A comprehensive evaluation of the potential of three next-generation short-read-based plant pan-genome construction strategies for the identification of novel non-reference sequence.

Pan-genome studies are important for understanding plant evolution and guiding the breeding of crops by containing all genomic diversity of a certain species. Three short-read-based strategies for plant pan-genome construction include iterative individual, iteration pooling, and map-to-pan. Their performance is very different under various conditions, while comprehensive evaluations have yet to be conducted nowadays. Here, we evaluate the performance of these three pan-genome construction strategies for plants under different sequencing depths and sample sizes. Also, we indicate the influence of length and repeat content percentage of novel sequences on three pan-genome construction strategies. Besides, we compare the computational resource consumption among the three strategies. Our findings indicate that map-to-pan has the greatest recall but the lowest precision. In contrast, both two iterative strategies have superior precision but lower recall. Factors of sample numbers, novel sequence length, and the percentage of novel sequences' repeat content adversely affect the performance of all three strategies. Increased sequencing depth improves map-to-pan's performance, while not affecting the other two iterative strategies. For computational resource consumption, map-to-pan demands considerably more than the other two iterative strategies. Overall, the iterative strategy, especially the iterative pooling strategy, is optimal when the sequencing depth is less than 20X. Map-to-pan is preferable when the sequencing depth exceeds 20X despite its higher computational resource consumption.

Dysfunction of cecal microbiota and CutC activity in mice mediating diarrhea with kidney-yang deficiency syndrome.

Objective: Previous studies have indicated that diarrhea with kidney-yang deficiency syndrome leads to a disorder of small intestine contents and mucosal microbiota. However, the relationship of TMA-lyase (CutC) activity and TMAO with diarrhea with kidney-yang deficiency syndrome remains unexplored. Therefore, this study explores the relationship between cecal microbiota and choline TMA-lyase (CutC) activity, as well as the correlation between trimethylamine oxide (TMAO), inflammatory index, and CutC activity. Method: Twenty SPF-grade male KM mice were randomly divided into the normal group (CN) and the diarrhea model group (CD). Diarrhea mouse models were established by adenine combined with Folium sennae administration. CutC activity, TMAO, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were detected, and the cecal content microbiota was sequenced. Result: After 14 days, diarrhea occurred in the CD group. Compared with the CN group, there was no significant change in the activity of CutC in the small intestine of the CD group, while the activity of CutC in the cecum was significantly increased, and the levels of TMAO, IL-6, and TNF-α showed a significant increase. The Chao1 index, Observed_species index, Shannon index, and Simpson index all exhibited a decreasing trend. The main changes at the bacterial genus level were Alistipes, Enterorhabdus, Desulfovibrio, Bacteroides, Candidatus_Saccharimonas, and [Ruminococcus]_torques_group. The results of LEfSe analysis, random forest analysis and ROC curve analysis revealed Paludicola, Blautia, Negativibacillus, Paraprevotella, Harryflintia, Candidatus_Soleaferrea, Anaerotruncus, Oscillibacter, Colidextribacter, [Ruminococcus]_torques_group, and Bacteroides as characteristic bacteria in the CD group. Correlation analysis showed a significant negative correlation between cecal CutC activity and Ligilactobacillus, and a significant positive correlation with Negativibacillus and Paludicola. The level of TMAO was significantly positively correlated with CutC activity and IL-6. Conclusion: Diarrhea with kidney-yang deficiency syndrome significantly affects the physiological status, digestive enzyme activity, CutC activity, TMAO levels, and inflammatory response in mice. Additionally, there are changes in the composition and function of cecal microbiota, indicating an important impact of diarrhea with kidney-yang deficiency syndrome on the host intestinal microbiota balance. The occurrence of diarrhea with kidney-yang deficiency syndrome may be associated with dysbiosis of intestinal microbiota, increased CutC activity, elevated TMAO levels, and heightened inflammatory factor levels.

Revealing Changes in Celecoxib Nanostructured Lipid Carrier's Bioavailability Using Hyaluronic Acid as an Enhancer by HPLC-MS/MS.

Purpose: Oral drug administration is the most common and convenient route, offering good patient compliance but drug solubility limits oral applications. Celecoxib, an insoluble drug, requires continuous high-dose oral administration, which may increase cardiovascular risk. The nanostructured lipid carriers prepared from drugs and lipid excipients can effectively improve drug bioavailability, reduce drug dosage, and lower the risk of adverse reactions. Methods: In this study, we prepared hyaluronic acid-modified celecoxib nanostructured lipid carriers (HA-NLCs) to improve the bioavailability of celecoxib and reduce or prevent adverse drug reactions. Meanwhile, we successfully constructed a set of FDA-compliant biological sample test methods to investigate the pharmacokinetics of HA-NLCs in rats. Results: The pharmacokinetic analysis confirmed that HA-NLCs significantly enhanced drug absorption, resulting in an AUC0-t 1.54 times higher than the reference formulation (Celebrex®). Moreover, compared with unmodified nanostructured lipid carriers (CXB-NLCs), HA-NLCs enhance the retention time and improve the drug's half-life in vivo. Conclusion: HA-NLCs significantly increased the bioavailability of celecoxib. The addition of hyaluronic acid prolonged the drug's in vivo duration of action and reduced the risk of cardiovascular adverse effects associated with the frequent administration of oral celecoxib.

Effect of proton pump inhibitors versus histamine-2 receptor antagonists on acute kidney injury in septic patients at high risk for developing stress ulcers.

BACKGROUND: To compare the effects of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers. METHODS: Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high-risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis-associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO-3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size. RESULTS: 4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO-3 rate was higher in the PPI group than in the H2RA group (log-rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11-1.58, p = 0.002] was associated with incident KDIGO-3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012). CONCLUSIONS: Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO-3 AKI compared with H2RA use.

Characterization of a new Camellia plant resource with low caffeine and high theobromine for production of a novel natural low-caffeine tea.

Yuanbaoshancha (YBSC) is characterized as a new wild tea relative morphologically and phytochemically distinguished from the closest wild tea plants Rongjiangcha (Camellia yungkiangensis, RJC) and Tulecha (Camellia costata, TLC). YBSC young leaves contain higher tea polyphenol and theobromine contents but lower caffeine and theanine as compared with RJC, TLC, and other tea landraces and modern cultivars. The major alkaloid detected in YBSC, TLC, and RJC is theobromine while caffeine is a minor; the primary catechins in YBSC leaves are non-galloylated catechins, significantly different from Camellia sinensis and other low-caffeine tea resources. The unique phytochemical profiles featured YBSC black tea with extremely lower caffeine and higher theobromine, as well as unique flavors and health benefits. This botanical characterization of YBSC and two related low-caffeine wild tea resources lays a foundation for future better utilization for the production of a highly valuable natural low-caffeine/high-theobromine tea. Chemical compounds: Caffeine (PubChem CID: 2519); Theobromine (PubChem CID: 5429); Catechins (PubChem CID: 9064); Epigallocatechin gallate (PubChem CID: 65064); Theanine (PubChem CID: 439378); Jasmone (PubChem CID: 1549018); cis-3-Hexenyl hexanoate (PubChem CID: 5352543); Hexyl 2-methylbutanoate (PubChem CID: 24838).

Plant genomic resources at National Genomics Data Center: assisting in data-driven breeding applications.

Genomic data serve as an invaluable resource for unraveling the intricacies of the higher plant systems, including the constituent elements within and among species. Through various efforts in genomic data archiving, integrative analysis and value-added curation, the National Genomics Data Center (NGDC), which is a part of the China National Center for Bioinformation (CNCB), has successfully established and currently maintains a vast amount of database resources. This dedicated initiative of the NGDC facilitates a data-rich ecosystem that greatly strengthens and supports genomic research efforts. Here, we present a comprehensive overview of central repositories dedicated to archiving, presenting, and sharing plant omics data, introduce knowledgebases focused on variants or gene-based functional insights, highlight species-specific multiple omics database resources, and briefly review the online application tools. We intend that this review can be used as a guide map for plant researchers wishing to select effective data resources from the NGDC for their specific areas of study. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00134-4.

GenBase: A Nucleotide Sequence Database.

The rapid advancement of sequencing technologies poses challenges in managing the large volume and exponential growth of sequence data efficiently and on time. To address this issue, we present GenBase (https://ngdc.cncb.ac.cn/genbase), an open-access data repository that follows the International Nucleotide Sequence Database Collaboration (INSDC) data standards and structures, for efficient nucleotide sequence archiving, searching, and sharing. As a core resource within the National Genomics Data Center (NGDC), of the China National Center for Bioinformation (CNCB; https://ngdc.cncb.ac.cn), GenBase offers bilingual submission pipeline and services, as well as local submission assistance in China. GenBase also provides a unique Excel format for metadata description and feature annotation of nucleotide sequences, along with a real-time data validation system to streamline sequence submissions. As of April 23, 2024, GenBase received 68,251 nucleotide sequences and 689,574 annotated protein sequences across 414 species from 2319 submissions. Out of these, 63,614 (93%) nucleotide sequences and 620,640 (90%) annotated protein sequences have been released and are publicly accessible through GenBase's web search system, File Transfer Protocol (FTP), and Application Programming Interface (API). Additionally, in collaboration with INSDC, GenBase has constructed an effective data exchange mechanism with GenBank and started sharing released nucleotide sequences. Furthermore, GenBase integrates all sequences from GenBank with daily updates, demonstrating its commitment to actively contributing to global sequence data management and sharing.