Cobaltaelectro-Catalyzed C-H Activation for Central and Axial Double Enantio-Induction.

In recent years, enantioselective electrocatalysis has surfaced as an increasingly-effective platform for sustainable molecular synthesis. Despite indisputable progress, strategies that allow the control of two distinct stereogenic elements with high selectivity remain elusive. In contrast, we, herein, describe electrochemical cobalt-catalyzed C-H activations that enable the installation of chiral stereogenic centers along with a chiral axis with high levels of enantio- and diastereoselectivities. The developed electrocatalysis strategy allowed for C-H/N-H activations/annulations with cyclic and non-cyclic alkenes providing expedient access to various central as well as atropo-chiral dihydroisoquinolinones paired to the valuable hydrogen evolution reaction. Studies on the atropo-stability of the obtained compounds demonstrated that the exceedingly mild conditions ensured by the electrocatalytic process were key for the achieved high stereoselectivities.

[Chemical constituents, pharmacological activities, processing and clinical application of traditional Chinese medicine Scrophulariae Radix: a review].

Traditional Chinese medicine Scrophulariae Radix, which is also called Yuan Shen, black Shen, is the dried root of Scrophularia ningpoensis of the Scrophulariaceae family. Research has indicated that the chemical constituents of Scrophulariae Radix mainly include terpenoids, phenylpropanoids, organic acids, volatile oils, steroids, sugars, flavonoids, alkaloids and phenols, among which iridoids and phenylpropanoids were the main active constituents. It has been reported that extracts of Scrophulariae Radix or its active substances have anti-inflammatory, antioxidant, hepatoprotective, anti-tumor, anti-fatigue, uric acid-lowering, anti-depression, myocardial cell-protective and other pharmacological activities, and can regulate cardiovascular system, central nervous system and immune system. This paper reviewed the present research achievements of Scrophulariae Radix in chemical constituents, pharmacological activities, processing methods, toxicity and other aspects, and the clinical application of Scrophulariae Radix in ancient and modern times was illustrated. This paper aimed to provide reference for further research of Scrophulariae Radix and facilitated its clinical application.

Absorbable Artificial Dura Versus Nonabsorbable Artificial Dura in Decompressive Craniectomy for Severe Traumatic Brain Injury: A Retrospective Cohort Study in Two Centers.

Background: Severe traumatic brain injury (TBI) patients usually need decompressive craniectomy (DC) to decrease intracranial pressure. Duraplasty is an important step in DC with various dura substitute choices. This study aims to compare absorbable dura with nonabsorbable dura in duraplasty for severe TBI patients. Methods: One hundred and three severe TBI patients who underwent DC and dura repair were included in this study. Thirty-nine cases used absorbable artificial dura (DuraMax) and 64 cases used nonabsorbable artificial dura (NormalGEN). Postoperative complications, mortality and Karnofsky Performance Scale (KPS) score in one year were compared in both groups. Results: Absorbable dura group had higher complication rates in transcalvarial cerebral herniation (TCH) (43.59% in absorbable dura group vs. 17.19% in nonabsorbable dura group, P = 0.003) and CSF leakage (15.38% in absorbable dura group vs. 1.56% in nonabsorbable dura group, P = 0.021). But severity of TCH described with hernial distance and herniation volume demonstrated no difference in both groups. There was no statistically significant difference in rates of postoperative intracranial infection, hematoma progression, secondary operation, hydrocephalus, subdural hygroma and seizure in both groups. KPS score in absorbable dura group (37.95 ± 28.58) was statistically higher than nonabsorbable dura group (49.05 ± 24.85) in one year after operation (P = 0.040), while no difference was found in the rate of functional independence (KPS ≥ 70). Besides, among all patients in this study, TCH patients had a higher mortality rate (P = 0.008), lower KPS scores (P < 0.001) and lower functionally independent rate (P = 0.049) in one year after surgery than patients without TCH. Conclusions: In terms of artificial biological dura, nonabsorbable dura is superior to absorbable dura in treatment of severe TBI patients with DC. Suturable nonabsorbable dura has fewer complications of TCH and CFS leakage, and manifest lower mortality and better prognosis. Postoperative TCH is an important complication in severe TBI which usually leads to a poor prognosis.

Electroacupuncture Prevents Osteoarthritis of High-Fat Diet-Induced Obese Rats.

The effects of acupuncture on osteoarthritis (OA) pathogenesis have been demonstrated in vitro and in animal models. However, the potential for acupuncture to mediate protective effects on obese-induced OA has not been examined. Here, we investigated the effects of different acupuncture patterns on OA pathogenesis in high-fat diet- (HFD-) induced obese rats. After 12-week diet-induced obesity, obese rats were treated with three acupuncture protocols for 2 weeks, including ST36, GB34, and ST36+GB34. The results showed that the three acupuncture protocols both prevented obesity-induced cartilage matrix degradation and MMP expression and mitigated obesity-induced systemic and local inflammation but had different regulatory effects on lipid metabolism and gut microbiota disorder of obese-induced OA rats. Furthermore, the three acupuncture protocols increased the microbial diversity and altered the structure of community of feces in obese rats. We found that ST36 and GB34 could inhibit proinflammatory shift in the gut microbiome with an increase in the ratio of Bacteroidetes/Firmicutes and promote the recovery of relative abundance of Clostridium, Akkermansia, Butyricimonas, and Lactococcus. Although both ST36 and GB34 had an anti-inflammatory effect on serum inflammatory mediators, only the acupuncture protocol with both ST36 and GB34 could effectively inhibit LPS-mediated joint inflammation in obesity rats. Therefore, relieving obesity-related chronic inflammation, lipid metabolism disorder, and gut microbiota disorder may be an important mechanism for acupuncture with ST36 and GB34 to promote OA recovery.

Flexible and Integrated Sensing Platform of Acoustic Waves and Metamaterials based on Polyimide-Coated Woven Carbon Fibers.

Versatile, in situ sensing and continuous monitoring capabilities are critically needed, but challenging, for components made of solid woven carbon fibers in aerospace, electronics, and medical applications. In this work, we proposed a unique concept of integrated sensing technology on woven carbon fibers through integration of thin-film surface acoustic wave (SAW) technology and electromagnetic metamaterials, with capabilities of noninvasive, in situ, and continuous monitoring of environmental parameters and biomolecules wirelessly. First, we fabricated composite materials using a three-layer composite design, in which the woven carbon fiber cloth was first coated with a polyimide (PI) layer followed by a layer of ZnO film. Integrated SAW and metamaterials devices were then fabricated on this composite structure. The temperature of the functional area of the device could be controlled precisely using the SAW devices, which could provide a proper incubation environment for biosampling processes. As an ultraviolet light sensor, the SAW device could achieve a good sensitivity of 56.86 ppm/(mW/cm2). On the same integrated platform, an electromagnetic resonator based on the metamaterials was demonstrated to work as a glucose concentration monitor with a sensitivity of 0.34 MHz/(mg/dL).

Teunomyces basidiocarpi sp. nov. and Teunomyces luguensis sp. nov., two ascomycetous yeast species related to the Candida kruisii clade isolated in Taiwan.

Four strains of anamorphic yeasts isolated from the fruiting bodies of mushrooms collected in Taiwan were found to represent two novel yeast species belonging to the genus Teunomyces, which was formally known as the Candida kruisii clade. Strains NY13M09T and NY14M14 were related to the type strains of Teunomyces panamensis, T. pallodes, T. tritomae and T. lycoperdinae, and strains GG4M07T and GG6M14 were related to T. kruisii NRRL Y-17087T and T. cretensis NRRL Y-27777T. However, strains NY13M09T and NY14M14 differed from their closest phylogenetic neighbours by 2.9-3.7 % in the D1/D2 domain sequence of the LSU rRNA gene and by 6.6-13.7 % in the internal transcribed spacer (ITS); GG4M07T and GG6M14 differed from their closest known species by 2.4 % in the D1/D2 domain sequence of the LSU rRNA gene and by 8.7-10.0 % in the ITS. Meanwhile, these strains were also clearly distinguished from their closest relatives based on the results of physiological tests. Based on the characteristics described above, the strains could be regarded as representing two novel species of the genus Teunomyces, for which the names Teunomyces basidiocarpi sp. nov. and Teunomyces luguensis sp. nov. are proposed. The holotypes are Teunomyces basidiocarpi BCRC 23475T and Teunomyces luguensis BCRC 23476T.

Taxonomy of the yeast genus Vanderwaltozyma and proposal of Vanderwaltozyma meishanica sp. nov., Vanderwaltozyma huisunica sp. nov., and Vanderwaltozyma molinica sp. nov.

Using electrophoretic karyotyping, RAPD fingerprinting and phylogenetic analysis of ribosomal RNA gene sequences, twenty-six Vanderwaltozyma strains were studied. Out of 19 strains isolated in mountainous areas of Taiwan, eighteen strains were isolated from soil and one strain was isolated from the fruiting body of mushroom, six were identified as V. polyspora and three as V. verrucispora. Based on the results of a multigene sequence analysis (D1/D2, ITS and mitochondrial COX II gene) and DNA-DNA reassociation, three new ascosporic members of the genus Vanderwaltozyma are formally described: V. huisunica sp. nov. (GA1S06T = CBS 12250T = BCRC 23260T), V. meishanica sp. nov. (EN4S02T = CBS 12249T = BCRC 23255T) and V. molinica sp. nov. (GJ8S05T = CBS 12251T = BCRC 23264T), and the holotypes of these novel species are assigned as BCRC 23260T, BCRC 23255T and BCRC 23264T, respectively.

Hepatitis B virus pre-S2 mutant large surface protein inhibits DNA double-strand break repair and leads to genome instability in hepatocarcinogenesis.

Although hepatitis B virus (HBV) has been established to cause hepatocellular carcinoma (HCC), the exact mechanism remains to be clarified. Type II ground glass hepatocytes (GGHs) harbouring the HBV pre-S2 mutant large surface protein (LHBS) have been recognized as a morphologically distinct hallmark of HCC in the advanced stages of chronic HBV infection. Considering its preneoplastic nature, we hypothesized that type II GGH may exhibit high genomic instability, which is important for the carcinogenic process in chronic HBV carriers. In this study we found that pre-S2 mutant LHBS directly interacted with importin α1, the key factor that recognizes cargos undergoing nuclear transportation mediated by the importin α/ß-associated nuclear pore complex (NPC). By interacting with importin α1, which inhibits its function as an NPC factor, pre-S2 mutant LHBS blocked nuclear transport of an essential DNA repair and recombination factor, Nijmegen breakage syndrome 1 (NBS1), upon DNA damage, thereby delaying the formation of nuclear foci at the sites of DNA double-strand breaks (DSBs). Pre-S2 mutant LHBS was also found to block NBS1-mediated homologous recombination repair and induce multi-nucleation of cells. In addition, pre-S2 mutant LHBS transgenic mice showed genomic instability, indicated by increased global gene copy number variations (CNVs), which were significantly higher than those in hepatitis B virus X mice, indicating that pre-S2 mutant LHBS is the major viral oncoprotein inducing genomic instability in HBV-infected hepatocytes. Consistently, the human type II GGHs in HCC patients exhibited increased DNA DSBs representing significant genomic instability. In conclusion, type II GGHs harbouring HBV pre-S2 mutant oncoprotein represent a high-risk marker for the loss of genome integrity in chronic HBV carriers and explain the complex chromosome changes in HCCs. Mouse array CGH raw data: GEO Accession No. GSE61378 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61378).

Toona sinensis inhibits LPS-induced inflammation and migration in vascular smooth muscle cells via suppression of reactive oxygen species and NF-κB signaling pathway.

Toona sinensis is one of the most popular vegetarian cuisines in Taiwan and it has been shown to possess antioxidant, antiangiogenic, and anticancer properties. In this study, we investigated the antiatherosclerotic potential of aqueous leaf extracts from Toona sinensis (TS; 25-100 µg/mL) and its major bioactive compound, gallic acid (GA; 5 µg/mL), in LPS-treated rat aortic smooth muscle (A7r5) cells. We found that pretreatment with noncytotoxic concentrations of TS and GA significantly inhibited inflammatory NO and PGE2 production by downregulating their precursors, iNOS and COX-2, respectively, in LPS-treated A7r5 cells. Furthermore, TS and GA inhibited LPS-induced intracellular ROS and their corresponding mediator, p47(phox). Notably, TS and GA pretreatment significantly inhibited LPS-induced migration in transwell assays. Gelatin zymography and western blotting demonstrated that treatment with TS and GA suppressed the activity or expression of MMP-9, MMP-2, and t-PA. Additionally, TS and GA significantly inhibited LPS-induced VEGF, PDGF, and VCAM-1 expression. Further investigation revealed that the inhibition of iNOS/COX-2, MMPs, growth factors, and adhesion molecules was associated with the suppression of NF-κB activation and MAPK (ERK1/2, JNK1/2, and p38) phosphorylation. Thus, Toona sinensis may be useful for the prevention of atherosclerosis.

Microtubule depolymerization activates the Epstein-Barr virus lytic cycle through protein kinase C pathways in nasopharyngeal carcinoma cells.

Elevated levels of antibodies against Epstein-Barr virus (EBV) and the presence of viral DNA in plasma are reliable biomarkers for the diagnosis of nasopharyngeal carcinoma (NPC) in high-prevalence areas, such as South-East Asia. The presence of these viral markers in the circulation suggests that a minimal level of virus reactivation may have occurred in an infected individual, although the underlying mechanism of reactivation remains to be elucidated. Here, we showed that treatment with nocodazole, which provokes the depolymerization of microtubules, induces the expression of two EBV lytic cycle proteins, Zta and EA-D, in EBV-positive NPC cells. This effect was independent of mitotic arrest, as viral reactivation was not abolished in cells synchronized at interphase. Notably, the induction of Zta by nocodazole was mediated by transcriptional upregulation via protein kinase C (PKC). Pre-treatment with inhibitors for PKC or its downstream signalling partners p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) abolished the nocodazole-mediated induction of Zta and EA-D. Interestingly, the effect of nocodazole, as well as colchicine and vinblastine, on lytic gene expression occurred only in NPC epithelial cells but not in cells derived from lymphocytes. These results establish a novel role of microtubule integrity in controlling the EBV life cycle through PKC and its downstream pathways, which represents a tissue-specific mechanism for controlling the life-cycle switch of EBV.

Autologous mesenchymal stem cells prevent transplant arteriosclerosis by enhancing local expression of interleukin-10, interferon-γ, and indoleamine 2,3-dioxygenase.

Transplant arteriosclerosis (TA) remains the major limitation of long-term graft survival in heart transplantation despite the advances in immunosuppressants. Mesenchymal stem cells (MSCs) have been demonstrated to suppress allogeneic immune responses by numerous in vitro studies. However, the immunomodulatory effects of MSCs in vivo are controversial and the underlying molecular mechanisms are not conclusive. In this study, we investigated the therapeutic potential of autologous bone marrow-derived MSCs on TA in a porcine model of femoral artery transplantation. MSCs or saline were injected into the soft tissue surrounding the arterial grafts immediately postanastomosis. Four weeks after transplantation, neointimal formation increased significantly in untreated allografts compared with the MSC-treated grafts as assessed by intravascular ultrasound (maximum luminal area stenosis: 40 ± 12% vs. 18 ± 6%, p < 0.001). Grafts harvested at 4 weeks showed dense perivascular lymphocyte infiltration accompanied by significant intimal hyperplasia in the untreated but not in the MSC-treated allografts. Serial angiographic examination showed that all of the untreated allografts became occluded at the 8th week whereas the majority of the MSC-treated grafts remained patent at the 12th week posttransplantation (n = 12 each group, p < 0.001). Quantitative PCR analysis revealed that Foxp3 expression was comparable between the untreated and the MSC-treated groups. However, expression of interleukin-10 (IL-10), interferon-γ (IFN-γ), and indoleamine 2,3-dioxygenase (IDO) was increased significantly in the MSC-treated allografts compared with that in the allograft controls (p = 0.021 for IL-10, p = 0.003 for IFN-γ, and p = 0.008 for IDO). In conclusion, local delivery of autologous MSCs alleviates TA by inducing allograft tolerance via enhanced expression of IL-10, IFN-γ, and IDO but not Foxp3-positive cells in the vessel wall. These results suggest that MSCs induce immune tolerance by activating the type 1 regulatory T-like cells.

Five novel species of the anamorphic genus Candida in the Cyberlindnera clade isolated from natural substrates in Taiwan.

Twelve strains representing five novel yeast species were isolated from natural samples distributed in mountain areas in Taiwan during 2007 and 2009. Sequence analysis of the D1/D2 domain of the large subunit (LSU) rRNA gene revealed that these species are members of the Cyberlindnera clade. These five new species have a greater than 1% difference from their closest relatives in the sequences of the D1/D2 domain of the LSU rRNA gene and were well separated from their closest relatives in terms of physiological characteristics. Moreover, a sexual state could not be found in these five novel yeast species. Therefore, the scientific names of Candida maesa sp. nov. (type strain GJ8L01(T)), Candida takata sp. nov. (type strain EN25S01(T)), Candida taoyuanica sp. nov. (type strain GY15S07(T)), Candida hungchunana sp. nov. (type strain NC3W71(T)) and Candida stauntonica sp. nov. (type strain GY13L05(T)) were proposed to accommodate these yeasts.

Asterotremella meifongana sp. nov. and Asterotremella nantouana sp. nov., two anamorphic basidiomycetous yeasts isolated from soil and mushrooms.

Two novel yeast species, Asterotremella meifongana sp. nov. and Asterotremella nantouana sp. nov., belonging to Asterotremellaceae within the Trichosporonales, are proposed to accommodate five strains isolated from Taiwanese samples of soil and basidiocarps during 2006-2007. Sequence analysis of the D1/D2 domains of the large subunit rRNA gene revealed that the two species are phylogenetically closely related to species of the genus Asterotremella, which indicates that they are members of the genus. The two species can be further differentiated from other Asterotremella species based on their internal transcribed spacer sequences, as well as on a few physiological test responses. The type strains are A. meifongana SN4S04(T) (=CBS 11424(T) = BCRC 23196(T)) and A. nantouana SN5S06(T) (=CBS 10890(T) = BCRC 23135(T)).

Lachancea dasiensis sp. nov., an ascosporogenous yeast isolated from soil and leaves in Taiwan.

A novel yeast species, Lachancea dasiensis sp. nov., is proposed in this paper based on two strains isolated from leaves and one strain from soil in Taiwan. The strains produce one or two spherical ascospores in each ascus, preceded by conjugation of individual cells. Genus assignment and distinction of the species from other recognized species of Lachancea are based on morphological and physiological characteristics and on phylogenetic analysis of nucleotide sequences of the D1/D2 domains of the large subunit (LSU) rRNA gene. Sequence analysis of the D1/D2 domains of the LSU rRNA gene reveals that the phylogenetically closest relatives of L. dasiensis sp. nov. are Lachancea thermotolerans and Lachancea waltii. The novel species could be differentiated from the latter two species based on electrophoretic karyotypes. The type strain of Lachancea dasiensis sp. nov. is SC5L02(T) (=CBS 10888(T) =BCRC 23139(T)), which was isolated from a leaf of Angiopteris lygodiifolia Rosenst. in Dasi, Taoyuan, Taiwan.

Kazachstania wufongensis sp. nov., an ascosporogenous yeast isolated from soil in Taiwan.

A new yeast species, Kazachstania wufongensis, is proposed in this paper based on six strains isolated from soil in Taiwan. The species may produce one to four ellipsoidal ascospores in each ascus, directly transformed from diploid cells. Genus assignment and distinction of the species from other recognized species of Kazachstania is based on morphological and physiological characteristics, and on phylogenetic analysis of nucleotide sequences of the D1/D2 domains of the large subunit (LSU) rRNA gene. Sequence analysis of the D1/D2 domains of the LSU rRNA gene reveals that K. wufongensis is a member of the Kazachstania exigua complex, and its phylogenetically closest relatives are K. exigua, K. barnettii, K. bulderi, and K. turicensis. The species can be further differentiated from the other phylogenetically related species based on internal transcribed spacer sequence and electrophoretic karyotype. Therefore, the new species Kazachstania wufongensis sp. nov. is proposed. The type strain of this new species, which was isolated from forest soil in Wufong, Hsinchu, Taiwan, is FN21S03(T) (=CBS 10886(T) = BCRC 23138(T)).