Prediction of subsolid pulmonary nodule growth rate using radiomics.

BACKGROUND: Pulmonary nodule growth rate assessment is critical in the management of subsolid pulmonary nodules (SSNs) during clinical follow-up. The present study aimed to develop a model to predict the growth rate of SSNs. METHODS: A total of 273 growing SSNs with clinical information and 857 computed tomography (CT) scans were retrospectively analyzed. The images were randomly divided into training and validation sets. All images were categorized into fast-growth (volume doubling time (VDT) ≤ 400 days) and slow-growth (VDT > 400 days) groups. Models for predicting the growth rate of SSNs were developed using radiomics and clinical features. The models' performance was evaluated using the area under the curve (AUC) values for the receiver operating characteristic curve. RESULTS: The fast- and slow-growth groups included 108 and 749 scans, respectively, and 10 radiomics features and three radiographic features (nodule density, presence of spiculation, and presence of vascular changes) were selected to predict the growth rate of SSNs. The nomogram integrating radiomics and radiographic features (AUC = 0.928 and AUC = 0.905, respectively) performed better than the radiographic (AUC = 0.668 and AUC = 0.689, respectively) and radiomics (AUC = 0.888 and AUC = 0.816, respectively) models alone in both the training and validation sets. CONCLUSION: The nomogram model developed by combining radiomics with radiographic features can predict the growth rate of SSNs more accurately than traditional radiographic models. It can also optimize clinical treatment decisions for patients with SSNs and improve their long-term management.

Molecular mechanism and history of non-sense to sense evolution of antifreeze glycoprotein gene in northern gadids.

A fundamental question in evolutionary biology is how genetic novelty arises. De novo gene birth is a recently recognized mechanism, but the evolutionary process and function of putative de novo genes remain largely obscure. With a clear life-saving function, the diverse antifreeze proteins of polar fishes are exemplary adaptive innovations and models for investigating new gene evolution. Here, we report clear evidence and a detailed molecular mechanism for the de novo formation of the northern gadid (codfish) antifreeze glycoprotein (AFGP) gene from a minimal noncoding sequence. We constructed genomic DNA libraries for AFGP-bearing and AFGP-lacking species across the gadid phylogeny and performed fine-scale comparative analyses of the AFGP genomic loci and homologs. We identified the noncoding founder region and a nine-nucleotide (9-nt) element therein that supplied the codons for one Thr-Ala-Ala unit from which the extant repetitive AFGP-coding sequence (cds) arose through tandem duplications. The latent signal peptide (SP)-coding exons were fortuitous noncoding DNA sequence immediately upstream of the 9-nt element, which, when spliced, supplied a typical secretory signal. Through a 1-nt frameshift mutation, these two parts formed a single read-through open reading frame (ORF). It became functionalized when a putative translocation event conferred the essential cis promoter for transcriptional initiation. We experimentally proved that all genic components of the extant gadid AFGP originated from entirely nongenic DNA. The gadid AFGP evolutionary process also represents a rare example of the proto-ORF model of de novo gene birth where a fully formed ORF existed before the regulatory element to activate transcription was acquired.

Evolution of chaperome gene expression and regulatory elements in the antarctic notothenioid fishes.

Confined within the cold-stable Southern Ocean, Antarctic notothenioid fishes have undergone an evolutionary loss of the inducible heat shock response (HSR), while facing perpetual low-temperature challenges to cellular proteostasis. This study examines how evolution in chronic cold has affected the shared cellular apparatus that mediates proteostasis under normal and heat stressed states. To deduce Antarctic-specific changes, we compared native expression levels across the full suite of chaperome genes and assessed the structural integrity of two crucial HSR regulators - Heat Shock Factor 1 (HSF1) that activates HSR, and heat shock elements (HSEs), the binding sites for HSF1 - between Antarctic fishes and the basal temperate notothenioid Eleginops maclovinus. Native expression levels of Antarctic fish chaperomes showed very modest changes overall, contrary to the common view of constitutive upregulation in the cold. Only a few cytosolic HSP70 genes showed greater transcription, with only the ancestrally-inducible HSPA6 strongly upregulated across all Antarctic species. Additionally, the constant cold has apparently not relaxed the selective pressures on maintaining HSF1 and HSEs in Antarctic fish. Instead, we found HSF1 experienced intensified selective pressure, with conserved sequence changes in Antarctic species suggesting optimization for non-heat-stress functional roles. HSEs of the HSP70 gene family have largely remained conserved in canonical sequence motifs and copy numbers as in E. maclovinus, showing limited impact of relaxed selective pressure. This study shows that evolution in chronic cold has led to both subtle and distinctive changes in the cellular apparatus for proteostasis and HSR, with functional consequences amenable to experimental evaluation.

ZCCHC13-mediated induction of human liver cancer is associated with the modulation of DNA methylation and the AKT/ERK signaling pathway.

BACKGROUND: Previous studies have shown that zinc-finger CCHC-type containing 13 (ZCCHC13) is located in an imprinted gene cluster in the X-inactivation centre, but few published studies have provided evidence of its expression in cancers. The CCHC-type zinc finger motif has numerous biological activities (such as DNA binding and RNA binding) and mediates protein-protein interactions. In an effort to examine the clinical utility of ZCCHC13 in oncology, we investigated the expression of the ZCCHC13 mRNA and protein in hepatocellular carcinoma (HCC). METHODS: The expression of the ZCCHC13 mRNA and protein was evaluated using real-time reverse transcriptase-PCR, Western blotting and immunochemistry. DNA methylation was measured by methylation-specific PCR and bisulfite sequencing. The role of ZCCHC13 methylation was further evaluated using the demethylating agent, 5-aza-2'-deoxycytidine. The presence of anti-ZCCHC13 antibodies was determined by an ELISA. RESULTS: ZCCHC13 expression was frequently upregulated in human liver cancer cells and tissues. Compared with heathy individuals, sera from patients with HCC displayed a significant response to the recombinant ZCCHC13 protein. The overexpression of ZCCHC13 in HCC was attributed to DNA hypomethylation in the promoter region. Moreover, overexpression of ZCCHC13 in liver cancer cells promoted cell cycle progression by facilitating the G1-S transition, which was related to aberrant activation of the ATK/ERK/c-MYC/CDK pathway. CONCLUSIONS: Based on our findings, ZCCHC13 functions an oncogene for HCC, and DNA hypomethylation is a driving factor in carcinogenesis.

A tale of two genes: divergent evolutionary fate of haptoglobin and hemopexin in hemoglobinless Antarctic icefishes.

The evolution of Antarctic notothenioid fishes in the isolated freezing Southern Ocean has led to remarkable trait gains and losses. One of the most extraordinary was the loss of the major oxygen carrier hemoglobin (Hb) in the icefishes (family Channichthyidae). Although the mechanisms of this loss and the resulting compensatory changes have been well studied, the impact of Hb loss on the network of genes that once supported its recycling and disposal has remained unexplored. Here, we report the functional fate and underlying molecular changes of two such key Hb-supporting proteins across the icefish family - haptoglobin (Hp) and hemopexin (Hx), crucial in removing cytotoxic free Hb and heme, respectively. Hp plays a critical role in binding free Hb for intracellular recycling and absent its primary client, icefish Hp transcription is now vanishingly little, and translation into a functional protein is nearly silenced. Hp genotype degeneration has manifested in separate lineages of the icefish phylogeny with three distinct nonsense mutations and a deletion frame shift, as well as mutated polyadenylation signal sequences. Thus, Hb loss appears to have diminished selective constraint on Hp maintenance, resulting in its stochastic, co-evolutionary drift towards extinction. Hx binds free heme for iron recycling in hepatocytes. In contrast to Hp, Hx genotype integrity is preserved in the icefishes and transcription occurs at levels comparable to those in the red-blooded notothenioids. The persistence of Hx likely owes to continued selective pressure for its function from mitochondrial and non-Hb cellular hemoproteins.

Effective capture of circulating tumor cells from an S180-bearing mouse model using electrically charged magnetic nanoparticles.

BACKGROUND: Technology enabling the separation of rare circulating tumor cells (CTCs) provides the potential to enhance our knowledge of cancer metastasis and improve the care of cancer patients. Modern detection approaches commonly depend on tumor antigens or the physical size of CTCs. However, few studies report the detection of CTCs by the electrical differences between cancer cells and normal cells. RESULTS: In this study, we report a procedure for capturing CTCs from blood samples using electrically charged superparamagnetic nanoparticles (NPs). We found that only positively charged NPs attached to cancer cells, while negatively charged NPs did not. The capture method with positively charged NPs offered a sensitivity of down to 4 CTCs in 1 mL blood samples and achieved a superior capture yield (> 70%) for a high number of CTCs in blood samples (103-106 cells/mL). Following an in vitro evaluation, S180-bearing mice were employed as an in vivo model to assess the specificity and sensitivity of the capture procedure. The number of CTCs in blood from tumor-bearing mice was significantly higher than that in blood from healthy controls (on average, 75.8 ± 16.4 vs. zero CTCs/100 µL of blood, p < 0.0001), suggesting the high sensitivity and specificity of our method. CONCLUSIONS: Positively charged NPs combined with an in vivo tumor model demonstrated that CTCs can be distinguished and isolated from other blood cells based on their electrical properties.

The emerging and diverse roles of F-box proteins in spermatogenesis and male infertility.

F-box proteins play essential roles in various cellular processes of spermatogenesis by means of ubiquitylation and subsequent target protein degradation. They are the substrate-recognition subunits of SKP1-cullin 1-F-box protein (SCF) E3 ligase complexes. Dysregulation of F­box protein­mediated proteolysis could lead to male infertility in humans and mice. The emerging studies revealed the physiological function, pathological evidence, and biochemical substrates of F-box proteins in the development of male germ cells, which urging us to review the current understanding of how F­box proteins contribute to spermatogenesis. More functional and mechanistic study will be helpful to define the roles of F-box protein in spermatogenesis, which will pave the way for the logical design of F-box protein-targeted diagnosis and therapies for male infertility, as the spermatogenic role of many F-box proteins remains elusive.

Diverse origins of near-identical antifreeze proteins in unrelated fish lineages provide insights into evolutionary mechanisms of new gene birth and protein sequence convergence.

Determining the origins of novel genes and the genetic mechanisms underlying the emergence of new functions is challenging yet crucial for understanding evolutionary innovations. The novel fish antifreeze proteins, exemplifying convergent evolution, represent excellent opportunities to investigate the evolutionary origins and pathways of new genes. Particularly notable is the near-identical type I antifreeze proteins (AFPI) in four phylogenetically divergent fish taxa. This study tested the hypothesis of protein sequence convergence beyond functional convergence in three unrelated AFPI-bearing fish lineages, revealing different paths by which a similar protein arose from diverse genomic resources. Comprehensive comparative analyses of de novo sequenced genome of the winter flounder and grubby sculpin, available high-quality genome of the cunner, and those of 14 other relevant species found that the near-identical AFPI originated from a distinct genetic precursor in each lineage, and independently evolved coding regions for the novel ice-binding protein while retaining sequence identity in the regulatory regions with their respective ancestor. The deduced evolutionary processes and molecular mechanisms is consistent with the Innovation-Amplification-Divergence (IAD) model applicable to AFPI formation in all three lineages, a new Duplication-Degeneration-Divergence (DDD) model we propose for the sculpin lineage, and a DDD model with gene fission for the cunner lineage. This investigation illustrates the multiple ways by which a novel functional gene with sequence convergence at the protein level could evolve across divergent species, advancing our understanding of the mechanistic intricacies in new gene formation.

A Novel Approach of Sea Urchin-like Fe-Doped Co3O4 Microspheres for Li-S Battery Enables High Energy Density and Long-Lasting.

The poor cycle stability caused by the shuttle effect of polysulfides which have been key scientific issue in the development of high-efficiency lithium-sulfur (Li-S) batteries. In this work, the authors report a Fe-doped Co3O4 (named FCO) that was used as a sulfur-loaded host material for Li-S batteries. We demonstrate the important roles of well-designed Co3O4 particles and Fe atoms in regulating polysulfide conversion due to the strong adsorption of polysulfides by polar Co3O4, whereas Fe atoms and Co3O4 catalyze polysulfide conversion. Therefore, the LiS batteries with FCO-180 (When the hydrothermal temperature is 180 °C) sea urchinlike composites exhibited a high superior energy density (992.7 mAh g-1 at 0.2 C, after 100 cycles) and long-term cyclability (649.4 mAh g-1 at 1 C, 300 cycles) with high sulfur loading (75 wt%). This work confirms that the FCO-180 sea urchinlike increases not only the capacity of high-rate but also a generic and feasible strategy to construct practical Li-S batteries for emerging energy-storage applications.

Positive and Relaxed Selective Pressures Have Both Strongly Influenced the Evolution of Cryonotothenioid Fishes during Their Radiation in the Freezing Southern Ocean.

Evolution in the chronic cold of the Southern Ocean has had a profound influence on the physiology of cryonotothenioid fishes. However, the suite of genetic changes underlying the physiological gains and losses in these fishes is still poorly surveyed. By identifying the genomic signatures of selection, this study aims to identify the functional classes of genes that have been changed following two major physiological transitions: the onset of freezing temperatures and the loss of hemoproteins. Looking at the changes that followed the onset of freezing temperatures, positive selective pressure was found among a set of broadly acting gene regulatory factors, suggesting a route through which cryonotothenioid gene expression has been retooled for life in the cold. Further, genes related to the cell cycle and cellular adhesion were found under positive selection suggesting that both present key challenges to life in freezing waters. By contrast, genes showing signatures of the relaxation of selective pressure showed a narrower biological impact, acting on genes related to mitochondrial function. Finally, although chronic cold-water temperatures appear correlated with substantial genetic change, the loss of hemoproteins resulted in little observable change in protein-coding genes relative to their red-blooded relatives. Combined, the influence of positive and relaxed selection shows that long-term exposure to cold has led to profound changes in cryonotothenioid genomes that may make it challenging for them to adapt to a rapidly changing climate.

Important Role of the Ihh Signaling Pathway in Initiating Early Cranial Remodeling and Morphological Specialization in Cromileptes altivelis.

In this study, we identified the important contribution of frontal bone remodeling in shaping the 'sunken head and humpback' appearance in C. altivelis. Our investigation identified a developmental milestone at a total length of 5-6 cm, making the onset of its morphologic specialization in this species. A comparative analysis with closely related species reveals heightened activity in the frontal osteoblasts of the humpback grouper, potentially providing a physiological basis for its remodeling. Furthermore, our findings highlight that a significant upregulation in the expression levels of Ihhb, Ptch1, and Gli2a genes was seen in C. altivelis within the specified developmental stage, indicating an important involvement of the Ihhb-Ptch1-Gli2a signaling pathway in initiating the morphological specialization. We hypothesized that Ihh signaling could be attributed to shifts in mechanical stress, resulting from muscle traction on the frontal bone due to changes in swimming patterns during development. This study not only offers significant insights into unraveling the molecular mechanisms that govern phenotypic specialization and ecological adaptations in the humpback grouper but also serves as a valuable reference for studies on fishes with a controversial morphology and molecular phylogeny.

Protein genes in repetitive sequence-antifreeze glycoproteins in Atlantic cod genome.

BACKGROUND: Highly repetitive sequences are the bane of genome sequence assembly, and the short read lengths produced by current next generation sequencing technologies further exacerbates this obstacle. An adopted practice is to exclude repetitive sequences in genome data assembly, as the majority of repeats lack protein-coding genes. However, this could result in the exclusion of important genotypes in newly sequenced non-model species. The absence of the antifreeze glycoproteins (AFGP) gene family in the recently sequenced Atlantic cod genome serves as an example. RESULTS: The Atlantic cod (Gadus morhua) genome was assembled entirely from Roche 454 short reads, demonstrating the feasibility of this approach. However, a well-known major adaptive trait, the AFGP, essential for survival in frigid Arctic marine habitats was absent in the annotated genome. To assess whether this resulted from population difference, we performed Southern blot analysis of genomic DNA from multiple individuals from the North East Arctic cod population that the sequenced cod belonged, and verified that the AFGP genotype is indeed present. We searched the raw assemblies of the Atlantic cod using our G. morhua AFGP gene, and located partial AFGP coding sequences in two sequence scaffolds. We found these two scaffolds constitute a partial genomic AFGP locus through comparative sequence analyses with our newly assembled genomic AFGP locus of the related polar cod, Boreogadus saida. By examining the sequence assembly and annotation methodologies used for the Atlantic cod genome, we deduced the primary cause of the absence of the AFGP gene family from the annotated genome was the removal of all repetitive Roche 454 short reads before sequence assembly, which would exclude most of the highly repetitive AFGP coding sequences. Secondarily, the model teleost genomes used in projection annotation of the Atlantic cod genome have no antifreeze trait, perpetuating the unawareness that the AFGP gene family is missing. CONCLUSIONS: We recovered some of the missing AFGP coding sequences and reconstructed a partial AFGP locus in the Atlantic cod genome, bringing to light that not all repetitive sequences lack protein coding information. Also, reliance on genomes of model organisms as reference for annotating protein-coding gene content of a newly sequenced non-model species could lead to omission of novel genetic traits.

Electroacupuncture as an effective therapy for Tapia's syndrome after transoral intubation for general anesthesia: a case report and review of the literature.

BACKGROUND: Tapia's syndrome is a rare complication of airway manipulation under general anesthesia. Injuries to the vagus nerve (X) and hypoglossal nerve (XII) during transoral intubation are the primary cause of the disease. The typical symptoms include hoarseness, dysarthria, dysphagia, tongue muscle atrophy, and tongue deviation toward the affected side. We report a case of Tapia's syndrome treated with electroacupuncture to accelerate the recovery process, and discuss the potential mechanism behind our findings based on previous research. CASE PRESENTATION: In this report, we describe a 57-year-old Chinese man who suffered Tapia's syndrome after craniotomy evacuation of hematoma with general anesthesia and transoral intubation. After 52 days of electroacupuncture therapy along with standard swallowing training, the patient achieved significant improvement in deglutition and speech function. CONCLUSION: Electroacupuncture is effective and safe for Tapia's syndrome. It can shorten the recovery time when combined with routine swallowing rehabilitation.

Therapeutic potential of exosomes/miRNAs in polycystic ovary syndrome induced by the alteration of circadian rhythms.

Polycystic ovary syndrome (PCOS) is a reproductive dysfunction associated with endocrine disorders and is most common in women of reproductive age. Clinical and/or biochemical manifestations include hyperandrogenism, persistent anovulation, polycystic ovary, insulin resistance, and obesity. Presently, the aetiology and pathogenesis of PCOS remain unclear. In recent years, the role of circadian rhythm changes in PCOS has garnered considerable attention. Changes in circadian rhythm can trigger PCOS through mechanisms such as oxidative stress and inflammation; however, the specific mechanisms are unclear. Exosomes are vesicles with sizes ranging from 30-120nm that mediate intercellular communication by transporting microRNAs (miRNAs), proteins, mRNAs, DNA, or lipids to target cells and are widely involved in the regulation of various physiological and pathological processes. Circadian rhythm can alter circulating exosomes, leading to a series of related changes and physiological dysfunctions. Therefore, we speculate that circadian rhythm-induced changes in circulating exosomes may be involved in PCOS pathogenesis. In this review, we summarize the possible roles of exosomes and their derived microRNAs in the occurrence and development of PCOS and discuss their possible mechanisms, providing insights into the potential role of exosomes for PCOS treatment.

ND6 gene "lost" and found: evolution of mitochondrial gene rearrangement in Antarctic notothenioids.

Evolution of Antarctic notothenioids in the frigid and oxygen-rich Southern Ocean had led to remarkable genomic changes, most notably the gain of novel antifreeze glycoproteins and the loss of oxygen-binding hemoproteins in the icefish family. Recently, the mitochondrial (mt) NADH dehydrogenase subunit 6 (ND6) gene and the adjacent transfer RNA(Glu) (tRNA(Glu)) were also reportedly lost. ND6 protein is crucial for the assembly and function of Complex I of the mt electron transport chain that produces adenosine triphosphate (ATP) essential for life; thus, ND6 absence would be irreconcilable with Antarctic notothenioids being thriving species. Here we report our discovery that the ND6 gene and tRNA(Glu) were not lost but had been translocated to the control region (CR) from their canonical location between ND5 and cytochrome b genes. We characterized the CR and adjacent sequences of 22 notothenioid species representing all eight families of Notothenioidei to elucidate the mechanism and evolutionary history of this mtDNA rearrangement. Species of the three basal non-Antarctic families have the canonical vertebrate mt gene order, whereas species of all five Antarctic families have a rearranged CR bearing the embedded ND6 (ND6(CR)) and tRNA(Glu), with additional copies of tRNA(Thr), tRNA(Pro), and noncoding region in various lineages. We hypothesized that an initial duplication of the canonical mt region from ND6 through CR occurred in the common ancestor to the Antarctic clade, and we deduced the succession of loss or modification of the duplicated region leading to the extant patterns of mt DNA reorganization that is consistent with notothenioid evolutionary history. We verified that the ND6(CR) gene in Antarctic notothenioids is transcribed and therefore functional. However, ND6(CR)-encoded protein sequences differ substantially from basal non-Antarctic notothenioid ND6, and we detected lineage-specific positive selection on the branch leading to the Antarctic clade of ND6(CR) under the branch-site model. Collectively, the novel mt ND6(CR) genotype of the Antarctic radiation represents another major molecular change in Antarctic notothenioid evolution and may reflect an adaptive change conducive to the functioning of the protein (Complex I) machinery of mt respiration in the polar environment, driven by the advent of freezing, oxygen-rich conditions in the Southern Ocean.

Propagation of a De Novo Gene under Natural Selection: Antifreeze Glycoprotein Genes and Their Evolutionary History in Codfishes.

The de novo birth of functional genes from non-coding DNA as an important contributor to new gene formation is increasingly supported by evidence from diverse eukaryotic lineages. However, many uncertainties remain, including how the incipient de novo genes would continue to evolve and the molecular mechanisms underlying their evolutionary trajectory. Here we address these questions by investigating evolutionary history of the de novo antifreeze glycoprotein (AFGP) gene and gene family in gadid (codfish) lineages. We examined AFGP phenotype on a phylogenetic framework encompassing a broad sampling of gadids from freezing and non-freezing habitats. In three select species representing different AFGP-bearing clades, we analyzed all AFGP gene family members and the broader scale AFGP genomic regions in detail. Codon usage analyses suggest that motif duplication produced the intragenic AFGP tripeptide coding repeats, and rapid sequence divergence post-duplication stabilized the recombination-prone long repetitive coding region. Genomic loci analyses support AFGP originated once from a single ancestral genomic origin, and shed light on how the de novo gene proliferated into a gene family. Results also show the processes of gene duplication and gene loss are distinctive in separate clades, and both genotype and phenotype are commensurate with differential local selective pressures.

Prospective Memory and Regional Functional Connectivity in Subcortical Ischemic Vascular Disease.

Objectives: Patients with subcortical ischemic vascular disease (SIVD) often have prominent frontal dysfunction. However, it remains unclear how SIVD affects prospective memory (PM), which strongly relies on the frontoparietal network. The present study aimed to investigate PM performance in patients with early stage SIVD as compared to those with Alzheimer's disease (AD) and to older adults with normal cognition, and to explore the neural correlates of PM deficits. Method: Patients with very-mild to mild dementia due to SIVD or AD and normal controls (NC) aged above 60 years were recruited. Seventy-three participants (20 SIVD, 22 AD, and 31 NC) underwent structural magnetic resonance imaging (MRI), cognitive screening tests, and a computerized PM test. Sixty-five of these participants (19 SIVD, 20 AD, and 26 NC) also received resting-state functional MRI. Results: The group with SIVD had significantly fewer PM hits than the control group on both time-based and non-focal event-based PM tasks. Among patients in the very early stage, only those with SIVD but not AD performed significantly worse than the controls. Correlational analyses showed that non-focal event-based PM in SIVD was positively correlated with regional homogeneity in bilateral superior and middle frontal gyri, while time-based PM was not significantly associated with regional homogeneity in any of the regions of interest within the dorsal frontoparietal regions. Conclusions: The findings of this study highlight the vulnerability of non-focal event-based PM to the disruption of regional functional connectivity in bilateral superior and middle frontal gyri in patients with SIVD.

Electrostatic reaction for the detection of circulating tumor cells as a potential diagnostic biomarker for metastasis in solid tumor.

The detection of circulating tumor cells (CTCs) from blood samples is important to predict metastatic spread of cancer cells. However, effective quantification and identification of CTCs in solid tumors remain a challenge. Aerobic glycolysis is a hallmark of cancer cells, which makes cancer cells have more negative membrane potentials than that of normal cells. Herein, we reported a CTC isolation method with 80.7% capture efficiency based on electrostatic reaction, which was accomplished within 30 min in mimic clinical samples. Following in vitro verification using Lewis lung carcinoma (LLC1) (EpCAM-positive) and B16F10 (EpCAM-negative) melanoma cells, syngeneic tumor models were used to evaluate specificity and sensitivity of the surface charged nanoparticles. After subcutaneous implantation, blood was drawn from mice every three days, and CTCs were successfully detected in all implanted subjects. From 100 µl blood samples, the minimum amount found in blood was 9-34 CTCs on 3 day and the maximum was 94-107 CTCs on 15 day. Besides, the isolated CTCs cells remained viable and verified by re-implantation. This study confirms that our multifunctional nanoparticles are highly efficient in detecting CTCs in tumor metastasis and has huge potential in translational medicine.

Association Between BAK1 Gene rs210138 Polymorphisms and Testicular Germ Cell Tumors: A Systematic Review and Meta-Analysis.

Background: Several studies including some genome-wide association studies (GWAS) had shown that BAK1 gene rs210138 polymorphisms might be associated with testicular germ cell tumors (TGCT). Here we tried to sum up the association through a systematic review and meta-analysis. Methods: Studies associated with BAK1 rs210138 and TGCT was systematically searched in databases. The effect size was pooled according to ORs and 95% CIs. Results: Our systematic review and meta-analysis comprised 14 articles. Significantly increased risk of TGCT was found in eligible GWAS and follow-up studies, in overall group and its Caucasian subgroup. Conclusions: Compared with adenine (A), BAK1 rs210138 guanine (G) is associated with increased risk of TGCT. Well-planned studies with larger sample size and more subgroups are needed to verify the risk identified in our systematic review and meta-analysis.