The Role of Retinal Dopamine D1 Receptors in Ocular Growth and Myopia Development in Mice.

Dopamine is a key neurotransmitter in the signaling cascade controlling ocular refractive development, but the exact role and site of action of dopamine D1 receptors (D1Rs) involved in myopia remains unclear. Here, we determine whether retinal D1Rs exclusively mediate the effects of endogenous dopamine and systemically delivered D1R agonist or antagonist in the mouse form deprivation myopia (FDM) model. Male C57BL/6 mice subjected to unilateral FDM or unobstructed vision were divided into the following four groups: one noninjected and three groups that received intraperitoneal injections of a vehicle, D1R agonist SKF38393 (18 and 59 nmol/g), or D1R antagonist SCH39166 (0.1 and 1 nmol/g). The effects of these drugs on FDM were further assessed in Drd1-knock-out (Drd1-KO), retina-specific conditional Drd1-KO (Drd1-CKO) mice, and corresponding wild-type littermates. In the visually unobstructed group, neither SKF38393 nor SCH39166 affected normal refractive development, whereas myopia development was attenuated by SKF38393 and enhanced by SCH39166 injections. In Drd1-KO or Drd1-CKO mice, however, these drugs had no effect on FDM development, suggesting that activation of retinal D1Rs is pertinent to myopia suppression by the D1R agonist. Interestingly, the development of myopia was unchanged by either Drd1-KO or Drd1-CKO, and neither SKF38393 nor SCH39166 injections, nor Drd1-KO, affected the retinal or vitreal dopamine and the dopamine metabolite DOPAC levels. Effects on axial length were less marked than effects on refraction. Therefore, activation of D1Rs, specifically retinal D1Rs, inhibits myopia development in mice. These results also suggest that multiple dopamine D1R mechanisms play roles in emmetropization and myopia development.SIGNIFICANCE STATEMENT While dopamine is recognized as a "stop" signal that inhibits myopia development (myopization), the location of the dopamine D1 receptors (D1Rs) that mediate this action remains to be addressed. Answers to this key question are critical for understanding how dopaminergic systems regulate ocular growth and refraction. We report here the results of our study showing that D1Rs are essential for controlling ocular growth and myopia development in mice, and for identifying the retina as the site of action for dopaminergic control via D1Rs. These findings highlight the importance of intrinsic retinal dopaminergic mechanisms for the regulation of ocular growth and suggest specific avenues for exploring the retinal mechanisms involved in the dopaminergic control of emmetropization and myopization.

MEG3 in hematologic malignancies: from the role of disease biomarker to therapeutic target.

Maternally expressed gene 3 (MEG3) is a noncoding RNA that is known as a tumor suppressor in solid cancers. Recently, a line of studies has emphasized its potential role in hematological malignancies in terms of tumorigenesis, metastasis, and drug resistance. Similar to solid cancers, MEG3 can regulate various cancer hallmarks via sponging miRNA, transcriptional, or posttranslational regulation mechanisms, but may regulate different key elements. In contrast with solid cancers, in some subtypes of leukemia, MEG3 has been found to be upregulated and oncogenic. In this review, we systematically describe the role and underlying mechanisms of MEG3 in multiple types of hematological malignancies. Particularly, we highlight the role of MEG3 in drug resistance and as a novel therapeutic target.

Transcriptome and Hormonal Analysis of Agaricus bisporus Basidiome Response to Hypomyces perniciosus Infection.

Agaricus bisporus (Lange) Imbach is the most widely cultivated mushroom in the world. A. bisporus wet bubble disease is one of the most severe diseases of white button mushrooms and is caused by the fungal pathogen Hypomyces perniciosus. The pathogen causes a drastic reduction in mushroom yield because of malformation and deterioration of the basidiomes. However, the mechanism of the button mushroom's malformation development after infection with H. perniciosus remains obscure. Therefore, to reveal the mechanism of A. bisporus malformation caused by H. perniciosus, the interaction between the pathogen and host was investigated in this study using histopathological, physiological, and transcriptomic analyses. Results showed that irrespective of the growth stages of A. bisporus basidiomes infected with H. perniciosus, the host's malformed basidiomes and enlarged mycelia and basidia indicated that the earlier the infection with H. perniciosus, the more the malformation of the basidiomes. Analyzing physiological and transcriptomic results in tandem, we concluded that H. perniciosus causes malformation development of A. bisporus mainly by affecting the metabolism level of phytohormones (N6-isopentenyladenosine, cis-zeatin, and N6-[delta 2-isopentenyl]-adenine) of the host's fruiting bodies rather than using toxins. Our findings revealed the mechanism of the button mushroom's malformation development after infection with H. perniciosus, providing a reference for developing realistic approaches to control mushroom diseases. Our results further clarified the interaction between A. bisporus and H. perniciosus and identified the candidate genes for A. bisporus wet bubble disease resistance breeding. Additionally, our work provides a valuable theoretical basis and technical support for studying the interaction between other pathogenic fungi and their fungal hosts.

Joint-GWAS, Linkage Mapping, and Transcriptome Analysis to Reveal the Genetic Basis of Plant Architecture-Related Traits in Maize.

Plant architecture is one of the key factors affecting maize yield formation and can be divided into secondary traits, such as plant height (PH), ear height (EH), and leaf number (LN). It is a viable approach for exploiting genetic resources to improve plant density. In this study, one natural panel of 226 inbred lines and 150 family lines derived from the offspring of T32 crossed with Qi319 were genotyped by using the MaizeSNP50 chip and the genotyping by sequence (GBS) method and phenotyped under three different environments. Based on the results, a genome-wide association study (GWAS) and linkage mapping were analyzed by using the MLM and ICIM models, respectively. The results showed that 120 QTNs (quantitative trait nucleotides) and 32 QTL (quantitative trait loci) related to plant architecture were identified, including four QTL and 40 QTNs of PH, eight QTL and 41 QTNs of EH, and 20 QTL and 39 QTNs of LN. One dominant QTL, qLN7-2, was identified in the Zhangye environment. Six QTNs were commonly identified to be related to PH, EH, and LN in different environments. The candidate gene analysis revealed that Zm00001d021574 was involved in regulating plant architecture traits through the autophagy pathway, and Zm00001d044730 was predicted to interact with the male sterility-related gene ms26. These results provide abundant genetic resources for improving maize plant architecture traits by using approaches to biological breeding.

Transcranial Magneto-Acoustic Stimulation Protects Synaptic Rehabilitation from Amyloid-Beta Plaques via Regulation of Microglial Functions.

Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic-acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aß) plaque and synaptic plasticity in Alzheimer's disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aß. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aß plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer's disease.

Angioimmunoblastic T-cell lymphoma: Novel recurrent mutations and prognostic biomarkers by cell-free DNA profiling.

Molecular and clinical stratification of patients with angioimmunoblastic T-cell lymphoma (AITL) is unsatisfactory, which hinders the development of personalized therapies. This study aimed to identify molecular biomarkers for AITL based on peripheral cell-free DNA (cfDNA) that could be used to predict prognosis and guide treatment non-invasively. A customized panel containing 46 genes was used to study pretreatment cfDNA and paired tumour tissues in 64 Chinese AITL patients from three clinical centres, and gene mutations in cfDNA and tumour tissue were assessed for concordance (34 paired samples). Then, the association of gene mutations and prognosis was analysed, and a functional enrichment analysis was performed. The sequencing results showed good consistency between cfDNA samples and paired tissue samples. KDM5A, STAT1, FANCM, ERBB4, PIK3R5 and NSD1 were identified as novel recurrent mutations. Mutations in FANCM or combinations of RHOA, KDM5A and FAT1 were associated with poor prognosis. Additionally, functional analysis revealed that RHOAG17 might serve as a predictive biomarker of PD-1 blockade respondence. Our findings confirmed the role of cfDNA as a liquid biopsy in AITL, and revealed novel molecular determinants that can stratify patients and guide treatment options.

Efficacy and safety of direct-acting antiviral therapies and baseline predictors for treatment outcomes in hepatitis C patients: A multicenter, real-world study in Guangdong, China.

The data on direct-acting antivirals (DAAs) in chronic hepatitis C (CHC) patients in southern China with multiple genotypes circulating are limited. This study aims to evaluate the efficacy and safety of DAA regimens among CHC patients in Guangdong, China. A total of 220 patients receiving a variety of DAA were enrolled. The primary outcome was sustained virologic response (SVR) at 12 weeks. Resistance associated substitutions (RASs) were evaluated by deep sequencing. The overall SVR rate was 96.4%, and was 97.7% for genotype 1, 100% for genotype 2, 91.9% for genotype 3, 95.7% for genotype 6, and 100% for untyped. The overall incidence of adverse events (AEs) was 8.2% (18/220) and all the AEs were mild. Nonstructural proteins 5A RAS, 30K/31M, and Y93H were most prevalent at baseline and the end of treatment in non-SVR patients, respectively. Logistics regression showed that elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at baseline were specifically associated with non-SVR in patients with genotype 3 and 6 infections (p = 0.029 and p = 0.017) but not genotype 1 infection (p = 0.746 and p = 0.971), and baseline AST was the best predictor for SVR in genotypes 3 and 6 patients (area under curve = 0.890). Our studies demonstrated all DAA regimens achieved ideal SVR and were well tolerated. NS5A RAS were prevalent in non-SVR patients. Elevated ALT and AST as baseline predictors for non-SVR in genotypes 3 and 6 infections warrant further research in a larger cohort.

Pyroptosis associated with immune reconstruction failure in HIV-1- infected patients receiving antiretroviral therapy: a cross-sectional study.

BACKGROUND: Highly active anti-retroviral therapy (HAART) can successfully suppress human immunodeficiency virus (HIV) viral replication and reconstruct immune function reconstruction in HIV-1-infected patients. However, about 15-30% of HIV-1-infected patients still fail to recover their CD4+ T cell counts after HAART treatment, which means immune reconstruction failure. Pyroptosis plays an important role in the death of CD4+ T cells in HIV-1- infected patients. The study aims to explore the association between the expression of pyroptosis in peripheral blood and immune function reconstruction in HIV-1- infected patients. METHODS: One hundred thirty-five HIV-1-infected patients including immunological non-responders (INR) group, immunological responders (IR) group and normal immune function control (NC) group were analyzed. The expression of GSDMD and Caspase-1 in peripheral blood of HIV-1-infected patients were measured by qPCR. The concentrations of GSDMD, Caspase-1, IL-1ß and IL-18 in the peripheral serum were quantified by ELISA. The associations between the expression of pyroptosis in peripheral blood and immune function reconstruction were analyzed using multivariate logistic models. RESULTS: The relative expression of GSDMD mRNA and caspase-1 mRNA in peripheral blood, as well as the expression of IL-18 cytokine in the INR, were significantly higher than those in the IR and NC (P < 0.05). There was no significant difference in the expression of IL-1ß cytokine (P > 0.05). Multivariate logistic analysis showed that the patients with baseline CD4+ T cell counts less than 100 cells/µL (aOR 7.051, 95% CI 1.115-44.592, P = 0.038), high level of expression of Caspase-1mRNA (aOR 2.803, 95% CI 1.065-7.377, P = 0.037) and IL-18 cytokine (aOR 10.131, 95% CI 1.616-63.505, P = 0.013) had significant poor CD4+ T cell recovery. CONCLUSIONS: The baseline CD4+ T cell counts less than 100 cells/µL, high relative expression of Caspase-1 mRNA, and high expression of IL-18 cytokine are associated factors that affect the reconstruction of immune function.

Morphology and Phylogeny Reveal Callistosporium subpetaloideum sp. nov. (Callistosporiaceae) from China.

A new species, Callistosporium subpetaloideum is described from Guizhou province, China. The key characteristics of C. subpetaloideum are its depressed, subpetaloid, finely pubescent pileus, pruinose apexed central stipe, large elliptical spores up to 7 µm long and 5 µm wide, lacking cystidia and clamp connection. Phylogenetic analyses based on the internal transcribed spacer region indicated that C. subpetaloideum occupies an isolated position, while morphological characteristics have also been compared with other phenotypically similar species.

Efficacy of 104-week Telbivudine-based optimization strategy in patients with HBeAg-negative chronic hepatitis B virus infections.

BACKGROUND: Evaluate the safety and efficacy of 104-week regimen of Telbivudine(LdT)-based optimization strategy for Chinese patients who have chronic hepatits B(CHB) with HBeAg-negative. METHODS: This multi-center, open-label, prospective study enrolled 108 HBeAg-negative CHB patients who received LdT (600 mg/day) for 24 weeks, Adefovir (ADV) was added if HBV DNA remained detectable at week 24, otherwise LdT was maintained to use until 104 weeks. HBV DNA, alanine amino transferase (ALT), hepatitis B surface antigen(HBsAg), creatinine kinase(CK), and estimated glomerular filtration rate (eGFR) were measured, safety was assessed. RESULTS: Eighty-eight patients (81%) had HBV-DNA undetectable at 24 weeks and maintained to receive LdT monotherapy until 104 weeks, whereas the other 20 patients had HBV-DNA detectable and ADV was used in combination. For all patients, 72% of patients reached ALT normalization at 24 weeks, which increased to 80% at 52 weeks and 104 weeks, respectively.. 81% of total patients had undetectable HBV-DNA at 24 weeks, 92% at 52 weeks, and 94% at 104 weeks. The HBsAg titre declined steadily from baseline to 104 weeks (3.62 vs. 2.98 log10 IU/mL, p < 0.05), and the eGFR increased steadily from baseline to 104 weeks (92.9 vs. 104.4 mL/min/1.73 m2, p < 0.05). Although 79 patients (73%) had at least one time of elevated CK, most of these patients had CK elevated in Grade 1/2. CONCLUSIONS: LdT was well tolerated and effective, and 94% of patients achieved virological suppression after 104 weeks. TRIAL REGISTRATION: This study was registered in clinicaltrials.gov on January 31, 2012 and the ID No. was NCT01521975 .

Chronic Mycobacterium avium skin and soft tissue infection complicated with scalp osteomyelitis possibly secondary to anti-interferon-γ autoantibody formation.

BACKGROUND: Nontuberculous mycobacterial (NTM) disease is commonly an opportunistic infection frequently found in immunocompromised individuals, but sometimes can also be found in the immunocompetent hosts, especially in East Asians. The NTM separation rate in China is increasing, which reminds us to focus on NTM infections in immunocompromised populations. CASE PRESENTATION: A 43-year-old woman with a recurrent fever for more than 8-month and a right forehead surgical wounds unhealed for more than 6-month was admitted to our hospital on February 22, 2018. On arrival, several elliptic ulcers were obvious on the right forehead with pus and fibrin exudation, and the skin around the lesions was tender, reddish, no sense of fluctuation. The result of HIV serology test was negative. CD4+ T cell count was normal and tuberculosis antibody was negative. CT of the chest and head showed bone destruction. Skin biopsy on the right forehead was performed on March 13, 2018, and pathological examination of the excisional biopsy specimen found inflammatory granuloma and suppurative inflammatory changes. Broad-spectrum antibiotics were treated but the effect seemed discontent. Then debridement and skin grafting were performed on the right frontal ulcer under general anesthesia on April 3, 2018. The skin tissue culture that resected on March 13, 2018 found Nontuberculous mycobacteria grown after 78 days, so clarithromycin, ethambutol, protionamide, and amoxicillin clavulanate potassium were prescribed for anti-nontuberculous mycobacteria treatment beginning on May 31, 2018. In reviewing the case, Mycobacterium avium (M. avium) was identified in the skin tissue resected on April 3, 2018 by polymerase chain reaction (PCR) and the serum test of anti-interferon-γ autoantibodies was positive. CONCLUSIONS: This is a case report of "Mycobacterium avium SSTI (skin and soft tissue infection) and OM (osteomyelitis) with possible secondary immunodeficiency syndrome induced by anti-interferon-γ autoantibody".

The effect of Hypomyces perniciosus on the mycelia and basidiomes of Agaricus bisporus.

Hypomyces perniciosus has been reported as a destructive pathogen of Agaricus bisporus. Previous research suggested that the pathogenesis may not only be perpetuated by H. perniciosus, but also by bacteria. Clarification of the interaction between A. bisporus and H. perniciosus is a prerequisite for the development of effective control measures against wet bubble disease. Here, the effects of H. perniciosus on A. bisporus mycelia are examined in dual culture on agar media and in open-ended test tubes. During disease development, the putative causal agents and cytology of wet bubble-diseased mushrooms were followed microscopically. The interaction between H. perniciosus and the basidiome of A. bisporus was also studied using dual-cultured H. perniciosus and basidiome tissues. Dual-cultured mycelia from both fungi showed that growth continued even after contact was made, without any observable antagonistic lines or cytoplasmic changes of A. bisporus mycelia. Hypomyces perniciosus could be isolated from diseased basidiomes any time after inoculation, but bacteria were only recovered after the basidiomes of A. bisporus had been killed by H. perniciosus. Dual culture of the basidiome tissue of A. bisporus and H. perniciosus on agar media established that H. perniciosus can independently and rapidly degrade the basidiomes of A. bisporus. We conclude that H. perniciosus has no pathogenic activity on the mycelial stage of A. bisporus, but it can destroy A. bisporus basidiomes in the absence of bacteria. Wet bubble disease is evidently not caused by bacteria, but by the fungus, although bacteria likely participate in the disease after invasion by the fungus.

Metformin, beyond an insulin sensitizer, targeting heart and pancreatic ß cells.

Metformin, a biguanide derivate, is known as the first-line antidiabetic agent for type 2 diabetes mellitus (T2DM) treatment. It reduces insulin resistance and decreases blood glucose concentration by inhibiting gluconeogenesis and suppressing hepatic glucose production with improved peripheral tissue insulin sensitivity. As an insulin sensitizer, metformin takes pleiotropic actions and exerts protective effects on multiple organs mainly in insulin-targeted tissues such as liver, muscle, and adipose tissues. Recent studies discover that metformin also plays essential roles in heart and pancreatic ß cells - two important organs in metabolic regulation. Metformin not only protects T2DM patients from cardiovascular diseases and heart failure, but also restores insulin secretion activities and protects pancreatic ß cells from lipotoxicity or glucotoxicity. Although accumulated evidence shed light on the metformin action, the precise mechanism of metformin is still under investigation. Further laboratory investigations and clinical trials are needed to pinpoint a map of metformin action. Based on recent findings, this review characterizes the beneficial role of metformin in cardiovascular diseases and pancreatic ß cells.

At least partial hematological response after first cycle of treatment predicts organ response and long-term survival for patients with AL amyloidosis receiving bortezomib-based treatment.

AL amyloidosis is a rare plasma cell dyscrasia characterized by multi-organ involvement and poor prognosis. We retrospectively evaluated the organ response (OR) and long-term survival of newly diagnosed AL amyloidosis patients who received first-line bortezomib-containing induction therapy, aiming to identify the clinical indication of a 50% reduction in the difference between involved and uninvolved free light chains (dFLC) after first cycle of treatment. Among the 89 patients included, 78.7% had cardiac involvement and 42.7% were diagnosed with 2004 Mayo stage III disease, while 75.3% of patients achieved a hematological response, including 37.1% with complete response and a median response time of 1 month. Cardiac and renal responses were observed in 44.3 and 53.1% of patients, respectively. Sixty-one (68.5%) patients achieved at least 50% reduction in dFLC after the first cycle of therapy. After a median follow-up duration of 12 months, the estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 61.3 and 61.7% respectively. At least 50% reduction in dFLC after the first cycle of therapy was predictive of achieving an OR (p = 0.002), as well as superior PFS (HR = 0.119; 95% CI = 0.045-0.313; p < 0.001) and OS (HR = 0.206; 95% CI = 0.078-0.541; p = 0.001). Additionally, the median PFS and OS were not reached for patients with rapid reduction of dFLC. These results demonstrated that early reduction of dFLC after the first cycle of treatment is predictive of achieving an OR and long-term survival in AL patients receiving bortezomib.

[The development of Agaricus bisporus wet bubble disease and the nuclear phase of pathogen].

Objective: We studied the dynamic nuclear behavior of Hypomyces perniciosus on axenic culture and its disease progression after infection on different growth stages of Agaricus bisporus. Methods: Infection process was initiated by inoculating different stages of A. bisporus fruit body, and different depths of compost and casing soil with H. perniciosus. Disease progression was studied by observing symptoms on the fruit body using light microscopy and scanning electron microscopy. The nuclear behavior of H. perniciosus was determined by observation using fluorescence light microscopy after binding of DNA specific fluorochrome dye (DAPI:4, 6-Diamidino-2-phenylindole dihydrochloride) to the nuclei. Results: Inoculating H. perniciosus on different depths of compost and casing soil resulted in different disease rate as follows:on the surface of casing soil>in the center of casing soil>between the casing soil and the compost>in the center of compost. H. perniciosus can infect any stage of fruit body development, when young primordial (up to 3 mm) was infected, large, irregular and tumorous fungal masses were formed. H. perniciosus directly penetrated A. bisporus without the formation of appressorium-like structures. The germination of the conidia led to a necrotic brown lesion symptom on A. bisporus at the beginning stages of disease development. The mycelium of A. bisporus plasmolysed, hydropically degenerated, cytoplasmolysed, emptied of mycelium cytosol and eventual death as the disease advanced. H. perniciosus produced two types of conidia. Group I conidia had no septa, colorless and smooth containing one nucleus. Group II didymoconidium had septa, containing two nuclei, separated by septa. The first round of mitosis occurred in conidia with no nucleus in the germinal tube. Another kind of asexual spore for thicker cell wall wart convex chlamydospore, chlamydospore had two cells. The upper cell had two nuclear while the basal cell had one or two nuclear, when germinated, it produced one or two germinal tubes. The number of nuclear in the germinal tube was irregular, usually contained 0 to 2 nuclear. Conclusion: H. perniciosus can infect any part of the A. bisporus fruit body and can cause tremendous cytology changed. If we perform single spore isolation to do genetic analysis, one must isolate conidia with no septa.

Identification of Resistance to Wet Bubble Disease and Genetic Diversity in Wild and Cultivated Strains of Agaricus bisporus.

Outbreaks of wet bubble disease (WBD) caused by Mycogone perniciosa are increasing across the world and seriously affecting the yield of Agaricus bisporus. However, highly WBD-resistant strains are rare. Here, we tested 28 A. bisporus strains for WBD resistance by inoculating M. perniciosa spore suspension on casing soil, and assessed genetic diversity of these strains using 17 new simple sequence repeat (SSR) markers developed in this study. We found that 10 wild strains originating from the Tibetan Plateau in China were highly WBD-resistant strains, and 13 cultivated strains from six countries were highly susceptible strains. A total of 88 alleles were detected in these 28 strains, and the observed number of alleles per locus ranged from 2 to 8. Cluster and genetic structure analysis results revealed the wild resources from China have a relatively high level of genetic diversity and occur at low level of gene flow and introgression with cultivated strains. Moreover, the wild strains from China potentially have the consensus ancestral genotypes different from the cultivated strains and evolved independently. Therefore, the highly WBD-resistant wild strains from China and newly developed SSR markers could be used as novel sources for WBD-resistant breeding and quantitative trait locus (QTL) mapping of WBD-resistant gene of A. bisporus.

Selection of Biopsy Site for Patients with Systematic Amyloidosis.

Objective To evaluate the sensitivities of various biopsy methods for the diagnosis of systematic amyloidosis (SA). Methods The clinical data and biopsy results of 194 SA patients who were treated in Peking Union Medical College Hospital from January 2009 to June 2015 were retrospectively analyzed. Results The highest sensitivity was achieved by biopsy of affected organs,with renal biopsy 97.4%,heart biopsy 95.0% and liver biopsy 87.5%. Among non-invasive biopsy methods,tongue biopsy was found to be 75% sensitive,followed by gingiva biopsy at 57%,abdominal fat pad aspiration at 57%,rectum biopsy at 16%,and bone marrow examination at 8%. Combination of tongue and abdominal fat pad biopsy yielded a detection rate of 93.1%. Conclusions Biopsy of the involved organ has the highest sensitivity. However,combination of multiple non-invasive biopsy methods may has sensitivity comparable to organ biopsy and is safer and more convenient.

De novo assembly and characterization of the skeletal muscle transcriptome of sheep using Illumina paired-end sequencing.

OBJECTIVE: In order to enrich the ovine genome and provide a basis for future molecular genetics and functional genomics analyses in sheep, we used de novo assembly to establish transcriptomes of skeletal muscle tissues of Dorper and Small-tailed Han sheep. RESULTS: A total of 103,058,824 clean Illumina paired-end sequencing reads from the two libraries were assembled into 145,524 unigenes in a de novo project. There were 5718 unigenes showing differential expression between the two transcriptomes, and 7437 coding SSRs were exploited. After further assembly, we identified a total of 70,348 all-unigenes with an average length of 863 bp; 35,201 of these all-unigenes could be annotated in the Nr database, and 12,219 were found in the clusters of orthologous groups database. Gene ontology searches indicated cell and binding as the main terms. Among 258 Kyoto Encyclopedia of Genes and Genomes database pathways, protein and amino acid metabolism pathways were the most commonly identified. CONCLUSION: We analyzed the ovine muscle transcriptome using high-throughput sequencing technology. Many unigenes were assembled and numerous molecular markers and differential expressed unigenes were identified.

Past hybridization between two East Asian long-tailed tits (Aegithalos bonvaloti and A. fuliginosus).

INTRODUCTION: Incomplete lineage sorting and hybridization are two major nonexclusive causes of haplotype sharing between species. Distinguishing between these two processes is notoriously difficult as they can generate similar genetic signatures. Previous studies revealed that the mitochondrial DNA (mtDNA) differentiation between two East Asian long-tailed tits (Aegithalos bonvaloti and A. fuliginosus) was extremely low, even lower than intraspecific differentiation in some other long-tailed tits. Using a combination of multilocus and coalescent analyses, we explored the causes of the anomalous lack of mtDNA differentiation between the two species. RESULTS: The mtDNA divergence between the two species was shallow, while the nuclear DNA (nuDNA) divergence was considerably deeper. The IMa analyses based on the mtDNA dataset suggested relatively high gene flow from A. fuliginosus to A. bonvaloti, while negligible gene flow in the opposite direction. In contrast to mtDNA, the migration rates at autosomal and Z-linked nuDNA loci were negligible or much lower. The NEWHYBRIDS analysis assigned all individuals except one to pure parental species with high posterior probability. The Bayesian skyline plot showed that both species underwent population expansions during the Last Glacial Maximum (LGM), and the ecological niche modelling suggested that their ranges overlapped more during the LGM than at present. CONCLUSIONS: We suggest that historical hybridization, in combination with selective sweep and/or genetic drift might be the main causes of the extremely low mtDNA differentiation between the two species. The hybridization probably occurred mainly between A. fuliginosus females and A. bonvaloti males. The LGM distribution expansion might have facilitated hybridization, while the post-LGM distribution contraction could have facilitated some mtDNA sorting. Ongoing hybridization between the two species might be very limited, but further studies with more samples from the contact zone are needed to test this conclusion.

Long non-coding RNA MALAT1 in hematological malignancies and its clinical applications.

ABSTRACT: Metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1 ) is a well-established oncogenic long non-coding RNA, the higher expression of which is strongly correlated with cancer events such as tumorigenesis, progression, metastasis, drug resistance, and treatment outcome in solid cancers. Recently, a series of studies has highlighted its potential role in hematological malignancies in terms of these events. Similar to solid cancers, MALAT1 can regulate various target genes via sponging and epigenetic mechanisms, but the miRNAs sponged by MALAT1 differ from those identified in solid cancers. In this review, we systematically describe the role and underlying mechanisms of MALAT1 in multiple types of hematological malignancies, including regulation of cell proliferation, metastasis, stress response, and glycolysis. Clinically, MALAT1 expression is related to poor treatment outcome and drug resistance, therefore exhibiting potential prognostic value in multiple myeloma, lymphoma, and leukemia. Finally, we discuss the evaluation of MALAT1 as a novel therapeutic target against cancer in preclinical studies.