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Scutellaria baicalensis and Scutellaria barbata, common medicinal plants of the Lamiaceae family, produce specific flavonoid compounds with antioxidant and antitumor activities, including baicalein, scutellarein, norwogonin, wogonin, and their glycosides. Here, we reported two chromosome-level genome assemblies of S. baicalensis and S. barbata with significant quantitative chromosomal variation (2n = 18 and 2n = 26, respectively). The divergence of S. baicalensis and S. barbata occurred far earlier than previously reported, and a whole-genome duplication event was identified. The insertion of long terminal repeat elements after speciation might be responsible for the observed chromosomal expansion and rearrangement. The comparative genome analysis of congeneric species elucidated the species-specific evolution of chrysin and apigenin biosynthetic genes, such as the S. baicalensis-specific tandem duplication of the phenylalanine ammonia lyase (PAL) and chalcone synthase (CHS) genes, and the S. barbata-specific duplication of 4-CoA ligase (4CL) genes. In addition, the paralogous duplication, collinearity, and expression diversity of CYP82D subfamily members revealed the functional divergence of flavone hydroxylase genes between S. baicalensis and S. barbata. These Scutellaria genomes highlight the common and species-specific evolution of flavone biosynthetic genes, promoting the development of molecular breeding and the study of the biosynthesis and regulation of bioactive compounds.

Camptotheca acuminata produces camptothecin (CPT), a monoterpene indole alkaloid (MIA) that is widely used in the treatment of lung, colorectal, cervical, and ovarian cancers. Its biosynthesis pathway has attracted significant attention, but the regulation of CPT biosynthesis by the APETALA2/ethylene-responsive factor (AP2/ERF) transcription factors (TFs) remains unclear. In this study, a systematic analysis of the AP2/ERF TFs family in C. acuminata was performed, including phylogeny, gene structure, conserved motifs, and gene expression profiles in different tissues and organs (immature bark, cotyledons, young flower, immature fruit, mature fruit, mature leaf, roots, upper stem, and lower stem) of C. acuminata. A total of 198 AP2/ERF genes were identified and divided into five relatively conserved subfamilies, including AP2 (26 genes), DREB (61 genes), ERF (92 genes), RAV (18 genes), and Soloist (one gene). The combination of gene expression patterns in different C. acuminata tissues and organs, the phylogenetic tree, the co-expression analysis with biosynthetic genes, and the analysis of promoter sequences of key enzymes genes involved in CPT biosynthesis pathways revealed that eight AP2/ERF TFs in C. acuminata might be involved in CPT synthesis regulation, which exhibit relatively high expression levels in the upper stem or immature bark. Among these, four genes (CacAP2/ERF123, CacAP2/ERF125, CacAP2/ERF126, and CacAP2/ERF127) belong to the ERF-B2 subgroup; two genes (CacAP2/ERF149 and CacAP2/ERF152) belong to the ERF-B3 subgroup; and two more genes (CacAP2/ERF095 and CacAP2/ERF096) belong to the DREB-A6 subgroup. These results provide a foundation for future functional characterization of the AP2/ERF genes to enhance the biosynthesis of CPT compounds of C. acuminata.

Understanding of the functional states and clonal dynamics of T cells after immune checkpoint blockade (ICB) is valuable for improving these therapeutic strategies. Here we performed Smart-seq2 single-cell RNA sequencing (scRNA-seq) analysis on 3,110 peripheral T cells of non-small cell lung cancer (NSCLC) patients before and after the initiation of programmed cell death protein 1 (PD-1) blockade. We identified individual peripheral T cell clones based on the full-length T cell receptor (TCR) sequences and monitored their dynamics during immunotherapy. We found a higher cytotoxic activity in the tumor-related CD4+ T cell clones than in the CD8+ T cell clones. Based on a large tumor-related CD4+ T cell clone, we observed a dramatically decreased abundance after progression, as well as a reduction in the percentage of PD-1+ T cells. We also detected 25 genes, such as CXCR4, DUSP2 and ZFP36, that were noticeably upregulated or downregulated following progression. In addition, the pseudotime trajectory of CD8+ T cell clones corresponded to the treatment time points, showing a decreased activity in the "cytokine and cytokine receptor interaction" pathway. These analyses provided an insight into the dynamics of peripheral T cell clones during PD-1 blockade in NSCLC.

Summary Single-cell RNA sequencing (scRNA-seq) is a powerful tool for defining cellular diversity in tumors, but its application toward dissecting mechanisms underlying immune-modulating therapies is scarce. We performed scRNA-seq analyses on immune and stromal populations from colorectal cancer patients, identifying specific macrophage and conventional dendritic cell (cDC) subsets as key mediators of cellular cross-talk in the tumor microenvironment. Defining comparable myeloid populations in mouse tumors enabled characterization of their response to myeloid-targeted immunotherapy. Treatment with anti-CSF1R preferentially depleted macrophages with an inflammatory signature but spared macrophage populations that in mouse and human expresses pro-angiogenic/tumorigenic genes. Treatment with a CD40 agonist antibody preferentially activated a cDC population and increased Bhlhe40+ Th1-like cells and CD8+ memory T cells. Our comprehensive analysis of key myeloid subsets in human and mouse identifies critical cellular interactions regulating tumor immunity and defines mechanisms underlying myeloid-targeted immunotherapies currently undergoing clinical testing.

In recent years, the development of Chinese herbal medicine (CHM) has been challenged by shortages of CHM resources and drug safety concerns related to end products. There have been significant efforts by Chinese scholars to tackle these challenges, which are revealed by analyzing the research trend of CHM resources via surveying Chinese Traditional and Herbal Drugs (Zhong Cao Yao), a representative journal in CHM. Our study focused on 781 articles in CHM resources from 2013 to 2018 and included four subject areas: germplasm resources, quality analysis and evaluation, cultivation, and bioengineering of CHM. Discussion and prospective for future investigations were also presented, including: construct the core germplasm of medicinal plants and expand germplasms; combine molecular research with field experiments and promote the deeper study of cultivation of CHM plants; improve the quality evaluation method of CHM and strengthen the identification of Chinese patented medicines; promote the sustainable development of CHM resources by utilizing bioengineering and synthetic biology. This study helps international scholars understand the status quo of CHM research and provides theoretical support for the healthy, modern, and international development of CHM, and it will facilitate the sustainable development of the traditional Chinese medicine industry.

The purpose of this research is to investigate the effects of dietary taurine supplementation on blood and urine taurine concentrations of the elderly women with dementia. Subjects were 31 female elderly with dementia hospitalized in a geriatric hospital. They were divided randomly into control group and dietary taurine supplemented group. Basically, same meals were served to both groups. Scorched rice water without taurine were served to control group. Scorched rice water containing 3 g of taurine were reserved to taurine group with lunch similarly. Food ingredients containing high concentration of taurine were eliminated from the meal menu. Blood and urine samples were obtained from each subject at the beginning of study, after 2 week and 4 weeks in the morning fasting state. Taurine concentrations in serum and urine were measured as taurine-fluorescamine derivatives using high performance liquid chromatography (HPLC). Data were analyzed using SPSS 20.0. The average taurine concentrations in serum and urine of subjects were 89.2 ± 9.5 μM and 876.7 ± 97.1 μM at the beginning. After 4 weeks, the taurine concentrations in serum and urine of dietary taurine supplemented group were 218.0 ± 15.6 μM and 6502.6 ± 380.6 μM, which were significantly higher compared to control group. Dietary taurine supplemented group showed positive changes in the score on language and execute performance. So taurine supplementation can provide beneficial effects to the elderly and the elderly with dementia.

This study was conducted to investigate the effects on the cognitive function of the elderly with dementia, after consumption of menus developed to prevent dementia. For the purpose of this study, we developed two menus incorporating lotus seeds and taurine which are known to be effective in preventing dementia: tea supplemented with taurine and lotus seed (TATL) and scorched glutinous rice water supplemented with taurine and lotus seed (SATL). The most optimized supplement was determined through sensory evaluation, and was served with the normal diet for 4 weeks. The subjects of this study were 46 elderly women with dementia, divided into three groups: 16 subjects in the taurine supplement group (TG), 15 subjects in the taurine and lotus seeds supplement group (TLG), and 15 subjects in the control group (CG). Cognitive function was assessed by comparing the scores of MMSE-DS (Mini-Mental State Examination-Dementia Screening) before and after dietary supplementation, with higher scores indicating better cognitive functions. Statistical analysis was performed using SPSS 20.0 for Windows. The total score of MMSE-DS before supplementation SATL was not significantly different between CG (14.1 points), TG (14.2 points), and TLG (13.8 points). However, after consuming the SATL supplement, the total score of TG (16.7 points) and TLG (16.9 points) significantly increased (p < 0.01). In particular, in the case of TG, a significant increase was observed in the score for ‘Judgment and abstract thinking’ (p < 0.05). An increased tendency was also observed for scores of ‘Place orientation’ (p = 0.071) and ‘Ability to execute’ (p = 0.054), although statistically not significant. In the case of TLG, score of ‘Place orientation’ and ‘Judgment and abstract thinking’ was significantly increased (p < 0.05). These results show that dietary taurine supplementation has positive effects on the cognitive function (MMSE-DS) of elderly women with dementia. There-fore, it is necessary to include dietary taurine supplementation for the treatment and prevention of dementia. In addition, it is necessary to develop and supply a variety of menus containing taurine.

Tumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties across different tumors remain elusive. Here, by performing a pan-cancer analysis of single myeloid cells from 210 patients across 15 human cancer types, we identified distinct features of TIMs across cancer types. Mast cells in nasopharyngeal cancer were found to be associated with better prognosis and exhibited an anti-tumor phenotype with a high ratio of TNF+/VEGFA+ cells. Systematic comparison between cDC1- and cDC2-derived LAMP3+ cDCs revealed their differences in transcription factors and external stimulus. Additionally, pro-angiogenic tumor-associated macrophages (TAMs) were characterized with diverse markers across different cancer types, and the composition of TIMs appeared to be associated with certain features of somatic mutations and gene expressions. Our results provide a systematic view of the highly heterogeneous TIMs and suggest future avenues for rational, targeted immunotherapies.

An increase in the use of iodinated contrast media, such as iohexol, iodixanol, iopamidol and iopromide, occasionally causes contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). The present study aimed to assess the effects of low levels of hemoglobin on the development of CIN in patients with normal renal function following CAG/PCI. A total of 841 consecutive patients undergoing CAG/PCI were divided into two groups: Patients with low levels of hemoglobin (male

Objective This meta-analysis aimed to assess the efficacy and safety of glucocorticoid versus traditional therapy for hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). Methods PubMed, Cochrane Central Register of Clinical Trials, and EMBASE were searched. All clinical studies, including randomized controlled studies and cohort studies, comparing glucocorticoids with traditional treatments (until November 1, 2018), were included. Results A total of 3 randomized controlled trials and 5 cohort studies (including 3 retrospective cohort studies), involving 538 patients, were subjected to the meta-analysis. The total bilirubin levels before treatment were not significantly different (odds ratio [OR]: -0.97; 95% confidence interval [CI]: -2.56 to 0.62; P = .23), and, however, they were significantly reduced after treatment in the corticosteroid group compared with the traditional treatment group (OR: -8.83; 95% CI: -14.99 to 2.67; P = .005). Moreover, prothrombin time was significantly long before treatment in either group, with no significant differences (OR: 0.28; 95% CI: -0.79 to 1.34; P = 0.61). However, after treatment, prothrombin time was significantly shortened in the traditional treatment group (OR: 31.71; 95% CI: 3.62-59.81; P = .03). Furthermore, inpatient mortality (OR: 0.23; 95% CI: 0.08-0.67; P = .007) and ascites events (OR: 0.35; 95% CI: 0.18-0.67; P = .90) were significantly lower in the corticosteroid treatment group. Conclusions Glucocorticoid is more effective for reducing the T-bili level, significantly decreasing in-hospital mortality and ascites events in HBV-related ACLF patients. Moreover, bilirubin may play a pivotal role in the early stage of HBV-related ACLF progression to advanced liver failure.

The long noncoding RNA myocardial infarction associated transcript (MIAT) has been shown to be a risk allele for myocardial infarction in a previous study. However, there is still controversy about whether MIAT can be used as a biomarker for acute myocardial infarction (AMI). Peripheral blood from patients with AMI and non‑AMI patients was collected to detect the expression levels of MIAT by reverse transcription‑quantitative PCR. Correlation analysis and receiver operating characteristic (ROC) curve analysis were performed to calculate the diagnostic value of MIAT. A rat AMI model was established to detect the expression of MIAT in plasma and cardiac samples. Neonatal rat cardiomyocytes were isolated and exposed to hypoxia, and MIAT small interfering RNAs were transfected into cells to test the expression levels of MIAT and to perform apoptosis‑related assays. The results showed that the plasma levels of MIAT were significantly increased in patients with AMI compared with non‑AMI patients. Correlation analysis showed that MIAT was positively associated with creatine kinase‑MB and cardiac troponin T (cTnT). ROC analysis indicated that MIAT had the same diagnostic value as cTnT. In addition, MIAT was expressed at low levels in the normal rat heart and was highly expressed in AMI hearts. Knockdown of MIAT significantly inhibited cardiomyocyte apoptosis. The present study demonstrated that MIAT may act as a novel potential biomarker for the diagnosis of AMI.

From Shen Nong’s Herbal Classic (Shennong Bencao Jing) to the Compendium of Materia Medica (Bencao Gangmu) and the first scientific Nobel Prize for the mainland of China, each milestone in the historical process of the development of traditional Chinese medicine (TCM) involves screening, testing and integrating. After thousands of years of inheritance and development, herbgenomics (bencaogenomics) has bridged the gap between TCM and international advanced omics studies, promoting the application of frontier technologies in TCM. It is a discipline that uncovers the genetic information and regulatory networks of herbs to clarify their molecular mechanism in the prevention and treatment of human diseases. The main theoretical system includes genomics, functional genomics, proteomics, transcriptomics, metabolomics, epigenomics, metagenomics, synthetic biology, pharmacogenomics of TCM, and bioinformatics, among other fields. Herbgenomics is mainly applicable to the study of medicinal model plants, genomic-assisted breeding, herbal synthetic biology, protection and utilization of gene resources, TCM quality evaluation and control, and TCM drug development. Such studies will accelerate the application of cutting-edge technologies, revitalize herbal research, and strongly promote the development and modernization of TCM.

The purpose of this study was to investigate the differences in dietary intake, serum level and urinary excretion of taurine between the elderly with dementia and the normal elderly. Subjects with dementia were 22 (8 men, 14 women) and normal were 26 (2 men, 24 women). The general characteristics, anthropometric data were considered together. The blood and urine samples were obtained from the elderly in the morning fasting state. Taurine concentrations in serum and urinary excretion were determined using high performance liquid chromatography (HPLC). Dietary intake data were collected using questionnaires, and analyzed by Computer Aided Nutritional analysis program (CAN-pro 4.0). Statistical analyses were carried out using SPSS 20.0. There were no significant differences in age and BMI (body mass index) between the elderly with dementia and the normal elderly, however, blood total cholesterol, LDL cholesterol and HDL cholesterol levels of the elderly with dementia were relatively higher than the normal elderly. The elderly men with dementia took more lipid, riboflavin higher than the normal elderly men (P < 0.05). The elderly women with dementia took more nutrients except vitamin D, vitamin B12 and taurine than the normal elderly (P < 0.001). There were slight differences in serum taurine level between the two groups. However, urinary excretion of taurine in the elderly with dementia was significantly higher than the normal elderly (41.2%, P < 0.05).

This study investigated the associations between dietary history of past taurine intake and cognitive function in the elderly. Subjects of this study were 40 elderly persons with dementia (men 14, women 26) and 37 normal elderly persons (men 5, women 32). Data were collected using questionnaires by investigator-based interview to the elderly and family caregivers. We examined their general characteristics, anthropometric data, cognitive function, and taurine index. Cognitive function was measured using MMSE-DS and higher score means better cognitive function. As dietary history of past taurine intake, taurine index was evaluated by scoring the intake frequency of 41 kinds of taurine-containing foods. Part correlation analysis (sex, age, and school educational period correction) was used to analyze associations between taurine index and cognitive function. The analysis of all data was carried out by the SPSS 20.0 program for windows. The age, height, weight, and BMI of elderly with dementia showed no statistical significance compared to normal elderly. The elderly with dementia had significantly higher school education period (7.4 years) than the normal elderly (4.8 years) (p < 0.01). Nevertheless, the average total score of cognitive function (MMSE-DS) of the elderly with dementia (18.1 points) was significantly lower than score of the normal elderly (21.7 points) (p < 0.05). The average taurine index of the elderly with dementia (104.7 points) was significantly lower than average taurine index of the normal elderly (123.7 points) (p < 0.01). There were positive correlations between total taurine index and total score of cognitive function in all the elderly subjects (p < 0.05). In particular, as taurine index was higher, there were significantly higher scores of cognitive function such as ‘time orientation’ and ‘judgement and abstract thinking’ (p < 0.01). In conclusion, these results suggest that past taurine intake may have a positive effect on present cognitive function in the elderly.

Summary The immune microenvironment of hepatocellular carcinoma (HCC) is poorly characterized. Combining two single-cell RNA sequencing technologies, we produced transcriptomes of CD45+ immune cells for HCC patients from five immune-relevant sites: tumor, adjacent liver, hepatic lymph node (LN), blood, and ascites. A cluster of LAMP3+ dendritic cells (DCs) appeared to be the mature form of conventional DCs and possessed the potential to migrate from tumors to LNs. LAMP3+ DCs also expressed diverse immune-relevant ligands and exhibited potential to regulate multiple subtypes of lymphocytes. Of the macrophages in tumors that exhibited distinct transcriptional states, tumor-associated macrophages (TAMs) were associated with poor prognosis, and we established the inflammatory role of SLC40A1 and GPNMB in these cells. Further, myeloid and lymphoid cells in ascites were predominantly linked to tumor and blood origins, respectively. The dynamic properties of diverse CD45+ cell types revealed by this study add new dimensions to the immune landscape of HCC.