CD44 polymorphisms have been previously associated with cancer risk. However, the results between independent studies were inconsistent. Here, a meta-analysis was performed to systematically evaluate associations between CD44 polymorphisms and cancer susceptibility. A comprehensive literature search conducted in PubMed, Embase, and Web of Science databases through August 10, 2016 yielded 11 eligible publications consisting of 5,788 cancer patients and 5,852 controls. Overall, odds ratios (OR) calculated with 95% confidence intervals (CI) identified a significant association between CD44 polymorphism rs13347 and cancer susceptibility under all genetic models. Additionally, the minor allele of polymorphism rs11821102 was associated with a decreased susceptibility to cancer in allele contrast, dominant, and heterozygous models, while no significant association was identified for polymorphisms rs10836347, rs713330, or rs1425802. Subgroup analysis by ethnicity revealed rs13347 was significantly associated with cancer susceptibility for Chinese but not for Indians. Linkage disequilibrium (LD) between different polymorphisms varied across diverse ethnic populations. In conclusion, the results indicate that CD44 polymorphism rs13347 acts as a risk factor for cancer, especially in Chinese, while the minor allele of polymorphism rs11821102 may be associated with a decreased susceptibility to cancer. Nevertheless, further studies on a larger population covering different ethnicities are warranted.

Both PET/CT and breast MRI are used to assess pathological complete response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. The aim is to compare the utility of PET/CT and breast MRI by using head-to-head comparative studies. Literature databases were searched prior to July 2016. Eleven studies with a total of 527 patients were included. For PET/CT, the pooled SEN was 0.87 (95% confidence interval (CI): 0.71-0.95) and SPE was 0.85 (95% CI: 0.70-0.93). For MRI, the pooled SEN was 0.79 (95% CI: 0.68-0.87) and SPE was 0.82 (95% CI: 0.72-0.89). In the conventional contrast enhanced (CE)-MRI subgroup, PET/CT outperformed conventional CE-MRI with a higher pooled sensitivity (0.88 (95% CI: 0.71, 0.95) vs. 0.74 (95% CI: 0.60, 0.85), P = 0.018). In the early evaluation subgroup, PET/CT was superior to MRI with a notable higher pooled specificity (0.94 (95% CI: 0.78, 0.98) vs. 0.83 (95% CI: 0.81, 0.87), P = 0.015). The diagnostic performance of MRI is similar to that of PET/CT for the assessment of breast cancer response to NAC. However, PET/CT is more sensitive than conventional CE-MRI and more specific if the second imaging scan is performed before 3 cycles of NAC.

Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions (2p13.3, rs6546481, Minor Allele (MA) = A, ANTXR1, P = 4.3 × 10-7; 5p13.2-p13.1, rs16903936, MA = G, EGFLAM, P = 5.1 × 10-6; 4q21.1, rs10518156, MA = G, SHROOM3, P = 7.1 × 10-6; 19q13.42, rs11882068, MA = G, NLRP9, P = 1.7 × 10-5; 12q24.33, rs4760542, MA = G, GLT1D1, P = 1.8 × 10-5; and 3q27.3, rs11714564, MA = G, RTP1, P = 2.9 × 10-5. Seven SNPs were associated with lower risk of moderate to severe xerostomia, of which only one mapped to specific genomic region (15q21.3, rs4776140, MA = G, LOC105370826, a ncRNA class RNA gene, P = 1.5 × 10-5). Although our small exploratory study did not reach genome-wide statistical significance, our study provides, for the first time, preliminary evidence of genetic susceptibility to xerostomia. Further studies are needed to elucidate the role of genetic susceptibility to xerostomia.

Ganoderma is well known for its use in traditional Chinese medicine and is widely cultivated in China, Korea, and Japan. Increased temperatures associated with global warming are negatively influencing the growth and development of Ganoderma. Nitric oxide is reported to play an important role in alleviating fungal heat stress (HS). However, the transcriptional profiling of Ganoderma oregonense in response to HS, as well as the transcriptional response regulated by NO to cope with HS has not been reported. We used RNA-Seq technology to generate large-scale transcriptome data from G. oregonense mycelia subjected to HS (32 °C) and exposed to concentrations of exogenous NO. The results showed that heat shock proteins (HSPs), "probable stress-induced proteins", and unigenes involved in "D-amino-acid oxidase activity" and "oxidoreductase activity" were significantly up-regulated in G. oregonense subjected to HS (P < 0.05). The significantly up-regulated HSPs, "monooxygenases", "alcohol dehydrogenase", and "FAD/NAD(P)-binding domain-containing proteins" (P < 0.05) regulated by exogenous NO may play important roles in the enhanced HS tolerance of G. oregonense. These results provide insights into the transcriptional response of G. oregonense to HS and the mechanism by which NO enhances the HS tolerance of fungi at the gene expression level.

Trametes species are efficient wood decomposers that are widespread throughout the world. Mitogenomes have been widely used to understand the phylogeny and evolution of fungi. Up to now, two mitogenomes from the Trametes genus have been revealed. In the present study, the complete mitogenomes of two novel Trametes species, Trametes versicolor and T. coccinea, were assembled and compared with other Polyporales mitogenomes. Both species contained circular DNA molecules, with sizes of 67,318 bp and 99,976 bp, respectively. Comparative mitogenomic analysis indicated that the gene number, length and base composition varied between the four Trametes mitogenomes we tested. In addition, all of the core protein coding genes in Trametes species were identified and subjected to purifying selection. The mitogenome of T. coccinea contained the largest number of introns among the four Trametes species tested, and introns were considered the main factors contributing to size variations of Polyporales. Several novel introns were detected in the Trametes species we assembled, and introns identified in Polyporales were found to undergo frequent loss/gain events. Large-scale gene rearrangements were detected between closely related Trametes species, including gene inversions, insertions, and migrations. A well-supported phylogenetic tree for 77 Basidiomycetes was obtained based on the combined mitochondrial gene set using 2 phylogenetic inference methods. The results showed that mitochondrial genes are effective molecular markers for understanding the phylogeny of Basidiomycetes. This study is the first to report the mitogenome rearrangement and intron dynamics of Trametes species, which shed light on the evolution of Trametes and other related species.

To study the mechanism of tea polyphenols (TP)-induced apoptosis of breast cancer cells. Proliferation of MCF-7 and SK-BR-3 cells was evaluated by MTT assays. Cellular ultrastructure was examined by electron microscopy. Apoptosis was detected by TUNEL. PCNA、 Cyclin D1、 Cyclin E and Survivin expression was measured by Western blot. Cell proliferation was significantly inhibited by TP. Spindle and round cells were loosely distributed with increased particles after TP treatment. Increased cell size, frequent nuclear atypia and a collapse of apoptosis were observed. The nucleus was pushed towards one side, while the cytoplasm was rich in free ribosome. The membrane of mitochondria was thickening, and the cell apoptotic body was observed. TP treated cells experienced significantly enhanced apoptosis compared with 5-Fu treated or control groups. The expression of survivin was downregulated by TP. To conclude, TP can inhibit cell growth and induce apoptosis through downregulating the expression of survivin in breast cancer.

In this study, we characterized FgIlv2 and FgIlv6, the catalytic and regulatory subunits of acetohydroxyacid synthase (AHAS) from the important wheat head scab fungus Fusarium graminearum. AHAS catalyzes the first common step in the parallel pathways toward branched-chain amino acids (BCAAs: isoleucine, leucine, valine) and is the inhibitory target of several commercialized herbicides. Both FgILV2 and FgILV6 deletion mutants were BCAA-auxotrophic and showed reduced aerial hyphal growth and red pigmentation when cultured on PDA plates. Conidial formation was completely blocked in the FgILV2 deletion mutant ΔFgIlv2-4 and significantly reduced in the FgILV6 deletion mutant ΔFgIlv6-12. The auxotrophs of ΔFgIlv2-4 and ΔFgIlv6-12 could be restored by exogenous addition of BCAAs but relied on the designated nitrogen source the medium contained. Deletion of FgILV2 or FgILV6 also leads to hypersensitivity to various cellular stresses and reduced deoxynivalenol production. ΔFgIlv2-4 lost virulence completely on flowering wheat heads, whereas ΔFgIlv6-12 could cause scab symptoms in the inoculated spikelet but lost its aggressiveness. Taken together, our study implies the potential value of antifungals targeting both FgIlv2 and FgIlv6 in F. graminearum.

Hidden hearing refers to the functional deficits in hearing without deterioration in hearing sensitivity. This concept is proposed based upon recent finding of massive noise-induced damage on ribbon synapse between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea without significant permanent threshold shifts (PTS). Presumably, such damage may cause coding deficits in auditory nerve fibers (ANFs). However, such deficits had not been detailed except that a selective loss of ANFs with low spontaneous rate (SR) was reported. In the present study, we investigated the dynamic changes of ribbon synapses and the coding function of ANF single units in one month after a brief noise exposure that caused a massive damage of ribbon synapses but no PTS. The synapse count and functional response measures indicates a large portion of the disrupted synapses were re-connected. This is consistent with the fact that the change of SR distribution due to the initial loss of low SR units is recovered quickly. However, ANF coding deficits were developed later with the re-establishment of the synapses. The deficits were found in both intensity and temporal processing, revealing the nature of synaptopathy in hidden hearing loss.

The Asian arowana (Scleropages formosus), one of the world's most expensive cultivated ornamental fishes, is an endangered species. It represents an ancient lineage of teleosts: the Osteoglossomorpha. Here, we provide a high-quality chromosome-level reference genome of a female golden-variety arowana using a combination of deep shotgun sequencing and high-resolution linkage mapping. In addition, we have also generated two draft genome assemblies for the red and green varieties. Phylogenomic analysis supports a sister group relationship between Osteoglossomorpha (bonytongues) and Elopomorpha (eels and relatives), with the two clades together forming a sister group of Clupeocephala which includes all the remaining teleosts. The arowana genome retains the full complement of eight Hox clusters unlike the African butterfly fish (Pantodon buchholzi), another bonytongue fish, which possess only five Hox clusters. Differential gene expression among three varieties provides insights into the genetic basis of colour variation. A potential heterogametic sex chromosome is identified in the female arowana karyotype, suggesting that the sex is determined by a ZW/ZZ sex chromosomal system. The high-quality reference genome of the golden arowana and the draft assemblies of the red and green varieties are valuable resources for understanding the biology, adaptation and behaviour of Asian arowanas.

Leukemia cells are superior to hematopoietic cells with a normal differentiation potential in buffering cellular stresses, but the underlying mechanisms for this leukemic advantage are not fully understood. Using CRISPR/Cas9 deletion of the canonical autophagy-essential gene Atg7, we found that erythroleukemia K562 cells are armed with two sets of autophagic machinery. Alternative mitophagy is functional regardless of whether the canonical autophagic mechanism is intact or disrupted. Although canonical autophagy defects attenuated cell cycling, proliferation and differentiation potential, the leukemia cells retained their abilities for mitochondrial clearance and for maintaining low levels of reactive oxygen species (ROS) and apoptosis. Treatment with a specific inducer of mitophagy revealed that the canonical autophagy-defective erythroleukemia cells preserved a mitophagic response. Selective induction of mitophagy was associated with the upregulation and localization of RAB9A on the mitochondrial membrane in both wild-type and Atg7(-/-) leukemia cells. When the leukemia cells were treated with the alternative autophagy inhibitor brefeldin A or when the RAB9A was knocked down, this mitophagy was prohibited. This was accompanied by elevated ROS levels and apoptosis as well as reduced DNA damage repair. Therefore, the results suggest that erythroleukemia K562 cells possess an ATG7-independent alternative mitophagic mechanism that functions even when the canonical autophagic process is impaired, thereby maintaining the ability to respond to stresses such as excessive ROS and DNA damage.

Quantum dots (QDs) have attracted increasing interest in bioimaging and sensing. Here, we report a biosensor of complex I using ubiquinone-terminated disulphides with different alkyl spacers (QnNS, n = 2, 5 and 10) as surface-capping ligands to functionalise CdSe/ZnS QDs. The enhancement or quenching of the QD bioconjugates fluorescence changes as a function of the redox state of QnNS, since QDs are highly sensitive to the electron-transfer processes. The bioconjugated QnNS-QDs emission could be modulated by complex I in the presence of NADH, which simulates an electron-transfer system part of the mitochondrial respiratory chain, providing an in vitro and intracellular complex I sensor. Epidemiological studies suggest that Parkinson's patients have the impaired activity of complex I in the electron-transfer chain of mitochondria. We have demonstrated that the QnNS-QDs system could aid in early stage Parkinson's disease diagnosis and progression monitoring by following different complex I levels in SH-SY5Y cells.

To enable rational multi-epitope vaccine and diagnostic antigen design, it is imperative to delineate complete IgG-epitome of the protein. Here, we describe results of IgG-epitome decoding of three proteins from high-risk (HR-) oncogenic human papillomavirus type 58 (HPV58). To reveal their entire epitomes, employing peptide biosynthetic approach, 30 precise linear B-cell epitopes (BCEs) were mapped on E6, E7 and L1 proteins using rabbits antisera to the respective recombinant proteins. Using sequence alignment based on BCE minimal motif, the specificity and conservativeness of each mapped BCE were delineated mainly among known HR-HPVs, including finding 3 broadly antibody cross-reactive BCEs of L1 that each covers almost all HR-HPVs. Western blots revealed that 13 of the 18 BCEs within L1-epitome were recognized by murine antisera to HPV58 virus-like particles, suggesting that these are antibody accessible BCEs. Also, a highly conserved epitope (YGD/XTL) of E6 was found to exist only in known common HR-HPVs, which could be used as the first peptide reference marker for judging HR-HPVs. Altogether, this study provides systemic and exhaustive information on linear BCEs of HR-HPV58 that will facilitate development of novel multi-epitope diagnostic reagents/chips for testing viral antibodies and 'universal' preventive HPV peptide vaccine based on L1 conserved BCEs.

Hearing loss has been associated with cognitive decline in the elderly and is considered to be an independent risk factor for dementia. One of the most common causes for acquired sensorineural hearing loss is exposure to excessive noise, which has been found to impair learning ability and cognitive performance in human subjects and animal models. Noise exposure has also been found to depress neurogenesis in the hippocampus. However, the effect is mainly attributed to the oxidant stress of noise on the cognitive brain. In the present study, young adult CBA/CAJ mice (between 1.5 and 2 months of age) were briefly exposed a high sound level to produce moderate-to-severe hearing loss. In both the blood and hippocampus, only transient oxidative stress was observed after noise exposure. However, a deficit in spatial learning/memory was revealed 3 months after noise exposure. Moreover, the deficit was correlated with the degree of hearing loss and was associated with a decrease in neurogenesis in the hippocampus. We believe that the observed effects were likely due to hearing loss rather than the initial oxidant stress, which only lasted for a short period of time.

Differential methylation of the homologous chromosomes, a well-known mechanism leading to genomic imprinting and X-chromosome inactivation, is widely reported at the non-imprinted regions on autosomes. To evaluate the transgenerational DNA methylation patterns in human, we analyzed the DNA methylomes of somatic and germ cells in a four-generation family. We found that allelic asymmetry of DNA methylation was pervasive at the non-imprinted loci and was likely regulated by cis-acting genetic variants. We also observed that the allelic methylation patterns for the vast majority of the cis-regulated loci were shared between the somatic and germ cells from the same individual. These results demonstrated the interaction between genetic and epigenetic variations and suggested the possibility of widespread sequence-dependent transmission of DNA methylation during spermatogenesis.

The artemisinin (ART), discovered in China, has been widely used against malaria in China over the last 30 years. Understanding the emergence and origin of ART resistance in China is therefore of great interest. We analyzed 111 culture-adapted isolates of P. falciparum from China-Myanmar (CM) border for their susceptibility to dihydroartemisinin using the ring stage survival assay (RSA0-3h) and genotyped their K13 genes. Of the isolates, 59 had a wild type of the K13 marker and a median ring survival rate of 0.26% (P95 = 1.005%). Among the remaining isolates harboring single mutations in the K13 marker, 26 survived at >P95(median survival rate = 2.95%). Further, we genotyped the K13 gene of 693 isolates collected from different regions in China and China-Myanmar/Thai-Cambodia/Thai-Myanmar (CM/TC/TM) borders, 308 (44.4%) had K13 mutations and marked differences in the patterns of K13 mutations were observed between the CM and the TC/TM borders. A network diagram showed that majority of the K13 mutant alleles from the CM border clustered together including those harboring the high resistant-associated R539T mutations. The resistant parasites carrying distinct halplotypes suggested the multiple indigenous origins of the resistant alleles, which highlight the importance of surveillance of resistance in all malaria endemic areas where ART has been introduced.

The EtOAc extract of Coreopsis tinctoria Nutt. significantly inhibited LPS-induced nitric oxide (NO) production, as judged by the Griess reaction, and attenuated the LPS-induced elevation in iNOS, COX-2, IL-1β, IL-6 and TNF-α mRNA levels, as determined by quantitative real-time PCR, when incubated with BV-2 microglial cells. Immunohistochemical results showed that the EtOAc extract significantly decreased the number of Iba-1-positive cells in the hippocampal region of LPS-treated mouse brains. The major effective constituent of the EtOAc extract, okanin, was further investigated. Okanin significantly suppressed LPS-induced iNOS expression and also inhibited IL-6 and TNF-α production and mRNA expression in LPS-stimulated BV-2 cells. Western blot analysis indicated that okanin suppressed LPS-induced activation of the NF-κB signaling pathway by inhibiting the phosphorylation of IκBα and decreasing the level of nuclear NF-κB p65 after LPS treatment. Immunofluorescence staining results showed that okanin inhibited the translocation of the NF-κB p65 subunit from the cytosol to the nucleus. Moreover, okanin significantly inhibited LPS-induced TLR4 expression in BV-2 cells. In summary, okanin attenuates LPS-induced activation of microglia. This effect may be associated with its capacity to inhibit the TLR4/NF-κB signaling pathways. These results suggest that okanin may have potential as a nutritional preventive strategy for neurodegenerative disorders.

Autophagy is essentially a metabolic process, but its in vivo role in nuclear radioprotection remains unexplored. We observed that ex vivo autophagy activation reversed the proliferation inhibition, apoptosis, and DNA damage in irradiated hematopoietic cells. In vivo autophagy activation improved bone marrow cellularity following nuclear radiation exposure. In contrast, defective autophagy in the hematopoietic conditional mouse model worsened the hematopoietic injury, reactive oxygen species (ROS) accumulation and DNA damage caused by nuclear radiation exposure. Strikingly, in vivo defective autophagy caused an absence or reduction in regulatory proteins critical to both homologous recombination (HR) and non-homologous end joining (NHEJ) DNA damage repair pathways, as well as a failure to induce these proteins in response to nuclear radiation. In contrast, in vivo autophagy activation increased most of these proteins in hematopoietic cells. DNA damage assays confirmed the role of in vivo autophagy in the resolution of double-stranded DNA breaks in total bone marrow cells as well as bone marrow stem and progenitor cells upon whole body irradiation. Hence, autophagy protects the hematopoietic system against nuclear radiation injury by conferring and intensifying the HR and NHEJ DNA damage repair pathways and by removing ROS and inhibiting apoptosis.

The microbiome has emerged as a new player on behavior, physiology and stress because of its significant effects on the brain-gut axis. The aim of this study was to increase our understanding of brain-gut function in dairy cows. We investigated the effects of a heat-stress (HS) environment and individual differences of heat sensitivity (IH) on bovine physiological characteristics and microbial composition. Results indicate that both HS and IH increased rectal temperature (RT) (P < 0.05). An HS environment increased plasma, as well as milk cortisol and cytokines in plasma; however, it decreased plasma, and milk oxytocin, triiodothyronine, and thyroxine (P < 0.05) levels. Exposure to an HS environment reduced the diversity of the fecal microbial population, and resulted in a higher expression of diseases, the environmental adaptation pathway, and the immune related pathway, whereas it lowered the expression of metabolic pathways (P < 0.05). High heat sensitive cows have upregulated metabolisms, environmental adaptation and cellular process pathways, and a downregulated neurodegenerative disease pathway (P < 0.05). Thus, we conclude that exposure to an HS environment modulates physiological characteristics, which may interplay with microbial activity, and in turn, alter the circulation levels of cytokines, implicating the role of the brain-gut axis in dairy cows. The HS environment affected physiological characteristics, cytokine levels, and microbial composition, but IH influenced RT and fecal microbial functions.

Inherited hearing loss is associated with gene mutations that result in sensory hair cell (HC) malfunction. HC structure is defined by the cytoskeleton, which is mainly composed of actin filaments and actin-binding partners. LIM motif-containing protein kinases (LIMKs) are the primary regulators of actin dynamics and consist of two members: LIMK1 and LIMK2. Actin arrangement is directly involved in the regulation of cytoskeletal structure and the maturation of synapses in the central nervous system, and LIMKs are involved in structural plasticity by controlling the activation of the actin depolymerization protein cofilin in the olfactory system and in the hippocampus. However, the expression pattern and the role of LIMKs in mouse cochlear development and synapse function also need to be further studied. We show here that the Limk genes are expressed in the mouse cochlea. We examined the morphology and the afferent synapse densities of HCs and measured the auditory function in Limk1 and Limk2 double knockout (DKO) mice. We found that the loss of Limk1 and Limk2 did not appear to affect the overall development of the cochlea, including the number of HCs and the structure of hair bundles. There were no significant differences in auditory thresholds between DKO mice and wild-type littermates. However, the expression of p-cofilin in the DKO mice was significantly decreased. Additionally, no significant differences were found in the number or distribution of ribbon synapses between the DKO and wild-type mice. In summary, our data suggest that the Limk genes play a different role in the development of the cochlea compared to their role in the central nervous system.

Emerging evidence supports that stem cells are regulated by both intrinsic and extrinsic mechanisms. However, factors that determine the fate of stem cells remain incompletely understood. The Drosophila testis provides an exclusive powerful model in searching for potential important regulatory factors and their underlying mechanisms for controlling the fate of germline stem cells (GSCs). In this study, we have found that Drosophila gilgamesh (gish), which encodes a homologue of human CK1-γ (casein kinase 1-gamma), is required intrinsically for GSC maintenance. Our genetic analyses indicate gish is not required for Dpp/Gbb signaling silencing of bam and is dispensable for Dpp/Gbb signaling-dependent Dad expression. Finally, we show that overexpression of gish fail to dramatically increase the number of GSCs. These findings demonstrate that gish controls the fate of GSCs in Drosophila testis by a novel Dpp/Gbb signaling-independent pathway.