Integrated transcriptomic and metabolomic analysis reveals the regulation mechanism of early bolting and flowering in two cultivars of Angelica sinensis.

The root of Angelica sinensis is utilized in Traditional Chinese medicine to enhance blood replenishment and facilitate blood circulation. The early bolting and flowering (EBF) of A. sinensis, however, compromises the quality of the roots and restricts the yield of medicinal substances. The study was conducted to compare the transcriptomic and metabolomic profiles between EBF plants and normal plants of two cultivars of A. sinensis, followed by validation of the transcriptome results using qRT-PCR. There were 3677 DEGs in EBF plants compared to normal plants of cultivar 2 (Mingui No.2), and cultivar 4 (Mingui No.4) was 3354. The main differential metabolites in the EBF and normal plants were phenolic acids, flavonoids, lignans, and coumarins. The analysis of 5 EBF-related pathways revealed 28 genes exhibiting differential expression and 5 metabolites showing differential accumulation. The expression of the Lhcb5, Lhcb2, Lhcb6, Lhcb1, Lhca4, ATPG1, EGLC, CELB, AMY, glgA, CYCD3, SnRK2, PYL, AHK2, AUX1, BSK, FabI/K, ACACA and FabV decreased and the expression of the PsbR, PsbA, LHY, FT, CO, malQ, HK, GPI and DELLA increased in EBF plants. In addition, the Abscisic acid, d-Glucose-6P, α-d-Glucose-1P, NADP+, and ADP were more significantly enriched in EBF plants. The findings offer novel perspectives on the EBF mechanisms in A. sinensis and other medicinal plants of the Apiaceae family.

Integrating High-Resolution Mass Spectral Data, Bioassays and Computational Models to Annotate Bioactives in Botanical Extracts: Case Study Analysis of C. asiatica Extract Associates Dicaffeoylquinic Acids with Protection against Amyloid-ß Toxicity.

Rapid screening of botanical extracts for the discovery of bioactive natural products was performed using a fractionation approach in conjunction with flow-injection high-resolution mass spectrometry for obtaining chemical fingerprints of each fraction, enabling the correlation of the relative abundance of molecular features (representing individual phytochemicals) with the read-outs of bioassays. We applied this strategy for discovering and identifying constituents of Centella asiatica (C. asiatica) that protect against Aß cytotoxicity in vitro. C. asiatica has been associated with improving mental health and cognitive function, with potential use in Alzheimer's disease. Human neuroblastoma MC65 cells were exposed to subfractions of an aqueous extract of C. asiatica to evaluate the protective benefit derived from these subfractions against amyloid ß-cytotoxicity. The % viability score of the cells exposed to each subfraction was used in conjunction with the intensity of the molecular features in two computational models, namely Elastic Net and selectivity ratio, to determine the relationship of the peak intensity of molecular features with % viability. Finally, the correlation of mass spectral features with MC65 protection and their abundance in different sub-fractions were visualized using GNPS molecular networking. Both computational methods unequivocally identified dicaffeoylquinic acids as providing strong protection against Aß-toxicity in MC65 cells, in agreement with the protective effects observed for these compounds in previous preclinical model studies.

The Dynamic Accumulation Rules of Chemical Components during the Medicine Formation Period of Angelica sinensis and Chemometric Classifying Analysis for Different Bolting Times Using ATR-FTIR.

The dried roots of the perennial herb Angelica sinensis (Oliv.) Diels (AS) are commonly used as medicinal and edible resources. In commercial planting, early bolting and flowering (EB) of ca. 60% in the medicine formation period reduces root yield and quality, becoming a significant bottleneck in agricultural production. In the cultivation process, summer bolting (SB) occurs from June to July, and autumn bolting (AB) occurs in September. The AB root is often mistaken for the AS root due to its similar morphological characteristics. Few studies have involved whether the root of AB could be used as herbal medicine. This study explored and compared the accumulation dynamics of primary and secondary metabolites in AS and EB roots during the vegetative growth stage (from May to September) by light microscopy, ultraviolet spectrometry, and HPLC methods. Under a microscope, the amount of free starch granules and oil chamber in the AS root increased. On the contrary, they decreased further from EB-Jul to EB-Sep. By comparison, the wall of the xylem vessel was slightly thickened and stacked, and the cell walls of parenchyma and root cortex tissue were thickened in the EB root. Early underground bolting reduces soluble sugar, soluble protein, free amino acids, total C element, total N element, ferulic acid, and ligustilide accumulation, accompanied by the lignification of the root during the vegetative growth stage. Furthermore, a total of 55 root samples from different bolting types of AS root (29 samples), SB root (14 samples), and AB root (12 samples) were collected from Gansu Province during the harvesting period (October). The later the bolting occurred, the less difference there was between unbolted and bolted roots in terms of morphological appearance and efficacy components. Fourier transform infrared spectroscopy with the attenuated total reflection mode (ATR-FTIR) provides a "holistic" spectroscopic fingerprinting of all compositions in the tested sample. The ATR-FTIR spectrum of the AB root was similar to that of the AS root. However, the number and location of absorption peaks in the spectra of SB were different, and only one strong absorption peak at 1021 cm-1 was regarded as the characteristic peak of C-O stretching vibration in lignin. The ATR-FTIR spectra can be effectively differentiated based on their various characteristics using orthogonal partial least squares discrimination analysis (OPLS-DA). Results were assessed using multiple statistical techniques, including Spearman's correlation, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and OPLS-DA. Among these methods, the ATR-FTIR data demonstrated the most effective outcomes in differentiating between viable and non-viable roots for their application in herbal medicine. Essential substances are ferulic acid and flavonoid, which are much more abundant in the AB root. It provides a material basis for the pharmacological action of the AB roots and a theoretical basis for improving their availability.

Identification of three cultivated varieties of Scutellaria baicalensis using the complete chloroplast genome as a super-barcode.

Scutellaria baicalensis has been one of the most commonly used traditional Chinese medicinal plants in China for more than 2000 years. The three new varieties cultivated could not be distinguished by morphology before flowering. It will hinder the promotion of later varieties. Chloroplast DNA has been widely used in species identification. Moreover, previous studies have shown that complete chloroplast genome sequences have been suggested as super barcodes for identifying plants. Therefore, we sequenced and annotated the complete chloroplast genomes of three cultivated varieties. The chloroplast genomes of SBW, SBR, and SBP were 151,702 bp, 151,799 bp, and 151,876 bp, which contained 85 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. The analysis of the repeat sequences, codon usage, and comparison of chloroplast genomes shared a high degree of conservation. However, the sliding window results show significant differences among the three cultivated varieties in matK-rps16 and petA-psbJ. And we found that the matK-rps16 sequence can be used as a barcode for the identification of three varieties. In addition, the complete chloroplast genome contains more variations and can be used as a super-barcode to identify these three cultivated varieties. Based on the protein-coding genes, the phylogenetic tree demonstrated that SBP was more closely related to SBW, in the three cultivated varieties. Interestingly, we found that S. baicalensis and S. rehderiana are closely related, which provides new ideas for the development of S. baicalensis. The divergence time analysis showed that the three cultivated varieties diverged at about 0.10 Mya. Overall, this study showed that the complete chloroplast genome could be used as a super-barcode to identify three cultivated varieties of S. baicalensis and provide biological information, and it also contributes to bioprospecting.

Machine learning-based predictive analysis of total polar compounds (TPC) content in frying oils: A comprehensive electrochemical study of 6 types of frying oils with various frying timepoints.

Standard approaches to determining the total polar compounds (TPC) content in frying oils such as the chromatographic techniques are slow, bulky, and expensive. This paper presents the electrochemical analysis of 6 types of frying oils inclusive of 52 frying timepoints, without sample preparation. This is achieved via impedance spectroscopy to capture sample-specific electrical polarization states. To the best of our knowledge, this is a first-of-its-kind comprehensive study of various types of frying oils, with progressively increasing frying timepoints for each type. The principal component analysis distinguishes the frying timepoints well for all oil types. TPC prediction follows, involving supervised machine learning with sample-wise leave-one-out implementation. The R2 values and mean absolute errors across the test samples measure 0.93-0.97 and 0.43-1.19 respectively. This work serves as a reference for electrochemical analysis of frying oils, with the potential for portable TPC predictors for rapid accurate screening of frying oils.

[Effects of Short-Term Nitrogen and Phosphorus Addition on Soil Respiration Components in a Subalpine Grassland of Qilian Mountains].

In order to investigate the effects of short-term nitrogen and phosphorus addition on soil respiration and its components in a subalpine grassland located on the Qilian Mountains, a random block design of nitrogen[10 g·(m2·a)-1, N], phosphorus[5 g·(m2·a)-1, P], nitrogen and phosphorus addition[10 g·(m2·a)-1N and 5 g·(m2·a)-1P, NP], the control (CK), and complete control (CK') was conducted from June to August 2019, and total soil respiration and its component respiration rates were measured. The results showed that nitrogen addition reduced soil total respiration and heterotrophic respiration rates at a lower rate than P addition[-16.71% vs. -19.20%; -4.41% vs. -13.05%], but the rate of decrease in autotrophic respiration was higher than that of P addition (-25.03% vs. -23.36%); N and P mixed application had no significant effect on soil total respiration rate. The total soil respiration rate and its components were significantly exponentially correlated with soil temperature, and the temperature sensitivity of soil respiration rate was decreased by nitrogen addition (Q10:-5.64%-0.00%). P increased Q10 (3.38%-6.98%), and N and P reduced autotrophic respiration rate but increased heterotrophic respiration rate Q10 (16.86%) and decreased total soil respiration rate Q10 (-2.63%- -2.02%). Soil pH, soil total nitrogen, and root phosphorus content were significantly correlated with autotrophic respiration rate (P<0.05) but not with heterotrophic respiration rate, and root nitrogen content was significantly negatively correlated with heterotrophic respiration rate (P<0.05). In general, autotrophic respiration rate was more sensitive to N addition, whereas heterotrophic respiration rate was more sensitive to P addition. Both N and P addition significantly reduced soil total respiration rate, whereas N and P mixture did not significantly affect soil total respiration rate. These results can provide a scientific basis for the accurate assessment of soil carbon emission in subalpine grassland.

Drug resistance profile of Mycobacterium kansasii clinical isolates before and after 2-month empirical antimycobacterial treatment.

OBJECTIVES: Mycobacterium kansasii pulmonary disease is frequently misdiagnosed and treated as tuberculosis, especially in countries with high tuberculosis burden. This study aimed to investigate the drug resistance profile of M.kansasii in patients with M.kansasii pulmonary disease in Shanghai and to determine the variations in drug resistance after 2 months of antimycobacterial treatment. METHODS: All patients with a diagnosis of M.kansasii pulmonary disease from 2017 to 2019 in Shanghai were retrospectively analysed. Whole-genome sequencing was performed, and the minimum inhibitory concentration (MIC) to antimycobacterial drugs was measured using the broth microdilution method. RESULTS: In total, 191 patients had a diagnosis of M.kansasii pulmonary disease. Of them, 24.1% (46/191) had persistent positive culture after 2 months of antimycobacterial treatment. Whole-genome sequencing revealed that the 46 paired isolates had a difference of <17 single nucleotide polymorphisms, thus excluding the possibility of exogenous reinfection. More than 90% of the baseline isolates were sensitive to rifampin, clarithromycin, moxifloxacin, or amikacin, whereas a high resistance to ethambutol (118/191, 61.8%) and 4 µg/mL of isoniazid (32/191, 16.8%) were observed. Two isolates presented high resistance to rifamycin (i.e. a rifampin MIC of >8 µg/mL and a rifabutin MIC of 8 µg/mL) both containing the rpoB mutation (S454L). The increase of MIC to rifampin, ethambutol, and/or isoniazid was identified in 50.0% (23/46) of the patients. DISCUSSION: A high prevalence of innate resistance to ethambutol and isoniazid was observed among circulating M.kansasii clinical strains in Shanghai. The increase in drug resistance under empirical antimycobacterial treatment highlighted the urgency of definitive species identification before initiating treatment.

Cordycepin Inhibits the Growth of Hepatocellular Carcinoma by Regulating the Pathway of Aerobic Glycolysis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, with a high incidence and mortality rate. Glucose metabolism reprogramming is a major characteristic of tumor cells. Increasing evidence indicates that aerobic glycolysis is associated with tumor growth and insensitivity to chemotherapy. Cordycepin inhibits the growth of HCC cells, but the mechanism is yet to be elucidated. Herein, in vitro and in vivo methods were utilized to investigate the cordycepin-inhibited growth of HCC by regulating the metabolic pathway of aerobic glycolysis. In vitro analyses using colony formation and flow cytometry revealed that cordycepin inhibits HCC cells' proliferation and promotes apoptosis. In addition, cordycepin reduced the production of lactic acid and pyruvate, reduced the uptake of glucose, and decreased the extracellular acidification in HCC cells. Specifically, cordycepin inhibited the expression of HK2, LDHA, and PKM2 in aerobic glycolysis via the AMPK-Akt pathway. Taken together, these findings revealed that cordycepin reduces the tumor energy supply and decreases lactic acid production, thereby inhibiting the growth of HCC cells by regulating the metabolic pathway of aerobic glycolysis. These findings might provide novel insights into the mechanisms underlying cordycepin-mediated inhibition of tumor growth as well as a new treatment for HCC.

Astaxanthin alleviates palmitic acid-induced hindrance of porcine oocyte maturation.

Increased palmitic acid (PA) levels have been found in females with reduced fertility due to metabolic disorders. However, effective antioxidant astaxanthin (AXE) might positively affect animal reproduction. Therefore, the present study was designed to evaluate the impact of a high concentration of PA on oocyte maturation and the possible protective effect of AXE against high PA concentration in pigs. Firstly, different concentrations (0.2, 0.5, 0.8 mM) of PA were conducted on in vitro maturation (IVM) of pig oocytes (PA0.2, PA0.5, and PA0.8), while no addition of PA was performed as the control group (Ctrl). Results showed that the cumulus cell expansion index (CCEI) was lower in PA0.5 and PA0.8 groups compared to Ctrl group (p < .05). In PA0.5 group, not only did the percentage of matured oocytes with the first polar body (PB1) reduced, that with more oocytes arrested at germinal vesicle (GV) stage (53.44% ± 7.16% vs. 20.93% ± 5.16%, p < .05), but also a higher number of transzonal projections (TZPs) was observed in PA0.5 than Ctrl group. Besides, supplement of PA resulted in a dose-dependent decrease in mitochondrial activity. Although no difference of lipid content was observed between PA0.5 and Ctrl groups, the lipid content was at a higher level in PA0.2 group than in the other three groups. Hence, concentration of 0.5 mM of PA was performed in the following experiments, and 2.5 µM AXE carried out to investigate the possible relief effects of PA (PA0.5 + AXE). Results showed that the percentage of matured oocytes with PB1 was higher in PA0.5 + AXE than in PA0.5 group (63.43% ± 1.50% vs. 55.33% ± 0.81%, p < .01), and ROS levels both in oocytes and their cumulus cells (CCs) reduced in PA0.5 + AXE when compared to PA0.5 group. In addition, the rate of CCs with apoptosis decreased in PA0.5 + AXE, and the expression level of caspase 3 and BAX was lower than PA0.5 group. In conclusion, the maturation of pig oocytes was inhibited by the high concentration of PA; however, this negative effect of PA-induced might be relieved by the supplement of AXE.

Periconception Red Blood Cell Folate and Offspring Congenital Heart Disease : Nested Case-Control and Mendelian Randomization Studies.

BACKGROUND: Periconception folic acid supplementation has been suggested to protect against congenital heart disease (CHD), but the association between maternal red blood cell (RBC) folate, the gold-standard biomarker of folate exposure, and subsequent offspring CHD risk is lacking. OBJECTIVE: To quantify the association between periconception maternal RBC folate and offspring CHD risk. DESIGN: Prospective, nested, case-control study and 1-sample Mendelian randomization. (ClinicalTrials.gov: NCT02737644). SETTING: 29 maternity institutions in 12 districts of Greater Shanghai, China. PARTICIPANTS: All 197 mothers of offspring with CHD and 788 individually matched mothers of unaffected offspring from the SPCC (Shanghai Preconception Cohort). MEASUREMENTS: Maternal RBC folate was measured before or at early pregnancy. Odds ratios [ORs] were estimated using conditional logistic regression after adjustment for covariates. Mendelian randomization was done using the methylenetetrahydrofolate reductase (MTHFR) C677T as the genetic instrument. RESULTS: Case patients had lower median maternal RBC folate concentrations than control participants (714 nmol/L [interquartile range, 482 to 1008 nmol/L] vs. 788 nmol/L [557 to 1094 nmol/L]). Maternal RBC folate concentrations were inversely associated with offspring CHD (adjusted OR per 100 nmol/L, 0.93 [95% CI, 0.89 to 0.99]). The adjusted OR for mothers with periconception RBC folate of 906 nmol/L or more (vs. <906 nmol/L) was 0.61 (CI, 0.40 to 0.93). Mendelian randomization showed that each 100-nmol increase in maternal RBC folate concentrations was significantly associated with reduced offspring CHD risk (OR, 0.75 [CI, 0.61 to 0.92]). LIMITATION: Potential confounding due to unmeasured covariates in the nested case-control study. CONCLUSION: Higher maternal RBC folate is associated with reduced offspring CHD risk. For primary CHD prevention, higher target RBC folate levels than currently recommended for neural tube defect prevention may be needed and warrant further study. PRIMARY FUNDING SOURCE: National Key Research and Development Program of China, National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.

Nitrogen effects on grassland biomass production and biodiversity are stronger than those of phosphorus.

Human-induced nitrogen (N) and phosphorus (P) enrichment have profound effects on grassland net primary production (NPP) and species richness. However, a comprehensive understanding of the relative contribution of N vs. P addition and their interaction on grassland NPP increase and species loss remains elusive. We compiled data from 80 field manipulative studies and conducted a meta-analysis (2107 observations world-wide) to evaluate the individual and combined effects of N and P addition on grassland NPP and species richness. We found that both N addition and P addition significantly enhanced grassland above-ground NPP (ANPP; 33.2% and 14.2%, respectively), but did not affect total NPP, below-ground NPP (BNPP), and species evenness. Species richness significantly decreased with N addition (11.7%; by decreasing forbs) probably due to strong decreased soil pH, but not with P addition. The combined effects of N and P addition were generally stronger than the individual effects of N or P addition, and we found the synergistic effects on ANPP, and additive effects on total NPP, BNPP, species richness, and evenness within the combinations of N and P addition. In addition, N and P addition effects were strongly affected by moderator variables (e.g. climate and fertilization type, duration and amount of fertilizer addition). These results demonstrate a higher relative contribution of N than P addition to grassland NPP increase and species loss, although the effects varied across climate and fertilization types. The existing data also reveals that more long-term (≥5 years) experimental studies that combine N and P and test multifactor effects in different climate zones (particularly in boreal grasslands) are needed to provide a more solid basis for forecasting grassland community response and C sequestration response to nutrient enrichment at the global scale.

Comparative Analysis of Chloroplast Genome and New Insights Into Phylogenetic Relationships of Polygonatum and Tribe Polygonateae.

Members of Polygonatum are perennial herbs that have been widely used in traditional Chinese medicine to invigorate Qi, moisten the lung, and benefit the kidney and spleen among patients. However, the phylogenetic relationships and intrageneric taxonomy within Polygonatum have long been controversial because of the complexity of their morphological variations and lack of high-resolution molecular markers. The chloroplast (cp) genome is an optimal model for deciphering phylogenetic relationships in related families. In the present study, the complete cp genome of 26 species of Trib. Polygonateae were de novo assembled and characterized; all species exhibited a conserved quadripartite structure, that is, two inverted repeats (IR) containing most of the ribosomal RNA genes, and two unique regions, large single sequence (LSC) and small single sequence (SSC). A total of 8 highly variable regions (rps16-trnQ-UUG, trnS-GCU-trnG-UCC, rpl32-trnL-UAG, matK-rps16, petA-psbJ, trnT-UGU-trnL-UAA, accD-psaI, and trnC-GCA-petN) that might be useful as potential molecular markers for identifying Polygonatum species were identified. The molecular clock analysis results showed that the divergence time of Polygonatum might occur at ∼14.71 Ma, and the verticillate leaf might be the ancestral state of this genus. Moreover, phylogenetic analysis based on 88 cp genomes strongly supported the monophyly of Polygonatum. The phylogenetic analysis also suggested that Heteropolygonatum may be the sister group of the Polygonatum, but the Disporopsis, Maianthemum, and Disporum may have diverged earlier. This study provides valuable information for further species identification, evolution, and phylogenetic research of Polygonatum.

Holistic review and meta-analysis of independent impact of the residual SYNTAX score on prognosis in patients with acute coronary syndrome.

Objectives. The appropriate extent of revascularization following primary intervention is unknown. We conducted a systematic review and meta-analysis of residual Syntax score (rSS) to predict the outcomes and provide guide to optimal management of revascularization following primary intervention. Designs. Previously published studies from 2007 to 2020 assessing the prognostic impact of rSS after ACS were included for this meta-analysis. The primary endpoint was defined as the major adverse clinical events (MACE) in multivariable analysis. The risk ratios (RRs) with 95% confidence intervals (CI) were calculated using the RevMan 5.4 software. Results. A total of 8,157 participants complicated with ACS from 12 clinical studies were included in this analysis. Based on the wide range of rSS studies available, we classified it into two major groups: rSS < 8 and rSS ≥ 8. In multivariate analysis, the rSS was an independent risk marker for MACE [RR = 1.04 (95%CI; 1.00-1.08)], all-cause mortality [RR = 1.05 (1.03-1.07)] and cardiovascular death [RR = 1.05 (1.03-1.07)]. Patients with incomplete revascularization (ICR) showed higher prevalence of MACE along with all-cause mortality, cardiovascular morality, and recurrent myocardial infarction without significant heterogeneity [RR = 1.60 (1.03-1.07), 2.30 (1.57-3.38), 3.57 (2.09-6.10) and 1.70 (1.38-2.09), respectively]. The patients with rSS ≥ 8 presented higher frequency of all-cause mortality [RR = 2.99 (2.18-4.09)], cardiovascular death [RR = 3.32 (2.22-4.95)], and recurrent myocardial infarction [RR = 1.64 (1.34-2.02)]. Conclusion. The meta-analysis indicated that an rSS value of 8 could be a reasonable cut-off for incomplete revascularization after ACS and is an efficient tool to guide revascularization. In future, detailed research should focus on investigation of the optimal value of the rSS score.

[One new phenylethanoid glycoside from Forsythiae Fructus].

One new phenylethanoid glycoside was isolated from the ethyl acetate fraction of the 75% EtOH extract of Forsythiae Fructus by various column chromatographies(HP20, silica gel, ODS) and preparative HPLC.Its structure was identified as forsythiayanoside E(1) by physicochemical properties and extensive spectroscopic analysis(HR-ESI-MS, 1 D and 2 D NMR).Compound 1 was evaluated for cytotoxic activities by MTT assay and showed weak cytotoxic activity against MCF-7 and A-375 cell lines with inhibition rates of 39.85% and 43.38% at 40 µmol·L~(-1), and no cytotoxic activity against PC-3 and HepG2 cell lines at 100 µmol·L~(-1).

Complete chloroplast genome of Gentianopsis barbata and comparative analysis with related species from Gentianaceae.

Gentianopsis barbata is an essential medicinal plant in China with high ornamental and medicinal values. Unfortunately, the study of the chloroplast genome of this plant still has a gap. This study sequenced and characterized the complete chloroplast genome of G. barbata. The complete chloroplast genome of G. barbata is a typical circular structure of 151 123 bp. It consists of a large single-copy region (82 690 bp) and a small single-copy region (17 887 bp) separated by a pair of inverted repeats (25 273 bp), which covers 78 protein-coding genes, 30 tRNAs, and 4 rRNAs. The long repeat sequence analysis showed that the P-type (palindromic) sequences were the major long repeat sequences. Thirty-seven simple sequence repeats were identified, most of which were single nucleotides. The Bayesian inference tree, maximum likelihood tree, and neighbor-joining tree suggested that G. barbata is grouped with Gentianopsis grandis and Gentianopsis paludosa. The divergence time analysis showed that G. barbata diverged at 1.243 Mya. Comparative analysis of chloroplast genomes can reveal interspecific diversity, and regions with high variation can be used to develop molecular markers applicable to various research areas. Our results provide a new insight into plastome evolution and a valuable resource for further studies on G. barbata.

Gut microbiome responses to dietary intervention with hypocholesterolemic vegetable oils.

Hypercholesterolemia is becoming a problem with increasing significance. Dietary vegetable oils may help to improve this condition due to presence of phytonutrients with potentially synergistic cholesterol-lowering effects. The objective of this 8-week double-blinded randomized clinical trial was to investigate the effects of consuming 30 g of two different blended cooking oils, rich in omega-3 alpha-linolenic acid and phytonutrients, or refined olive oil on the intestinal microbiota in 126 volunteers with borderline hypercholesterolemia. Multi-factor analysis of relationships between the gut microbiota composition at various taxonomic ranks and the clinical trial parameters revealed the association between beneficial effects of the dietary intervention on the blood lipid profile with abundance of Clostridia class of the gut microbiota. This microbiota feature was upregulated in the course of the dietary intervention and associated with various plasma markers of metabolic health status, such as Triglycerides, Apolipoprotein B and Total Cholesterol to HDL ratio in a beneficial way. The relative abundance of a single species-Clostridium leptum-highly increased during the dietary intervention in all the three study groups. The oil blend with the highest concentration of omega-3 PUFA is associated with faster and more robust responses of the intestinal microbiota, including elevation of alpha-diversity. Butyrate production is being discussed as a plausible process mediating the observed beneficial influence on the plasma lipid profile. Causal mediation analysis suggested that Clostridium genus rather than the higher rank of the phylogeny-Clostridia class-may be involved in the diet-induced improvements of the blood lipid profile.

RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort.

BACKGROUND: The protective effects of maternal folate on neural tube defects are well-established. Emerging evidence has shown paternal folate also is related to pregnancy outcome and offspring health. OBJECTIVES: This study aimed to assess the status of red blood cell (RBC) folate and serum folate, vitamin B-12, and homocysteine (Hcy) and their associated factors in a cohort of pregnancy-preparing couples. METHODS: This was a cross-sectional study involving 14,178 participants from the extension of the Shanghai Preconception Cohort conducted in 2018-2021. Circulating biomarker concentrations were measured, and the prevalence of abnormal status was reported. Linear and logistic regression analyses were conducted to examine associations of demographic factors (age, education, and income), lifestyle factors (smoking, drinking, and folic acid supplement use), and BMI with concentrations of the folate-related biomarkers, abnormal status of folate (deficiency and insufficiency) and vitamin B-12 (deficiency and marginal deficiency), and hyperhomocysteinemia. RESULTS: The geometric mean (95% CI) concentrations of RBC folate, serum folate, vitamin B-12, and Hcy were 490 nmol/L (485, 496 nmol/L), 20.1 nmol/L (19.8, 20.3 nmol/L), 353 pmol/L (350, 357 pmol/L), and 7.54 µmol/L (7.48, 7.60 µmol/L) in females, respectively, and 405 nmol/L (401, 409 nmol/L), 13.5 nmol/L (13.4, 13.7 nmol/L), 277 pmol/L (274, 279 pmol/L), and 12.0 µmol/L (11.9, 12.2 µmol/L) in males, respectively. Prevalence of abnormal status was higher in males than females for the 4 folate-related biomarkers: RBC folate deficiency (<340 nmol/L, 32.2% compared with 18.9%), serum folate deficiency (<10.0 nmol/L, 26.5% compared with 7.3%), RBC folate insufficiency (<906 nmol/L, 96.6% compared with 90.1%), serum folate insufficiency (<15.9 nmol/L, 65.5% compared with 31.4%), vitamin B-12 marginal deficiency (148-221 pmol/L, 21.4% compared with 8.8%), and hyperhomocysteinemia (>15.0 µmol/L, 22.1% compared with 2.5%). CONCLUSIONS: Most pregnancy-preparing couples failed to achieve the optimal RBC folate status (>906 nmol/L) as recommended by the WHO. These findings call for attention to the insufficiency status of folate and promising strategies to improve the folate status of the pregnancy-preparing population not exposed to folic acid fortification.

Opposite trends of glycosides and alkaloids in Dendrobium nobile of different age based on UPLC-Q/TOF-MS combined with multivariate statistical analyses.

INTRODUCTION: Alkaloids and glycosides are the active ingredients of the herb Dendrobium nobile, which is used in traditional Chinese medicine. The pharmacological effects of alkaloids include neuroprotective effects and regulatory effects on glucose and lipid metabolism, while glycosides improve the immune system. The pharmacological activities of the above chemical components are significantly different. In practice, the stems of 3-year-old D. nobile are usually used as the main source of Dendrobii Caulis. However, it has not been reported whether this harvesting time is appropriate. OBJECTIVE: The aim of this study was to compare the chemical characteristics of D. nobile in different growth years (1-3 years). METHODS: In this study, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) was employed to analyze the constituents of D. nobile. The relative abundance of each constituent was analyzed with multivariate statistical analyses to screen the characteristic constituents that contributed to the characterization and classification of D. nobile. Dendrobine, a component of D. nobile that is used for quality control according to the Chinese Pharmacopoeia, was assayed by gas chromatography. RESULTS: As a result, 34 characteristic constituents (VIP > 2) were identified or tentatively identified as alkaloids and glycosides based on MS/MS data. Moreover, the content of alkaloids decreased over time, whereas the content of glycosides showed the opposite trend. The absolute quantification of dendrobine was consistent with the metabolomics results. CONCLUSION: Our findings provide valuable information to optimize the harvest period and a reference for the clinical application of D. nobile.

Gallic Acid: A Potential Anti-Cancer Agent.

Cancer is one of the most devastating diseases worldwide and definitive therapeutics for treating cancer are not yet available despite extensive research efforts. The key challenges include limiting factors connected with traditional chemotherapeutics, primarily drug resistance, low response rates, and adverse side-effects. Therefore, there is a high demand for novel anti-cancer drugs that are both potent and safe for cancer prevention and treatment. Gallic acid (GA), a natural botanic phenolic compound, can mediate various therapeutic properties that are involved in anti-inflammation, anti-obesity, and anti-cancer activities. More recently, GA has been shown to exert anti-cancer activities via several biological pathways that include migration, metastasis, apoptosis, cell cycle arrest, angiogenesis, and oncogene expression. This review discusses two aspects, one is the anti-cancer potential of GA against different types of cancer and the underlying molecular mechanisms, the other is the bibliometric analysis of GA in cancer and tumor research. The results indicated that lung cancer, prostate cancer, stomach cancer, and colon adenocarcinoma may become a hot topic in further research. Overall, this review provides evidence that GA represents a promising novel, potent, and safe anti-cancer drug candidate for treating cancer.

Oral Chinese Patent Medicines for Breast Cancer：A Scoping Review of Clinical Evidence / 中国实验方剂学杂志

To clarify the research progress and existing problems in the clinical research on oral Chinese patent medicine in the treatment of breast cancer. National drug catalogs and databases were searched for oral Chinese patent medicines against breast cancer. Chinese and English databases were searched for clinical trials on oral Chinese patent medicines in the treatment of breast cancer. The main functions，drug composition，literature basic characteristics，intervention measures， and outcome indicators of Chinese patent medicines were comprehensively analyzed and evaluated by a scoping review based on visual charts. In 68 Chinese patent medicines included，53% of them were potent in activating blood， resolving stasis， tonifying the kidney， and strengthening the spleen. In terms of frequency， the top drugs were Ligustri Lucidi Fructus， Astragali Radix， Moutan Cortex， Poria， and Olibanum，indicating the importance of the therapeutic principles of activating blood， resolving stasis， tonifying the kidney， and strengthening the spleen for breast cancer treatment. In 161 included clinical trials，70.71% of the intervention measures were Chinese patent medicine combined with chemotherapy. Literature studies mainly reported Xihuang pills and Huaier granules，which may be related to the combination of chemotherapy and the inclusion in the medical insurance. The outcome evaluation was mainly based on immune indexes，tumor markers，Karnofsky score，safety report and objective response rate，while the survival time and characteristic outcome indicators of traditional Chinese medicine （TCM） were insufficient. The application and research on oral Chinese patent medicine in the treatment of breast cancer have advanced in recent years，but most of the clinical research evidence is not robust，and the evaluation of outcome indicators is not standardized，which needs to be improved.