BLMP-1 promotes developmental cell death in C. elegans by timely repression of ced-9 transcription.

Programmed cell death (PCD) is a common cell fate in metazoan development. PCD effectors are extensively studied, but how they are temporally regulated is less understood. Here, we report a mechanism controlling tail-spike cell death onset during Caenorhabditis elegans development. We show that the zinc-finger transcription factor BLMP-1, which controls larval development timing, also regulates embryonic tail-spike cell death initiation. BLMP-1 functions upstream of CED-9 and in parallel to DRE-1, another CED-9 and tail-spike cell death regulator. BLMP-1 expression is detected in the tail-spike cell shortly after the cell is born, and blmp-1 mutations promote ced-9-dependent tail-spike cell survival. BLMP-1 binds ced-9 gene regulatory sequences, and inhibits ced-9 transcription just before cell-death onset. BLMP-1 and DRE-1 function together to regulate developmental timing, and their mammalian homologs regulate B-lymphocyte fate. Our results, therefore, identify roles for developmental timing genes in cell-death initiation, and suggest conservation of these functions.

Use of consecutive transcutaneous oxygen measurement when assessing the need for revascularization and association with the outcomes of ischemic diabetic ulcers.

This study compared the ankle-brachial index (ABI) with transcutaneous oxygen pressure (TcPO2 ) in assessing peripheral vascular disease (PVD) prevalence in 100 diabetic foot ulcer (DFU) patients. Patients were categorized into vascular or nonvascular reconstruction groups and underwent both ABI and TcPO2 measurements four times over 6 months. Predictive validity for PVD diagnosis was analysed using the area under the receiver-operating characteristic curve (AUC). The study found TcPO2 to be a superior predictor of PVD than ABI. Among the DFU patients, 51 with abnormal TcPO2 values underwent vascular reconstruction. Only TcPO2 values showed significant pretreatment differences between the groups and increased post-reconstruction. These values declined over a 6-month follow-up, whereas ABI values rose. For those with end-stage renal disease (ESRD), TcPO2 values saw a sharp decrease within 3 months. Pre-reconstruction TcPO2 was notably lower in amputation patients versus limb salvage surgery patients. In conclusion, TcPO2 is more effective than ABI for evaluating ischemic limb perfusion and revascularization necessity. It should be prioritized as the primary follow-up tool, especially for ESRD patients.

C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8.

Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. The aECM is highly dynamic and constantly undergoes remodeling during animal development. How aECM dynamics is temporally regulated during development, and whether and how its mis-regulation may impact epidermal cell morphology or function remains to be fully elucidated. Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. The apical epidermal morphological defect is suppressed by reduction of bus-8 or mlt-8. BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. MLT-8::GFP fusion protein is localized to lysosomes and secreted to aECM. BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition.

Multidisciplinary Strategies With Real-Time Fluorescence Images and Negative Pressure Wound Therapy to Manage Organ/Space Surgical Site Infection in Transplanted Kidneys.

BACKGROUND: Surgical site infection (SSI) after kidney transplantation can severely compromise graft function and prolong hospital stay. Organ/space SSI (osSSI) is a severe type of SSI associated with a significantly higher mortality rate. AIMS AND OBJECTIVES: This study aims to provide new strategies of managing (osSSI) after kidney transplant and other high-risk wound infections. METHOD: This is a single-center, retrospective study that analyzed the treatment outcomes of 4 patients who developed osSSI after kidney transplant at Shuang-Ho Hospital. The management strategy included real-time fluorescence imaging with MolecuLight, negative-pressure wound therapy (NPWT) with Si-Mesh, and incisional NPWT (iNPWT). RESULT: The average length of hospital stay was 18 days (range, 12-23 days). During hospitalization, all patients obtained high-quality debridement under real-time fluorescence image confirmation. The average duration of NPWT was 11.8 days (range, 7-17 days) and iNPWT was 7 days. All transplanted kidneys were preserved with normal function after 6 months of follow-up. CONCLUSIONS: Our strategies with real-time fluorescence imaging provide a novel and effective method that can be used in adjunct with the standard of care for managing osSSI after kidney transplantation. More studies are warranted to validate the efficacy of our approach.

Tuberculosis among migrant workers in Taiwan.

BACKGROUND: Although the worldwide incidence of tuberculosis (TB) has been slowly decreasing, the migrant workers remains an important gap for regional TB control. In Taiwan, the numbers of the migrant workers from countries with high TB incidence increase significantly in past decades and the impact on public health remains unknown. This study aimed to explore the difference of TB incidence between Taiwanese and the migrant workers. METHODS: The migrant workers are obligated to receive pre-arrival, post-arrival and regular chest X-ray screening during their stay in Taiwan. We retrospectively collected these data extracted from the Alien Workers Health Database in Centers for Disease Control, Taiwan from Jan. 1, 2004 to Dec. 31, 2013. Poisson regression models were used to compare the hazard ratios of TB between Taiwanese and the migrant workers after adjusting gender and age groups. RESULTS: The total migrant workers in Taiwan reached 314,034 persons in 2004 and 489,134 persons in 2013, accounting for 2% of Taiwan population. The TB incidence of migrant workers was similar to Taiwanese (53-73.7 per 105 vs 45.5-76.8 per 105). Comparing with Taiwanese, the TB risk was significantly lower in male migrant workers (HR: 0.76; 95% CI: 0.70-0.83, P < 0.001), but higher in female migrant workers (HR: 1.40; 95% CI: 1.35-1.46, P < 0.001). Besides, we found that the TB risk in migrant workers was 5.30-fold (95% CI: 4.83-5.83, P < 0.001) in youngest group (≤24 year-old) comparing with Taiwanese. CONCLUSIONS: Migrant workers in Taiwan have higher TB incidence than Taiwanese in young groups, especially in females. The mainstay young laborers with latent tuberculosis infection risk is an important vulnerability for public health. Further investigation and health screening are warranted.

Attitudes and awareness of medical assistance while traveling abroad.

BACKGROUND: With globalization, more and more people travel to countries where they are at risk of injuries and travel-related diseases. To protect travelers' health, it is crucial to understand whether travelers accurately perceive medical assistance resources before and during their trips. This study investigated the need, awareness, and previous usage of overseas emergency medical assistance services (EMAS) among people traveling abroad. METHODS: Anonymous questionnaires were distributed to patients (n = 500) at a travel clinic in Taipei, Taiwan. RESULTS: The results showed that EMAS were important, especially in the following categories: 24-h telephone medical consultation (91.8%), emergent medical repatriation (87.6%), and assistance with arranging hospital admission (87.4%). Patients were less aware of the following services: arrangement of appointments with doctors (70.7%) and monitoring of medical conditions during hospitalization (73.0%). Less than 5% of respondents had a previous experience with EMAS. CONCLUSIONS: EMAS are considered important to people who are traveling abroad. However, approximately 20-30% of travelers lack an awareness of EMAS, and the percentage of travelers who have previously received medical assistance through these services is extremely low. The discrepancy between the need and usage of EMAS emphasizes the necessity to adapt EMAS materials in pre-travel consultations to meet the needs of international travelers.

LIN-3/EGF promotes the programmed cell death of specific cells in Caenorhabditis elegans by transcriptional activation of the pro-apoptotic gene egl-1.

Programmed cell death (PCD) is the physiological death of a cell mediated by an intracellular suicide program. Although key components of the PCD execution pathway have been identified, how PCD is regulated during development is poorly understood. Here, we report that the epidermal growth factor (EGF)-like ligand LIN-3 acts as an extrinsic signal to promote the death of specific cells in Caenorhabditis elegans. The loss of LIN-3 or its receptor, LET-23, reduced the death of these cells, while excess LIN-3 or LET-23 signaling resulted in an increase in cell deaths. Our molecular and genetic data support the model that the LIN-3 signal is transduced through LET-23 to activate the LET-60/RAS-MPK-1/ERK MAPK pathway and the downstream ETS domain-containing transcription factor LIN-1. LIN-1 binds to, and activates transcription of, the key pro-apoptotic gene egl-1, which leads to the death of specific cells. Our results provide the first evidence that EGF induces PCD at the whole organism level and reveal the molecular basis for the death-promoting function of LIN-3/EGF. In addition, the level of LIN-3/EGF signaling is important for the precise fine-tuning of the life-versus-death fate. Our data and the previous cell culture studies that say EGF triggers apoptosis in some cell lines suggest that the EGF-mediated modulation of PCD is likely conserved in C. elegans and humans.

BLMP-1/Blimp-1 regulates the spatiotemporal cell migration pattern in C. elegans.

Spatiotemporal regulation of cell migration is crucial for animal development and organogenesis. Compared to spatial signals, little is known about temporal signals and the mechanisms integrating the two. In the Caenorhabditis elegans hermaphrodite, the stereotyped migration pattern of two somatic distal tip cells (DTCs) is responsible for shaping the gonad. Guidance receptor UNC-5 is necessary for the dorsalward migration of DTCs. We found that BLMP-1, similar to the mammalian zinc finger transcription repressor Blimp-1/PRDI-BF1, prevents precocious dorsalward turning by inhibiting precocious unc-5 transcription and is only expressed in DTCs before they make the dorsalward turn. Constitutive expression of blmp-1 when BLMP-1 would normally disappear delays unc-5 transcription and causes turn retardation, demonstrating the functional significance of blmp-1 down-regulation. Correct timing of BLMP-1 down-regulation is redundantly regulated by heterochronic genes daf-12, lin-29, and dre-1, which regulate the temporal fates of various tissues. DAF-12, a steroid hormone receptor, and LIN-29, a zinc finger transcription factor, repress blmp-1 transcription, while DRE-1, the F-Box protein of an SCF ubiquitin ligase complex, binds to BLMP-1 and promotes its degradation. We have therefore identified a gene circuit that integrates the temporal and spatial signals and coordinates with overall development of the organism to direct cell migration during organogenesis. The tumor suppressor gene product FBXO11 (human DRE-1 ortholog) also binds to PRDI-BF1 in human cell cultures. Our data suggest evolutionary conservation of these interactions and underscore the importance of DRE-1/FBXO11-mediated BLMP-1/PRDI-BF1 degradation in cellular state transitions during metazoan development.

Anti-PRRSV effect and mechanism of tetrahydroaltersolanol C in vitro.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important arterivirus that causes substantial economic losses to the swine industry. Current control strategies against PRRSV are still inadequate and there is an urgent need for new antiviral therapies. Tetrahydroaltersolanol C (TD-C) is a new anthraquinone derivative isolated from the marine-derived fungi. In the present study, we first demonstrated its anti-PRRSV activity in vitro through assessing the inhibition of TD-C on cytopathic effect, viral ORF7 gene and N protein expressions, progeny virions production by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, relative-quantitative RT-PCR, Western blotting, and indirect immunofluorescence assay. Our experimental results showed that TD-C could significantly inhibit PRRSV replication in a dose-dependent manner. The 50% effective concentration, 50% cytotoxic concentration and the selectivity index were 12.11, 395.31 µM, and 32.64, respectively. Furthermore, the possible anti-PRRSV mechanism was explored by virucidal assay, virus adsorption inhibition assay, and the time-of-addition assay. The results showed that TD-C might inhibit the internalization and replication of PRRSV, but did not directly inactivate the virus or block its adsorption to cell surface. In conclusion, our findings indicated that TD-C possessed a significant anti-PRRSV activity, and provided a strong basis for further exploration of this compound as an antiviral agent against PRRSV.

Integrin α PAT-2/CDC-42 signaling is required for muscle-mediated clearance of apoptotic cells in Caenorhabditis elegans.

Clearance of apoptotic cells by engulfment plays an important role in the homeostasis and development of multicellular organisms. Despite the fact that the recognition of apoptotic cells by engulfment receptors is critical in inducing the engulfment process, the molecular mechanisms are still poorly understood. Here, we characterize a novel cell corpse engulfment pathway mediated by the integrin α subunit PAT-2 in Caenorhabditis elegans and show that it specifically functions in muscle-mediated engulfment during embryogenesis. Inactivation of pat-2 results in a defect in apoptotic cell internalization. The PAT-2 extracellular region binds to the surface of apoptotic cells in vivo, and the intracellular region may mediate signaling for engulfment. We identify essential roles of small GTPase CDC-42 and its activator UIG-1, a guanine-nucleotide exchange factor, in PAT-2-mediated cell corpse removal. PAT-2 and CDC-42 both function in muscle cells for apoptotic cell removal and are co-localized in growing muscle pseudopods around apoptotic cells. Our data suggest that PAT-2 functions through UIG-1 for CDC-42 activation, which in turn leads to cytoskeletal rearrangement and apoptotic cell internalization by muscle cells. Moreover, in contrast to PAT-2, the other integrin α subunit INA-1 and the engulfment receptor CED-1, which signal through the conserved signaling molecules CED-5 (DOCK180)/CED-12 (ELMO) or CED-6 (GULP) respectively, preferentially act in epithelial cells to mediate cell corpse removal during mid-embryogenesis. Our results show that different engulfing cells utilize distinct repertoires of receptors for engulfment at the whole organism level.

Early identification of delayed wound healing in complex diabetic foot ulcers treated with a dermal regeneration template: a novel clinical target and its risk factors.

BACKGROUND: The dermal regeneration template (DRT), a tissue-engineered skin substitute composing a permanent dermal matrix and an upper temporary silicone layer that serves as the epidermis, has demonstrated efficacy in treating uncomplicated diabetic foot ulcers (DFUs). Our institution has obtained good outcomes with DRT in patients with more complicated DFUs. Because of its chronicity, the authors are working to identify a clinical target that anticipates delayed healing early in the treatment in addition to determining the risk factors linked to this endpoint to increase prevention. MATERIALS AND METHODS: This retrospective single-center study analyzed patients with DFUs who underwent wound reconstruction using DRT between 2016 and 2021. The patients were categorized into poor or good graft-take groups based on their DRT status on the 21st day after the application. Their relationship with complete healing (CH) rate at day 180 was analyzed. Variables were collected for risk factors for poor graft take at day 21. Independent risk factors were identified after multivariable analysis. The causes of poor graft take were also reported. RESULTS: This study examined 80 patients (38 and 42 patients in the poor and good graft-take groups, respectively). On day 180, the CH rate was 86.3% overall, but the poor graft-take group had a significantly lower CH rate (76.3 vs. 95.2%, P =0.021) than the good graft-take group. Our analysis identified four independent risk factors: transcutaneous oxygen pressure less than 30 mmHg (odds ratio, 154.14), off-loading device usage (0.03), diabetic neuropathy (6.51), and toe wound (0.20). The most frequent cause of poor graft take was infection (44.7%), followed by vascular compromise (21.1%) and hematoma (15.8%). CONCLUSION: Our study introduces the novel concept of poor graft take at day 21 associated with delayed wound healing. Four independent risk factors were identified, which allows physicians to arrange interventions to mitigate their effects or select patients more precisely. DRT represents a viable alternative to address DFUs, even in complicated wounds. A subsequent split-thickness skin graft is not always necessary to achieve CH.

Is Prompt Hyperbaric Oxygen Adjunctive Therapy Able to Reduce Mortality and Amputation in Management of Necrotizing Soft-Tissue Infection?

Background: Necrotizing soft-tissue infection (NSTI) is a rare and serious disease with high morbidity and mortality. Standard therapeutic concepts have included urgent surgical intervention, broad-spectrum antibiotic treatment, and intensive care. Hyperbaric oxygen therapy (HBOT) is used as adjuvant therapy in some centers, but its benefits remain controversial. Methods: A retrospective analysis was conducted in which 98 patients with a clinical diagnosis of NSTI were treated with standard treatments plus HBOT. The clinical outcomes were wound healing, performance status, hospital length, complication rate, recurrence rate, morbidity (amputation rate), and mortality. Primary or secondary outcomes were compared between the time interval of HBOT and the clinical outcomes. Results: The average times from diagnosis of NSTI to initial HBO treatment and from initial surgery to initial HBO treatment were both significantly longer in dead patients than in surviving patients (P = 0.031; P = 0.020). These two time intervals were both significantly longer in amputated patients than in preserved patients (P = 0.031; P = 0.037). Conclusions: Using combined treatment with early surgical debridement combined with HBOT, it is possible to reduce hospital stay, intensive care unit stay, number of debridements, improve complete wound healing rate, and lower amputation and mortality rates among patients with NSTI. The early onset of HBOT soon after diagnosis, especially during critical conditions, is proved to be associated with higher survival and preservation rates.

Peimine impairs pro-inflammatory cytokine secretion through the inhibition of the activation of NF-κB and MAPK in LPS-induced RAW264.7 macrophages.

In the previous study, we found that peimine has good anti-inflammatory effects in vivo. However, the anti-inflammatory mechanism of peimine remains unclear. We, therefore, assessed the effects of peimine on inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that peimine (0-25 mg/L) significantly inhibited tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, and increased IL-10 production. Furthermore, peimine significantly inhibited the phosphorylation of p38, ERK and c-jun N-terminal kinase (JNK) as well as decreased p65 and IκB. The present results indicate that peimine inhibits the production of inflammatory cytokines induced by LPS through blocking MAPKs and NF-κB signaling pathways.

Nanoplastics exposure disrupts circadian rhythm associated with dysfunction of the endolysosomal pathway and autophagy in Caenorhabditis elegans.

Nanoplastics (NPs), an emerging pollutant, have raised great safety concerns due to their widespread applications and continuous release into the environment, which lead to potential human and environmental risks. Recently, polystyrene NPs (100 nm; 100 mg/L) exposure has been reported to disrupt circadian rhythms under five days temperature entrainment and be associated with stress resistance decline in Caenorhabditis elegans. This study explored the possible relationship between circadian rhythm disruption and endocytosis and autophagy under polystyrene NPs exposure in C. elegans. We show that the disrupted circadian rhythm induced by NPs exposure reduced stress resistance via endocytosis and autophagy impairment. Furthermore, we found that most NPs taken up by intestinal cells were localized to early endosomes, late endosomes, and lysosomes and delivered to autophagosomes. In addition, the disruption of circadian rhythm inhibited NPs localization to these organelles. These findings indicate that NPs exposure disrupts circadian rhythm and alters its subcellular trafficking, leading to enhanced toxicity in C. elegans. Our results shed light on the prominent role of NPs exposure in circadian rhythm disruption associated with endocytosis and autophagy impairments, which may be conserved in higher animals such as humans.

Synthesis and Evaluation of Alginate-Based Nanogels as Sustained Drug Carriers for Caffeine.

The objective of this study is to design a polymeric network of nanogels for sustained release of caffeine. Therefore, alginate-based nanogels were fabricated by a free-radical polymerization technique for the sustained delivery of caffeine. Polymer alginate was crosslinked with monomer 2-acrylamido-2-methylpropanesulfonic acid by crosslinker N',N'-methylene bisacrylamide. The prepared nanogels were subjected to sol-gel fraction, polymer volume fraction, swelling, drug loading, and drug release studies. A high gel fraction was seen with the increasing feed ratio of polymer, monomer, and crosslinker. Greater swelling and drug release were observed at pH 4.6 and 7.4 as compared to pH 1.2 due to the deprotonation and protonation of functional groups of alginate and 2-acrylamido-2-methylpropanesulfonic acid. An increase was observed in swelling, loading, and release of the drug with the incorporation of a high feed ratio of polymer and monomer, while a reduction was seen with the increase in crosslinker feed ratio. Similarly, an HET-CAM test was used to evaluate the safety of the prepared nanogels, which showed that the prepared nanogels have no toxic effect on the chorioallantoic membrane of fertilized chicken eggs. Similarly, different characterizations techniques such as FTIR, DSC, SEM, and particle size analysis were carried out to determine the development, thermal stability, surface morphology, and particle size of the synthesized nanogels, respectively. Thus, we can conclude that the prepared nanogels can be used as a suitable agent for the sustained release of caffeine.

Negative regulation of Caenorhabditis elegans epidermal damage responses by death-associated protein kinase.

Wounding of epidermal layers triggers multiple coordinated responses to damage. We show here that the Caenorhabditis elegans ortholog of the tumor suppressor death-associated protein kinase, dapk-1, acts as a previously undescribed negative regulator of barrier repair and innate immune responses to wounding. Loss of DAPK-1 function results in constitutive formation of scar-like structures in the cuticle, and up-regulation of innate immune responses to damage. Overexpression of DAPK-1 represses innate immune responses to needle wounding. Up-regulation of innate immune responses in dapk-1 requires the TIR-1/p38 signal transduction pathway; loss of function in this pathway synergizes with dapk-1 to drastically reduce adult lifespan. Our results reveal a previously undescribed function for the DAPK tumor suppressor family in regulation of epithelial damage responses.

Early developmental nanoplastics exposure disturbs circadian rhythms associated with stress resistance decline and modulated by DAF-16 and PRDX-2 in C. elegans.

Plastics pollution is an emerging environmental problem and nanoplastics (NPs) toxicity has received great concern. This study investigated whether early developmental exposure to polystyrene NPs influence the circadian rhythms and the possible underlying mechanisms in C. elegans. We show that early developmental NPs exposure disturbs circadian rhythms in C. elegans and ASH neurons and G protein-coupled receptor kinase (GRK-2) are involved in the level of chemotaxis response. A higher bioconcentration factor in entrained worms was observed, suggesting that circadian interference results in increased NPs bioaccumulation in C. elegans. In addition, we show that reactive oxygen species produced by NPs exposure and peroxiredoxin-2 (PRDX-2) are related to the disturbed circadian rhythms. We further show that the NPs-induced circadian rhythms disruption is associated with stress resistance decline and modulated by transcription DAF-16/FOXO signaling. Because circadian rhythms are found in most living organisms and the fact that DAF-16 and PRDX-2 are evolutionarily conserved, our findings suggest a possible negative impact of NPs on circadian rhythms and stress resistance in higher organisms including humans.

Development of a water refractive index-matched microneedle integrated into a light sheet microscopy system for continuous embryonic cell imaging.

In this study, microneedle-integrated light sheet microscopy (LSM) was developed for trapping and continuously imaging embryos of Caenorhabditis elegans with subcellular resolution. To reduce aberrations when the light sheet was propagated into the device, a microneedle was fabricated using a transparent, water refractive index-matched polymer. It was proven that when the light sheet emerged from the water-immersed objective and penetrated through the microneedle with a circular surface, even with a non-perpendicular incident angle, fewer aberrations were found. An embryo was injected into and trapped at the tip of the microneedle, which was positioned at the interrogation window of the LSM apparatus with the image plane perpendicular to the light sheet, and this setup was used to sequentially acquire embryo images. By applying the light sheet, higher-resolution, higher-contrast images were obtained. The system also showed low photobleaching and low phototoxicity to embryos of C. elegans. Furthermore, three-dimensional embryo images with a whole field of view of the microneedle could be achieved by stitching together images and reconstructing sequential two-dimensional embryo images.

Multiomic characterization and drug testing establish circulating tumor cells as an ex vivo tool for personalized medicine.

Matching the treatment to an individual patient's tumor state can increase therapeutic efficacy and reduce tumor recurrence. Circulating tumor cells (CTCs) derived from solid tumors are promising subjects for theragnostic analysis. To analyze how CTCs represent tumor states, we established cell lines from CTCs, primary and metastatic tumors from a mouse model and provided phenotypic and multiomic analyses of these cells. CTCs and metastatic cells, but not primary tumor cells, shared stochastic mutations and similar hypomethylation levels at transcription start sites. CTCs and metastatic tumor cells shared a hybrid epithelial/mesenchymal transcriptome state with reduced adhesive and enhanced mobilization characteristics. We tested anti-cancer drugs on tumor cells from a metastatic breast cancer patient. CTC responses mirrored the impact of drugs on metastatic rather than primary tumors. Our multiomic and clinical anti-cancer drug response results reveal that CTCs resemble metastatic tumors and establish CTCs as an ex vivo tool for personalized medicine.

Quantum-dot-embedded silica nanotubes as nanoprobes for simple and sensitive DNA detection.

We have developed a new technique using fluorescent silica nanotubes for simple and sensitive DNA detection. The quantum-dot-embedded silica nanotubes (QD-SNTs) were fabricated by a sol-gel reaction using anodic aluminum silica oxide (AAO) as a template. The fluorescent QD-SNTs of different colors were then immobilized with single-stranded DNA and used as nanoprobes for DNA detection. The optical and structural properties of QD-SNT nanoprobes were examined using photoluminescence spectroscopy, confocal microscopy and transmission electron microscopy (TEM). The QD-SNT nanoprobes were applied to detect dye-labeled target DNA in a solution phase. The obvious color change of the QD-SNT nanoprobes was observed visually under a simple microscope after the successful detection with target DNA. The quantitative analyses indicated that ∼ 100 attomole of target DNA in one nanoprobe can generate a distinguishable and observable color change. The detection results also demonstrated that our assay exhibited high specificity, high selectivity and very low nonspecific adsorption. Our simple DNA assay based on QD-SNT nanoprobes is expected to be quite useful for the needs of fast DNA screening and detection applications.