Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship.

Background: The 2019 novel coronavirus has continuous outbreaks around the world. Lung is the main organ that be involved. There is a lack of clinical data on the respiratory sounds of COVID-19 infected pneumonia, which includes invaluable information concerning physiology and pathology. The medical resources are insufficient, which are now mainly supplied for the severe patients. The development of a convenient and effective screening method for mild or asymptomatic suspicious patients is highly demanded. Methods: This is a retrospective case series study. 10 patients with positive results of nucleic acid were enrolled in this study. Lung auscultation was performed by the same physician on admission using a hand-held portable electronic stethoscope delivered in real time via Bluetooth. The recorded audio was exported, and was analyzed by six physicians. Each physician individually described the abnormal breathing sounds that he heard. The results were analyzed in combination with clinical data. Signal analysis was used to quantitatively describe the most common abnormal respiratory sounds. Results: All patients were found abnormal breath sounds at least by 3 physicians, and one patient by all physicians. Cackles, asymmetrical vocal resonance and indistinguishable murmurs are the most common abnormal breath sounds. One asymptomatic patient was found vocal resonance, and the result was correspondence with radiographic computed tomography. Signal analysis verified the credibility of the above abnormal breath sounds. Conclusions: This study describes respiratory sounds of patients with COVID-19, which fills up for the lack of clinical data and provides a simple screening method for suspected patients.

Hypertension has been recognized as one of the highest risk factors for cardiovascular diseases. Anti-hypertension agent screening and development has been recognized as a pharmaceutical therapy approach for the cardiovascular diseases treatment. Many kinds of traditional Chinese medicines, such as pine needle, have been used for the treatment of hypertension for a long time, but the bioactive ingredients which responsible for their therapeutic effectiveness are remain unclear. Therefore, screening bioactive chemicals in natural sources is still the most straightforward strategy for novel Angiotensin-converting enzyme inhibitor (ACEi)-based anti-hypertension agents discovery. In this study, we demonstrated a bioactivity-guided fractionation strategy for identifying bioactive fractions and chemicals from pine needle based on LC/MS assay as well as elucidating their mechanisms of pharmacological activity. And we found out the compound in pine needle extracts being ACE-inhibitory active is catechin. When ACE activity was assayed in rat tissue membranes, it was observed that catechin demonstrate ACE inhibition in kidney, lung and testes tissue. All these presents catechin in pine needle could be a potential cardiovascular medicine.

Gram staining (GS) is one of the routine microbiological operations to classify bacteria based on the cell wall structure. Accurate GS classification of pathogens is of great significance since it...

Scopolia tangutica (S. tangutica) is a traditional Chinese medicinal plant used for antispasmodics, anesthesia, analgesia and sedation. Its pharmacological activities are mostly associated with the antagonistic activity at muscarinic acetylcholine receptors (mAchRs) of several known alkaloids such as atropine and scopolamine. With our recent identification of four hydroxycinnamic acid amides from S. tangutica, we hypothesized that this plant may contain previously unidentified alkaloids that may also contribute to its in vivo effect. Herein, we used a bioassay-guided multi-dimension separation strategy to discover novel mAchR antagonists from S. tangutica. The core of this approach is to use label-free cell phenotypic assay to first identify active fractions, and then to guide purification of active ligands. Besides four tropanes and six cinnamic acid amides that have been previously isolated from S. tangutica, we recently identified two new tropanes, one new cinnamic acid amide, and nine other compounds. Six tropane compounds purified from S. tangutica for the first time were confirmed to be competitive antagonists of muscarinic receptor 3 (M3), including the two new ones 8 and 12 with IC50 values of 1.97 μM and 4.47 μM, respectively. Furthermore, the cinnamic acid amide 17 displayed 15-fold selectivity for M1 over M3 receptors. These findings will be useful in designing lead compounds for mAchRs and elucidating mechanisms of action of S. tangutica.

Background As a rare subtype of prostate carcinoma, basal cell carcinoma (BCC) has not been studied extensively and thus lacks systematic molecular characterization. Methods Here, we applied single‐cell genomic amplification and RNA‐Seq to a specimen of human prostate BCC (CK34βE12+/P63+/PAP−/PSA−). The mutational landscape was obtained via whole exome sequencing of the amplification mixture of 49 single cells, and the transcriptomes of 69 single cells were also obtained. Results The five putative driver genes mutated in BCC are CASC5, NUTM1, PTPRC, KMT2C, and TBX3, and the top three nucleotide substitutions are C>T, T>C, and C>A, similar to common prostate cancer. The distribution of the variant allele frequency values indicated that these single cells are from the same tumor clone. The 69 single cells were clustered into tumor, stromal, and immune cells based on their global transcriptomic profiles. The tumor cells specifically express basal cell markers like KRT5, KRT14, and KRT23 and epithelial markers EPCAM, CDH1, and CD24. The transcription factor covariance network analysis showed that the BCC tumor cells have distinct regulatory networks. By comparison with current prostate cancer datasets, we found that some of the bulk samples exhibit basal cell signatures. Interestingly, at single‐cell resolution the gene expression patterns of prostate BCC tumor cells show uniqueness compared with that of common prostate cancer‐derived circulating tumor cells. Conclusions This study, for the first time, discloses the comprehensive mutational and transcriptomic landscapes of prostate BCC, which lays a foundation for the understanding of its tumorigenesis mechanism and provides new insights into prostate cancers in general.

COVID-19 is now causing a global pandemic, there is a demand to explain the different clinical patterns between children and adults. To clarify the organs/cell types vulnerable to COVID-19 infection and the potential age-depended expression patterns of five factors (ACE2, TMPRSS2, MTHFD1, CTSL, CTSB) associated with clinical symptoms. In this study, we analyzed expression levels of five COVID-19 host dependency factors in multiple adult and fetal human organs. The results allowed us to grade organs at risk and also pointed towards the target cell types in each organ mentioned above. Based on these results we constructed an organ-and cell type-specific vulnerability map of the expression levels of the five COVID-19 factors in the human body, providing insight into the mechanisms behind the symptoms, including the non-respiratory symptoms of COVID-19 infection and injury. Also, the different expression patterns of the COVID-19 factors well demonstrate an explanation that the different clinical patterns between adult and children/infants.

Background and Aims: LPAR6 is the most recently determined G protein-coupled receptor of lysophosphatidic acid, and hardly any study has demonstrated the performance of LPAR6 in cancers. We sought to clarify the relationship of LPAR6 to prognosis potential and tumor infiltration immune cells in different cancers. Methods: The expression of LPAR6 and its clinical characteristics were evaluated on various databases. The association between LPAR6 and immune infiltrates of various types of cancer were investigated via TIMER. Results: We determined that higher LPAR6 expression level was associated with a better overall survival. Additionally, high LPAR6 expression level was significantly associated with better disease-specific survival (DSS) in bladder cancer, and better overall survival (OS)/ progression-free survival (PFS)/ distant metastasis-free survival (DMFS)/ relapse-free survival (RFS) in breast cancer and some other types of cancers. Moreover, LPAR6 significantly affects the prognosis of various cancers via The Cancer Genome Atlas (TCGA). Further research exposed that the mRNA level of LPAR6 was positively coordinated with infiltrating levels of devious immune cells in hepatocellular carcinoma. Conclusions: Our results imply that LPAR6 is associated with prognosis potential and immune infiltration levels in liver cancer. Moreover, LPAR6 expression possibly contributes to the activation of CD8+ T, naive T, effector T cells and natural killer cells and inactivates T regulatory cells, decreases T cell exhaustion and regulate T helper cells in liver cancer. These discoveries imply that LPAR6 could be a novel biomarker of prognosis for indicating prognosis potential and immune-infiltrating level in hepatocellular carcinoma.