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Inflammation is the response of the immune system to infection and injury, with complex interactions with the body, tissues and cells, and plays an important role in the initiation and progression of many diseases such as cancer and cardiovascular disease. Traditional excipients functioning as drug delivery systems can reduce the side effects of systemic distribution of inflammatory drugs. Oil phase, a common excipient in nanoemulsions (NEs), has the advantages of assisting the formation of emulsions, loading lipophilic drugs, thermodynamic stability, wide sources, low price and easy availability. In particular, some of them, like linolenic acid and medium chain triglyceride (MCT), also function as inhibitors of systemic inflammation marker and vascular inflammation marker. However, the influences of different oil phases on the construction of NEs and their distribution in vivo have not been fully investigated. Herein, Tween 80 and ethyl alcohol were screened out as emulsifiers and co-emulsifiers, and three different oil phases used in clinical practice widely, including MCT, oleic acid (OA), and ethyl oleate (EO), were selected as the oil phase to prepare NEs delivery platform. Three NEs had consistent size, potential, morphology, excellent stability and mitochondrial localization function. Importantly, they exhibited superior cellular uptake capacity in inflammatory-injuried human umbilical vein endothelial cells and significantly targeted the brain, lung, heart and thoracic aorta in the lipopolysaccharide-induced mouse and zebrafish larvae inflammation models. Meanwhile, the fluorescence intensities of three NEs were different in these organs, suggesting that their differential enrichment might provide alternative delivery platform for disease treatment in the corresponding organs.

Three arecophila-like fungal samples were collected on dead culms of gramineous plants in China. Morphological studies of our new collections and the herbarium specimen of Arecophila gulubiicola (generic type) were conducted and the morphological affinity of our new collections with Arecophila was confirmed. Maximum likelihood and Bayesian analyses using combined ITS, LSU, rpb2 and β-tubulin data from our collections revealed the phylogeny of Cainiaceae. The monospecific genus Alishanica (type species Al. miscanthi), which had been accepted in Cainiaceae, is revisited and synonymised under Arecophila. Based on morphology and phylogeny, Arecophila australis sp. nov. and A. clypeata sp. nov. are introduced as new species, while A. miscanthi is a new record for China. All the new collections are illustrated and described.

The bioactive ingredients of essential oil from Valerianae Jatamansi Rhizoma et Radix (the Rhizome et Radix from Valerianae Jatamansi Jones) (EOVJRR) on the efficacy of inhibiting microglial activation were investigated with the approach of spectrum-efficacy relationship. Fourteen batches of Valerianae Jatamansi Rhizoma et Radix were extracted and analyzed by gas chromatography-mass spectrometry (GC-MS), and their activities in the efficacy of inhibiting microglial activation were assayed by measuring the inflammatory responses induced by lipopolysaccharide (LPS) in microglia cells from mice. The spectrum-efficacy relationships between fingerprints and the efficacy of inhibiting microglial activation of EOVJRR were established by grey relational analysis (GRA). Twenty common peaks were obtained from the GC-MS fingerprints of EOVJRR. P12 (vetivenol), P1 (bornyl acetate), P5 (seychellene), and P3 (β-elemene) indicated inhibition on microglia activation together, according to the spectrum-efficacy relationships. The current results established a general model for the spectrum-efficacy relationships of EOVJRR by GC-MS and the efficacy of inhibiting microglial activation, which could be applied to identify the bioactive ingredient and control the quality of herbs.

Guizhou and Yunnan Provinces (Yungui Plateau) in Southwestern China are well known as biodiversity hotspots. We introduce two new species in this study viz., Mucispora hydei (in Fuscosporellaceae, Fuscosporellales, Sordariomycetes) and Tolypocladium cucullae (Ophiocordycipitaceae, Hypocreales, Sordariomycetes) and six new records based on morpho-molecular analyses. Full descriptions, color photographs and phylogenetic trees to indicate the placements of new species are provided.

Five taxa that morphologically resemble Astrocystis and Collodiscula were collected on bamboo culms from Guizhou, Hainan and Yunnan provinces in China. Based on morphology and molecular analyses (combined ITS, RPB2, β-tubulin and α-actin genes), these species were identified as Astrocystis cocoes (a new record to China), A. bambusicola, Collodiscula japonica and two new species (A. multiloculata and C. lancangjiangensis). Astrocystis multiloculata can be distinguished from other Astrocystis species by its superficial stromata containing many perithecia and larger ascospores (19–25 × 7–11 μm). Collodiscula lancangjiangensis has larger ascospores (26–36.5 × 5–7.5 μm) than those of the most similar species C. fangjingshanensis (19–25.5 × 4.5–6 μm). It also has larger, 3-septate ascospores than C. japonica (1-septate, 19–26 × 4.5–5.5 μm).

In the process of studying the diversity of Xylariales in China, three species owning characteristics of Graphostromataceae were observed in China. Morphology of the described species with illustrations and their phylogeny based on regions of internal transcribed spacers (ITS), the second-largest subunit of the RNA polymerase II (RPB2), β-tubulin (TUB2) and α-actin (ACT) are provided. Two new species and one new record from China are identified. Morphologically, Biscogniauxia glaucae sp. nov. differs from B. atropunctata var. maritima, B. citriformis var. macrospora, B. fuscella and B. mediterranea by its stromata with raised margins, clear outlines, punctate ostioles openings and ascospores which are equilateral with broadly rounded ends, a straight spore-length germ slit on the more concave side, lacking appendages and sheathes. Graphostroma guizhouensis is identified as a new species based on the multi-gene phylogenetic tree. Camillea broomeana with scanning electron microscope description of ascospores is illustrated as a new record from China. Cryptostroma is proposed in Graphostromataceae based on molecular data. Vivantia is accepted in Graphostromataceae based on its morphological characteristics and Nodulisporiurn anamorphs which are similar to those of Biscogniauxia.

During an investigation of Xylariaceae from 2019 to 2020, isolates representing eight Nemania (Xylariacese) species were collected from Yunnan, Guizhou and Hainan Provinces in China. Morphological and multi-gene phylogenetic analyses, based on combined ITS, α-actin, rpb2 and β-tubulin sequences, confirmed that six of them are new to science, viz. Nemania camelliae, N. changningensis, N. cyclobalanopsina, N. feicuiensis, N. lishuicola and N. rubi; one is a new record (N. caries) for China and one is a known species (N. diffusa). Morphological descriptions and illustrations of all species are detailed. In addition, the characteristics of Nemania are summarised and prevailing contradictions in generic concepts are discussed.

A pair of new lignan conformers (1-2), one new flavonoid glycoside (3), as well as nineteen known compounds were purified from the twigs and leaves of Cajanus cajan (L.) Millsp.. The planar structures of the unknown compounds were determined via NMR and high-resolution mass spectrometry, while their absolute configurations were elucidated via comparison between their experimental and calculated electronic circular dichroism (ECD) values. All the isolated compounds were assayed for their α-glucosidase inhibitory activities. The results demonstrated that compounds 8-12, 15-16, 18-19, 21-22 had strong inhibition activities, with compound 10 (IC

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 6.4 million deaths worldwide and is still spreading among global populations. The prevalent comorbidity between hypertension and severe COVID-19 suggests common genetic factors may affect the outcome of both diseases. As both hypertension and severe COVID-19 demonstrate sex-specific prevalence, common genetic factors among the two diseases may display gender-based differential associations. By evaluating COVID-19 association signals of 172-candidate hypertension single nucleotide polymorphisms derived from more than one million European individuals in two severe COVID-19 genome-wide association studies from UK BioBank with European ancestry, we revealed one functional cis expression quantitative trait locus of SPEG (rs12474050) associating with both hypertension and severe COVID-19 in female. The risk allele of rs12474050*T is correlated with lower SPEG expression in muscle-skeletal, heart-atrial appendage, and heart-left ventricle; among these tissues the SPEG expression is higher in female than in male COVID-19 patients. Further analysis revealed SPEG is mainly expressed in cardiomyocytes in heart and is upregulated upon SARS-CoV-2 infection, with significantly higher folder change of SPEG expression observed in female compared to male COVID-19 patients. Taken together, our analyses strongly suggest the involvement of SPEG in both hypertension and severe COVID-19 in female, which provides new insights for sex-specific effect of severe COVID-19 in female.

Vascular dementia (VD) is a common disease that occurs during human aging. Gastrodin (GAS) has potential benefits for the prevention and treatment of VD. In the present study, we investigated the effects of GAS on cognitive dysfunction in rats with VD induced by permanent middle cerebral artery occlusion (pMCAO) and explored the underlying mechanism. Immunohistochemical and western blot analyses revealed that GAS attenuated hippocampal levels of LC3 (microtubule-associated protein 1 light chain 3), p62, and phosphorylated CaMKII (Ca2+-calmodulin stimulated protein kinase II) in VD rats. Additionally, our results revealed that cobalt chloride blocked autophagic flux in HT22 cells, which was confirmed by increased levels of LC3 and p62 when combined with chloroquine. Notably, GAS ameliorated the impaired autophagic flux. Furthermore, we confirmed that GAS combined with KN93 (a CaMKII inhibitor) or CaMKII knockdown did not impact the reduced p62 levels when compared with GAS treatment alone. Furthermore, a co-immunoprecipitation assay demonstrated that endogenous p62 bound to CaMKII, as confirmed by mass spectrometric analysis after the immunoprecipitation of p62 from HT22 cells. These findings revealed that GAS attenuated autophagic flux dysfunction by inhibiting the Ca2+/CaMKII signaling pathway to ameliorate cognitive impairment in VD.

G-Quadruplex (G4), as a non-canonical nucleic acid secondary structure, has been proved to be prevalent in genomes and plays important roles in many biological processes. Ligands targeting G4, especially small-molecular fluorescent light-up probes with selectivity for special conformations, are essential for studying the relationship between G4 folding and the cellular response. However, their development still remains challenging but is attracting massive attention. Here, we synthesized a new tetraphenylethene derivative, namely TPE-B, as a parallel G4 probe. Fluorescence experiments showed that TPE-B could give out a strong fluorescence response to the G4 structure. Moreover, it gave a much higher fluorescence intensity response to parallel G4s than anti-parallel ones, which indicated that TPE-B could serve as a special tool for probing parallel G4s. The circular dichroism (CD) spectra and melting curves showed that TPE-B could selectively bind and stabilize parallel G4s without changing their topology. ESI-MS studies showed that TPE-B could bind to parallel G4 with a 1 : 1 stoichiometry. The gel staining results showed that TPE-B was a good candidate for probing parallel G4s. Altogether, the TPE-B molecule may serve as a promising new probe that can discriminate parallel G4s.

A species of Hypoxylon, found on dead wood in China, differs from H. hypomiltum and H. samuelsii in having highly carbonaceous stromata, asci with a long stipe and wider ascospores. Based on morphology and molecular phylogeny, it is described as a new species, H. wujiangensis sp. nov. A detailed description and illustration are provided, along with molecular evidence for the new species.

A new Collodiscula, found on a bamboo culms in China, differs from C. japonica, C. fangjingshanensis, C. leigongshanensis, C. bambusae and C. chiangraiensis in having 5-septate ascospores (42.5–65 × 10–15.5 µm). It is described as a new species, Collodiscula tubulosa sp. nov. based on the morphology and molecular phylogeny.

Several micro fungi were gathered from bamboo and palm in Guizhou Province, China. In morphology, these taxa resemble Neomassaria, Roussoella and Oxydothis. Multi-gene phylogenetic analyses based on combined ITS, LSU, SSU, rpb2 and tef1 loci confirmed that two are new geographical records for China, (viz. Roussoella siamensis, Neomassaria fabacearum), while two of them are new to science (viz. Oxydothis fortunei sp. nov. and Roussoella bambusarum sp. nov.). The stromata of Roussoella bambusarum are similar to those of R. thailandica, but its ascospores are larger. In addition, multi-gene phylogenetic analyses show that Oxydothis fortunei is closely related to O. inaequalis, but the J- ascus subapical ring as well as the ascospores of O. inaequalis are smaller. Morphological descriptions and illustrations of all species are provided.

Three arecophila-like fungal samples were collected on dead culms of gramineous plants in China. Morphological studies of our new collections and the herbarium specimen of

Drug resistance is a major hurdle for the effectiveness of tamoxifen (TAM) to provide clinical benefit. Therefore, it is essential to identify a sensitizer that could be used to improve TAM efficacy in treating TAM‐resistant breast cancer. Here, we investigated the ability of baicalein to reverse TAM resistance. We found that baicalein increased the efficacy of TAM in inhibiting proliferation and inducing apoptosis of TAM‐resistant cells. It also enhanced the TAM‐induced growth reduction of resistant cells from NOD/SCID mouse mammary fat pads, without causing obvious systemic toxicity. Analyses using the CellMiner tool and the Kaplan–Meier plotter database showed that HIF‐1α expression was inversely correlated with TAM therapeutic response in NCI‐60 cancer cells and breast cancer patients. HIF‐1α expression was increased in TAM‐resistant cells due to an increase in mRNA levels and reduced ubiquitin‐mediated degradation. Baicalein reduced HIF‐1α expression by promoting its interaction with PHD2 and pVHL, thus facilitating ubiquitin ligase‐mediated proteasomal degradation and thereby suppressing the nuclear translocation, binding to the hypoxia‐response element, and transcriptional activity of HIF‐1α. As a result, baicalein downregulated aerobic glycolysis by restricting glucose uptake, lactate production, ATP generation, lactate/pyruvate ratio and expression of HIF‐1α‐targeted glycolytic genes, thereby enhancing the antiproliferative efficacy of TAM. Furthermore, baicalein interfered with HIF‐1α inhibition of mitochondrial biosynthesis, which increased mitochondrial DNA content and mitochondrial numbers, restored the generation of reactive oxygen species in mitochondria, and thus enhanced the TAM‐induced mitochondrial apoptotic pathway. The HIF‐1α stabilizer dimethyloxallyl glycine prevented the baicalein‐induced downregulation of glycolysis and mitochondrial biosynthesis and reduced the effects of baicalein on reversing TAM resistance. Our results indicate that baicalein is a promising candidate to help overcome TAM resistance by sensitizing resistant cells to TAM‐induced growth inhibition and apoptosis. The mechanism underlying the effects of baicalein consists of inhibition of HIF‐1α–mediated aerobic glycolysis and mitochondrial dysfunction., • Baicalein possesses the ability to reverse TAM resistance. • Baicalein reduces the expression and activity of HIF‐1α via the promotion of its interaction with PHD2 and pVHL and facilitates the ubiquitin ligase‐mediated proteasomal degradation in TAM‐resistant cells. • Baicalein inhibits HIF‐1α–mediated aerobic glycolysis and relieves HIF‐1α–restrained mitochondrial biosynthesis and reactive oxygen species generation, thereby enhancing TAM‐induced proliferation and mitochondrial‐mediated apoptosis.

Resumo Fundamento: A doença cardiovascular é a principal causa de morte em todo o mundo. A apoptose mediada por hipóxia em cardiomiócitos é uma das principais causas de distúrbios cardiovasculares. O tratamento com a proteína do fator de crescimento endotelial vascular (VEGF, do inglês vascular endothelial growth factor) foi testado, mas as dificuldades operacionais limitaram seu uso. Entretanto, com os avanços da terapia gênica, aumentou o interesse na terapia gênica baseada no VEGF em doenças cardiovasculares. No entanto, o mecanismo preciso pelo qual a reposição de VEGF resgata os danos pós-hipóxia em cardiomiócitos não é conhecido. Objetivos: Investigar o efeito da expressão de VEGF121 pós-hipóxia utilizando cardiomiócitos de ratos neonatos. Métodos: Cardiomiócitos isolados de ratos neonatos foram utilizados para estabelecer um modelo in vitro de lesão cardíaca induzida por hipóxia. O efeito da superexpressão de VEGF, isolado ou em conjunto com inibidores de moléculas pequenas que têm como alvo os canais de cálcio, receptores sensíveis ao cálcio (CaSR, do inglês calcium-sensitive receptors) e calpaína, no crescimento e proliferação celular em lesão de cardiomiócitos induzidos por hipóxia, foram determinados com ensaio de MTT, coloração TUNEL, coloração com Anexina V/PI, lactato desidrogenase e atividade da caspase. Para análise estatística, um valor de p

Li-Zhou Wang,1,* Xiao-Xia Hu,2,* Xiang-Chun Shen,2,3 Tian-Cheng Wang,4 Shi Zhou1 1Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2The State Laboratory of Functions and Application of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 4Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tian-Cheng WangDepartment of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaTel +86 15073190153Email 421176806@qq.comShi ZhouDepartment of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of ChinaTel +86 13809477708Email zhoushi@gmc.edu.cnObjective: To investigate the sustained release of lidocaine from a lidocaine–epirubicin–lipiodol emulsion created by water-in-oil (W/O) technique in vivo and evaluate the efficacy and safety of intraarterial lidocaine administration for intra- and postoperative pain control in transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Methods: The in vivo concentrations of lidocaine were determined in tumor tissues after VX2 rabbit models for hepatic tumor were administered with intra-arterial lidocaine–epirubicin–lipiodol emulsion. A prospective randomized controlled clinical trial was performed, enrolling 70 consecutive patients who underwent TACE. Patients were randomized into two groups: Group A received an immediate bolus intraarterial lidocaine injection before TACE, and Group B received a lidocaine–epirubicin–lipiodol emulsion during TACE. Pain intensity was compared between the two groups using a visual analog scale (VAS) score before (Tbefore) and at 0 h (T0), 4 h (T4), 8 h (T8), 24 h (T24), 48 h (T48), and 72 h (T72) after the procedure. Adverse events and intake of analgesics were evaluated and compared between the two groups.Results: The concentrations of lidocaine in tumor tissues were higher in experimental group than in control group at T0.5 (P=0.004), T1 (P=0.038), T4 (P=0.036), and T8 (P=0.029). In the clinical trial, VAS scores in Group B were significantly lower than in Group A at T0 (P=0.006), T4 (P=0.001), T8 (P=0.002), and T24 (P=0.005). The tramadol intake in Group B was significantly lower than in Group A (P=0.021). No significant difference was observed regarding the incidence of adverse events between the two groups.Conclusion: This study demonstrated the effectiveness and safety of intraarterial lidocaine administration using the W/O technique in controlling intra- and post-TACE pain.Keywords: carcinoma, hepatocellular, chemoembolization, therapeutic, lidocaine hydrochloride, pain management

In this study, fungal specimens of the family Diatrypaceae were collected from karst areas in Guizhou, Hainan and Yunnan Provinces, China. Morpho-molecular analyses confirmed that these new collections comprise a new genusPseudodiatrype, three new species (Diatrype lancangensis,Diatrypella pseudooregonensisandEutypa cerasi), a new combination (Diatrypella oregonensis), two new records (Allodiatrype thailandicaandDiatrypella vulgaris) from China and two other known species (Neoeutypella baoshanensisandParaeutypella citricola). The new taxa are introduced, based on multi-gene phylogenetic analyses (ITS, β-tubulin), as well as morphological analyses. The new genusPseudodiatrypeis characterised by its wart-like stromata with 5–20 ascomata immersed in one stroma and the endostroma composed of thin black outer and inner layers of large white cells with thin, powdery, yellowish cells. These characteristics separate this genus from two similar generaAllodiatrypeandDiatrype. Based on morphological as well as phylogenetic analyses,Diatrype lancangensisis introduced as a new species ofDiatrype. The stromata ofDiatrype lancangensisare similar to those ofD. subundulataandD. undulate, but the ascospores are larger. Based on phylogenetic analyses,Diatrype oregonensisis transferred to the genusDiatrypellaasDiatrypella oregonensiswhileDiatrypella pseudooregonensisis introduced as a new species ofDiatrypellawith 8 spores in an ascus. In addition, multi-gene phylogenetic analyses show thatEutypa cerasiis closely related toE. lata, but the ascomata and asci ofEutypa cerasiare smaller. The polyphyletic nature of some genera of Diatrypaceae has led to confusion in the classification of the family, thus we discuss whether the number of ascospores per asci can still be used as a basis for classification.

Purpose Oxymatrine, an alkaloid extracted from the Chinese herb Sophora flavescens Aiton, possesses anti-inflammatory, anti-immune, anti-hepatic fibrosis, and anti-cancer properties. However, the effects of oxymatrine on epithelial-mesenchymal transition (EMT) of breast cancer cells are still unclear. Aim The present study was performed to investigate whether oxymatrine reverses EMT in breast cancer cells and to explore the underlying molecular mechanisms. Materials and methods MTT assay was performed to evaluate cell viability. Wound-healing assay and transwell chamber assay were used to assess cell migration and invasion, respectively. Immunofluorescence and Western blot were used to study the expression of EMT-related molecules and αⅤβ3 integrin/focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling transduction. Fibronectin, a physiologic ligand of αⅤβ3 integrin, was used to stimulate αⅤβ3 integrin signaling. Results Our results demonstrated that oxymatrine effectively suppressed the viability of MDA-MB-231 and 4T1 breast cancer cells, and oxymatrine showed less cytotoxicity on normal breast mammary epithelial MCF-10A cells. In addition, oxymatrine reversed EMT in the MDA-MB-231 and 4T1 cells at nontoxic concentrations. Oxymatrine significantly inhibited cell migration and invasion, downregulated the expression of N-cadherin, vimentin, and Snail in MDA-MB-231 and 4T1 cells, but upregulated the expression of E-cadherin in 4T1 cells. The mechanism revealed that oxymatrine decreased the expression of αⅤ and β3 integrin and their co-localization. It also inhibited αⅤβ3 integrin downstream activation by suppressing the phosphorylation of FAK, PI3K, and Akt. Furthermore, oxymatrine prevented fibronectin-induced EMT and αⅤβ3 integrin/FAK/PI3K/Akt signaling activation. Conclusion Our results revealed that oxymatrine effectively reversed EMT in breast cancer cells by depressing αⅤβ3 integrin/FAK/PI3K/Akt signaling. Thus, oxymatrine could be a potential therapeutic candidate with anti-metastatic potential for the treatment of breast cancer.

Four Durotheca-like taxa have been collected from Guizhou Province, China. ITS, RPB2, LSU, and β-tubulin loci sequences were amplified and analyzed using maximum likelihood and Bayesian analyses. Phylogenetic analyses of a combined ITS, LSU, RPB2, and β-tubulin gene dataset showed that our strains were species of Durotheca. Both morphological and molecular evidence confirmed that two are new species, Durotheca crateriformis and Durotheca guizhouensis, while Durotheca eurima (≡ Theissenia eurima) is a new record for China. Durotheca rogersii (≡ Theissenia rogersii) is a new record for Chinese mainland. Durotheca crateriformis differs from other species by its ascospores (13.5 × 5.5 μm) and crater-shaped ostioles. D. guizhouensis has unique smaller ascospores (10.5 × 4 μm). All new collections are illustrated and morphological descriptions are provided.

Inflammatory bowel disease (IBD) is an uncontrolled chronic inflammatory intestinal disorder, which requires medications for long-term therapy. Facing the challenges of severe side effects and drug resistance of conventional medications, to develop the strategies meet the stringent safety and effectiveness in the long-term treatment are urgent in the clinics. In this regard, a growing body of evidence confirms plant-sourced phenols, such as flavonoids, catechins, stilbenes, coumarins, quinones, lignans, phenylethanoids, cannabinoid phenols, tannins, phenolic acids and hydroxyphenols, exert potent protective benefits with fewer undesirable effects in conditions of acute or chronic intestinal inflammation through improvement of colonic oxidative and pro-inflammatory status, preservation of the epithelial barrier function and modulation of gut microbiota. In this review, the great potential of plant-sourced phenols and their action mechanisms for the treatment or prevention of IBD in recent research are summarized, which may help further development of new preventive/adjuvant regimens for IBD.

Three species possessing characteristics of Graphostromataceae were observed in China. Morphology of the described species with illustrations and their phylogeny based on regions of internal transcribed spacers (ITS), the second largest subunit of the RNA polymerase II (RPB2), β-tubulin (TUB2) and α-actin (ACT) are provided. Two new species and one new record from China were identified. Morphologically, Biscogniauxia glaucae sp. nov. differs from B. atropunctata var. maritima, B. citriformis var. macrospora, B. fuscella and B. mediterranea by its stromata with raised margins, with clear outlines, with punctate ostioles openings and ascospores which are equilateral with broadly rounded ends, with a straight germ slit on the more concave side, nearly full spore length, lacking appendages and sheathes. ITS sequence difference between Graphostroma guizhouensis sp. nov and type strain of G. platystomum is 7%, which support identifying it as a new species. Camillea broomeana with scanning electron microscope description of ascospores was illustrated as a new record from China. Cryptostroma was proposed in Graphostromataceae based on molecular data. Vivantia was accepted in Graphostromataceae based on its morphological characteristics and Nodulisporiurn anamorphs which is similar with that of Biscogniauxia.

Background: Endothelial Mesenchymal Transformation (EndMT) contributes to the development of cardiovascular disease. Krüpple factor 4 (KLF4) is a zinc finger transcription factor whose N-terminus can recruit acetyltransferase to promote histone acetylation, thereby affecting the transcription activation of downstream genes. Our previous studies have shown that EOFAZ has protective effects on HUVECs oxidative stress induced by TGF-β1. However, whether EOFAZ has a protective effect on EndMT induced by TGF-β1 and whether it is related to the regulation of downstream signals by KLF4 has not yet been elucidated.Methods: The protective effects of EOFAZ were evaluated in TGF-β1-treated EndMT in Human umbilical vein endothelial cells (HUVECs). Cell mobility was evaluated by wound-healing, transwell assays and angiogenesis experiment. Western blot analysis, Quantitative real-time PCR analysis (qRT-PCR) and immunofluorescence staining were utilized to determine the expression of endothelial and mesenchymal markers , KLF4, Histone 3 acetylation and Notch/Snail signaling axis. Small interfering RNA (siRNA) and adenovirus infection were used to determine the effciency of KLF4 inhibition and overexpression. Immunoprecipitation experiments were performed to analyze protein interactions.Results: We reported that EOFAZ has a protective effect on EndMT induced by TGF-β1. Deletion of KLF4 inhibited EndMT induced by TGF-β1 in HUVECs. EOFAZ pretreatment and KLF4 knockout reduced the migration ability of HUVECs , and increased endothelial markers accompanied by decreased mesenchymal markers, meanwhile caused the change of Notch/Snail signal axis. In addition, TGF-β1 upregulated the expression of KLF4, while the high expression of KLF4 promoted the acetylation of histone H3, and there was a protein interaction between the acetylated histone H3 and KLF4. Conclusions: These results suggest that TGF-β1 may promote the acetylation of histone H3 and activate the transduction of Notch/Snail signal axis by up-regulating the expression of KLF4, which may induce EndMT and this effect may be reversed by EOFAZ. Therefore, EOFAZ may inhibit EndMT induced by TGF-β1 by down-regulating KLF4 expression.

1,8-Cineole (also known as eucalyptol) is mostly extracted from the essential oils of plants, which showed extensively pharmacological properties including anti-inflammatory and antioxidant mainly via the regulation on NF-κB and Nrf2, and was used for the treatment of respiratory diseases and cardiovascular, etc. Although various administration routes have been used in the application of 1.8-cineole, few formulations have been developed to improve its stability and bioavailability. This review retrospects the researches on the source, biological activities, mechanisms, and application of 1,8-cineole since 2000, which provides a view for the further studies on the application and formulations of 1,8-cineole.

Background The couplet Medicinals, Gastrodia Elata and Radix Aconitic Lateralis preparata (GERA), is an established formula extensively used in Chinese medicine for treating rheumatoid arthritis (RA). However, the anti-RA mechanisms of GERA are still unclear. This paper aims to explore the anti-RA mechanisms of GERA by a combined strategy of untargeted metabolomics and network pharmacology. Methods Three water extracts were prepared as propotions: Gastrodia Elata compared with Radix Aconitic Lateralis (w/w): 1:1, 3:2, or 2:3. The untargeted metabolomics were executed with UPLC-MS. The metabolites were annotated and identified by Human metabolome database (HMDB) and Lipid maps database. Finally, key genes and pathways related to anti-RA activities of GERA were mined by network pharmacology. Results The untargeted metabolomics profile displayed that four differentially expressed metabolites were involved in isoflavonoid biosynthesis and biosynthesis of unsaturated fatty acids (p

This study aimed at investigating the cytoprotective effect of an ethyl acetate extract of insect fungi against high glucose- (HG-) induced oxidative damage in human umbilical vein endothelial cells (HUVECs). An insect fungus strain termed CH180672 (CH) was found for protecting HUVECs from HG-induced damage. In this study, CH was identified as Simplicillium sp. based on a phylogenetic analysis of ITS‐rDNA sequences. Ethyl acetate extract (EtOAc) of this strain (CH) was subjected to the following experiments. Cell viability was examined with the MTT method. To evaluate the protection of CH, intracellular reactive oxygen species (ROS), malondialdehyde (MDA) levels, and the activities of antioxidant enzymes were measured and the expression of oxidation-associated proteins was assessed. In the current study, it has been found that CH can increase the survival rate of HUVECs induced by HG. Additionally, we found that HG-induced nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) signal decreased and increased the intracellular ROS and MDA generation in HUVECs. However, CH treatment strongly promoted the translocation of Nrf2 and its transregulation on HO-1 and ultimately inhibited the high level of ROS and MDA induced by HG. The regulatory ability of CH was similar to Nrf2 agonist bardoxolone, while the effect was abolished by ML385, suggesting that Nrf2 mediated the inhibition of CH on HG-induced oxidative stress in HUVECs. Taken together, CH can improve HG-induced oxidative damage of HUVECs, and its mechanism may be related to the regulation of the Nrf2/HO-1 pathway.

Vascular dementia (VD) is a common disease that occurs during human aging. Gastrodin (GAS) has potential benefits for the prevention and treatment of VD. In the present study, we investigated the effects of GAS on cognitive dysfunction in rats with VD induced by permanent middle cerebral artery occlusion (pMCAO) and explored the underlying mechanism. Immunohistochemical and western blot analyses revealed that GAS attenuated hippocampal levels of LC3 (microtubule-associated protein 1 light chain 3), p62, and phosphorylated CaMKII (Ca2+-calmodulin stimulated protein kinase II) in VD rats. Additionally, our results revealed that cobalt chloride blocked autophagic flux in HT22 cells, which was confirmed by increased levels of LC3 and p62 when combined with chloroquine. Notably, GAS ameliorated the impaired autophagic flux. Furthermore, we confirmed that GAS combined with KN93 (a CaMKII inhibitor) or CaMKII knockdown did not impact the reduced p62 levels when compared with GAS treatment alone. Furthermore, a co-immunoprecipitation assay demonstrated that endogenous p62 bound to CaMKII, as confirmed by mass spectrometric analysis after the immunoprecipitation of p62 from HT22 cells. These findings revealed that GAS attenuated autophagic flux dysfunction by inhibiting the Ca2+/CaMKII signaling pathway to ameliorate cognitive impairment in VD.