Integrated metabolome and transcriptome analyses of anthocyanin biosynthesis reveal key candidate genes involved in colour variation of Scutellaria baicalensis flowers.

BACKGROUND: Bright flower colour assists plants attract insects to complete pollination and provides distinct ornamental values. In some medicinal plants, diverse flower colour variations usually imply differences in active ingredients. Compared to the common bluish purple of Scutellaria baicalensis flower (SB), the natural variants present rose red (SR) and white (SW) flowers were screened out under the same growing conditions in the genuine producing area Shandong Province, China. However, the mechanism of flower colour variation in S. baicalensis was remain unclear. In the present study, we conducted integrated transcriptome and metabolome analyses to uncover the metabolic difference and regulation mechanism in three S. baicalensis flowers. RESULTS: The results showed that 9 anthocyanins were identified. Among which, 4 delphinidin-based anthocyanins were only detected in SB, 4 cyanidin-based anthocyanins (without cyanidin-3-O-glucoside) mainly accumulated in SR, and no anthocyanin but high level of flavanone, naringenin, was detected in SW. The gene expression profile indicated that the key structural genes in the flavonoid and anthocyanin biosynthesis pathway differentially expressed in flowers with different colours. Compared to SB, the down-regulated expression of F3'5'H, ANS, and 3GT gene in SR might influence the anthocyanin composition. Especially the InDel site with deletion of 7 nucleotides (AATAGAG) in F3'5'H in SR might be the determinant for lack of delphinidin-based anthocyanins in rose red flowers. In SW, the lower expression levels of DFR and two F3H genes might reduce the anthocyanin accumulation. Notably the SNP site of G > A mutation in the splicing site of DFR in SW might block anthocyanin biosynthesis from flavanones and thus cause white flowers. In addition, several key transcription factors, including MYB, bHLH, and NAC, which highly correlated with structural gene expression and anthocyanin contents were also identified. CONCLUSIONS: These results provide clues to uncover the molecular regulatory mechanism of flower colour variation in S. baicalensis and promote novel insights into understanding the anthocyanin biosynthesis and regulation.

Integrated metabolic profiling and transcriptome analysis of Lonicera japonica flowers for chlorogenic acid, luteolin and endogenous hormone syntheses.

The active ingredients of many medicinal plants are the secondary metabolites associated with the growth period. Lonicera japonica Thunb. is an important traditional Chinese medicine, and the flower development stage is an important factor that influences the quality of medicinal ingredients. In this study, transcriptomics and metabolomics were performed to reveal the regulatory mechanism of secondary metabolites during flowering of L. japonica. The results showed that the content of chlorogenic acid (CGA) and luteolin gradually decreased from green bud stage (Sa) to white flower stage (Sc), especially from white flower bud stage (Sb) to Sc. Most of the genes encoding the crucial rate-limiting enzymes, including PAL, C4H, HCT, C3'H, F3'H and FNSII, were down-regulated in three comparisons. Correlation analysis identified some members of the MYB, AP2/ERF, bHLH and NAC transcription factor families that are closely related to CGA and luteolin biosynthesis. Furthermore, differentially expressed genes (DEGs) involved in hormone biosynthesis, signalling pathways and flowering process were analysed in three flower developmental stage.

Is physician online information sharing always beneficial to patient education? An attention perspective.

Aims: With the development of information technology, online health platforms and physician online information sharing play an important role in public health management and patient education. Is physician online information sharing always beneficial to patient education? From the attention perspective, this study aims to explore how physician online information sharing influences patient education, considering the contingent roles of physician online reputation and offline expertise. Methods: A 6-month panel data of 61,566 physician-month observations from an online health platform in China was used to tested the proposed hypotheses. Considering the inefficiency and estimated bias of the ordinary least squares regression model, this study conducted the fixed models to test the direct and moderating effects. Results: The results indicate that physician online information sharing is positively related to potential patient education, while the relationship between physician online information sharing and realized patient education is an inverted U-shape. Physician online reputation enhances the positive relationship between physician online information sharing and potential patient education, but physician offline expertise weakens the abovementioned relationship. In addition, physician offline expertise flattens the curvilinear effect of physician online information sharing on realized patient education. Conclusion: This study contributes to the literature about attention theory and information sharing for patient education, and provides implications for practice.

Comparative study on the removal of organic pollutants by magnetic composite and pre-magnetized zero-valent iron activated persulfate.

The rapid development of global logistics has led to the overuse of packaging cartons, causing problems for municipal solid waste disposal. Diverse methods of exploiting the potential value of waste cartons are needed. Herein, we fabricated a magnetic composite (MC) from waste cartons via a one-step hydrothermal treatment and characterized. Using methylene blue (MB) as a model organic pollutant, tests of the activation of persulfate (PS) via the MC for the removal of MB were performed. Meanwhile, a comparison with activation with pre-magnetized zero-valent iron (Pre-ZVI/PS) was made. The comparative results show that the removal of MB was successfully accomplished with both Pre-ZVI/PS and MC/PS. Specifically, MC/PS could remove almost 100 % of MB, with the COD removal efficiency reaching over 70 % when the MB concentration was 50 mg/L at 80 min under different pH conditions. Even when reused twice, the MC still displayed robust activation performance. Additionally, we evaluated the lifetime of magnetic memory for Pre-ZVI, and first found its consecutive loss of pre-magnetization over 30 days, corresponding to the incremental attenuation of reaction rate constants in the Pre-ZVI-activated PS process. Overall, activating PS using the MC is a promising advanced oxidation technology and also provides a valuable reference on the valorization of lignocellulosic biomass.

Fabrication and characterization of quercetin loaded casein phosphopeptides-chitosan composite nanoparticles by ultrasound treatment: Factor optimization, formation mechanism, physicochemical stability and antioxidant activity.

Ultrasound treatment was used to successfully prepare Quercetin (Qu)-loaded Casein phosphopeptides (CPP)/chitosan (CS) nanoparticles. Compared with the control, the above ternary nanoparticles with the smallest size (241.27 nm, decreased by 34.32%), improved encapsulation efficiency of Qu (78.55%, increased by 22.12%) when prepared under following conditions: ultrasonic frequency, 20/35/50 kHz; the power density, 80 W/L; the time, 20 min, and the intermittent ratio, 20 s/5s. Electrostatic interactions, hydrogen bonding, and hydrophobic interactions were the main driving forces for nanoparticles formulation, which were strengthened by ultrasound treatment. The compact, homogeneous and spherical composite nanoparticles obtained by sonication were clearly observed by scanning electron microscope and atomic force microscope. The environmental stability (NaCl, pH, exposure time, storage time, and simulated gastrointestinal digestion) and antioxidant activity of the ternary nanoparticles were remarkably enhanced after ultrasonic treatment. Furthermore, the ternary nanoparticles prepared by ultrasound exhibited excellent stability in simulated gastrointestinal digestion. The above results indicate that ultrasound not only increases the loading of the nanoparticles on bioactive substances but also improves the environmental stability and antioxidant activity of the formed nanoparticles. Ultrasound-assisted preparation of nanoparticles loaded with bioactive substances could be well used in the functional food and beverage industry.

Traditional Chinese medicine combined with pulmonary drug delivery system and idiopathic pulmonary fibrosis: Rationale and therapeutic potential.

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary interstitial inflammatory disease of unknown etiology, and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Nintedanib and pirfenidone are the only two known drugs which are conditionally recommended for the treatment of IPF by the FDA. However, these drugs pose some adverse side effects such as nausea and diarrhoea during clinical applications. Therefore, it is of great value and significance to identify effective and safe therapeutic drugs to solve the clinical problems associated with intake of western medicine. As a unique medical treatment, Traditional Chinese Medicine (TCM) has gradually exerted its advantages in the treatment of IPF worldwide through a multi-level and multi-target approach. Further, to overcome the current clinical problems of oral and injectable intakes of TCM, pulmonary drug delivery system (PDDS) could be designed to reduce the systemic metabolism and adverse reactions of the drug and to improve the bioavailability of drugs. Through PubMed, Google Scholar, Web of Science, and CNKI, we retrieved articles published in related fields in recent years, and this paper has summarized twenty-seven Chinese compound prescriptions, ten single TCM, and ten active ingredients for effective prevention and treatment of IPF. We also introduce three kinds of inhaling PDDS, which supports further research of TCM combined with PDDS to treat IPF.

Comparison of diffusion-weighted imaging mono-exponential mode with diffusion kurtosis imaging for predicting pathological grades of clear cell renal cell carcinoma.

PURPOSE: To evaluate the role of diffusion kurtosis imaging (DKI1) in the characterization of clear cell renal cell carcinoma (ccRCC2) compared with standard diffusion-weighted imaging (DWI3). METHODS: 89 patients with histologically proven ccRCC were evaluated by DKI and DWI on a 3-T scanner. All ccRCCs were classified as grade 1-4 according to the Fuhrman classification system. The apparent diffusion coefficient (ADC4), fractional anisotropy (FA5), mean diffusivity (MD6), mean kurtosis (MK7), axial kurtosis (Ka8) and radial kurtosis (Kr9) values were recorded. The differences in DWI and DKI parameters were evaluated by independent-sample t test and a receiver operating characteristic (ROC10) analysis was performed. The DeLong test was performed to compare the ROCs. RESULTS: Compared to normal renal parenchyma, ADC and MD values of ccRCC decreased and MK, Ka, and Kr values increased (p < 0.05). ADC and MD values of ccRCC decreased with the increase in pathological grade, while MK, Ka, and Kr values were increased (p < 0.05). ADC could discriminate G1 vs G3, G1 vs G4, G2 vs G3, G2 vs G4, and G3 vs G4 (p < 0.05) except for G1 vs G2 (p > 0.05). Ka and Kr could discriminate G1 vs G2, G1 vs G3, G1 vs G4, G2 vs G4, and G3 vs G4 (p < 0.05) except for G2 vs G3 (p > 0.05). MD and MK could discriminate G1 vs G2, G1 vs G3, G1 vs G4, G2 vs G3, G2 vs G4, and G3 vs G4 (p < 0.05). The AUC of MK was the highest. The DeLong test showed that there were significant differences regarding ROCs between ADC/MK, ADC/Ka, ADC/Kr in grading G1/G2, and ADC/MK, MK/Ka in grading G3/G4 (p < 0.05). CONCLUSION: DKI was superior compared to the mono-exponential mode of DWI in grading ccRCC.

History of uses, phytochemistry, pharmacological activities, quality control and toxicity of the root of Stephania tetrandra S. Moore: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: the root of Stephania tetrandra S. Moore, known as Fangji in China (Chinese: ), is a traditional Chinese medicine (TCM) with a long history of use. Fangji is a type of medicine used to treat various diseases, including rheumatism, arthralgia, edema and beriberi, unfavorable urination, and eczema. AIM OF THIS REVIEW: There are many newly published reports on the history of uses, phytochemistry, pharmacological activity, quality control and toxicity of Fangji; however, no comprehensive systematic review exists. Therefore, the purpose of this review is to compile the latest and most comprehensive information on Fangji and provide a scientific basis for future research. MATERIALS AND METHODS: A systematic literature search was conducted using multiple electronic databases, including SciFinder, Web of Science, PubMed, Science Direct, ACS Publications, J-stage, SpringerLink, Thieme, Wiley, and CNKI. Information was also collected from journals and Chinese Pharmacopoeia. RESULT: Thus far, there were uses of Fangji against 20 different diseases/disorders, such as relieving edema and rheumatism pain, treating cough and asthma, treating enuresis, astringent urine and beriberi edema, purging blood and damp heat, and dispelling wind evil and dampness, etc. 48 compounds have been isolated from Fangji, belonging to alkaloids, flavonoids, and steroids, other compounds. The crude extracts and isolated compound of Fangji have shown a wide range of pharmacological activities, such as anti-tumor, anti-inflammatory, and neuroprotective activities, as well as role in reoxygenation, and antimicrobial effect, etc. Moreover, qualitative and quantitative analyses of quality control are reviewed, including qualitative analyses for the identification of compounds, as well as fingerprint and quantitative analyses by high performance liquid chromatography (HPLC) and capillary electrochromatography (CE). In the toxicity study, the hepatotoxicity, hepatorenal toxicity, nephrotoxicity, subacute and acute toxicities of the alcohol extract and water extract of Fangji, and tetrandrine were studied in-vitro and in-vivo experiments. CONCLUSION: In the history of uses, Fangji can be used to treat a variety of diseases, most of which are manifested in removing wind and dampness. In recent years, the phytochemistry of Fangji has rarely been reported. The pharmacological activities of Fangji mainly focus on the compounds, tetrandrine and fangchinoline, and there are a few reports on the pharmacological studies of other compounds in Fangji. Moreover, the quality control of Fangji lacks a standard fingerprint to distinguish Fangji from other easily-confused medicinal materials. In the toxicity study, there is no report on the mechanism of toxicity research. Therefore, further studies on such mechanisms are needed.

Toxicity of Carbon Nanotubes as Anti-Tumor Drug Carriers.

Nanoparticle drug formulations have enormous application prospects owing to achievement of targeted and sustained release drug delivery, improvement in drug solubility and reduction of adverse drug reactions. Recently, a variety of efficient drug nanometer carriers have been developed, among which carbon nanotubes (CNT) have been increasingly utilized in the field of cancer therapy. However, these nanotubes exert various toxic effects on the body due to their unique physical and chemical properties. CNT-induced toxicity is related to surface modification, degree of aggregation in vivo, and nanoparticle concentration. This review has focused on the potential toxic effects of CNTs utilized as anti-tumor drug carriers. The main modes by which CNTs enter target sites, the toxicity expressive types and the factors affecting toxicity are discussed.

Preliminary Study on Molecular Subtypes of Breast Cancer Based on Magnetic Resonance Imaging Texture Analysis.

OBJECTIVE: The aim of the study was to investigate the molecular subtypes of breast cancer based on the texture features derived from magnetic resonance images (MRIs). METHODS: One hundred seven patients with preoperative confirmed breast cancer were recruited. One hundred eight breast lesions were divided into 4 subtypes according to the status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor type 2, and Ki67. Fisher discriminant analysis was performed on the texture features that extracted from the enhanced high-resolution T1-weighted images and diffusion weighted images to establish the classification model of molecular subtypes. RESULTS: The differentiation accuracies of Fisher discriminant analysis on the enhanced high-resolution T1-weighted images were 82.8% and 86.4% for 1.5T and 3.0T imaging. Fisher discriminant analysis on diffusion weighted imaging texture features were achieved with a classification ability of 73.4% and 88.6%. The combined discriminant results for 2 kinds magnetic resonance images were 95.0%, 97.7% in 1.5T and 3.0T imaging, respectively. CONCLUSIONS: The fine results indicated a promising approach to predict the molecular subtypes of breast cancer.

[Application of 18F-FDG PET/CT in cervical cancer with elevated levels of serum squamous cell carcinoma antigen during the follow-up].

BACKGROUND AND OBJECTIVE: Accurate and early diagnosis of recurrence for cervical cancer after the treatment and aggressive salvage treatment could improve the prognosis of this disease. Serum squamous cell carcinoma antigen (SCCAg) is the most commonly used tumor marker for the detection of asymptomatic recurrence of cervical cancer. This study was to evaluate the application and value of (18)F-FDG PET/CT in cervical cancer with elevated of serum SCCAg level during the follow-up. METHODS: Thirty-one patients with cervical cancer with elevated serum SCCAg level during the follow-up undergoing (18)F-FDG PET/CT in Sun Yat-sen University Cancer Center between August 2005 and November 2008 were entered into this retrospective study. The pathological types, the serum SCCAg level, PET/CT results, results of other imaging modalities, pathological and clinical follow-ups were recorded. RESULTS: All 31 patients'pathological examination showed squamous cell carcinoma, including three adenosquamous carcinoma. Lesions of all patients were examined by PET/CT. Three patients had local recurrence in the uterus or vagina, 28 had metastatic disease. Of these 31 patients, three were confirmed to have local recurrent disease, 27 were verified to have metastatic disease and one was diagnosed as primary lung squamous cell carcinoma by pathological or clinical manifestations. The total detection rate of PET/CT for malignancy was 100% (31/31); the diagnostic accuracy of PET/CT for recurrent cervical cancer was 96.8% (30/31). The levels of serum SCCAg during the follow-up were 1.5-37.8 ng/ml. There was no relation between the level of serum SCCAg and the maximum standard uptake value (SUVmax) of PET/CT. Compared with other imaging modalities, PET/CT was more efficient in detecting recurrence and finding more lesions. CONCLUSIONS: An elevated level of SCCAg in cervical cancer during the follow-up indicates tumor recurrence. PET/CT is efficient in detecting the recurrence and has high diagnostic accuracy.