell apoptosis was detected using terminal- deoxynucleoitidyl transferase mediated nick end labeling assay, and autophagy was detected using transmission electron microscopy. RESULTS: HK-2 cells exposed to Urografin for 2 h induced a significant increase in miR-30e-5p. miR-30e-5p had a targeting effect on Beclin1. Moreover, Urografin exposure can enhance cell apoptosis by increasing caspase 3 gene expression and inhibiting autophagy, which was induced by decreased Beclin1 expression regulated by miR-30e-5p, thereby resulting in renal cell injury. Downregulation of miR-30e-5p or upregulation of Beclin1 restored cell vitality by promoting autophagy and suppressing apoptosis in Urografin-treated cells. CONCLUSION: Urografin increased the expression of miR-30e-5p in HK-2 cells and thus decreased Beclin1 levels to inhibit autophagy, but induced apoptosis, which may be the mechanism for CI-AKI.

DeepCSO: A Deep-Learning Network Approach to Predicting Cysteine S-Sulphenylation Sites.

Cysteine S-sulphenylation (CSO), as a novel post-translational modification (PTM), has emerged as a potential mechanism to regulate protein functions and affect signal networks. Because of its functional significance, several prediction approaches have been developed. Nevertheless, they are based on a limited dataset from Homo sapiens and there is a lack of prediction tools for the CSO sites of other species. Recently, this modification has been investigated at the proteomics scale for a few species and the number of identified CSO sites has significantly increased. Thus, it is essential to explore the characteristics of this modification across different species and construct prediction models with better performances based on the enlarged dataset. In this study, we constructed several classifiers and found that the long short-term memory model with the word-embedding encoding approach, dubbed LSTM WE , performs favorably to the traditional machine-learning models and other deep-learning models across different species, in terms of cross-validation and independent test. The area under the receiver operating characteristic (ROC) curve for LSTM WE ranged from 0.82 to 0.85 for different organisms, which was superior to the reported CSO predictors. Moreover, we developed the general model based on the integrated data from different species and it showed great universality and effectiveness. We provided the on-line prediction service called DeepCSO that included both species-specific and general models, which is accessible through http://www.bioinfogo.org/DeepCSO.

lnc-REG3G-3-1/miR-215-3p Promotes Brain Metastasis of Lung Adenocarcinoma by Regulating Leptin and SLC2A5.

This study aims to explore the role and mechanism of specific lncRNA in brain metastasis (BM) from lung adenocarcinoma (LADC), providing an effective biomarker for early diagnosis and targeted therapy of BM from LADC. Based on the gene expression profiles of lncRNA and mRNA in LADC and BM tissues detected by Gene Chip, lnc-REG3G-3-1 was selected, and the related genes, including miR-215-3p, leptin, and SLC2A5, were identified by data analysis. Human LADC cell lines A549 and H1299 were cultured. Dual-luciferase and endogenous validation experiments were used to confirm the regulation between these genes. Real-time quantitative reverse transcription-polymerase chain reaction and Western blotting were used to detect gene expression. The tumor metastasis-related gene function of lnc-REG3G-3-1 and miR-215-3p in H1299 cells was verified by Transwell invasion, migration assays, and scratch testing. Nude mice xenograft tumors constructed with decreased lnc-REG3G-3-1 confirmed the influences on gene expression in vivo. lnc-REG3G-3-1 was highly expressed in BM tissues that originated from LADC compared with that in primary cancer tissues. lnc-REG3G-3-1 reduced miR-215-3p expression, thereby regulating the target genes leptin and SLC2A5 and the signaling pathways, taking part in the lnc-REG3G-3-1/miR-215-3p axis in the process of BM from LADC. lnc-REG3G-3-1, leptin, and SLC2A5 through regulating signaling pathways may be jointly involved in the regulation of the biological process of BM in patients with LADC.

The endometrium histopathology and cell ultrastructure in bitches with pyometra induced using progesterone and Escherichia coli.

BACKGROUND: We investigated uterine histopathological and ultrastructural changes in female dogs with pyometra induced by Escherichia coli (E. coli) inoculation using progesterone and/or estradiol. METHODS: Dogs were ovariectomized and classified into six groups: Groups 1-6 corresponding to estradiol treatment followed by progesterone supplementation, progesterone supplementation only, estradiol supplementation only, simultaneous treatment using estradiol and progesterone, similar to Group 1 but with a double dose, and control group, respectively. RESULTS: Pyometra was successfully induced in Groups 1, 2, 4, and 5, but not in Group 3. An uneven endometrial surface was observed, along with a purulent discharge, bleeding, inflammatory lesions, cystic endometrial hyperplasia (CEH) or cystic endometrial atrophy. Endometrial thickness percentage, uterine wall thickness, and the percentage of endometrial cyst area increased. Endometrial epithelial mushroom-like hyperplasia and the honeycomb-like structure exposed under the epithelium after flaky exfoliation were found, and the glandular epithelial villi became longer or shorter. Mitochondria expansion and increased lysosome were observed. Endoplasmic reticulum dilation and swelling and many inflammatory cells, especially plasma cell infiltration in the stroma, were found. CONCLUSIONS: Endometrial histopathology and ultrastructural changes in affected dogs were accompanied by induction of pyometra, and they were affected by different hormonal patterns and E. coli.

Importance of Effective Regulation for the Chinese Genetic Testing Industry.

The genetic testing industry is progressing rapidly. In particular, the demand of patients with tumors for diagnosis, treatment, and testing drives genetic testing to develop further. Simultaneously, the potential risks of genetic testing cause severe challenges to regulatory departments. In China, a targeted, clear, and unified management model remains absent.

Application of CRISPR/Cas9 gene editing technique in the study of cancer treatment.

In recent years, gene editing, especially that using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9, has made great progress in the field of gene function. Rapid development of gene editing techniques has contributed to their significance in the field of medicine. Because the CRISPR/Cas9 gene editing tool is not only powerful but also has features such as strong specificity and high efficiency, it can accurately and rapidly screen the whole genome, facilitating the administration of gene therapy for specific diseases. In the field of tumor research, CRISPR/Cas9 can be used to edit genomes to explore the mechanisms of tumor occurrence, development, and metastasis. In these years, this system has been increasingly applied in tumor treatment research. CRISPR/Cas9 can be used to treat tumors by repairing mutations or knocking out specific genes. To date, numerous preliminary studies have been conducted on tumor treatment in related fields. CRISPR/Cas9 holds great promise for gene-level tumor treatment. Personalized and targeted therapy based on CRISPR/Cas9 will possibly shape the development of tumor therapy in the future. In this study, we review the findings of CRISPR/Cas9 for tumor treatment research to provide references for related future studies on the pathogenesis and clinical treatment of tumors.