Macrophages promote anti-androgen resistance in prostate cancer bone disease.

Metastatic castration-resistant prostate cancer (PC) is the final stage of PC that acquires resistance to androgen deprivation therapies (ADT). Despite progresses in understanding of disease mechanisms, the specific contribution of the metastatic microenvironment to ADT resistance remains largely unknown. The current study identified that the macrophage is the major microenvironmental component of bone-metastatic PC in patients. Using a novel in vivo model, we demonstrated that macrophages were critical for enzalutamide resistance through induction of a wound-healing-like response of ECM-receptor gene expression. Mechanistically, macrophages drove resistance through cytokine activin A that induced fibronectin (FN1)-integrin alpha 5 (ITGA5)-tyrosine kinase Src (SRC) signaling cascade in PC cells. This novel mechanism was strongly supported by bioinformatics analysis of patient transcriptomics datasets. Furthermore, macrophage depletion or SRC inhibition using a novel specific inhibitor significantly inhibited resistant growth. Together, our findings elucidated a novel mechanism of macrophage-induced anti-androgen resistance of metastatic PC and a promising therapeutic approach to treat this deadly disease.

Root-Associated Microbiomes of Panax notoginseng under the Combined Effect of Plant Development and Alpinia officinarum Hance Essential Oil.

Essential oils (EOs) have been proposed as an alternative to conventional pesticides to inhibit fungal pathogens. However, the application of EOs is considerably limited due to their highly volatile nature and unpredictable effects on other microbes. In our study, the composition of bacterial and fungal communities from the rhizosphere soil of P. notoginseng under four treatment levels of Alpinia officinarum Hance EO was characterized over several growth stages. Leaf weight varied dramatically among the four EO treatment levels after four months of growth, and the disease index at a low concentration (0.14 mg/g) of EO addition was the lowest among the P. notoginseng growth stages. The content of monomeric saponins was elevated when EO was added. Bacterial and fungal diversity in the absence of plants showed a decreasing trend with increasing levels of EO. Bacterial diversity recovery was more correlated with plant growth than was fungal diversity recovery. Compared with the control (no EO addition), a low concentration of EO significantly accumulated Actinomycota, including Acidothermus, Blastococcus, Catenulispora, Conexibacter, Rhodococcus, and Sinomonas, after one month of plant-microbial interaction. Overall, the results showed that both the plant growth stage and EOs drive changes in the microbial community composition in the rhizosphere of P. notoginseng. Plant development status had a stronger influence on bacterial diversity than on fungal diversity. EO had a more significant effect on fungal community composition, increasing the dominance of Ascomycota when EO concentration was increased. Under the interaction of P. notoginseng growth and EO, a large number of bacterial genera that have been described as plant growth-promoting rhizobacteria (PGPR) responded positively to low concentrations of EO application, suggesting that EO may recruit beneficial microbes in the root zone to cope with pathogens and reduce root rot disease. These results offer novel insights into the relationship between EO application, altered microbial communities in the plant roots, plant growth stage, and disease occurrence.

Chord: an ensemble machine learning algorithm to identify doublets in single-cell RNA sequencing data.

High-throughput single-cell RNA sequencing (scRNA-seq) is a popular method, but it is accompanied by doublet rate problems that disturb the downstream analysis. Several computational approaches have been developed to detect doublets. However, most of these methods may yield satisfactory performance in some datasets but lack stability in others; thus, it is difficult to regard a single method as the gold standard which can be applied to all types of scenarios. It is a difficult and time-consuming task for researchers to choose the most appropriate software. We here propose Chord which implements a machine learning algorithm that integrates multiple doublet detection methods to address these issues. Chord had higher accuracy and stability than the individual approaches on different datasets containing real and synthetic data. Moreover, Chord was designed with a modular architecture port, which has high flexibility and adaptability to the incorporation of any new tools. Chord is a general solution to the doublet detection problem.

Clinical Auditory Phenotypes Associated with GATA3 Gene Mutations in Familial Hypoparathyroidism-deafness-renal Dysplasia Syndrome.

BACKGROUND: Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene mutations, and hearing loss is the most frequent phenotypic feature. This study aimed at identifying the causative gene mutation for a three-generation Chinese family with HDR syndrome and analyzing auditory phenotypes in all familial HDR syndrome cases. METHODS: Three affected family members underwent otologic examinations, biochemistry tests, and other clinical evaluations. Targeted genes capture combining next-generation sequencing was performed within the family. Sanger sequencing was used to confirm the causative mutation. The auditory phenotypes of all reported familial HDR syndrome cases analyzed were provided. RESULTS: In Chinese family 7121, a heterozygous nonsense mutation c.826C>T (p.R276*) was identified in GATA3. All the three affected members suffered from sensorineural deafness and hypocalcemia; however, renal dysplasia only appeared in the youngest patient. Furthermore, an overview of thirty HDR syndrome families with corresponding GATA3 mutations revealed that hearing impairment occurred earlier in the younger generation in at least nine familial cases (30%) and two thirds of them were found to carry premature stop mutations. CONCLUSIONS: This study highlights the phenotypic heterogeneity of HDR and points to a possible genetic anticipation in patients with HDR, which needs to be further investigated.

Seroprevalence and genetic characterization of Toxoplasma gondii in masked palm civet (Paguma larvata) in Hainan province, tropical China.

In the present study, the seroprevalence, risk factors and genotyping of Toxoplasma gondii in masked palm civet were investigated in tropical China. A total of 500 serum were collected from five administrative farms in tropical China, and assayed for T. gondii antibodies by modified agglutination test (MAT). The brain samples of 20 aborted fetuses were examined by semi-nested-PCR, and positive aborted fetuses (50%) were necropsied to collect the brain tissue for molecular and bioassay examinations. Genomic DNA was extracted from the 29 brain tissues of infected mice and T. gondii B1 gene was amplified using multilocus PCR-RFLP. Overall, 27.6% (95% CI: 23.682-31.518) of the animals was positive for T. gondii antibodies. Ages of masked palm civet was considered as a main risk factor associated with T. gondii infection. 4 DNA samples (13.8%) were positive for the T. gondii B1 gene. Three samples belong to ToxoDB#9, and one belongs to genotype the type II variant (ToxoDB genotype#3). Our results indicated that ToxoDB Genotype#9 has a distribution in masked palm civet that could be potential reservoirs for T. gondii transmission, which may pose a threat to human health.

Seroprevalence and risk factors of Chlamydia psittaci infection in domestic geese Anser domestica, in Hainan province of China.

Chlamydia psittaci, the agent of psittacosis in humans, infects a wide range of bird species. To assess the risk of psittacosis posed by domestic geese in China, the seroprevalence of C. psittaci infection in domestic geese in Hainan province, tropical China was examined using indirect hemagglutination assay (IHA). The overall seroprevalence was estimated at 25.6% (461/1800; 95% CI: 23.6-27.6). The C. psittaci seroprevalence ranged from 19% (95% CI: 14.6-23.4) to 34% (95% CI: 28.6-39.4) among different regions in Hainan province, and the differences were statistically significant (P<0.01). The risk factors significantly associated with C. psittaci seroprevalence were the presence of hygiene conditions, age, gender, and environment of geese in the farms. The results of the present investigation indicated the high seroprevalence of C. psittaci infection in geese in Hainan province, tropical China. Close contact with these geese is associated with a risk of zoonotic transmission of C. psittaci. Public education should be implemented to reduce the risk of avian to human transmission of such a pathogenic agent. To the best of our knowledge, this is the first report documenting the occurrence of C. psittaci seroprevalence in geese in China.

Seroprevalence, risk factors and genotyping of Toxoplasma gondii in domestic geese (Anser domestica) in tropical China.

BACKGROUND: Little information is available about the seroprevalence of Toxoplasma gondii infection in geese (Anser domestica) in China. In the present investigation, the seroprevalence, risk factors and genotyping of T. gondii in geese were investigated in Hainan province, tropical China. FINDINGS: A total of 600 serum samples and 150 brain tissue samples were collected from six administrative regions in tropical China, and assayed for T. gondii antibodies by Indirect Haemagglutination (IHA) test. Genomic DNA was extracted from the 30 brain tissues of seropositive geese and T. gondii B1 gene was amplified using a semi-nested PCR. DNA samples giving positive B1 amplification were then genetically characterized using multi-locus PCR-RFLP. Overall, 17% (95% CI: 14-20) of the animals were positive for T. gondii antibodies. Presence of cats in the household (odds ratio, OR 3), hygiene (OR 2.3) and presence of stray cat around the house (OR 2.3) were considered as main risk factors associated with T. gondii infection. Of 30 DNA samples, three were positive for the T. gondii B1 gene, two showed complete genotyping results. Only one genotype (type II) was identified. CONCLUSIONS: The results of the present survey indicated the presence of T. gondii infection in geese in tropical China. Therefore, it is imperative that improved integrated measures be carried out to prevent and control T. gondii infection in geese in this province. This is the first report documenting the occurrence of T. gondii genotype in geese in China.

Genetic diagnosis of two dopa-responsive dystonia families by exome sequencing.

Dopa-responsive dystonia, a rare disorder typically presenting in early childhood with lower limb dystonia and gait abnormality, responds well to levodopa. However, it is often misdiagnosed with the wide spectrum of phenotypes. By exome sequencing, we make a rapid genetic diagnosis for two atypical dopa-responsive dystonia pedigrees. One pedigree, presented with prominent parkinsonism, was misdiagnosed as Parkinson's disease until a known mutation in GCH1 (GTP cyclohydrolase 1) gene (NM_000161.2: c.631_632delAT, p.Met211ValfsX38) was found. The other pedigree was detected with a new compound heterozygous mutation in TH (tyrosine hydroxylase) gene [(NM_000360.3: c.911C>T, p.Ala304Val) and (NM_000360.3: c.1358G>A, p.Arg453His)], whose proband, a pregnant woman, required a rapid and less-biased genetic diagnosis. In conclusion, we demonstrated that exome sequencing could provide a precise and rapid genetic testing in the diagnosis of Mendelian diseases, especially for diseases with wide phenotypes.

Seroprevalence and molecular detection of Mycoplasma ovipneumoniae in goats in tropical China.

In the present study, the seroprevalence and genetic identification of Mycoplasma ovipneumoniae infection in goats were investigated in Hainan Province, tropical China between October 2012 and October 2013. A total of 1,210 serum samples collected from 16 herds in various administrative regions in tropical China were evaluated using indirect hemagglutination assay (IHA). Antibodies to M. ovipneumoniae were tested in (31.7 %, 95 % confidence interval (CI) 29-34.3) 383 of 1,210 serum samples (IHA titer ≥1:16). The M. ovipneumoniae seroprevalence ranged from 26.8 % (95 % CI 20.8-32.9) to 39 % (95 % CI 30.8-47.2) among different regions in tropical China, and the difference was statistically significant (P < 0.01). The seroprevalence of M. ovipneumoniae infection in goats was higher in winter (46.1 %, 95 % CI 39.6-52.5) and spring (33.8 %, 95 % CI 28.3-39.3) than in autumn (27.5 %, 95 % CI 22.6-32.3) and summer (24.7 %, 95 % CI 20.3-29.1), and the difference was statistically significant (P < 0.01). In addition, DNA was extracted from nasal swab; lung samples and the 16S rRNA gene sequences were amplified by polymerase chain reaction (PCR) and then sequenced. Twenty-four of 329 (7.3 %) nasal swab samples and 73 of 280 (26.1 %) pneumonic lung tissues were found to contain M. ovipneumoniae, respectively. The results of the present survey indicate that M. ovipneumoniae infection is highly prevalent in goats in tropical China. This is the first report of the comprehensive survey of M. ovipneumoniae prevalence in goats in China.

Identification and characterization of genes related to the development of skeletal muscle in the Hainan black goat.

In total, 185 unigenes were identified from 380 clones of postnatal skeletal muscle of Hainan Black goats by suppression subtractive hybridization (SSH) technology. Most of the differentially expressed genes involved energy metabolism and muscle contraction. The expression of 19 genes was analyzed in the longissimus dorsi muscles of 2-, 6-, 12-, 24-month olds, and four gene expression patterns were found by hierarchical cluster analysis. Most genes in first expression pattern belonged to myofibrillar proteins and had higher expression levels at 2 months old; genes of the secondary expression pattern had higher expression levels at 12 months old; tropomyoain 1 (alpha) (TPM1) was classified into the third expression pattern, and its expression level showed decreases tendency as age increased. Tropomyoain 2 (beta) (TPM2) was classified into the third expression pattern, which had the opposite expression pattern against TPM1.

Association of thyroglobulin gene variants with carcass and meat quality traits in beef cattle.

Thyroid hormones play an important role in regulating metabolism and can affect homeostasis of fat deposition. The gene encoding thyroglobulin (TG), producing the precursor for thyroid hormones, has been proposed as a positional and functional candidate gene for a QTL with an effect on fat deposition. In the present study, we identified 6 novel SNPs at the 3' flanking region of the TG gene. The SNP marker association analysis indicated that the T354C, G392A, A430G and T433G SNP markers were significantly associated with marbling score (P < 0.05). Animals with the new homozygote genotype had higher marbling score than those with the other genotypes. Otherwise, the linkage disequilibrium analysis indicated that these four SNPs were completely linked (r (2) = 1). Results from this study suggest that TG gene-specific SNP may be a useful marker for meat quality traits in future marker assisted selection programs in beef cattle.