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Tumor microenvironment (TME) plays an important role in the tumorigenesis, proliferation, invasion and metastasis. Thereby developing synergistic anticancer strategies with multiple mechanisms are urgent. Copper is widely used in the treatment of tumor chemodynamic therapy (CDT) due to its excellent laser-mediated photo-Fenton-like reaction. Additionally, copper can induce cell death through cuproptosis, which is a new modality different from the known death mechanisms and has great promise in tumor treatment. Herein, we report a natural small molecules carrier-free injectable hydrogel (NCTD Gel) consisted of Cu2+-mediated self-assembled glycyrrhizic acid (GA) and norcantharidin (NCTD), which are mainly governed by coordination and hydrogen bonds. Under 808 nm laser irradiation, NCTD Gel can produce reactive oxygen species (ROS), consume glutathione (GSH) and overcome hypoxia in TME, leading to synergistically regulate TME via apoptosis, cuproptosis and anti-inflammation. In addition, NCTD Gel's CDT display high selectivity and good biocompatibility as it relies on the weak acidity and H2O2 overexpression of TME. Notably, NCTD Gel's components are originated from clinical agents and its preparation process is easy, green and economical, without any excipients. This study provides a new carrier-free hydrogel synergistic antitumor strategy, which has a good prospect in industrial production and clinical transformation.

Abstract Through the self-assembled strategy to improve the clinical efficacy of the existing drugs is the focus of current research. Herbal formula granule is a kind of modern dosage form of traditional Chinese medicine (TCM) which has sprung up in recent decades. However, whether it is equivalent to the TCM decoction that has been used for thousands of years has always been a controversial issue. In this paper, taking the herb pair of Coptidis Rhizoma—Scutellariae Radix and its main component berberine—baicalin as examples, the differences and mechanisms of self-assemblies originated from the co-decoction and physical mixture were studied, respectively. Moreover, the relationship between the morphology and antibacterial effects of self-assemblies was illuminated via multi-technology. Our study revealed that the physical mixture’s morphology of both the herb pair and the phytochemicals was nanofibers (NFs), while their co-decoction’s morphology was nanospheres (NPs). We also found that the antibacterial activity was enhanced with the change of self-assemblies’ morphology after the driving by thermal energy. This might be attributed to that NPs could influence amino acid biosynthesis and metabolism in bacteria. Current study provides a basis that co-decoction maybe beneficial to enhance activity and reasonable use of herbal formula granule in clinic.

Abstract Background Oral administration of insulin (INS) could be absorbed into systemic circulation only if the carrier protected it from the hostile gastrointestinal conditions. However, traditional macromolecular carriers have not totally overcome challenges in addressing these biological barriers. Result In this study, inspired by small molecule natural products (SMNPs), we demonstrate the multi-functional self-assembly nanoparticles (BA-Al NPs) originating from baicalin (BA) and AlCl3 through coordination bonds and hydrogen bonds. As a novel carrier for oral insulin delivery (INS@BA-Al NPs), it displayed effective capacity in pH stimuli-responsive insulin release, intestinal mucoadhesion and transepithelial absorption enhance. Meanwhile, BA improved the paracellular permeability for insulin absorption, because of its downregulation at both mRNA and protein level on internal tight junction proteins. In vivo experiments exhibited remarkable bioavailability of INS and an ideal glucose homeostasis in the type I diabetic rat model. Conclusion This study offers a novel frontier of multi-functional carriers based on SMNPs with self-assembly character and bioactivity, which could be a promising strategy for diabetes therapy. Graphical Abstract

It is crucial to inhibit tumor growth and distant metastasis for breast cancer (BC) therapy. However, the treatment primarily dependent on surgery, chemotherapy, and radiotherapy is far from satisfactory. It had been demonstrated that the CXCL1/2-S100A8/9 axis played an essential role in BC therapy. Therefore, we constructed a natural product hydrogel for BC therapy by blocking CXCL1 signaling. The GK-GA (phytochemicals of Genkwa Flos-glycyrrhizic acid) hydrogel was designed in a one-step “green” approach. The pharmacodynamics study showed GK-GA exhibited significant anti-tumor and anti-lung metastasis activities, resulting in the inhibition rate of tumor growth (IRG) over 90 % at 6.25 mg·kg−1, and did not display any obvious toxicity. In addition, the potent antitumor efficiency was also attributed to aggregation/assembly-induced retention (AIR) property. RNA sequencing analysis revealed the gene expression was significantly down-regulated in the GK-GA group, which were BCL2, CASP3, CXCL1, CXCL2, CXCR2, S100A8, S100A9, and confirmed further by western blot (WB). Our findings indicated natural product GK-GA hydrogel inhibited tumor growth and lung metastasis via the BCL2-CASP3 mitochondrial apoptosis pathway as well as the CXCL1/2-S100A8/9 pathway. This study provides inspiration for the fabrication of new excipients-free nano-dispersion in a one-step, no‐carrier‐added, organic solvent-free, “green” approach, particularly for small molecular antitumor agents.

MPOG (microbial prospecting of oil and gas) technology has its unique advantages, and the microbial anomaly index system lays the basis for comprehensive evaluation of MPOG data and prospect prediction of target areas. In view of the problem that the current exploration technology is limited in the areas where seismic exploration is difficult to reach or difficult to implement, this article uses modern biotechnology to discuss the technical mechanism of microbial exploration technology and the indicators of abnormal technology system in detail, on the basis of known oil and gas properties of completed wells. In order to establish a reference system suitable for the actual geological characteristics of oilfields, and to further improve the index system for identifying oil and gas microbial abnormalities in oil and gas areas, specific microbial abnormal indicators are isolated, cultivated, and detected. Combining the geological characteristics of the work area, drilling and oil testing data, and classification evaluation of oil and gas-bearing areas, as well as oil and gas prospects, is performed. MPOG technology has a certain applicability in the evaluation of oil and gas properties. The research in this article can provide a favorable reference for the selection of favorable oil and gas zones and well location deployment.

Researchers often focus on the mechanisms of synergistic agents, a few explore drug combinations that enhance toxicity, while few have studied the internal mechanism of compatibility enhancement in chemical level. Herein, we present a comprehensive analysis based on ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) and a self-assembled supramolecular strategy, which reveals the toxicity-enhancing essence of glycyrrhizic acid originated in licorice when combined with Genkwa Flos. Through this method, we discovered the toxicity was enhanced through the formation of a supramolecular complex from Genkwa Flos/glycyrrhizic acid. The morphology and size distribution of the self-assembled nanoparticles were characterized by scanning electron microscopy and dynamic light scattering Furthermore, a total of 58 constituents (eight diterpenoids, 35 flavonoids, five phenylpropanoids, four nucleosides, two amino acids, and four other compounds) consisted from the supramolecular complex were identified through accurate-mass measurements in full-scan MS/data-dependent MS/MS mode. Based on the hydrophobic interaction of glycyrrhizic acid with yuanhuacine (one of main ingredients from Genkwa Flos), the supramolecular self-assembly mechanism was revealed with proton nuclear magnetic resonance (1H-NMR) and NOESY 2D NMR. The toxicity of Genkwa Flos and Genkwa Flos/glycyrrhizic acid supramolecular complex were compared through in vitro studies on L-02 cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; and 4′,6-diamidino-2-phenylindole (DAPI) staining was performed to further confirm the enhancement inhibition of Genkwa Flos/glycyrrhizic acid supramolecular complex than Genkwa Flos. This study provides fundamental scientific evidence of the formation of a self-assembled phytochemical supramolecular when Genkwa Flos and glycyrrhizic acid are combined, enabling to understand their clinical incompatibility and contraindication.

Grain appearance quality and milling quality are the main determinants of market value of rice. Breeding for improved grain quality is a major objective of rice breeding worldwide. Identification of genes/QTL controlling quality traits is the prerequisite for increasing breeding efficiency through marker-assisted selection. Here, we reported a genome-wide association study in indica rice to identify QTL associated with 10 appearance and milling quality related traits, including grain length, grain width, grain length to width ratio, grain thickness, thousand grain weight, degree of endosperm chalkiness, percentage of grains with chalkiness, brown rice rate, milled rice rate and head milled rice rate. A diversity panel consisting of 272 indica accessions collected worldwide was evaluated in four locations including Hangzhou, Jingzhou, Sanya and Shenzhen representing indica rice production environments in China and genotyped using genotyping-by-sequencing and Diversity Arrays Technology based on next-generation sequencing technique called DArTseq™. A wide range of variation was observed for all traits in all environments. A total of 16 different association analysis models were compared to determine the best model for each trait-environment combination. Association mapping based on 18,824 high quality markers yielded 38 QTL for the 10 traits. Five of the detected QTL corresponded to known genes or fine mapped QTL. Among the 33 novel QTL identified, qDEC1.1 (qGLWR1.1), qBRR2.2 (qGL2.1), qTGW2.1 (qGL2.2), qGW11.1 (qMRR11.1) and qGL7.1 affected multiple traits with relatively large effects and/or were detected in multiple environments. The research provided an insight of the genetic architecture of rice grain quality and important information for mining genes/QTL with large effects within indica accessions for rice breeding.

In order to study the unfolding process of Z-type folding wing which is commonly used in folding wing, the mechanism model and mathematical model are established based on the working principle and practical requirements of folding mechanism. The virtual simulation software ADAMS was used to establish the simulation model, and the main parameters such as the time, angular velocity and the required driving force of the folding wing were simulated. Through the analysis of the simulation results, the parametric model and three different design variables were established, and the influence degree of single design variable and multiple variables on the objective is analyzed, and obtain the optimal design parameters. The overall research results enhance the reliability of the design of folding wing unfolding mechanism, and have an important impact on the development and application of Z-type folding wing. [ABSTRACT FROM AUTHOR]

Some projectile enterprises counter with some problems, such as the disunity of product models and low efficiency in the projectile producing process. As to the problems, this thesis analyzes MBD model and the projectile producing process, adopts 3D process modeling method which is based on MBD model, standardizes parameterized modeling with MBD model, simplifies the analytical model, reduces the input of the process information and data conversion. The technology can reduce product design cycle, improve product rapid manufacturing capacity, and reduce costs to make important contributions to our country's weapons enterprises. [ABSTRACT FROM AUTHOR]