[Situation analysis of off-label drug use in China].

To introduce current literature reporting situations of the off-label drug use(OLDU) by analyzing relevant literatures published in China, this study comprehensively focused on literatures about OLDU in China in seven Chinese and English databases, then extracted and analyzed the data by different literature types. A total of 667 papers were analyzed. The number of literatures about OLDU data analyzed in hospitals was 325, and the number of clinical studies relating to OLDU was 329, in which case series and case reports were the majority(69.91%). In addition, there were 13 expert consensuses of OLDU and another 56 studies about drug use based on the real-world data characteristics and influencing factors. The number of OLDU data studies has increased year by year. Based on the existing studies, there were more western medicine reports than traditional Chinese medicines, and OLDU types were mainly for over-dosage use. The literatures from OLDU data in hospital were mostly limited to one or several tertiary hospitals in a certain area, and the OLDU types were not uniform. Clinical studies were mainly clinical control trials and case series/reports, but with contradictory reporting results. There were fewer OLDU consensus, and the recommended classification was not uniform. The characteristics and analysis of influencing factors of drug using data in real-world focused on traditional Chinese medicine injections, and the results were not the same. In the future, we shall pay more attention to and strengthen reporting and analysis of OLDU, define study objectives, and unify the content and reporting standards, so as to promote the integrated utilization of OLDU data and reflect real situations in our country.

UPLC-ESI-MS/MS-based widely targeted metabolomics reveals differences in metabolite composition among four Ganoderma species.

The Chinese name "Lingzhi" refers to Ganoderma genus, which are increasingly used in the food and medical industries. Ganoderma species are often used interchangeably since the differences in their composition are not known. To find compositional metabolite differences among Ganoderma species, we conducted a widely targeted metabolomics analysis of four commonly used edible and medicinal Ganoderma species based on ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Through pairwise comparisons, we identified 575-764 significant differential metabolites among the species, most of which exhibited large fold differences. We screened and analyzed the composition and functionality of the advantageous metabolites in each species. Ganoderma lingzhi advantageous metabolites were mostly related to amino acids and derivatives, as well as terpenes, G. sinense to terpenes, and G. leucocontextum and G. tsugae to nucleotides and derivatives, alkaloids, and lipids. Network pharmacological analysis showed that SRC, GAPDH, TNF, and AKT1 were the key targets of high-degree advantage metabolites among the four Ganoderma species. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes demonstrated that the advantage metabolites in the four Ganoderma species may regulate and participate in signaling pathways associated with diverse cancers, Alzheimer's disease, and diabetes. Our findings contribute to more targeted development of Ganoderma products in the food and medical industries.

Fungal Inhibition of Agricultural Soil Pathogen Stimulated by Nitrogen-Reducing Fertilization.

Plant health is the fundamental of agricultural production, which is threatened by plant pathogens severely. The previous studies exhibited the effects of different pathogen control strategies (physical, chemical, and microbial methods), which resulted from bringing in exogenous additives, on microbial community structures and functions. Nevertheless, few studies focused on the potential inhibitory abilities of native microbial community in the soil, which could be activated or enhanced by different fertilization strategies. In this study, three plant diseases (TMV, TBS, and TBW) of tobacco, fungal community of tobacco rhizosphere soil, and the correlation between them were researched. The results showed that nitrogen-reducing fertilization strategies could significantly decrease the occurrence rate and the disease index of three tobacco diseases. The results of bioinformatics analyses revealed that the fungal communities of different treatments could differentiate the nitrogen-reducing fertilization group and the control group (CK). Furthermore, key genera which were responsible for the variation of fungal community were explored by LEfSe analysis. For instance, Tausonia and Trichocladium increased, while Naganishia and Fusicolla decreased under nitrogen-reducing fertilization conditions. Additionally, the correlation between tobacco diseases and key genera was verified using the Mantel test. Moreover, the causal relationship between key genera and tobacco diseases was deeply explored by PLS-PM analysis. These findings provide a theoretical basis for a nitrogen-reducing fertilization strategy against tobacco diseases without exogenous additives and make contributions to revealing the microbial mechanism of native-valued fungal key taxa against tobacco diseases, which could be stimulated by agricultural fertilization management.

The novel lncRNA GPC5-AS1 stabilizes GPC5 mRNA by competitively binding with miR-93/106a to suppress gastric cancer cell proliferation.

Long non-coding RNAs (lncRNAs) are of importance in the genesis and progression of gastric cancer (GC). GPC5-AS1 is a novel lncRNA associated with methyl-CpG-binding protein 2 (MeCP2), identified in our previous microarray analysis; however, the role of GPC5-AS1 in GC remains unknown. In the present study, we demonstrate that GPC5-AS1 is downregulated in GC cells and tissues, and this aberrant expression is regulated by MeCP2 through CpG site binding in the promoter region. Importantly, we also demonstrate that GPC5-AS1 overexpression suppresses cell proliferation, colony formation, and cell cycle transition; induces apoptosis in vitro; and inhibits tumorigenicity in vivo. The expression of the controversial gene GPC5 was downregulated in GC tissues, and elevated GPC5 level could inhibit GC cell growth. Mechanistically, we demonstrated that GPC5-AS1 stabilizes GPC5 mRNA by acting as a molecular sponge for miR-93 and miR-106a, thereby reducing GC tumor progression. In conclusion, our results suggest that GPC5-AS1 may play a pivotal role in GC and serve as a potential diagnostic biomarker and a powerful therapeutic target for GC.

Determining why continuous cropping reduces the production of the morel Morchella sextelata.

Artificial cultivation of Morchella sextelata and other morels is expanding in China, but continuous cropping reduces Morchella for unknown reasons. Here, we investigated soil that had been used or not used for M. sextelata cultivation for 0, 1, and 2 years. We found that the continuous cropping of M. sextelata substantially reduced the pH and the nutrient content of the hyphosphere soil and increased sclerotia formation by M. sextelata. Changes in the structure of bacterial and fungal communities were associated with levels of available nitrogen (N) and phosphorus in the soil. With continuous cropping, the richness and diversity of fungal and bacterial communities increased, but the abundance of Bacillus and Lactobacillus decreased and the abundance of pathogenic fungi increased. FAPROTAX analysis indicated that N cycle functions were enriched more with than without continuous cultivation, and that enrichment of N cycle and sulfate respiration functions was higher in the second than in the first year of cultivation. FunGuild analysis indicated that the functions related to pathotrophs and wood saprotrophs were enriched by M. sextelata cultivation. Overall, the results suggest that continuous cropping may reduce M. sextelata production by acidifying the soil and increasing the abundance of pathogenic fungi. Additional research is needed to determine whether increases in the abundance of pathogenic fungi and changes in soil chemistry result in the declines in production that occur with continuous M. sextelata cultivation.

Microbial Responses to the Reduction of Chemical Fertilizers in the Rhizosphere Soil of Flue-Cured Tobacco.

The overuse of chemical fertilizers has resulted in the degradation of the physicochemical properties and negative changes in the microbial profiles of agricultural soil. These changes have disequilibrated the balance in agricultural ecology, which has resulted in overloaded land with low fertility and planting obstacles. To protect the agricultural soil from the effects of unsustainable fertilization strategies, experiments of the reduction of nitrogen fertilization at 10, 20, and 30% were implemented. In this study, the bacterial responses to the reduction of nitrogen fertilizer were investigated. The bacterial communities of the fertilizer-reducing treatments (D10F, D20F, and D30F) were different from those of the control group (CK). The alpha diversity was significantly increased in D20F compared to that of the CK. The analysis of beta diversity revealed variation of the bacterial communities between fertilizer-reducing treatments and CK, when the clusters of D10F, D20F, and D30F were separated. Chemical fertilizers played dominant roles in changing the bacterial community of D20F. Meanwhile, pH, soil organic matter, and six enzymes (soil sucrase, catalase, polyphenol oxidase, urease, acid phosphatase, and nitrite reductase) were responsible for the variation of the bacterial communities in fertilizer-reducing treatments. Moreover, four of the top 20 genera (unidentified JG30-KF-AS9, JG30-KF-CM45, Streptomyces, and Elsterales) were considered as key bacteria, which contributed to the variation of bacterial communities between fertilizer-reducing treatments and CK. These findings provide a theoretical basis for a fertilizer-reducing strategy in sustainable agriculture, and potentially contribute to the utilization of agricultural resources through screening plant beneficial bacteria from native low-fertility soil.

Cognitive deficits and Alzheimer-like neuropathological impairments during adolescence in a rat model of type 2 diabetes mellitus.

Numerous studies have shown that many patients who suffer from type 2 diabetes mellitus exhibit cognitive dysfunction and neuronal synaptic impairments. Therefore, growing evidence suggests that type 2 diabetes mellitus has a close relationship with occurrence and progression of neurodegeneration and neural impairment in Alzheimer's disease. However, the relationship between metabolic disorders caused by type 2 diabetes mellitus and neurodegeneration and neural impairments in Alzheimer's disease is still not fully determined. Thus, in this study, we replicated a type 2 diabetic animal model by subcutaneous injection of newborn Sprague-Dawley rats with monosodium glutamate during the neonatal period. At 3 months old, the Barnes maze assay was performed to evaluate spatial memory function. Microelectrodes were used to measure electrophysiological function in the hippocampal CA1 region. Western blot assay was used to determine expression levels of glutamate ionotropic receptor NMDA type subunit 2A (GluN2A) and GluN2B in the hippocampus. Enzyme-linked immunosorbent assay was used to determine levels of interleukin-1ß, tumor necrosis factor α, and interleukin-6 in the hippocampus and cerebral cortex, as well as hippocampal amyloid beta (Aß)1-40 and Aß1-42 levels. Our results showed that in the rat model of type 2 diabetes mellitus caused by monosodium glutamate exposure during the neonatal period, latency was prolonged and the number of errors increased in the Barnes maze. Further, latency was increased and time in the escape platform quadrant shortened. Number of times crossing the platform was also reduced in the Morris water maze. After high frequency stimulation of the hippocampus, synaptic transmission was inhibited, expression of GluN2A and GluN2B were decreased in the hippocampus, expression of interleukin 1ß, interleukin 6, and tumor necrosis factor α was increased in the hippocampus and cortex, and levels of Aß1-40 and Aß1-42 were increased in the hippocampus. These findings confirm that type 2 diabetes mellitus induced by neonatal monosodium glutamate exposure results in Alzheimer-like neuropathological changes and further causes cognitive deficits and neurodegeneration in young adulthood.