Traditional Chinese medicine (TCM) plays an important role in the treatment of type 2 diabetes mellitus (T2DM). However, the lack of adequate and scientifically rigorous evidence has limited its application in this disorder. Sanbai melon seed oil (SMSO) is used in folk medicine to treat DM; however, only few literature reports exist regarding its mechanism. Herein, we aimed to confirm the antidiabetic activity of SMSO in a T2DM model and further elucidate its possible mechanisms. The T2DM rat model was induced by high-fat and sugar diet and streptozocin (STZ, 40 mg/kg). SMSO was administered at doses of 0.7 g/kg, 1.4 g/kg, and 2.8 g/kg. Several biochemical parameters and antioxidant protein levels were measured to evaluate the hyperglycemic and antioxidant activities of SMSO. Western blotting was performed to determine its potential mechanism. Based on the results, SMSO treatment significantly reduced blood glucose levels, increased plasma insulin, and repaired islet tissue injury in diabetic rats (P < 0.05). To add, it markedly reduced MDA levels and increased that of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Western blot results showed that SMSO induced n-Nrf2 and HO-1 expression and Akt and GSK-3β phosphorylation in a dose-dependent manner. Further studies showed that LY294002, aPI3K inhibitor, abolished the effects of SMSO on GSK-3β phosphorylation and Nrf2 nuclear translocation as well as the protective effects on pancreatic β cells. Together, these results suggest that SMSO regulates the Akt/GSK-3β/Nrf2 pathway and induces the expression of antioxidant proteins to impede oxidative stress in rats with T2DM.

Photosynthesis is a very important process for the current biosphere which can maintain such a subtle and stable circulatory ecosystem on earth through the transformation of energy and substance. Even though been widely studied in various aspects, the physiological activities, such as intrinsic structural vibration and self-regulation process to stress of photosynthetic proteins, are still not in-depth resolved in real-time. Herein, utilizing silicon nanowire biosensors with ultrasensitive temporal and spatial resolution, real-time responses of a single photosystem I-light harvesting complex I (PSI-LHCI) supercomplex of Pisum sativum to various conditions, including gradient variations in temperature, illumination, and electric field, are recorded. Under different temperatures, there is a bi-state switch process associated with the intrinsic thermal vibration behavior. When the variations of illumination and the bias voltage are applied, two additional shoulder states, probably derived from the self-conformational adjustment, are observed. Based on real-time monitoring of the dynamic processes of the PSI-LHCI supercomplex under various conditions, it is successively testified to promising nanotechnology for protein profiling and biological functional integration in photosynthesis studies.

Promyelocytic Leukemia (PML) protein can interact with a multitude of cellular factors and has been implicated in the regulation of various processes, including protein sequestration, cell cycle regulation and DNA damage responses. Previous studies reported that misfolded proteins or proteins containing polyglutamine tracts form aggregates with PML, chaperones, and components of the proteasome, supporting a role for PML in misfolded protein degradation.

The intensified global warming during grain filling deteriorated rice quality, in particular increasing the frequency of chalky grains which markedly impact market value. The formation of rice quality is a complex process influenced by multiple genes, proteins and physiological metabolic processes. Proteins responsive to stimulus can adjust the ability of plants to respond to unfavorable environments, which may be an important protein involved in the regulation of quality formation under elevated temperature. However, relatively few studies have hindered our further understanding of rice quality formation under elevated temperature.

Our previous study has shown that nitrogen plays an important role in dealing with significantly increased chalkiness caused by elevated temperature. However, the role of nitrogen metabolites has not been given sufficient attention, and its regulatory mechanism is not clear. This study investigated the effects of high temperature and nitrogen fertilizer on the synthesis of grain storage protein and further explored the quality mechanism under the actual scenario of field warming. Results showed that increased temperature and nitrogen fertilizer could affect the activities of nitrogen metabolism enzymes, namely, glutamate synthetase, glutamine synthetase, glutamic pyruvic transaminase, and glutamic oxaloacetic transaminase, and the expressions of storage protein synthesis factor genes, namely, GluA and GluB, and subfamily genes, namely, pro14, BiP1, and PDIL1, which co-induced the changes of storage protein synthesis in rice grains. Furthermore, the increased temperature changed the balance of grain storage substances which may lead to the significantly increased chalky rate (197.67%) and chalkiness (532.92%). Moreover, there was a significant negative correlation between prolamin content and chalkiness, indicating that nitrogen fertilizer might regulate the formation of chalkiness by affecting the synthesis of prolamin. Results suggested that nitrogen application could regulate the related core factors involved in nitrogen metabolism pathways, which, in turn, affects the changes in the storage protein components in the grain and further affects quality. Therefore, as a conventional cultivation measure, nitrogen application would have a certain value in future rice production in response to climate warming.

With the intensification of global warming, rice production is facing new challenges. Field evidence indicates that elevated temperature during rice grain-filling leads to the further deterioration of grain quality. In order to clarify the potential regulatory mechanism of elevated temperature on the formation of rice quality, the DIA mass spectrometry method under the background of field warming was conducted to investigate the regulatory effects of high temperature on grain development and material accumulation pathways. The results showed that a total of 840 differentially expressed proteins were identified during the grain-filling process under elevated temperature. These differentially expressed proteins participated in carbon metabolism, amino acid biosynthesis, signal transduction, protein synthesis, and alternately affected the material accumulation of rice grains. The significant up-regulation of PPROL 14E, PSB28, granule-bound starch synthase I, and the significant down-regulation of 26.7 kDa heat shock protein would lead to the component difference in grain starch and storage proteins, and that could be responsible for the degradation of rice quality under elevated temperature. Results suggested that proteins specifically expressed under elevated temperature could be the key candidates for elucidating the potential regulatory mechanism of warming on rice development and quality formation. In-depth study on the metabolism of storage compounds would be contributed in further proposing high-quality cultivation control measures suitable for climate warming.

Despite advances in the diagnosis and treatment in recent years, lung cancer is still one of the primary causes of cancer-associated morbidity and mortality in globally. Abnormally expressed microRNAs (miRNAs/miRs) in tumor tissues serve vital roles in the pathological mechanism of tumors and have become prospective biomarkers for cancer diagnosis. The present study aimed to investigate the effects of the miR-140-5p/zinc finger protein 800 (ZNF800) axis in lung carcinoma, and determine its potential underlying molecular mechanisms. The degree of cell proliferation was assessed via the MTT assay, while the migratory and invasive abilities of lung cancer cells were determined via the Transwell and Matrigel assays. The expression levels of miR-140-5p and ZNF800 were detected via reverse transcription-quantitative PCR and western blot analyses. The results demonstrated that miR-140-5p expression was notably higher in normal human bronchial epithelial cells compared with the respective lung cancer cell lines, H292, PC-9, CL1-5 and H460. Furthermore, miR-140-5p expression increased in the lung cancer cells compared with the control cells following transfection with miR-140-5p mimic. Overexpressing miR-140-5p significantly suppressed the proliferative, invasive and migratory abilities of H460 and PC-9 cells, and stimulated cell apoptosis by upregulating the expression of cleaved-caspase-3. Notably, these effects were reversed following transfection with miR-140-5p inhibitor. miR-140-5p was predicted as a negative regulator of ZNF800, and ZNF800 knockdown significantly suppressed the proliferative and metastatic abilities of lung adenocarcinoma (LUAD) cells, which was comparable to the effects of miR-140-5p mimic. Taken together, these results suggest that miR-140-5p may block the malignant phenotype of LUAD by negatively regulating ZNF800 expression. Thus, the miR-140-5p/ZNF800 axis may be used as an alternative therapeutic target for lung carcinoma in general, and LUAD in particular.

Mortality from prostate cancer (PCa) is due to the formation of metastatic disease. Understanding how that process is regulated is therefore critical. We previously demonstrated that endoglin, a type III transforming growth factor β (TGFβ) superfamily receptor, suppresses human PCa cell invasion and metastasis. Endoglin-mediated suppression of invasion was also shown by us to be dependent upon the type I TGFβ receptor, activin receptor-like kinase 2 (ALK2), and the downstream effector, Smad1. In this study we demonstrate for the first time that two type II TGFβ receptors are required for endoglin-mediated suppression of invasion: activin A receptor type IIA (ActRIIA) and bone morphogenetic protein receptor type II (BMPRII). Downstream signaling through these receptors is predominantly mediated by Smad1. ActRIIA stimulates Smad1 activation in a kinase-dependent manner, and this is required for suppression of invasion. In contrast BMPRII regulates Smad1 in a biphasic manner, promoting Smad1 signaling through its kinase domain but suppressing it through its cytoplasmic tail. BMPRII's Smad1-regulatory effects are dependent upon its expression level. Further, its ability to suppress invasion is independent of either kinase function or tail domain. We demonstrate that ActRIIA and BMPRII physically interact, and that each also interacts with endoglin. The current findings demonstrate that both BMPRII and ActRIIA are necessary for endoglin-mediated suppression of human PCa cell invasion, that they have differential effects on Smad1 signaling, that they make separate contributions to regulation of invasion, and that they functionally and physically interact.

Intrinsically disordered proteins (IDPs) play crucial roles in cellular processes and hold promise as drug targets. However, the dynamic nature of IDPs remains poorly understood. Here, we construct a single-molecule electrical nanocircuit based on silicon nanowire field-effect transistors (SiNW-FETs) and functionalize it with an individual disordered c-Myc bHLH-LZ domain to enable label-free, in situ, and long-term measurements at the single-molecule level. We use the device to study c-Myc interaction with Max and/or small molecule inhibitors. We observe the self-folding/unfolding process of c-Myc and reveal its interaction mechanism with Max and inhibitors through ultrasensitive real-time monitoring. We capture a relatively stable encounter intermediate ensemble of c-Myc during its transition from the unbound state to the fully folded state. The c-Myc/Max and c-Myc/inhibitor dissociation constants derived are consistent with other ensemble experiments. These proof-of-concept results provide an understanding of the IDP-binding/folding mechanism and represent a promising nanotechnology for IDP conformation/interaction studies and drug discovery.

Anubias Schott (Araceae) have high ornamental properties as aquarium plants. However, the genus has difficulties in species identification, and the mechanism of its adaptation to the aquatic environment is unknown. To better identify species and understand the evolutionary history of Anubias, the plastomes of Anubias barteri Schott, A. barteri var. nana (Engl.) Crusio, and A. hastifolia Engl., were sequenced. The sizes of the plastomes of Anubias ranged from 169,841 bp to 170,037 bp. These plastomes were composed of conserved quadripartite circular structures and comprised 112 unique genes, including 78 protein-coding genes, 30 transfer RNA genes, and 4 ribosomal RNA genes. The comparative analysis of genome structure, repeat sequences, codon usage and RNA editing sites revealed high similarities among the Anubias plastomes, indicating the conservation of plastomes of Anubias. Three spacer regions with relatively high nucleotide diversity, trnL-CAA-ndhB, ycf1-ndhF, and rps15-ycf1, were found within the plastomes of Anubias. Phylogenetic analysis, based on 75 protein-coding genes, showed that Anubias was sister to Montrichardia arborescens (L.) Schott (BS = 99). In addition, four genes (ccsA, matK, ndhF, and ycf4) that contain sites undergoing positive selection were identified within the Anubias plastomes. These genes may play an important role in the adaptation of Anubias to the aquatic environment. The present study provides a valuable resource for further studies on species identification and the evolutionary history of Anubias.

The degradation process of RNA is decisive in guaranteeing high-fidelity translation of genetic information in living organisms. However, visualizing the single-base degradation process in real time and deciphering the degradation mechanism at the single-enzyme level remain formidable challenges. Here, we present a reliable in-situ single-PNPase-molecule dynamic electrical detector based on silicon nanowire field-effect transistors with ultra-high temporal resolution. These devices are capable of realizing real-time and label-free monitoring of RNA analog degradation with single-base resolution, including RNA analog binding, single-nucleotide hydrolysis, and single-base movement. We discover a binding event of the enzyme (near the active site) with the nucleoside, offering a further understanding of the RNA degradation mechanism. Relying on systematic analyses of independent reads, approximately 80% accuracy in RNA nucleoside sequencing is achieved in a single testing process. This proof-of-concept sets up a Complementary Metal Oxide Semiconductor (CMOS)-compatible playground for the development of high-throughput detection technologies toward mechanistic exploration and single-molecule sequencing.