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Chemotherapy is widely used to treat colorectal cancer (CRC). Despite its substantial benefits, the development of drug resistance and adverse effects remain challenging. This study aimed to elucidate a novel role of glucagon in anti‐cancer therapy. In a series of in vitro experiments, glucagon inhibited cell migration and tube formation in both endothelial and tumor cells. In vivo studies demonstrated decreased tumor blood vessels and fewer pseudo‐vessels in mice treated with glucagon. The combination of glucagon and chemotherapy exhibited enhanced tumor inhibition. Mechanistic studies demonstrated that glucagon increased the permeability of blood vessels, leading to a pronounced disruption of vessel morphology. Signaling pathway analysis identified a VEGF/VEGFR‐dependent mechanism whereby glucagon attenuated angiogenesis through its receptor. Clinical data analysis revealed a positive correlation between elevated glucagon expression and chemotherapy response. This is the first study to reveal a role for glucagon in inhibiting angiogenesis and vascular mimicry. Additionally, the delivery of glucagon‐encapsulated PEGylated liposomes to tumor‐bearing mice amplified the inhibition of angiogenesis and vascular mimicry, consequently reinforcing chemotherapy efficacy. Collectively, the findings demonstrate the role of glucagon in inhibiting tumor vessel network and suggest the potential utility of glucagon as a promising predictive marker for patients with CRC receiving chemotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Confined by the volatile property, pesticides are overused and lost significantly during and after spraying, weakening the ecological microbalance among different species of lives. Acid‐responsive pesticide is a type of smartly engineered pesticides that contribute to the improvement of utilization efficiency of pesticidal active ingredients in acid‐controlled manner, whilst the implementation of acidic solutions may disturb the balance of microenvironment surrounding targeted plants or cause secondary pollution, underscoring the input of acid in a more precise strategy. RESULTS: Chitosan was chemically modified with a photoacid generator (2‐nitrobenzaldehyde) serving as a light‐maneuvered acid self‐supplier, based on which a smart pesticide was formulated by the integration of attapulgite and organophosphate insecticide chlorpyrifos. Under the irradiation of UV light (365 nm), the modified chitosan would undergo a photolytic reaction to generate an acid and pristine chitosan, which seized the labile protons and facilitated the release of chlorpyrifos based on its inherent pH‐responsive flexibility. According to the pesticide release performance, the release rate of chlorpyrifos under UV light (27.2 mW/cm2) reached 78%, significantly higher than those under sunlight (22%, 4.2 mW/cm2) and in the dark (20%) within the same time, consistent with the pH reduction to 5.3 under UV light and no obvious pH change for the two other situations, exhibiting an attractive UV light‐controlled, acid‐propelled release behavior. CONCLUSION: Compared to direct acid spray approach, the proposed in situ photo‐induced generation of acid locally on the spots of applied pesticide circumvents the problem of acid contamination to nontargets, demonstrating higher efficiency and biocompatibility for the controlled delivery of acid‐responsive pesticides and pest management. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In China, the rice (Oryza sativa L.)–rapeseed (Brassica napus L.) rotation system is facing great challenges, including constantly growing demand, on‐going labor shortages, and increasing environmental burdens. Thus, producing more food and higher benefits while minimizing environmental costs is required for future development. A 2‐yr field experiment comparing three nitrogen (N) fertilization treatments (non‐N treatment as control [CK], conventional urea application [CU], one‐time application of controlled‐release urea [CRU]) was performed. Results showed that the rice season dominated annual CH4 emissions (>95%) and on average contributed more than 50% of the annual N2O emissions. Additionally, the main forms of mineral N leaching were different for rape and rice. Nitrate (NO3–)–N was the major component of leaching in rape season, while for rice season NO3––N and NH4+–N were equal. Relative to CU, CRU significantly increased the rapeseed yield by 10.7∼13.9% and maintained the rice productivity, reduced mineral N leaching losses by 19.6∼20.8% for the rice season, and resulted in less total methane (CH4) and nitrous oxide (N2O) emissions (TGHGs) by 12.1% across the two rotations. Furthermore, a net economic benefit (NEB) considering yields, fertilizer input, labor, and other input costs indicated CRU increased the economic return by 58.3%. However, CRU did not improve partial factor productivity of nitrogen fertilizer (PFPN) and decreased the NEB by 3.1% without considering the labor cost. It indicated a one‐time application of the CRU for rice–rapeseed rotation system was an environmentally and economically profitable technology. This paper provided a promising solution for farmers to enhance rice–rapeseed productivity and increase income while minimizing the environmental footprint. Core Ideas: The integrated effects of controlled‐release urea on rice–rapeseed rotation were quantified.The rice‐growing season contributed more than 95 and 50% of the annual CH4 and N2O emissions.Nitrate was the main leaching loss in rape season, while for rice season NO3– and NH4+ were equal.Controlled‐release urea reduced mean annual total CH4 and N2O emissions and N leaching by 10.7 and 12.1%, without sacrificing crop yield.Labor cost savings could offset the high cost of controlled‐release urea. [ABSTRACT FROM AUTHOR]

Although the process of microbial degradation of coal to produce biomethane has got much attention from many research works, the products profiles of coal at the initial stage of methanogenic bioconversion are not clear yet. In this study, five coal‐degrading bacterial strains (CD1, CD10, CD20, CD24, and CD25) from a methanogenic community were isolated and identified. Among them, CD1 and CD24 belong to Paenibacillus sp., CD10 and CD20 belong to Bacillus sp., and CD25 belongs to Stenotrophomonas sp. After biotreatment of lignite and bituminous coal, the kinds of newly produced compounds were 33 and 45, respectively. Metabolomics analysis showed that a large number of alkane compounds and heterocyclic aromatic compounds were produced after degradation of bituminous coal and lignite by isolated bacteria, and most of the compounds had been produced in a hydroxylated or acylated manner, indicating that the initial microbial treatment enhanced the bioavailability of coal. Some alkaloids and biosurfactants were also detected in the aforementioned products, such as glycerophosphocholine, proveratrol A, proveratrol B, surfactin, etc. These microbial metabolites may play an important role in solubilization during the degradation of coal. This study added to the understanding of the complicated metabolic process of methanogenic coal bioconversion and enabled effective production of biomethane with appropriate metabolic strategies. [ABSTRACT FROM AUTHOR]

Our objective was to determine the molecular mechanisms by which lncRNA HOXA‐AS3 regulates the biological behaviour of glioblastoma multiforme (GBM). We used an lncRNA microarray assay to identify GBM‐related lncRNA expression profiles. Qrt‐PCR was used to survey the levels of expression of long non‐coding RNA (lncRNA) HOXA‐AS3 and the target gene. Dual‐luciferase reporter assays were used to investigate the interaction of lncRNA HOXA‐AS3, the target gene and miRNA. Western blot analysis was used to examine the expression of USP3 and epithelial‐mesenchymal transition (EMT) genes. The MTT assay, transwell assay and wound healing assay were used to analyse the effects of lncRNA HOXA‐AS3 on GBM cell viability, mobility and invasiveness, respectively. Our results showed that lncRNA HOXA‐AS3 was significantly up‐regulated in GBM cells and could promote GBM cell proliferation, invasion and migration in vitro and in vivo. HOXA‐AS was found to be associated with poor survival prognosis in glioma patients. The dual‐luciferase reporter assay also revealed that lncRNA HOXA‐AS3 acts as a mir‐455‐5p sponge by up‐regulating USP3 expression to promote GBM progression. Western blot analysis showed that lncRNA HOXA‐AS3 could up‐regulate EMT‐related gene expression in GBM. Experiments showed mir‐455‐5p could rescue the effect of lncRNA HOXA‐AS3 on cell proliferation and invasion. The newly identified HOXA‐AS3/mir‐455‐5p/USP3 pathway offers important clues to understanding the key mechanisms underlying the action of lncRNA HOXA‐AS3 in glioblastoma. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most lethal brain malignancy which involves multi‐gene abnormality. Unfortunately, effective therapy against GBM remains lacking. Previously, we found that NRP‐1 and its downstream NRP‐1/GIPC1 pathway played an important role in GBM. In our study, we further investigated the upstream signaling of NRP‐1 to understand how it is regulated. First, we identified that hsa‐miR‐124‐3p was miRNA differentially expressed in GBM and in normal brain tissues by high‐throughput sequencing. Then, by dual luciferase reporter gene, we found miR‐124‐3p can specially bind to the 3′UTR region of the NRP‐1 thus suppresses its expression. Moreover, miR‐124‐3p overexpression significantly inhibited GBM cell proliferation, migration and tumor angiogenesis which resulted in GBM apoptosis and cell cycle arrest, putatively via NRP‐1 mediated PI3K/Akt/NFκB pathways activation in GBM cells. Meanwhile, miR‐124‐3p overexpression also suppressed tumor growth and reduced tumor angiogenesis when targeted by NRP‐1 in a PDX model. Furthermore, NRP‐1 mAb exerted synergistic inhibitory effects with miR‐124‐3p overexpression in GBM. Thus, we discovered that miR‐124‐3p acts as the upstream suppressor of NRP‐1 which promotes GBM cell development and growth by PI3K/Akt/NFκB pathway. The miR‐124‐3p/NRP‐1/GIPC1 pathway as a new pathway has a vital role in GBM, and it could be considered as the potential target for malignant gliomas in future. [ABSTRACT FROM AUTHOR]

In this study, a high-performance T1- T2 dual-model contrast agent by gadolinium-doped iron oxide nanoparticle (GION) is developed. Following its development, the application of this agent in vivo by combining doxorubicin (DOX) and folic acid (FA) (FA-GION-DOX) for targeted drug delivery to monitor cancer treatment is explored. GION showed transverse and longitudinal relaxivities up to 182.7 × 10−3 and 7.87 × 10−3 m−1 s−1, respectively, upon Gd/Fe ratio in GION at 1/4. DOX released from FA-GION-DOX is pH dependent and only kills cancer cell after FA receptor-mediated internalization into the acidic environment of endosomes and lysosomes. Systemic delivery of FA-GION-DOX significantly inhibits the growth of tumors and shows good magnetic resonance enhancement in a human cervical cancer xenograft model. Thus, FA-GION-DOX has a potential application for the targeted and magnetic resonance imaging guided therapy of cervical cancer. [ABSTRACT FROM AUTHOR]

Magnetic iron oxide coated in hydrogenation silica (Fe3O4@HSiO2) is constructed as both a tumor drug carrier and a magnetic resonance (MR) contrast agent. Colchicine (COLC) is loaded in Fe3O4@HSiO2 with the highest amount of 28.3 wt% at pH 9. The release performance of COLC can be controlled by pH, as the porous HSiO2 shell can partially shed at pH below 3.0 to facilitate the release of COLC. MR imaging (MRI) tests prove that Fe3O4@HSiO2 at pH 3.0 (H+-Fe3O4@HSiO2) shows a stronger MR contrast enhancement than Fe3O4. Cytotoxicity experiment indicates that Fe3O4@HSiO2 has excellent biocompatibility and magnetic targeting performance. Additionally, COLC-loaded Fe3O4@HSiO2 (Fe3O4@HSiO2-COLC) displays a higher inhibition effect on tumor cells under a magnetic field than free COLC. The visibility upon MRI, high targeting, and pH-controlled release characteristics of Fe3O4@HSiO2-COLC are favorable to achieve the aim of reducing side effects to normal tissues, making Fe3O4@HSiO2-COLC an attractive drug delivery system for nanomedicine. [ABSTRACT FROM AUTHOR]

In the title mol-ecule, [ZnCl(2)(C(11)H(10)N(2)O(2))(2)], the Zn(II) ion, situated on a twofold axis, is in a distorted tetra-hedral coordination environment formed by two chloride anions and two pyridine N atoms of the two organic ligands. In the pyrrole-2-carboxyl-ate unit, the pyrrole N-H group and the carbonyl group point approximately in the same direction. The dihedral angle between the two pyridine rings is 54.8 (3)°. The complex mol-ecules are connected into chains extending along [101] by N-H⋯Cl hydrogen bonds. The chains are further assembled into (-101) layers by C-H⋯O and C-H⋯Cl inter-actions.

In the title mol-ecule, C(20)H(20)ClN(3)O(4), both the pyrrole N-H groups adopt a syn conformation with respect to the carbonyl groups. In the crystal, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into layers parallel to (102).

There are two independent molecules in the asymmetric unit of the title compound, C(25)H(24)F(2)N(6), in which the N=N bonds adopt a trans configuration with distances in the range 1.262 (2)-1.269 (3) Å. The dihedral angles between heterocycles are 86.7 (2) and 85.6 (2)° in the two molecules while the dihedral angles between the heterocylic rings and the adjacent benzene rings are 13.4 (2) and 13.4 (2)° in one molecule and 5.3 (2) and 6.5 (2)° in the other. In the crystal, pairs of independent mol-ecules are held together by four N-H⋯N hydrogen bonds, forming inter-locked dimers.