Two chromosome-level genome assemblies of Rhodiola shed new light on genome evolution in rapid radiation and evolution of the biosynthetic pathway of salidroside.

Rhodiola L. is a genus that has undergone rapid radiation in the mid-Miocene and may represent a typic case of adaptive radiation. Many species of Rhodiola have also been widely used as an important adaptogen in traditional medicines for centuries. However, a lack of high-quality chromosome-level genomes hinders in-depth study of its evolution and biosynthetic pathway of secondary metabolites. Here, we assembled two chromosome-level genomes for two Rhodiola species with different chromosome number and sexual system. The assembled genome size of R. chrysanthemifolia (2n = 14; hermaphrodite) and R. kirilowii (2n = 22; dioecious) were of 402.67 and 653.62 Mb, respectively, with approximately 57.60% and 69.22% of transposable elements (TEs). The size difference between the two genomes was mostly due to proliferation of long terminal repeat-retrotransposons (LTR-RTs) in the R. kirilowii genome. Comparative genomic analysis revealed possible gene families responsible for high-altitude adaptation of Rhodiola, including a homolog of plant cysteine oxidase 2 gene of Arabidopsis thaliana (AtPCO2), which is part of the core molecular reaction to hypoxia and contributes to the stability of Group VII ethylene response factors (ERF-VII). We found extensive chromosome fusion/fission events and structural variations between the two genomes, which might have facilitated the initial rapid radiation of Rhodiola. We also identified candidate genes in the biosynthetic pathway of salidroside. Overall, our results provide important insights into genome evolution in plant rapid radiations, and possible roles of chromosome fusion/fission and structure variation played in rapid speciation.

Reevaluation of prognostic and severity indicators for COVID-19 patients in the emergency department.

AIMS: This study aimed to re-evaluate whether the scoring systems, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were effective in predicting prognosis and severity of COVID-19 patients in the emergency department (ED). METHODS: COVID-19 patients enrolled in this retrospective study divided into the death (DEA) and survival (SUR) groups, the severe/critical (SC) and non-severe/critical (non-SC) groups. The Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), National Early Warning Score (NEWS) and CCEDRRN COVID-19 Mortality Score were calculated. The neutrophil, lymphocyte and platelet counts were extracted from the first routine blood examination, and NLR and PLR were calculated accordingly. Receiver Operating Characteristic (ROC) curve and logistic regression were performed. RESULTS: All the scoring systems, as well as NLR and PLR, significantly increased in both the DEA and SC groups. The ROC curve showed that the CCEDRRN COVID-19 Mortality Score had the highest predictive value for mortality and severity (AUC 0.779, 0.850, respectively), which outperformed the APACHE II, SOFA and NEWS. NLR presented better predictive ability for severity (AUC 0.741) than death (AUC 0.702). The APACHE II, NEWS and CCEDRRN COVID-19 Mortality Score were positively correlated with both prognosis and severity, whereas NLR only with severity. CONCLUSION: The NEWS and CCEDRRN COVID-19 Mortality Score were reconfirmed for early and rapid predicting the poor prognosis and severity of COVID-19 patients in ED, especially the CCEDRRN COVID-19 Mortality Score with the highest discrimination capacity, and NLR was more appropriate for predicting the severity.

[Effect of release of hydroxypropylmethyl cellulose on single and bilayer sustained-release matrix tablets].

OBJECTIVE: To study the influence of HPMC as hydrophilic matrix materials and controlled-layer components on the drug release of sustained-release matrix tablets and bilayer tablets. METHODS: Diltiazem hydrochloride was chosen as the water-soluble model drug to prepare different kinds of matrix tablets and double layer tablets with different formulations, and evaluate how the levels and grades of HPMC affect the drug release in sustained-release tablets and bilayer tablets. RESULTS: HPMC with high viscosity and the amount of 20%-40% could delay the drug release to certain degree, but it was difficult to further slow down the drug release up to 24 h, especially for a water soluble drug. Combining HPMC with 5%-20% of CMC-Na was proven to be an effective way to achieve the 24 h release profile with the water soluble drug. HPMC was also investigated as a component in the double layer tablet as base layer. Drug release was complicated compared with EC as the base layer in the double layer tablet due to the great swelling ability of HPMC. HPMC's larger swilling let it form a big cap to retard the drug release, which could significantly affect the drug release with a large ratio of the base layer to the drug layer; furthermore increasing the quality of 10%-40% of the base layer and the proportion of HPMC could reduce the initial burst release. CONCLUSION: The grade/level of HPMC and combinations with other matrix materials had a big impact on the drug release. HPMC could be used in the base layer of the double tablet to alternate the drug release profile, and reduce the initial burst release of the double-layer matrix tablet, and potentially change the drug mechanism.

[Study of sustained-matrix tablets Ambroxol hydrochloride and potential impact of different fillers on the matrix tablet's scale-up].

OBJECTIVE: To study the release profiles of Ambroxol hydrochloride in matrix tablets with different fillers and controlled release materials, and investigate the potential impact on different fillers on the matrix tablet's scale-up. METHODS: Ambroxol hydrochloride was chosen as the model drug to make single-layer matrix tablets with different types of hydroxylpropyl methylcellulose as matrix material, and lactose or microcrystalline cellulose as the filler. In vitro dissolution test was used to evaluate the drug release performance of the matrix tablets made. Also ethyl cellulose was used to prepare double-layer matrix tablets to investigate how different kinds of hydroxypropyl methylcellulose (HPMC) and fillers would affect the drug release in double-layer matrix tablets. RESULTS: The drug release rate of single-layer tablets with lactose and HPMC decreased significantly with the increase of the level and viscosity of HPMC. However the release profile only slightly slowed down with the increase of the content and viscosity of HPMC for single-layer matrix tablets of microcrystalline cellulose (MCC). Compared with the single-layer tablets, the level and viscosity of HPMC had less impact on the drug release of the double-layer matrix tablets. CONCLUSION: The matrix tablet with lactose and HPMC has greater flexibility to design formulations with different drug release rate, however the introduction of other process parameters during the scale-up could lead the shifting of the drug release profile from small scale batches. The drug release profiles of matrix tablets with insoluble filler-MCC only change within a small range with the increase of the level and viscosity of HPMC. From the formulation design point of view, it could be necessary to select different type of controlled release polymers to meet the design requirement.