BAP1 loss confers sensitivity to bromodomain and extra-terminal inhibitors in renal cell carcinoma.

The tumor suppressor gene BRCA1 associated protein-1 (BAP1) is frequently mutated in renal cell carcinoma (RCC). BAP1 loss-of-function mutations are associated with poor survival outcomes. However, personalized therapy for BAP1-mutated RCC is currently not available. Previously, we found that BAP1 loss renders RCC cells more sensitive to bromodomain and extra-terminal (BET) inhibitors, as demonstrated in both cell culture and xenografted nude mice models. Here, we demonstrate that BAP1 loss in murine RCC cells enhances sensitivity to BET inhibitors in ectopic and orthotopic allograft models. While BAP1 deletion suppresses RCC cell survival in vitro, it does not impede tumor growth in immunocompetent murine models. Thus, the effect of BAP1 loss on the interactions between tumor cells and host microenvironment plays a predominant role in RCC growth, highlighting the importance of utilizing immunocompetent animal models to assess the efficacy of potential anticancer therapies. Mechanistically, BAP1 deletion compromises DNA repair capacity, rendering RCC cells more vulnerable to DNA damage induced by BET inhibitors. Our results indicate that BET inhibitors show promise as targeted therapy for BAP1-deficient RCC.

Novel Insights into the Promoted Accumulation of Nitro-Polycyclic Aromatic Hydrocarbons in the Roots of Legume Plants.

Substituted polycyclic aromatic hydrocarbons (sub-PAHs) are receiving increased attention due to their high toxicity and ubiquitous presence. However, the accumulation behaviors of sub-PAHs in crop roots remain unclear. In this study, the accumulation mechanism of sub-PAHs in crop roots was systematically disclosed by hydroponic experiments from the perspectives of utilization, uptake, and elimination. The obtained results showed an interesting phenomenon that despite not having the strongest hydrophobicity among the five sub-PAHs, nitro-PAHs (including 9-nitroanthracene and 1-nitropyrene) displayed the strongest accumulation potential in the roots of legume plants, including mung bean and soybean. The nitrogen-deficient experiments, inhibitor experiments, and transcriptomics analysis reveal that nitro-PAHs could be utilized by legumes as a nitrogen source, thus being significantly absorbed by active transport, which relies on amino acid transporters driven by H+-ATPase. Molecular docking simulation further demonstrates that the nitro group is a significant determinant of interaction with an amino acid transporter. Moreover, the depuration experiments indicate that the nitro-PAHs may enter the root cells, further slowing their elimination rates and enhancing the accumulation potential in legume roots. Our results shed light on a previously unappreciated mechanism for root accumulation of sub-PAHs, which may affect their biogeochemical processes in soils.

Clinical impact of hepatic steatosis on chronic hepatitis B patients in Asia: A systematic review and meta-analysis.

Chronic hepatitis B (CHB) and hepatic steatosis (HS) are two prevalent chronic liver diseases in Asia. The incidence of CHB combined with HS is increasing due to the rising obesity rates. However, the impact of HS on CHB remains a topic of debate. Hereby, this meta-analysis aims to examine the effect of HS on Asian patients with CHB. Searches were conducted on four databases to identify articles published from 2005 to 2023. The random-effects or fixed-effects model was used to calculate pooled odds ratios (ORs), weighted mean difference (WMD), and confidence intervals (CIs) for the included articles. Of the 15,959 records screened, 88 studies were included in the analysis of HS prevalence in Asian CHB patients with a prevalence of 36.5% (95% CI: 33.7%-39.3%). In addition, age, sex, body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT) and combined metabolic diseases have varying degrees of impact on HS in CHB patients. Furthermore, the coexistence of HS was negatively associated with the response to antiviral therapy, including hepatitis B surface antigen (HBeAg) seroconversion (OR = 0.69, 95% CI: 0.53-0.89) and ALT normalization (OR = 0.75, 95% CI: 0.61-0.92) in CHB patients after 48 weeks of treatment. Regarding disease prognosis, HS was not significantly associated with fibrosis or cirrhosis in CHB patients, while an inverse association was observed between HS and hepatocellular carcinoma (HCC) (OR = 2.93, 95% CI: 1.23-6.99). This implies that the coexistence of HS in CHB patients may exacerbate the progression of HCC, which needs to be verified by further studies.

Association of nonalcoholic fatty liver disease and growth hormone deficiency: a systematic review and meta-analysis.

An association exists between nonalcoholic fatty liver disease (NAFLD) and growth hormone (GH). Patients with growth hormone deficiency (GHD) may be more susceptible to NAFLD. The prevalence of NAFLD and nonalcoholic steatohepatitis (NASH) in GHD patients is currently unknown. Multiple databases were searched for experiments related to NAFLD (or NASH) and GHD. Screening, quality evaluation and data extraction were carried out independently by two authors. Analyses used random or fixed effects models, including NAFLD prevalence, NASH prevalence, odds ratio (OR) and 95% confidence interval (CI). We included 10 studies with a total of 782 participants. The results showed that the prevalence of NAFLD in GHD patients was 51% (95% CI: 39-63). The risk of NAFLD in GHD patients was significantly higher than that in controls (age-, sex- or body mass index-matched, without GHD) (pooled OR = 4.27, 95% CI: 1.33-13.68%, p = 0.015). The prevalence of NASH in GHD patients was 18% (95% CI: 5-31). The prevalence of NAFLD in GHD patients is significantly higher than that in the general population, especially NASH. There is a need to develop targeted strategies for the early identification, prevention, or control of NAFLD/NASH in patients with GHD.

Barriers and enabling factors in weight management of patients with nonalcoholic fatty liver disease: A qualitative study using the COM-B model of behaviour.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. Lifestyle modifications aimed at promoting weight loss and weight maintenance remain the current first-line treatments for NAFLD. OBJECTIVE: We aim to identify barriers and enabling factors in weight management among patients with NAFLD using the capability, opportunity, motivation, behaviour (COM-B) model of behaviour. DESIGN: This study adopted a qualitative design using semistructured interviews analysed with content analysis and the COM-B framework. SETTING AND PARTICIPANTS: Interviews were conducted with 27 patients with NAFLD who experienced successful or unsuccessful weight reduction. RESULTS: Our study included 27 participants: 15 participants with successful weight loss (successful weight loss refers to a decrease in body weight ≥7% of the initial body weight for patients with NAFLD) and 12 participants with unsuccessful weight loss. Thirty-five themes (19 barriers and 16 facilitators) were mapped onto the COM-B model as barriers and facilitators to weight management among patients with NAFLD. The key barriers were lack of time and energy, lack of awareness of weight, lack of attention to NAFLD, treating food as a reward or compensation and social entertainment. The key facilitators were having basic weight loss knowledge and skills, strong motivation, attention to NAFLD, unsuccessful weight loss experiences and positive feedback from phased success. CONCLUSION: In addition to identifying factors consistent with existing studies, this study identified factors that influence weight management in NAFLD patients, such as basic weight loss skills and rational thinking before weight loss, which were not previously reported. This has clinical implications for clinical healthcare providers and health management services for the improvement of education and support regarding lifestyle improvement and weight management in patients with NAFLD. PATIENT OR PUBLIC CONTRIBUTION: We recruited potential participants from the Bariatric Clinic, Hepatology Clinic and Physical Examination Center of hospitals between March 2021 and October 2021. Twenty-seven patients with NAFLD who had successful or unsuccessful weight loss experiences participated in the study and responded to questions on weight management.

Reciprocal positive regulation between BRD4 and YAP in GNAQ-mutant uveal melanoma cells confers sensitivity to BET inhibitors.

Uveal melanoma (UM) is the most common intraocular cancer in adults. UMs are usually initiated by a mutation in GNAQ or GNA11 (encoding Gq or G11, respectively), unlike cutaneous melanomas (CMs), which usually carry a BRAF or NRAS mutation. Currently, there are no clinically effective targeted therapies for UM carrying Gq/11 mutations. Here, we identified a causal link between Gq activating mutations and hypersensitivity to bromodomain and extra-terminal (BET) inhibitors. BET inhibitors transcriptionally repress YAP via BRD4 regardless of Gq mutation status, independently of Hippo core components LATS1/2. In contrast, YAP/TAZ downregulation reduces BRD4 transcription exclusively in Gq-mutant cells and LATS1/2 double knockout cells, both of which are featured by constitutively active YAP/TAZ. The transcriptional interdependency between BRD4 and YAP identified in Gq-mutated cells is responsible for the preferential inhibitory effect of BET inhibitors on the growth and dissemination of Gq-mutated UM cells compared to BRAF-mutated CM cells in both culture cells and animal models. Our findings suggest BRD4 as a viable therapeutic target for Gq-driven UMs that are addicted to unrestrained YAP function.

Simple and eco-friendly synthesis of crude orange-peel-derived carbon nanoparticles for detection of Fe3+ and ascorbic acid.

Although fluorescence sensors based on carbon dots (CDs) have been developed widely, multicomponent detection using CDs without extra and tedious surface modification remains a challenge. Here, the crude carbon nanoparticles (CPs) as a fluorescence sensor were prepared through one-pot hydrothermal process using orange peel as the precursor. The method was simple, rapid, economical, and eco-friendly given that such extra steps as dialysis and lyophilization were not required. By adding ethanol into the reaction solvent, the fluorescence properties of orange-peel-derived CPs as well as their sensitivity of detecting Fe3+ with a limit of detection of 0.25 µM were improved. Additionally, orange-peel-derived CPs could be used as a fluorescence sensor for detection of ascorbic acid (AA) with a LOD of 5 µM. More importantly, the proposed fluorescence methods were successfully used to qualitatively and quantitatively analyze Fe3+ and AA in real samples. Recovery of Fe3+ from tap water was within the range 97.2-105.4%. Conversely, recovery of AA from vitamin C tablets and orange juices laid within the ranges 97.7-99.3% and 93.2-97.6%, respectively.

[Bayesian network Meta-analysis of Chinese medicine injections in treatment of chronic renal insufficiency].

In this study, Honghua Injection, Danshen Injection, Shenkang Injection, Shuxuetong Injection, Lulutong Injection, Shenxiong Glucose Injection and Chuanxiong Injection were compared for their clinical efficacy on chronic renal insufficiency by using the method of network Meta-analysis, with Western medicine as the common reference. The randomized controlled trial(RCT) of Hong-hua Injection, Danshen Injection, Shenkang Injection, Shuxuetong Injection, Lulutong Injection, Shenxiong Glucose Injection and Chuanxiong Injection for the treatment of chronic renal insufficiency were obtained by computer-based retrieval. The literature quality was evaluated by using the method in Cochrane Reviewer's Handbook 5.1 after independent screening of the included literature by two reviewers. The RJAGS package and GEMTC package of RevMan 5.3, GEMTC software, R software were used for statistical analysis to compare and sort the different injections in terms of efficacy. A total of 6 197 patients with chronic renal failure were included in 79 RCTs, involving 8 treatment measures. The effective rates of conventional treatment combined with Shenxiong Injection(OR=3.55, 95%CI[1.98, 6.37], P<0.000 1), Honghua Injection(OR=3.77, 95%CI[2.45, 5.81], P<0.000 01), Shuxuetong Injection(OR=6.71, 95%CI[3.30, 13.65], P<0.000 01) and Shenkang Injection(OR=4.14, 95%CI[3.42, 5.03], P<0.000 01) were all better than that in control group, and the effective rate of Honghua Injection combined with conventional treatment(OR=3.89, 95%CI[1.73, 8.74], P=0.001) was better than that in Danshen Injection combined with conventional treatment, all with statistically significant differences. By comprehensive comparison, Shuxuetong Injection, Honghua Injection and Shenkang Injection combined with Western medicine had good clinical effect on the effective rate, serum creatinine reduction and urea nitrogen reduction in patients with chronic renal insufficiency. However, due to the relatively low quality of the included literature, the conclusion has yet to be verified clinically.

HIV infection suppresses TLR3 activation-mediated antiviral immunity in microglia and macrophages.

Monocytic-lineage cells in the central nervous system (CNS), including microglia and brain resident macrophages, are the key players in the CNS innate immunity against viral infections, including human immunodeficiency virus (HIV). However, these cells also serve as the major targets and reservoirs for HIV in the CNS. To address the question of how HIV can establish persistent infection in the target cells in the CNS, we examined whether HIV has the ability to counteract Toll-like receptor 3 (TLR3) activation-mediated antiviral immunity in microglia and macrophages. We observed that HIV latently infected microglial cells (HC69·5) expressed reduced levels of TLR3 and TLR3 activation-mediated interferons (IFN-α/ß and IFN-λ) as compared with the uninfected control cells (C20). In addition, HIV infection of primary human macrophages suppressed the expression of TLR3 and the IFNs. HIV infection also inhibited the expression of the antiviral IFN-stimulated genes (ISGs) and the HIV-restriction miRNAs. Mechanistically, HIV infection inhibited the phosphorylation of IFN regulatory factors (IRF3 and IRF7) and signal transducer and activator of transcription proteins (STAT1 and STAT3) in both HIV latently infected microglia and acutely infected macrophages. These findings provide previously unrecognized and sound mechanisms for HIV infection and persistence in the primary target and reservoir cells in the brain.

Influence of extending expansive open-door laminoplasty to C1 and C2 on cervical sagittal parameters.

BACKGROUND: For patients with spinal canal stenosis in the upper cervical spine who undergo C3-7 laminoplasty alone, it remains impossible to achieve full decompression due to its limited range. This study explores the extension of expansive open-door laminoplasty (EODL) to C1 and C2 for the treatment of cervical spinal stenosis of the upper cervical spine and its effects on cervical sagittal parameters. METHODS: A retrospective analysis of 33 patients presenting with symptoms of cervical spondylosis myelopathy (CSM) and ossification in the posterior longitudinal ligament (OPLL) of the upper cervical spine from February 2013 to December 2015 was performed. Furthermore, the changes in the C0-2 Cobb angle, C1-2 Cobb angle, C2-7 Cobb angle, C2-7 SVA, and T1-Slope in lateral X-rays of the cervical spine were measured before, immediately after, and 1 year after the operation. JOA and NDI scores were used to evaluate spinal cord function. RESULTS: The C0-2 and C1-2 Cobb angles did not significantly increase (P = 0.190 and P = 0.081), but the C2-7 Cobb angle (P = 0.001), C2-7 SVA (P < 0.001), and T1-Slope (P < 0.001) significantly increased from preoperative to 1 year postoperative. In addition, C2-7 SVA was significantly correlated with the T1-Slope (Pearson = 0.376, P < 0.001) and C0-2 Cobb angle (Pearson = 0.287, P = 0.004), and the C2-7 SVA was negatively correlated with the C2-7 Cobb angle (Pearson = - 0.295, P < 0.001). The average preoperative and postoperative JOA scores were 8.3 ± 1.6 and 14.6 ± 1.4 points, respectively, indicating in a postoperative neurological improvement rate of approximately 91.6%. The average preoperative and final follow-up NDI scores were 12.62 ± 2.34 and 7.61 ± 1.23. CONCLUSIONS: The sagittal parameters of patients who underwent EODL extended to C1 and C2 included loss of cervical curvature, increased cervical anteversion and compensatory posterior extension of the upper cervical spine to maintain visual balance in the field of vision. However, the changes in cervical spine parameters were far less substantial than the alarm thresholds reported in previous studies. We believe that EODL extended to C1 and C2 for the treatment of patients with spinal canal stenosis in the upper cervical spine is a feasible and safe procedure with excellent outcomes.

Obesity's effect on asthma extends to diagnostic criteria.

BACKGROUND: The use of inflammatory biomarkers to delineate the type of lung inflammation present in asthmatic subjects is increasingly common. However, the effect of obesity on these markers is unknown. OBJECTIVES: We aimed to determine the effect of obesity on conventional markers of inflammation in asthmatic subjects. METHODS: We performed secondary analysis of data from 652 subjects previously enrolled in 2 Asthma Clinical Research Network trials. We performed linear correlations between biomarkers and logistic regression analysis to determine the predictive value of IgE levels, blood eosinophil counts, and fraction of exhaled nitric oxide values in relationship to sputum eosinophil counts (>2%), as well as to determine whether cut points existed that would maximize the sensitivity and specificity for predicting sputum eosinophilia in the 3 weight groups. RESULTS: Overall, statistically significant but relatively weak correlations were observed among all 4 markers of inflammation. Within obese subjects, the only significant correlation found was between IgE levels and blood eosinophil counts (r = 0.33, P < .001); furthermore, all other correlations between inflammatory markers were approximately 0, including correlations with sputum eosinophil counts. In addition, the predictive value of each biomarker alone or in combination was poor in obese subjects. In fact, in obese subjects none of the biomarkers of inflammation significantly predicted the presence of high sputum eosinophil counts. Obese asthmatic subjects have lower cut points for IgE levels (268 IU), fraction of exhaled nitric oxide values (14.5 ppb), and blood eosinophil counts (96 cells/µL) than all other groups. CONCLUSIONS: In obese asthmatic subjects conventional biomarkers of inflammation are poorly predictive of eosinophilic airway inflammation. As such, biomarkers currently used to delineate eosinophilic inflammation in asthmatic subjects should be approached with caution in these subjects.

Identification and Analysis of Micro-Exon Genes in the Rice Genome.

Micro-exons are a kind of exons with lengths no more than 51 nucleotides. They are generally ignored in genome annotation due to the short length, whereas recent studies indicate that they have special splicing properties and important functions. Considering that there has been no genome-wide study of micro-exons in plants up to now, we screened and analyzed genes containing micro-exons in two indica rice varieties in this study. According to the annotation of Zhenshan 97 (ZS97) and Minghui 63 (MH63), ~23% of genes possess micro-exons. We then identified micro-exons from RNA-seq data and found that >65% micro-exons had been annotated and most of novel micro-exons were located in gene regions. About 60% micro-exons were constitutively spliced, and the others were alternatively spliced in different tissues. Besides, we observed that approximately 54% of genes harboring micro-exons tended to be ancient genes, and 13% were Oryza genus-specific. Micro-exon genes were highly conserved in Oryza genus with consistent domains. In particular, the predicted protein structures showed that alternative splicing of in-frame micro-exons led to a local structural recombination, which might affect some core structure of domains, and alternative splicing of frame-shifting micro-exons usually resulted in premature termination of translation by introducing a stop codon or missing functional domains. Overall, our study provided the genome-wide distribution, evolutionary conservation, and potential functions of micro-exons in rice.

[Analysis on regularity of traditional Chinese patent medicine in treating hyperlipidemia].

To explore the regularity of traditional Chinese patent medicines for the treatment of hyperlipidemia recorded in Newly Edited National Chinese Traditional Patent Medicines,the Composition Principles of Chinese Patent Drugs,New Drug Conversion Standard,the Compilation of National Standard for Traditional Chinese Medicines and Chinese Pharmacopoeia. Researchers extracted the information of prescriptions from these cases according to the inclusion and exclusion criteria. Then microsoft excel 2010 was used to conduct frequency statistics and count the frequency of traditional Chinese medicine. SPSS Clementine( ver.12. 0) and SPSS( ver. 18. 0)were adopted respectively for frequency analysis,association rules analysis,cluster analysis and factor analysis. Besides,KMO test and Bartlett spherical test were performed for factor adaptation test. Finally,a total of 173 traditional Chinese medicines were included,involving 94 Chinese patent medicine prescriptions. The frequency results of traditional Chinese medicine showed that there were 33 kinds of high-frequency traditional Chinese medicine,mainly including those for tonifying medicine,activating blood and resolving stasis and blood-stasis,and clearing damp. The association rules analysis found out 12 association rules of drug pairs,3-herb pairs of 25 and4-herb pairs of 6. Totally 11 medicine groups with relevance were respectively extracted by cluster analysis. KMO test and Bartlett spherical test indicated that the method was suitable for factor analysis and 11 common factors were respectively extracted by factor analysis. The association rules reflected the therapeutic method for tonify the liver and kidney,activating blood and resolving stasis. Cluster analysis and factor analysis showed the therapeutic method of Qi-enriching and Yin-nourishing,and the factor analysis focused more on removing blood stasis and dampness. The decision tree with hawthorn as the dependent variable reflects the importance of alisma orientalis and fructus schisandrae in the drug matching. In conclusion,data mining technique can comprehensively analyze the regularity of prescriptions of traditional Chinese patent medicine for hyperlipidemia,and is helpful for guiding the development of Chinese patent medicines and the clinical practice of traditional Chinese medicine.

Renewed classification within Goniurosaurus (Squamata: Eublepharidae) uncovers the dual roles of a continental island (Hainan) in species evolution.

Continental islands are often dynamic in regard to the origin and evolution of their biota. Although colonizations from mainland Southeast Asia to Hainan Island have been reported, the role of Hainan Island as a source for continental biota has not been considered. Goniurosaurus is a genus comprised of nocturnal ground geckos. We reexamined the evolutionary history of Goniurosaurus using both molecular phylogenetics and morphological comparisons. All phylogenetic trees recovered G. zhoui as sister to G. hainanensis + G. lichtenfelderi, which together are the sister lineage of G. bawanglingensis. The recovery of this "Hainan clade" contradicts previous classifications that placed G. bawanglingensis within the G. luii group. Moreover, ancestral trait reconstruction revealed that body band number might have decreased two or three times independently within Goniurosaurus from four to three. The divergence between the continental G. luii group and the Hainan clade was estimated at ∼34.7 Mya (CI = 22.3-48.6), possibly correlating with the vicariance event between Hainan Island and the mainland. G. lichtenfelderi diverged from G. hainanensis very recently, which might be associated with a historical dispersal event from Hainan Island to Vietnam during glacial periods. Our study improves the understanding of Goniurosaurus systematics and reveals the important role of Hainan Island in bidirectional colonizations.

IFN-λ4 inhibits HIV infection of macrophages through signalling of IFN-λR1/IL-10R2 receptor complex.

The recently discovered IFN-λ4 has been found to have antiviral activity against several viruses. However, it's unknown whether IFN-λ4 can inhibit HIV infection. Here, we show that IFN-λ4 could suppress HIV infection of macrophages. This IFN-λ4-mediated HIV inhibition was compromised by the antibodies against IFN-λ receptor complex, IFN-λR1/IL-10R2. IFN-λ4 enhanced the phosphorylation of STAT1, and induced antiviral interferon-stimulated genes. These findings indicated that IFN-λ4 can inhibit HIV via JAK/STAT signalling pathway.

[Study on Indicator Densitometry Determination Method of Hemodynamic Parameters].

Measurement for hemodynamic parameters has always been a hot spot of clinical research. Methods for measuring hemodynamic parameters clinically have the problems of invasiveness, complex operation and being unfit for repeated measurement. To solve the problems, an indicator densitometry analysis method is presented based on near-infrared spectroscopy (NIRS) and indicator dilution theory, which realizes the hemodynamic parameters measured noninvasively. While the indocyanine green (ICG) was injected into human body, circulation carried the indicator mixing and diluting with the bloodstream. Then the near-nfrared probe was used to emit near-infrared light at 735, 805 and 940 nm wavelengths through the sufferer's fingertip and synchronously capture the transmission light containing the information of arterial pulse wave. By uploading the measured data, the computer would calculate the ICG concentration, establish continuous concentration curve and compute some intermediate variables such as the mean transmission time (MTT) and the initial blood ICG concentration (c(t0)). Accordingly Cardiac Output (CO) and Circulating Blood Volume (CBV) could be calculated. Compared with the clinical "gold standard" methods of thermodilution and I-131 isotope-labelling method to measure the two parameters by clinical controlled trials, ten sets of data were obtained. The maximum relative errors of this method were 8.88% and 4.28% respectively, and both of the average relative errors were below 5%. The result indicates that this method can meet the clinical accuracy requirement and can be used as a noninvasive, repeatable and applied solution for clinical hemodynamnic parameters measurement.

Phylogeny and origins of hantaviruses harbored by bats, insectivores, and rodents.

Hantaviruses are among the most important zoonotic pathogens of humans and the subject of heightened global attention. Despite the importance of hantaviruses for public health, there is no consensus on their evolutionary history and especially the frequency of virus-host co-divergence versus cross-species virus transmission. Documenting the extent of hantavirus biodiversity, and particularly their range of mammalian hosts, is critical to resolving this issue. Here, we describe four novel hantaviruses (Huangpi virus, Lianghe virus, Longquan virus, and Yakeshi virus) sampled from bats and shrews in China, and which are distinct from other known hantaviruses. Huangpi virus was found in Pipistrellus abramus, Lianghe virus in Anourosorex squamipes, Longquan virus in Rhinolophus affinis, Rhinolophus sinicus, and Rhinolophus monoceros, and Yakeshi virus in Sorex isodon, respectively. A phylogenetic analysis of the available diversity of hantaviruses reveals the existence of four phylogroups that infect a range of mammalian hosts, as well as the occurrence of ancient reassortment events between the phylogroups. Notably, the phylogenetic histories of the viruses are not always congruent with those of their hosts, suggesting that cross-species transmission has played a major role during hantavirus evolution and at all taxonomic levels, although we also noted some evidence for virus-host co-divergence. Our phylogenetic analysis also suggests that hantaviruses might have first appeared in Chiroptera (bats) or Soricomorpha (moles and shrews), before emerging in rodent species. Overall, these data indicate that bats are likely to be important natural reservoir hosts of hantaviruses.

The Brachypodium distachyon BdWRKY36 gene confers tolerance to drought stress in transgenic tobacco plants.

KEY MESSAGE: The expression of BdWRKY36 was upregulated by drought treatment. BdWRKY36 -overexpressing transgenic tobacco increased drought tolerance by controlling ROS homeostasis and regulating transcription of stress related genes. WRKY transcription factor plays important roles in plant growth, development and stress response. However, the function of group IIe WRKYs is less known. In this study, we cloned and characterized a gene of group IIe WRKY, designated as BdWRKY36, from Brachypodium distachyon. Transient expression of BdWRKY36 in onion epidermal cell suggested its localization in the nucleus. Transactivation assay revealed that the C-terminal region, instead of full length BdWRKY36, had transcriptional activity. BdWRKY36 expression was upregulated by drought. Overexpression of BdWRKY36 in transgenic tobacco plants resulted in enhanced tolerance to drought stress. Physiological-biochemical indices analyses showed that BdWRKY36-overexpressing tobacco lines had lesser ion leakage (IL) and reactive oxygen species (ROS) accumulation, but higher contents of chlorophyll, relative water content (RWC) and activities of antioxidant enzyme than that in control plants under drought condition. Meanwhile expression levels of some ROS-scavenging and stress-responsive genes were upregulated in BdWRKY36-overexpressing tobacco lines under drought stress. These results demonstrate that BdWRKY36 functions as a positive regulator of drought stress response by controlling ROS homeostasis and regulating transcription of stress related genes.