Glutamine deficiency drives transforming growth factor-ß signaling activation that gives rise to myofibroblastic carcinoma-associated fibroblasts.

Tumor-promoting carcinoma-associated fibroblasts (CAFs), abundant in the mammary tumor microenvironment (TME), maintain transforming growth factor-ß (TGF-ß)-Smad2/3 signaling activation and the myofibroblastic state, the hallmark of activated fibroblasts. How myofibroblastic CAFs (myCAFs) arise in the TME and which epigenetic and metabolic alterations underlie activated fibroblastic phenotypes remain, however, poorly understood. We herein show global histone deacetylation in myCAFs present in tumors to be significantly associated with poorer outcomes in breast cancer patients. As the TME is subject to glutamine (Gln) deficiency, human mammary fibroblasts (HMFs) were cultured in Gln-starved medium. Global histone deacetylation and TGF-ß-Smad2/3 signaling activation are induced in these cells, largely mediated by class I histone deacetylase (HDAC) activity. Additionally, mechanistic/mammalian target of rapamycin complex 1 (mTORC1) signaling is attenuated in Gln-starved HMFs, and mTORC1 inhibition in Gln-supplemented HMFs with rapamycin treatment boosts TGF-ß-Smad2/3 signaling activation. These data indicate that mTORC1 suppression mediates TGF-ß-Smad2/3 signaling activation in Gln-starved HMFs. Global histone deacetylation, class I HDAC activation, and mTORC1 suppression are also observed in cultured human breast CAFs. Class I HDAC inhibition or mTORC1 activation by high-dose Gln supplementation significantly attenuates TGF-ß-Smad2/3 signaling and the myofibroblastic state in these cells. These data indicate class I HDAC activation and mTORC1 suppression to be required for maintenance of myCAF traits. Taken together, these findings indicate that Gln starvation triggers TGF-ß signaling activation in HMFs through class I HDAC activity and mTORC1 suppression, presumably inducing myCAF conversion.

ADMS simulation and influencing factors of bioaerosol diffusion from BRT under different aeration modes in six wastewater treatment plants.

Bioaerosols produced by municipal wastewater treatment plants (MWTP) can spread in air, thereby polluting the atmosphere and causing safety hazards to workers and surrounding residents. In this study, the biological reaction tanks (BRTs) of six MWTPs undergoing typical processes in North China, Yangtze River Delta, and the Greater Bay Area were selected to set up sampling points and investigate the production characteristics of bioaerosols. The Atmospheric Dispersion Modelling System method was used to simulate the diffusion of bioaerosols in the MWTPs. The concentrations of bacteria and, specifically, intestinal bacteria in the bioaerosols ranged from 389 CFU/m3 to 1,536 CFU/m3 and 30 CFU/m3 to 152 CFU/m3, respectively, and the proportion of the intestinal bacteria was 8.85%. The concentration of soluble chemicals (SCs) in the bioaerosols was 18.36 µg/m3-82.19 µg/m3, and the main SCs found were Mg2+, Ca2+, and SO42-. The proportion of intestinal bacteria (75.79%) produced via surface aeration by a BRT attached to large-sized bioaerosol particles was higher than that of a BRT undergoing the bottom aeration process (37.28%). The main microorganisms found in the bioaerosols included Moraxellaceae, Escherichia-Shigella, Psychrobacter, and Cyanobacteria. The generation of bioaerosols exhibited regional characteristics. The wastewater treatment scale, wastewater quality, and aeration mode were the main factors influencing bioaerosol production. Model simulation showed that, after 1 h, the diffusion distance of bioaerosol was 292 m-515 m, and the affected area was 42,895 m2-91,708 m2. The diffusion distance and range of the bioaerosols were significantly correlated with the concentration at the bioaerosol source and the aeration mode adopted by the BRTs. Wind speed and direction were two environmental factors that affected the diffusion of bioaerosols. With an increase in the diffusion distance, the concentration of microorganisms, intestinal bacteria, ions, and fine particles in the bioaerosols decreased significantly, resulting in a corresponding reduction in the exposure risk. This study provides new insights to help predict bioaerosol risks at MWTPs and identify safe areas around MWTPs. The study also provides a basis for selecting safe MWTP sites and reducing bioaerosol pollution risks.

Prediction and verification of potential lead analgesic and antiarrhythmic components in Corydalis yanhusuo W. T. Wang based on voltage-gated sodium channel proteins.

Corydalis yanhusuo W. T. Wang, a traditional Chinese herbal medicine, has been used as an analgesic for thousands of years and it also promotes blood circulation. In this study, 33 Corydalis yanhusuo alkaloid active components were acquired from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). A total of 543 pain-related targets, 1774 arrhythmia targets, and 642 potential targets of these active components were obtained using Swiss Target Prediction, GeneCards, Open Target Platform, and Therapeutic Target Database. Fifty intersecting targets were visualized through a Venn diagram, KEGG and GO pathway enrichment analysis. The analysis proposed that sodium ion channels are likely potential targets of Corydalis yanhusuo active components as analgesia and anti-arrhythmia agents. Molecular docking showed that the 33 components could bind to Nav1.7 and Nav1.5 (two subtypes of ion channel proteins) with different binding energies. In a patch clamp study, dihydrosanguinarine and dihydrochelerythrine, two monomers with the strongest binding effects, could inhibit the peak currents and promote both activation and inactivation phases of Nav1.5. Meanwhile, dihydrosanguinarine and dihydrochelerythrine could also inhibit peak currents and promote the activation phase of Nav1.7. Therefore, the findings from this study provide valuable information for future uses of traditional Chinese medicines to treat pain and cardiovascular disease.

Analgesic effect of the main components of Corydalis yanhusuo (yanhusuo in Chinese) is caused by inhibition of voltage gated sodium channels.

ETHNOPHARMACOLOGY RELEVANCE: Pain often causes a series of abnormal changes in physiology and psychology, which can lead to disease and even death. Drug therapy is the most basic and commonly used method for pain relief and management. Interestingly, at present, hundreds of traditional Chinese medicines have been reported to be used for pain relief, most of which are monomer preparations, which have been developed into new painkillers. Corydalis yanhusuo is a representative of one of these medicines and is available for pain relief. AIM OF THE STUDY: This study aims to determine the analgesic effect and the potential targets of the monomers derived from Corydalis yanhusuo, and to explore any possible associated cardiac risk factors. MATERIALS AND METHODS: In this study, four monomers derived from Corydalis yanhusuo (tetrahydropalmatine, corydaline, protopine, dehydrocorydaline) were tested in vivo, using the formalin-induced pain model to determine their analgesic properties. Their potential targets were also determined using whole cell patch clamp recordings and myocardial enzyme assays. RESULTS: The results showed that all monomers showed analgesic activity and inhibited the peak currents, promoted the activation and inactivation phases of Nav1.7, which indicating that Nav1.7 might be involved in the analgesic mechanism of Corydalis yanhusuo. Protopine increased the level of creatine kinase-MB (CK-MB) and inhibited the peak currents, promoted the activation and inactivation phases of Nav1.5, indicating that Nav1.5 might be involved in the cardiac risk associated with protopine treatment. CONCLUSION: These data showed that tetrahydropalmatine produced the best analgesic effect and the lowest cardiac risk. Thus, voltage gated sodium channels (VGSCs) might be the main targets associated with Corydalis yanhusuo. This study, therefore, provides valuable information for future studies and use of traditional Chines medicines for the alleviation of pain.

[Gray mold disease of Paris polyphylla var. yunnanensis and its pathogen identification].

Gray mold disease is one of the most important diseases of planted Paris polyphylla var. yunnanensis, the disease appeared primarily as blossom blights and fruit rots, but also as stem rots, leaf rots.In this study, the pathogenetic fungi was isolated from plant tissue or sclerotia that covering the fruit of diseased P. polyphylla var. yunnanensis, the pathogen was certified according to Koch's Postulation. The pathogen produced abundant black, irregular sclerotia on surface of diseased plants and potato dextrose agar. The conidiophores and clusters of oval conidia resembled a grape-like cluster, the size of conidia was 9.70-13.70 µm [average of (11.32±0.82)µm]×7.05-9.12 µm [average of (8.24±0.48)µm], the microconidia produced on potato dextrose agar were spherical,and the size was （3.34±0.31） µm,the pathogen was identified as Botrytis sp based on morphological characteristics. The DNA sequence analysis of the G3PDH, HSP60, RPB2 genes placed the pathogen in a single clade that outside defined species of Botrytis, so the pathogen could be identified as a new species of Botrytis. The pathogen requires 20 °C, pH 8, darkness or low light condition for the best growth.

Seasonal vitamin D and bone metabolism in women of reproductive age in urban Beijing.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the relationship between serum 25-hydroxy-vitamin D and bone metabolism in healthy women of reproductive age. METHODS AND STUDY DESIGN: This study included 100 healthy female residents of Beijing (23-30 years old), who underwent bone ultrasonography as well as testing to evaluate serum25-hydroxy-vitamin D, parathyroid hormone, bone alkaline phosphatase, calcium, sodium, phosphorus, and alkaline phosphatase. RESULTS: Mean 25-hydroxy-vitamin D in the winter (22.3±3.55 nmol/L) was significantly lower than that in the summer (46.2±16.3 nmol/L). In the winter, a negative correlation was observed between 25-hydroxy-vitamin D and parathyroid hormone(r=0.300, p=0.002) and bone alkaline phosphatase (r=0.274, p=0.016). In the summer, a negative correlation was observed between 25-hydroxy-vitamin D and parathyroid hormone (r=0.386, p<0.001) and bone alkaline phosphatase (r=0.523, p<0.001). Serum calcium, sodium, phosphorus, and alkaline phosphatase were within the normal ranges for both winter and summer, and exhibited no significant correlations with serum 25-hydroxy-vitamin D. The mean speed of sound during bone ultrasonography was 4,125±365 m/s, and a linear correlation was observed between 25-hydroxy-vitamin D and the speed of sound (r=0.215, p=0.031). Serum alkaline phosphatise was not correlated with bone alkaline phosphatase. CONCLUSION: Serum vitamin D deficiency was common among healthy women of childbearing age in Beijing during both winter and summer. Furthermore, bone ultrasonography findings and serum vitamin D, parathyroid hormone, and bone alkaline phosphatase accurately reflected these women's bone metabolism status.

[DNA Barcode Screening and Identifying for Anredera cordifolia and Its Related Species].

Objective: To identify Anredera cordifolia and its closely related species using the DNA barcode. Methods: 28 individuals of Anredera cordifolia and its close related species were collected from different habitats. ITS and ITS2 of ribosomal DNA,matK,rbcL and psb A-trn H of chloroplast DNA were amplified and sequenced. The amplification and sequencing success rate,barcoding gap,and NJ trees were used to evaluate the efficiency of species identification. Results: After amplified and sequenced, base deletion was occurred in psb A-trnH sequences of Basella alba. The sequencing success rates of mat K,rbc L,ITS and ITS2 were 100%,100%,78. 75% and64. 28%,respectively. Among the four DNA barcoding sequences,ITS and mat K had remarkable barcoding gap. The NJ tree showed that Anredera cordifolia could differed obviously from its closely related species by ITS and mat K. Conclusion: The sequences of ITS and matK provide an effective and fast tool for the identification and authentication of medicinal plant of Anredera cordifolia and its related species.

Cytotoxic oxepinochromenone and flavonoids from the flower buds of Rosa rugosa.

A new oxepinochromenone, rugosachromenone A (1), seven new flavonoids, rugosaflavonoids A-G (2-8), and 11 known compounds (9-19) were isolated from the flower buds of Rosa rugosa. Compound 1 is found from Nature for the first time. Compound 2 displayed cytotoxicity against NB4, SHSY5Y, and MCF7 cells with IC50 values of 2.2, 2.5, and 2.3 µM, respectively, and 3 was toxic to A549 and MCF7 cells with IC50 values of 1.2 and 2.8 µM, respectively.

Antiviral chromones from the stem of Cassia siamea.

Seven new chromones, siamchromones A-G (1-7), and 12 known chromones (8-19) were isolated from the stems of Cassia siamea. Compounds 1-19 were evaluated for their antitobacco mosaic virus (anti-TMV) and anti-HIV-1 activities. Compound 6 showed antitobacco mosaic virus (anti-TMV) activity with an inhibition rate of 35.3% and IC50 value of 31.2 µM, which is higher than that of the positive control, ningnamycin. Compounds 1, 10, 13, and 16 showed anti-TMV activities with inhibition rates above 10%. Compounds 4, 6, 13, and 19 showed anti-HIV-1 activities with therapeutic index values above 50.

[Morphological variations of Paris polyphylla var. yunnansensis in different population].

OBJECTIVE: To study the morphological variations of Paris polyphylla var. yunnansensis in different population for genetic diversity and breeding. METHOD: The characters of roots, stalks, leave and flowers were observed. The results were analyzed by DPS software. RESULT AND CONCLUSION: P. polyphylla var. yunnansensis showed plenty genetic diversity, there existed obvious differences in morphological characters of different population. Principal components analysis showed that the number of calyces, petal, carpels, stamens is main factor,which causes the morphological variations in different population. Cluster analysis shows that 26 populations are incorporates in two types as 45.08 Euclidean distance. Leaf area index is distinct different in this two types.