A Phytophthora infestans RXLR effector AVR8 suppresses plant immunity by targeting a desumoylating isopeptidase DeSI2.

The potato's most devastating disease is late blight, which is caused by Phytophthora infestans. Whereas various resistance (R) genes are known, most are typically defeated by this fast-evolving oomycete pathogen. However, the broad-spectrum and durable R8 is a vital gene resource for potato resistance breeding. To support an educated deployment of R8, we embarked on a study on the corresponding avirulence gene Avr8. We overexpressed Avr8 by transient and stable transformation, and found that Avr8 promotes colonization of P. infestans in Nicotiana benthamiana and potato, respectively. A yeast-two-hybrid (Y2H) screen showed that AVR8 interacts with a desumoylating isopeptidase (StDeSI2) of potato. We overexpressed DeSI2 and found that DeSI2 positively regulates resistance to P. infestans, while silencing StDeSI2 downregulated the expression of a set of defense-related genes. By using a specific proteasome inhibitor, we found that AVR8 destabilized StDeSI2 through the 26S proteasome and attenuated early PTI responses. Altogether, these results indicate that AVR8 manipulates desumoylation, which is a new strategy that adds to the plethora of mechanisms that Phytophthora exploits to modulate host immunity, and StDeSI2 provides a new target for durable resistance breeding against P. infestans in potato.

Habitat differentiation and conservation gap of Magnolia biondii, M. denudata, and M. sprengeri in China.

The flower buds of Magnolia biondii, M. denudata, and M. sprengeri are the materials of Xinyi, a traditional Chinese medicine. The harvest of flower buds and habitat fragmentation caused by human disturbance heavily threatens the natural regeneration and survival of these three Magnolia species. With the aim to support the conservation and improve the effectiveness of conservation, we performed an assessment on habitat suitability, influences of environmental variables on habitat suitability, and the conservation gap of these three Magnolia species, based on the Maxent modeling method. The results indicated that: (1) altitude, annual mean temperature, extreme temperature, temperature fluctuation, annual precipitation, and extreme precipitation are the most influential environmental variables for the distribution of M. sprengeri, M. biondii, and M. denudata; (2) obvious habitat differentiations were observed among M. biondii, M. denudata, and M. sprengeri. M. sprengeri tends to be located in further northern areas with higher altitudes, lower temperatures, and lower precipitation compared to M. biondii and M. denudata; and (3) a large proportion of suitable habitats have been left without protection. Woodland and forest shared the largest area out of the suitable habitats. However, grassland, agricultural land, residential land, and mining and industry areas also occupied large areas of suitable habitats.

Traditional, complementary, and alternative medicine approaches to mental health care and psychological wellbeing in India and China.

India and China face the same challenge of having too few trained psychiatric personnel to manage effectively the substantial burden of mental illness within their population. At the same time, both countries have many practitioners of traditional, complementary, and alternative medicine who are a potential resource for delivery of mental health care. In our paper, part of The Lancet and Lancet Psychiatry's Series about the China-India Mental Health Alliance, we describe and compare types of traditional, complementary, and alternative medicine in India and China. Further, we provide a systematic overview of evidence assessing the effectiveness of these alternative approaches for mental illness and discuss challenges in research. We suggest how practitioners of traditional, complementary, and alternative medicine and mental health professionals might forge collaborative relationships to provide more accessible, affordable, and acceptable mental health care in India and China. A substantial proportion of individuals with mental illness use traditional, complementary, and alternative medicine, either exclusively or with biomedicine, for reasons ranging from faith and cultural congruence to accessibility, cost, and belief that these approaches are safe. Systematic reviews of the effectiveness of traditional, complementary, and alternative medicine find several approaches to be promising for treatment of mental illness, but most clinical trials included in these systematic reviews have methodological limitations. Contemporary methods to establish efficacy and safety-typically through randomised controlled trials-need to be complemented by other means. The community of practice built on collaborative relationships between practitioners of traditional, complementary, and alternative medicine and providers of mental health care holds promise in bridging the treatment gap in mental health care in India and China.

The safety and usefulness of neutron brachytherapy and external beam radiation in the treatment of patients with gastroesophageal junction adenocarcinoma with or without chemotherapy.

PURPOSE: To assess the safety and usefulness of neutron brachytherapy (NBT) as an adjuvant in the treatment of patients with gastroesophageal junction adenocarcinoma (GEJAC) with external beam radiation (EBRT), with or without chemotherapy. METHODS AND MATERIALS: In total, 197 patients with localized, advanced GEJAC received EBRT and NBT with or without chemotherapy. Radiotherapy consisted of external irradiation to a total dose of 40-54 Gy (median 50 Gy) and brachytherapy to 8-25 Gy (median 20 Gy) in two to five fractions. In total, 88 patients received chemotherapy that consisted of two cycles of a regimen with CDDP and 5FU from days l-4. The cycles were administered on days 1 and 29. MMC was given alone in bolus injection on day 1 each week. The cycles were administered on days 1, 8, 15 and 22. RESULTS: The duration of follow-up ranged from six to 106 months (median 30.4 months). The median survival time for the 197 patients was 13.3 months, and the one, two, three- and five-year rates for overall survival were 57.1%, 35.1%, 23.0% and 9.2%, respectively. For acute toxicity, no incidences of fistula and massive bleeding were observed during this treatment period. In total, 159 (80.7%) patients developed Grade 2 hematologic toxicity and 146 (74.1%) patients developed Grade ≥ 2 esophagitis. The median times of incidence of fistula and bleeding were 9.5 (3-27.3) months and 12.7 (5-43.4) months, respectively. The incidence of severe, late complications was related to higher NBT dose/f (20-25 Gy/5 F) and higher total dose(≥70 Gy). In total, 75.2% of the patients resumed normal swallowing and 2.0% had some residual dysphagia (non-malignant) requiring intermittent dilatation. CONCLUSION: A combination of EBRT and NBT with the balloon type applicator was feasible and well tolerated. Better local-regional control and overall survival cannot achieved by a higher dose, and in contrast, a higher dose caused more severe esophageal injury.

Galangin induces apoptosis of hepatocellular carcinoma cells via the mitochondrial pathway.

AIM: To investigate the mechanism by which galangin, a polyphenolic compound derived from medicinal herbs, induces apoptosis of hepatocellular carcinoma (HCC) cells. METHODS: The 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to measure cell viability. Apoptosis was evaluated by in situ uptake of propidium iodide and Hoechst 33258 and was then detected by fluorescence microscopy. Protein expressions were detected by Western blotting. To confirm the apoptotic pathway mediated by galangin, cells were transfected by bcl-2 gene to overexpress Bcl-2 or siRNA to down-regulate Bcl-2 expression. RESULTS: Galangin (46.25-370.0 micromol/L) exerted an anti-proliferative effect, induced apoptosis, and decreased mitochondrial membrane potential in a dose and time-dependent manner. Treatment with galangin induced apoptosis by translocating the pro-apoptotic protein Bax to the mitochondria, which released apoptosis-inducing factor and cytochrome c into the cytosol. Overexpression of Bcl-2 attenuated galangin-induced HepG2 cell apoptosis, while decreasing Bcl-2 expression enhanced galangin-induced cell apoptosis. CONCLUSION: Our data suggests that galangin mediates apoptosis through a mitochondrial pathway, and may be a potential chemotherapeutic drug for the treatment of HCC.

Effect of one week treatment with Ginkgo biloba extract (EGb761) on ischemia-induced infarct volume in gerbils.

The present study was designed to evaluate the neuroprotective effects of Ginkgo biloba leaf extract (EGb761) in male gerbils subjected to focal cerebral ischemia produced by permanent occlusion of the right middle cerebral artery. In this study, gerbils were fed standard chow with or without EGb761 (100 mg/kg/day, i.g.) prior to cerebral ischemia for 1 week. Gerbils were anesthetized and craniectomized to expose the right middle cerebral artery (MCA). The right MCA was constricted with an 8-0 suture to produce a permanent ligation. Infarct volume was assessed by TTC (2,3,5-triphenyl-tetrazolium chloride) staining 24 hours after initiation of cerebral ischemia. Results showed that the EGb761 group had significant reduction of infarct volume 4 and 6 mm from the frontal pole by 40% and 30%, respectively when compared to the control group (p < 0.05). Mean locomotor activity of gerbils was reduced 24 hours after the occlusion of the MCA in both groups. However, there was no difference in locomotor activity between groups either 30 minutes before or 24 hours after the occlusion (p > 0.05).