Organocatalytic Enantioselective Chloroiminocyclization for the Synthesis of Imidazoline.

Imidazoline is an important scaffold in organic synthesis and a pharmacophore in medicinal chemistry. We apply basic imines as nucleophiles for the catalytic asymmetric chloroiminocyclization to furnish tetrasubstituted stereocenter-containing imidazolines in excellent yields and enantioselectivities. The reaction can be conducted in the polar solvent acetonitrile under concentrated reaction conditions.

Cellular senescence of renal tubular epithelial cells in renal fibrosis.

Renal fibrosis (RF) is the common pathological manifestation of virtually all chronic kidney diseases (CKD) and one of the major causes of end-stage renal disease (ESRD), but the pathogenesis of which is still unclear. Renal tubulointerstitial lesions have been identified as a key pathological hallmark of RF pathology. Renal tubular epithelial cells are the resident cells of the tubulointerstitium and play an important role in kidney recovery versus renal fibrosis following injury. Studies in recent years have shown that senescence of renal tubular epithelial cells can accelerate the progression of renal fibrosis. Oxidative stress(OS), telomere attrition and DNA damage are the major causes of renal tubular epithelial cell senescence. Current interventions and therapeutic strategies for cellular senescence include calorie restriction and routine exercise, Klotho, senolytics, senostatics, and other related drugs. This paper provides an overview of the mechanisms and the key signaling pathways including Wnt/ß-catenin/RAS, Nrf2/ARE and STAT-3/NF-κB pathway involved in renal tubular epithelial cell senescence in RF and therapies targeting renal tubular epithelial cell senescence future therapeutic potential for RF patients. These findings may offer promise for the further treatment of RF and CKD.

[Research Progress of SOA Formation from Anthropogenic VOCs Under Complex Pollution Condition].

Although the air quality in China has been greatly improved in recent years, the air pollution remains severe. The annual mean PM2.5 concentrations have not met the second grade of the National Ambient Air Quality Standards in China and are still much higher than the guideline value of the World Health Organization. Thus, the PM2.5 concentration needs to be further reduced. Secondary organic aerosol (SOA) is an important component of PM2.5 and has an important impact on air quality, global climate change, and human health. Therefore, understanding the formation mechanism of SOA is an important basis to control SOA and further reduce PM2.5. As an important precursor of SOA, volatile organic compounds (VOCs) can be oxidized by oxidants such as ·OH, NO3[KG-*2/3]·, Cl·, and O3 to generate low volatile organic compounds and further to form SOA through gas-particle partitioning, homogeneous nucleation, aqueous phase reaction, and heterogeneous reaction processes. The formation of SOA can be affected by many factors, such as the types and initial concentrations of VOCs, VOCs/NOx ratios, relative humidity (RH), temperature (T), seed aerosols, oxidants, aqueous phase process, and photochemical process. The observed SOA concentration is always underestimated by air quality models because a comprehensive understanding of the complexity of SOA chemical composition and formation mechanisms is still lacking, especially that under the highly complex air pollution conditions in China. Therefore, the formation mechanism and influencing factors of SOA under highly complex air pollution conditions have become an important concern in the field of atmospheric sciences. Recently, much laboratory work has focused on the formation of SOA under complex conditions. The research progress of SOA formation from different anthropogenic VOCs are reviewed here, and the methods used and the impact of different influencing factors on SOA formation are introduced. Finally, the key scientific issues that exist in the research of the SOA mechanism at present are put forward, and the future research direction is projected.

Anti-apoptotic effect of HeidihuangWan in renal tubular epithelial cells via PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Heidihuang Wan (HDHW) is a classic Chinese herbal formula, which was first recorded in the "Suwen Bingji Qiyi Baoming Collection" written by Liu Wansu during the Jin Dynasty (1115-1234 AD). It is commonly used clinically for the treatment of kidney diseases and its curative effect is stable. Previous animal experiments have confirmed that HDHW can effectively improve renal fibrosis. However, the underlying pharmacological mechanism remains unclear. AIMS OF THIS STUDY: Renal tubular epithelial cell (RTEC) apoptosis is one of the main pathological features of renal fibrosis. This study aimed to observe the effect and underlying mechanism of HDHW on the apoptosis of RTECs to further explore the pathological mechanism of HDHW against renal fibrosis. MATERIALS AND METHODS: We examined the HDHW composition in rat serum. In vitro, we first screened out the optimal intervention concentration of HDHW on RTECs using the MTT assay. Hypoxia/reoxygenation was then used to induce apoptosis of RTECs (H/R-RTECs), which were divided into H/R-RTEC, astragaloside IV (positive control), HDHW, and RTECs groups. After 48 h of drug intervention, apoptosis of RTECs was detected using flow cytometry and protein expression was detected by western blotting. The 5/6 nephrectomy rat model was constructed and divided into the normal control, 5/6 nephrectomy, HDHW, and astragaloside IV groups. After 8 weeks of treatment, TUNEL staining was used to detect cell apoptosis, and western blotting was used to detect protein expression. RESULTS: HDHW downregulated the expression of pro-apoptotic proteins Bax and Caspase3, up-regulated the expression of anti-apoptotic protein Bcl-2, activated the PI3K/Akt/mTOR signaling pathway, and reversed the early apoptosis of RTECs, thereby resisting the apoptosis of RTECs. CONCLUSION: HDHW inhibits apoptosis of RTECs by modulating the PI3K/Akt/mTOR signaling pathway. This study provides experimental evidence for the anti-fibrotic effect of HDHW on the kidneys and partially elucidates its pharmacological mechanism of action.

Component analysis and network pharmacology of flavonoids in Sophora flavescens tissues at anthesis / 药学学报

italic>Sophora flavescens is a traditional Chinese medicine rich in flavonoids and has wide application potential in drug development and clinical practice. In this study, a total of 227 flavonoids were detected among five tissues of S. flavescens during anthesis using widely targeted metabolomics techniques. There were 137 flavonoids shared by five S. flavescens tissues and 18 root-specific flavonoids. There were 156, 155, 156 and 150 differentially accumulated metabolites identified in stem, leaf, flower, and young pod, respectively, compared with root. Forty-seven potentially active flavonoid components in S. flavescens were identified using the PubChem and SwissADME databases. The 58 potential target proteins for these potentially active components were predicted to be important in the treatment of type 2 diabetes mellitus (T2DM) based on the SwissTargetPrediction and GeneCards database. These 58 target proteins were used to construct a protein-protein interaction network through the STRING database, from which we performed GO and KEGG functional enrichment analysis. The mechanisms by which S. flavescens flavonoids may be useful in the treatment of T2DM was further explored in a multi-level and systematic way based on a "component-target-pathway" network. Finally, ten key potentially effective components were identified and found to be mainly distributed in the roots, flowers, and pods, and their content varied significantly between tissues. The results predict that the key targets of S. flavescens flavonoids in the treatment of T2DM are AKT1, ESR1, EGFR, PIK3R1, TNF and PTGS2, and that they play a hypoglycemic role through the regulation of endocrine resistance, AGE-RAGE, the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance and other signaling pathways. This analysis of the tissue distribution and network pharmacology of S. flavescens flavonoids provides a theoretical basis for further studies on S. flavescens metabolites, the rational development and utilization of the S. flavescens aboveground parts, and initiates a comprehensive exploration of the mechanisms by which S. flavescens can be used in the treatment of T2DM.

Heidihuangwan alleviates renal fibrosis in rats with 5/6 nephrectomy by inhibiting autophagy.

Renal fibrosis is a common pathway for the progression of various chronic kidney diseases (CKD), and the formation and deterioration will eventually lead to end-stage renal failure, which brings a heavy medical burden to the world. HeidihuangWan (HDHW) is a herbal formulation with stable and reliable clinical efficacy in the treatment of renal fibrosis. However, the mechanism of HDHW in treating renal fibrosis is not clear. In this study, we aimed to investigate the mechanism of HDHW to improve renal fibrosis. Wistar rats were randomly divided into the normal control group, 5/6 Nephrectomy group, astragaloside IV (AS-IV) group, HDHW group, and HDHW + IGF-1R inhibitor (JB1) group. Except for the normal control group, the rat renal fibrosis model was established by 5/6 nephrectomy and intervened with drugs for 8 weeks. Blood samples were collected to evaluate renal function. Hematoxylin-Eosin (HE), Periodic Acid-Schiff (PAS), Modified Masson's Trichrome (Masson) staining were used to evaluate the pathological renal injury, and immunohistochemistry and Western blotting were used to detect the protein expression of renal tissue. The results showed that HDHW was effective in improving renal function and reducing renal pathological damage. HDHW down-regulated the levels of fibrosis marker proteins, including α-smooth muscle actin (α-SMA), vimentin, and transforming growth factors-ß(TGF-ß), which in turn reduced renal fibrosis. Further studies showed that HDHW down-regulated the expression of autophagy-related proteins Beclin1 and LC3II, indicating that HDHW inhibited autophagy. In addition, we examined the activity of the class I phosphatidylinositol-3 kinase (PI3K)/serine-threonine kinase (Akt)/mTOR pathway, an important signaling pathway regulating autophagy, and the level of insulin-like growth factor 1 (IGF-1), an upstream activator of PI3K/Akt/mTOR. HDHW upregulated the expression of IGF-1 and activated the PI3K/Akt/mTOR pathway, which may be a vital pathway for its inhibition of autophagy. Application of insulin-like growth factor 1 receptor (IGF-1R) inhibitor further confirmed that the regulation of autophagy and renal fibrosis by HDHW was associated with IGF-1-mediated activation of the PI3K/Akt/mTOR pathway. In conclusion, our study showed that HDHW inhibited autophagy by upregulating IGF-1 expression, promoting the binding of IGF-1 to IGF-1R, and activating the PI3K/Akt/mTOR signaling pathway, thereby reducing renal fibrosis and protecting renal function. This study provides support for the application and further study of HDHW.

Three new sesquiterpene polyol esters from Celastrus angulatus.

Three new sesquiterpene polyol ester compounds angulatins S-U, together with three known compounds were isolated from Celastrus angulatus Maxim. According to mainly 1D NMR and 2D NMR analysis, the structures of the new compounds were completely determined as angulatin S (1ß-furoyloxy-2ß,8α-diisobutanoyloxy-9ß-benzoyloxy-15-acetoxy-4α,6α-dihydroxy-ß-dihydroagarofuran), angulatin T (1ß,2ß,6α-triacetoxy-8ß,15-diisobutanoyloxy-9α-benzoyloxy-ß-dihydroagrofuran), and angulatin U (1ß,6α,15-triacetoxy-8ß-isobutanoyloxy-9α-benzoyloxy-ß-dihydroagarofuran).

Correlation Between Functional Components in Codonopsis pilosula Roots and Soil Factors / 中国实验方剂学杂志

ObjectiveTo explore the correlation between the content of 4 functional components in Codonopsis pilosula roots from different areas and soil factors， and thereby to lay a theoretical basis for soil ecological regulation and improvement of quality of C. pilosula roots. MethodThe content of lobetyolin， atractylenolide Ⅲ， alcohol extract， and polysaccharides， as well as soil fertility and 16 soil factors in 24 batches of samples from different producing areas were determined. Principal component analysis （PCA） and Pearson's correlation analysis were used to explore the key soil factors leading to the variation of chemical component content in C. pilosula roots. ResultThe content of lobetyolin and atractylenolide Ⅲ in samples from Longxi was the highest， and the content of polysaccharides peaked in samples from Huguan. The content of lobetyolin was in positive correlation with soil total nitrogen， total phosphorus， total potassium， alkali-hydrolyzable nitrogen， and available potassium （P<0.01）， as well as soil organic matter， pH， available manganese， and available zinc （P<0.05）. There was a positive correlation between pH and atractylenolide Ⅲ content （P<0.05）. Soil total potassium was in positive correlation with alcohol extract and polysaccharide content （P<0.01）. Soil available zinc was positively correlated with alcohol extract and the polysaccharide content （P<0.05）. Sample sites with higher PCA scores were Pingshun， Huguan， and Longxi， which were significantly positively correlated with the content of polysaccharides in C. pilosula roots in different habitats. ConclusionThe content of functional components in C. pilosula roots can be improved by raising soil organic matter content and applying specific fertilizers.

The essential roles of Mps1 in spermatogenesis and fertility in mice.

Monopolar spindle 1 (MPS1), which plays a critical role in somatic mitosis, has also been revealed to be essential for meiosis I in oocytes. Spermatogenesis is an important process involving successive mitosis and meiosis, but the function of MPS1 in spermatogenesis remains unclear. Here, we generated Mps1 conditional knockout mice and found that Ddx4-cre-driven loss of Mps1 in male mice resulted in depletion of undifferentiated spermatogonial cells and subsequently of differentiated spermatogonia and spermatocytes. In addition, Stra8-cre-driven ablation of Mps1 in male mice led to germ cell loss and fertility reduction. Spermatocytes lacking Mps1 have blocked at the zygotene-to-pachytene transition in the prophase of meiosis I, which may be due to decreased H2B ubiquitination level mediated by MDM2. And the expression of many meiotic genes was decreased, while that of apoptotic genes was increased. Moreover, we also detected increased apoptosis in spermatocytes with Mps1 knockout, which may have been the reason why germ cells were lost. Taken together, our findings indicate that MPS1 is required for mitosis of gonocytes and spermatogonia, differentiation of undifferentiated spermatogonia, and progression of meiosis I in spermatocytes.

Preparation of Boronic Acid-Functionalized Silica Nanocomposites for Selective Enrichment of Glycoproteins.

A facile method was developed for synthesis of boronic acid-functionalized silica nanocomposites (SiO2 -BA) by 'thiol-ene' click reaction, where silica nanoparticles were synthesized by using tetraethoxysilane (TEOS) and γ-mercaptopropyl trimethoxysilane (γ-MPTS) as precursors. The morphology and structure properties of the resultant SiO2 -BA were characterized by transmission electronic microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and Brunner-Emmet-Teller measurements (BET). The adsorption behavior of the SiO2 -BA for glycoproteins was evaluated. Under the optimized conditions, the SiO2 -BA exhibited higher adsorption capacity towards glycoproteins (ovalbumin, OVA, 7.64 µmol/g) than non-glycoproteins (bovine serum albumin, BSA, 0.83 µmol/g). In addition, the practicality of the SiO2 -BA was further assessed by selective enrichment of glycoproteins from egg white samples.

Effects of Saccharomyces cerevisiae on alleviating cytotoxicity of porcine jejunal epithelia cells induced by deoxynivalenol.

Deoxynivalenol (DON) is one of the mycotoxins most frequently encountering in cereal-based foods throughout the world. Saccharomyces cerevisiae was used to alleviate porcine jejunal epithelia cell (IPEC-J2) injury induced by DON in this study. The results indicated that cell viability and proliferation rates were significantly decreased when DON concentrations were increased from 0 to 64 µM after 24 h incubation (p < 0.05). The longer incubation time and higher DON concentrations would cause more serious effects on cell viability. S. cerevisiae could significantly degrade DON and decrease lactic dehydrogenase (LDH) release in the cells induced by DON (p < 0.05). DON (4 µM) could increase necrotic and apoptotic cell rates as well as decrease viable cell rates, compared with the control group (p < 0.05). However, S. cerevisiae addition in the DON group could decrease necrotic, late apoptotic and early apoptotic cell rates by 38.05%, 46.37% and 44.78% respectively, increase viable cell rates by 2.35%, compared with the single DON group (p < 0.05). In addition, S. cerevisiae addition could up-regulate mRNA abundances of IL-6, IL-8 and IL-10 in IPEC-J2 cells (p < 0.05), but down-regulate mRNA abundances of tight junction proteins (TJP-1) and occludin by 36.13% and 50.18% at 1 µM of DON (p < 0.05). It could be concluded that S. cerevisiae was able to alleviate IPEC-J2 cell damage exposed to DON.

Two new sesquiterpene pyridine alkaloids from root barks of Celastrus angulatus.

Two new sesquiterpene pyridine alkaloids, Chinese bittersweet alkaloid A (1) and Chinese bittersweet alkaloid B (2), together with five known compounds 3ß- hydroxyolean-9(11),12-diene, ß-sitosterol, 1ß,2ß,6α,15ß-tetraacetoxy-8ß,9α- dibenzoyloxy-ß-dihydroagarofuran, angulatin A and angulatin J, were isolated from the root barks of Celastrus angulatus. The structures of 1 and 2 were elucidated as 1ß,6α,8ß,9ß-tetraacetoxy-2ß,4α-dihydroxy-15ß-isobutanoyloxy-(3,12)-evoninoyloxy-ß-dihydroagarofuran and 1ß,2ß,6α,8ß,9ß-pentaacetoxy-4α-hydroxy-15ß- isobutanoyloxy- (3,12)- evoninoyloxy-ß-dihydroagarofuran mainly by NMR spectroscopic means.

Establishment of HPLC Fingerprint and Principal Component Analysis of Xiaojin Capsules / 中国药房

OBJECTIVE： To establish HPLC fingerprint of Xiaojin capsules， and to conduct principal component analysis. METHODS： HPLC method was adopted. The determination was performed on Agilent TC-C18（2） column with mobile phase consisted of acetonitrile-0.2％ formic acid solution （gradient elution） at the flow rate of 1.0 mL/min. The detection wavelength was 240 nm， and column temperature was 25 ℃. The sample size was 20 μL. Acetyl-11-keto-β-boswellic acid was used as reference and HPLC fingerprints of 15 batches of Xiaojin capsules were determined. The similarity evaluation of common peaks was conducted by using the TCM Chromatographic Fingerprint Similarity Evaluation System （2004A edition） to confirm common peaks. Principal component analysis was conducted by using Minitab 17.0 software. RESULTS： The similarity of 1 batch of sample was lower than 0.800； there was no common peaks No. 13， 14， 15 in HPLC chromatogram of the batch， compared with other 14 batches. There were 15 common peaks in the HPLC fingerprints of 14 batches of samples and three chromatographic peaks were identified， such as quercetin，amentoflavone， acetyl-11-keto-β-boswellic acid. The similarity of 14 batches ranged 0.889-0.990. Through principal component analysis， accumulative contribution rate of 2 principal component factors was 94.4％. It was indicated that the content change of corresponding components of common peaks No. 8， 9， 11， 12， 14 in samples was an important reason for the quality difference of samples， especially common peaks No.8， 9. CONCLUSIONS： The established HPLC fingerprint and principal component analysis can provide reference for quality evaluation of Xiaojin capsules.

[VOCs Emission from Motor Vehicles in China and Its Impact on the Atmospheric Environment].

Volatile organic compounds (VOCs) are important precursors of O3 and secondary organic aerosols (SOAs). In order to fully understand the impacts of VOCs from motor vehicles on urban air quality, the current state-of-the-art research results on source apportionment are systematically introduced. The contribution of VOCs from motor vehicles to secondary pollutants in China is further discussed. It was found that motor vehicle exhaust is the largest source of urban atmospheric VOCs, and the average contribution ratio is up to 36.8%, wherein motorcycles and light gasoline vehicles are the main emission sources. The results showed that VOCs from vehicles play an important role in O3 and SOA formation in urban areas, whereas with the improvement of emission standards and operating conditions, the motor vehicle emission factors and ozone formation potentials (OFPs) are obviously reduced. Moreover, the composition profile of the exhaust is mainly composed of aromatic hydrocarbons and alkenes, which contribute more to secondary pollution. This work can aid in providing data and theoretical support for the control of VOCs from motor vehicles in the future.

Characterization of the complete mitochondrial genome of band-rumped Storm-petrel, Hydrobates castro.

In this study, the complete mitochondrial genome of band-rumped Storm-petrel, Hydrobates castro, was determined through sequencing of PCR fragments. The complete mitochondrial genome of H. castro was 17,065 bp in length and encoded 13 protein-coding genes, 22 transfer RNA (tRNA) genes, and two ribosomal RNA genes. The overall nucleotide composition is: 30.4% A, 24.5% T, 30.9% C, and 14.2% G, with a total G + C content of 45.1%. By phylogenetic analysis using Bayes method, H. castro showed the closest relationship with the white-faced storm petrel (Pelagodroma marina).

miR-101a targeting EZH2 promotes the differentiation of goat skeletal muscle satellite cells.

miR-101a promotes the differentiation of goat skeletal muscle satellite cells (SMSCs), as we previously reported, but the underpinning mechanism remains to be illuminated. In this study, we predicted the target gene of miR-101a by employing online softwares PicTar, TargetScan and miRanda, and found that enhancer of zeste homologue 2 (EZH2) was targeted by miR-101a. Further we identified that EZH2 contained miR-101a binding sites at its 3'UTR by using the dual-luciferase reporter assay system. In addition, we showed that during SMSC differentiation, the downregulated levels of EZH2 mRNA and protein were accompanied by increasing miR-101a expression via qRT-PCR and Western blot. Additionally, the expression of EZH2 significantly increased (P<0.01) when miR-101a was suppressed, whereas overexpressing miR-101a almost had no effect on EZH2 expression (P>0.05). These data demonstrated that miR-101a promotes SMSC differentiation directly through EZH2, which provides a theoretical reference for further elucidating the mechanism of miR-101a in SMSC differentiation.

Gliding locomotion of manta rays, killer whales and swordfish near the water surface.

The hydrodynamic performance of the locomotive near the water surface is impacted by its geometrical shape. For marine animals, their geometrical shape is naturally selective; thus, investigating gliding locomotion of marine animal under the water surface may be able to elucidate the influence of the geometrical shape. We investigate three marine animals with specific geometries: the killer whale is fusiform shaped; the manta ray is flat and broad-winged; and the swordfish is best streamlined. The numerical results are validated by the measured drag coefficients of the manta ray model in a towing tank. The friction drag of the three target models are very similar; the body shape affected form drag coefficient is order as swordfish < killer whale < manta ray; the induced wave breaking upon the body of the manta ray performs different to killer whale and swordfish. These bio-inspired observations provide a new and in-depth understanding of the shape effects on the hydrodynamic performances near the free surface.

Hydrodynamic analysis of human swimming based on VOF method.

A 3-D numerical model, based on the Navier-Strokes equations and the RNG k-ε turbulence closure, for studying hydrodynamic drag on a swimmer with wave-making resistance taken into account is established. The volume of fluid method is employed to capture the undulation of the free surface. The simulation strategy is evaluated by comparison of the computed results with experimental data. The computed results are in good agreement with data from mannequin towing experiments. The effects of the swimmer's head position and gliding depth on the drag force at different velocities are then investigated. It is found that keeping the head aligned with the body is the optimal posture in streamlined gliding. Also wave-making resistance is significant within 0.3 m depth from the free surface.

Neural stem cell transplantation for the treatment of primary torsion dystonia: A case report.

Primary torsion dystonia (PTD) occurs due to a genetic mutation and often advances gradually. Currently, there is no therapy available that is able to inhibit progression. Neural stem cells (NSCs) are being investigated as potential therapies for neurodegenerative diseases, such as stroke and trauma. The present study evaluated the clinical effectiveness of NSC transplantation in an 18-year-old male patient with PTD, to assess the ability of this therapy to inhibit PTD progression. Genetic testing of the patient revealed a mutation in the torsion dystonia-1 (DYT1) gene (907-909 delGAG). NSCs were bilaterally implanted in the globus pallidus of the patient through stereotactic surgery. Prior to surgery, the patient's Burke-Fahn-Marsden dystonia movement score (BFMDMS) was 21, which progressively decreased after surgery to 18, 17, 15 and 13 at 1, 2, 3 and 4 postoperative years, respectively. BFMDMS was improved by 38.1% over the 4 postoperative years. Although computed tomography and magnetic resonance imaging examinations showed no significant changes prior to and following surgery, postoperative brain positron emission tomography scans revealed increased glucose metabolism in the transplanted region. The clinical efficacy of NSC transplantation in this patient suggests its potential for the treatment of DYT1-positive patients with PTD.

Extracellular α-synuclein--a possible initiator of inflammation in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease involving the loss of dopamine-producing neurons of the substantia nigra and the presence of Lewy bodies which contain high levels of α-synuclein. Although the causative factors of PD remain unclear, the progression of PD is accompanied by a highly localized inflammatory response mediated by reactive microglia. Recently, attention has focused on the relationship between α-synuclein and microglial activation. This review examines the role of α-synuclein on microglia in PD pathogenesis and progression, we also discuss the way of α-synuclein induced microglial activation.