Novel automated antifungal susceptibility testing system for yeasts based on dual-detection algorithm of turbidimetry and colorimetry.

Introduction. The increasing prevalence and growing resistance of fungi present a significant peril to public health. There are only four classes of antifungal medicines available today, and few candidates are in clinical trials.Hypothesis/Gap Statement. Rapid and sensitive diagnostic techniques are lacking for most fungal pathogens, and those that do exist are expensive or hard to obtain.Aim. This study aimed to evaluate the feasibility of a novel automated antifungal susceptibility testing system, Fungus AST, in comparison to the broth microdilution method (BMD) recommended by the Clinical and Laboratory Standards Institute (CLSI).Methodology. A total of 101 clinical Candida spp. isolates were collected from the Zengcheng Branch of Nanfang Hospital and subjected to antifungal susceptibility testing. Antifungal susceptibility was assessed using the Fungus AST method and the BMD.Results. In this study, we introduce a novel automated antifungal susceptibility testing system, Fungus AST, which detects the turbidity and/or colour intensity of microdilution wells using a four-wavelength detection technology in real time and is designed to match the growth characteristics of strains over time. Based on our analysis, all reportable ranges of Fungus AST were suitable for clinical fungal isolates in PR China. Within ±twofold dilutions, reproducibility was 100 %. Considering the BMD as a referenced method, ten antifungal agents (anidulafungin, caspofungin, micafungin, fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B, 5-flucytosine and nystatin) showed an essential agreement of >95 %. The category agreement of five antifungal agents (anidulafungin, caspofungin, micafungin, fluconazole and voriconazole) was excellent at >90 %. One Candida albicans isolate and voriconazole showed a major error (ME) (1.7 %), and no other ME or very ME agents were found.Conclusion. Given the above, it can be argued that the utilization of Fungus AST is a discretionary automated approach. More improvements are needed in Fungus AST compared to the BMD system for a wider range of clinical isolates, including different types of fungi.

A dual-signal amplification strategy based on rolling circle amplification and APE1-assisted amplification for highly sensitive and specific miRNA analysis for early diagnosis of alzheimer's disease.

MicroRNA (miRNA) is involved in the progression of Alzheimer's disease (AD) and emerges as a promising AD biomarker and therapeutic target. Therefore, there is an urgent need to develop convenient and precise miRNA detection methods for AD diagnosis. Herein, a dual-signal amplification strategy based on rolling circle amplification and APE1-assisted amplification for miRNA analysis for early diagnosis of AD was proposed. The strategy consisted of dumbbell-shaped probe (DP) as amplification template and a reporter probe (RP) with an AP site modification. In the presence of the target miRNA, the miRNAs bound to the toehold domain of DP and DP was activated into a circular template. Then, RCA reaction was triggered, producing a large number of long-stranded products containing repeated sequences. After RCA, APE1 enzyme recognized and removed AP site in the complex of RCA/RP products. By coupling RCA with APE1-assisted amplification, this method has high sensitivity with the limit of detection (LOD) of 1.82 fM. Moreover, by using DP as template for RCA reaction, high specificity can be achieved. By detecting miR-206 in serum using this method, the expression of miR-206 can be accurately distinguished between AD patients and healthy individuals, indicating that this method has broad application prospects in clinical diagnosis.

Clinical implications and immune implications features of TARS1 in breast cancer.

Background: There has been an increase in the number of women suffering from breast cancer in recent years, and discovering new therapeutic targets and efficacy predictive markers is critical for comprehensive breast cancer treatment. Methods: First, we used bioinformatics methods to analyze TARS1(encoding cytoplasmicthreonyl-tRNA synthetase) expression, prognosis, and clinicopathological characteristics in TCGA database breast cancers, and then we collected breast cancer specimens from our center for validation. TARS1 was then subjected to GSEA (Gene Set Enrichment Analysis) enrichment analysis, GO/KEGG pathway enrichment analysis, and breast cancer immune infiltration characterization. As a last step, we examined TARS1's effects on breast cancer cell behavior with cellular assays. Results: The overexpression of TARS1 has been found in several malignant tumors, including breast cancer, and has been linked to poor prognoses. Breast cancers with large primary tumors and negative hormone receptors are more likely to overexpress TARS1. Overexpression of TARS1 promotes the infiltration of T cells, such as Tregs and Th2s, while inhibiting the infiltration of NK cells and CD8+ T cells, which are anticancer cells in breast cancer. TARS1 was also found to be co-expressed with the majority of immune checkpoint-related genes, and breast cancer with TARS1 overexpression responded better to immunotherapy. By knocking down TARS1, breast cancer cells were prevented from proliferating and invading, as well as exhibiting other malignant biological properties. Conclusion: According to our study, TARS1 may be an oncogene in breast cancer and may be a biomarker of efficacy or a target of immunotherapy in breast cancer.

Erratum: Lentinan-functionalized Selenium Nanoparticles target Tumor Cell Mitochondria via TLR4/TRAF3/MFN1 pathway: Erratum.

[This corrects the article DOI: 10.7150/thno.46467.].

miR-671-5p repressed progression of papillary thyroid carcinoma via TRIM14.

The pivotal role of dysregulated miRNAs in development of papillary thyroid carcinoma has been emphasized in recent research. miR-671-5p was previously documented to function as a tumor suppressor. However, the role and mechanism of miR-671-5p in progression of papillary thyroid carcinoma remain to be further studied. Data from functional assays indicated that forced expression of miR-671-5p decreased cell viability, repressed cell proliferation, migration, and invasion in papillary thyroid carcinoma cells. In vivo study showed that miR-671-5p overexpression inhibited tumor growth, downregulated Ki67, and decreased tumor volume and weight. Tripartite motif containing 14 (TRIM14) was verified as downstream target of miR-671-5p. The expression of TRIM14 was suppressed by miR-671-5p in papillary thyroid carcinoma. Overexpression of TRIM14 increased cell viability, and promoted the proliferation, migration, and invasion of papillary thyroid carcinoma. Moreover, TRIM14 counteracted the suppressive effect of miR-671-5p overexpression on papillary thyroid carcinoma cell growth. In conclusion, miR-671-5p repressed progression of papillary thyroid carcinoma through downregulation of TRIM14, providing a promising target for therapy of papillary thyroid carcinoma.

A chromosome-level genome of the spider Trichonephila antipodiana reveals the genetic basis of its polyphagy and evidence of an ancient whole-genome duplication event.

BACKGROUND: The spider Trichonephila antipodiana (Araneidae), commonly known as the batik golden web spider, preys on arthropods with body sizes ranging from ∼2 mm in length to insects larger than itself (>20‒50 mm), indicating its polyphagy and strong dietary detoxification abilities. Although it has been reported that an ancient whole-genome duplication event occurred in spiders, lack of a high-quality genome has limited characterization of this event. RESULTS: We present a chromosome-level T. antipodiana genome constructed on the basis of PacBio and Hi-C sequencing. The assembled genome is 2.29 Gb in size with a scaffold N50 of 172.89 Mb. Hi-C scaffolding assigned 98.5% of the bases to 13 pseudo-chromosomes, and BUSCO completeness analysis revealed that the assembly included 94.8% of the complete arthropod universal single-copy orthologs (n = 1,066). Repetitive elements account for 59.21% of the genome. We predicted 19,001 protein-coding genes, of which 96.78% were supported by transcriptome-based evidence and 96.32% matched protein records in the UniProt database. The genome also shows substantial expansions in several detoxification-associated gene families, including cytochrome P450 mono-oxygenases, carboxyl/cholinesterases, glutathione-S-transferases, and ATP-binding cassette transporters, reflecting the possible genomic basis of polyphagy. Further analysis of the T. antipodiana genome architecture reveals an ancient whole-genome duplication event, based on 2 lines of evidence: (i) large-scale duplications from inter-chromosome synteny analysis and (ii) duplicated clusters of Hox genes. CONCLUSIONS: The high-quality T. antipodiana genome represents a valuable resource for spider research and provides insights into this species' adaptation to the environment.

Lentinan-functionalized Selenium Nanoparticles target Tumor Cell Mitochondria via TLR4/TRAF3/MFN1 pathway.

Rationale: Malignant ascites caused by cancer cells results in poor prognosis and short average survival time. No effective treatment is currently available for malignant ascites. In this study, the effects of lentinan (LNT)-functionalized selenium nanoparticles (Selene) on malignant ascites were evaluated. Furthermore, the mechanism of Selene targeting mitochondria of tumor cells were also investigated. Methods: Selene were synthesized and characterized by TEM, AFM and particle size analysis. The OVCAR-3 and EAC cells induced ascites models were used to evaluate the effects of Selene on malignant ascites. Proteomic analysis, immunofluorescence, TEM and ICP-MS were used to determine the location of Selene in tumor cells. Mitochondrial membrane potential, ROS, ATP content, and caspase-1/3 activity were detected to evaluate the effect of Selene on mitochondrial function and cell apoptosis. Immunofluorescence, Co-IP, pull-down, duolink, Western blot, and FPLC were used to investigate the pathway of Selene targeting mitochondria. Results: Selene could effectively inhibit ascites induced by OVCAR-3 and EAC cells. Selene was mainly located in the mitochondria of tumor cells and induced apoptosis of tumor cells. The LNT in Selene was involved in caveolae-mediated endocytosis through the interaction between toll-like receptor-4 (TLR4) and caveolin 1 (CAV1). Furthermore, the Selene in the endocytic vesicles could enter the mitochondria via the mitochondrial membrane fusion pathway, which was mediated by TLR4/TNF receptor associated factor 3 (TRAF3)/mitofusin-1 (MFN1) protein complex. Conclusion: Selene is a candidate anticancer drug for the treatment of malignant ascites. And TLR4/TRAF3/MFN1 may be a specific nano-drug delivery pathway that could target the mitochondria.

Bimetal-organic Framework-derived Co9 S8 /ZnS@NC Heterostructures for Superior Lithium-ion Storage.

Heterostructure engineering of electrode materials, which is expected to accelerate the ion/electron transport rates driven by a built-in internal electric field at the heterointerface, offers unprecedented promise in improving their cycling stability and rate performance. Herein, carbon nanotubes with Co9 S8 /ZnS heterostructures embedded in a N-doped carbon framework (Co9 S8 /ZnS@NC) have been rationally designed via an in-situ vapor chemical transformation strategy with the aid of thiophene, which not only acted as carbon source for the growth of carbon nanotubes but also as sulfur source for the sulfurization of metal Zn and Co. Density functional theory (DFT) calculation shows an about 3.24 eV electrostatic potential difference between ZnS and Co9 S8 , which results in a strong electrostatic field across the interface that makes electrons transfer from Co9 S8 to the ZnS side. As expected, a stable cycling performance with reversible capacity of 411.2 mAh g-1 at 1000 mA g-1 after 300 cycles, excellent rate capability (324 mAh g-1 at 2000 A g-1 ) and a high percentage of pseudocapacitance contribution (87.5% at 2.2 mv/s) for lithium-ion batteries (LIBs) are achieved. This work provides a possible strategy for designing multicomponent heterostructural materials for application in energy storage and conversion fields.

Simple and green fabrication process of nano silver conductive ink and the application in frequency selective surface.

A simple and green method for fabrication of nano silver conductive ink was developed for use in frequency selective surface (FSS). The hydrogen peroxide and ethyl cellulose were used as reducing agents and dispersants to synthesize silver nanoparticles (Ag NPs), and the ethyl cellulose was be used as binders of nano silver conductive ink eventually. The reaction byproducts of hydrogen peroxide are water and oxygen, the synthesized Ag NPs were be cleaned using purified water and alcohol without centrifugation and drying process. The conductive ink with 30 wt% silver content was formulated with the Ag NPs capped with ethyl cellulose, solvent and additive, the residual water and alcohol were be evaporated using vacuum distillation process. The prepared Ag NPs were characterized by SEM, XRD, TGA and FT-IR. The viscosity and surface tension of Ag NPs ink were tested, and the conductive ink was inkjet printed on Polyimide (PI) film to fabricate the FSS. The results showed the printed FSS had reflection resonances at 16.5 GHz and nulls deeper than the required -20 dB level, with depths of -32 dB.

Graphene-Ag nanohexagonal platelets-based ink with high electrical properties at low sintering temperatures.

Printed-electronics inks belong to a class of novel functional conductive inks that can be used to form high-precision conducting lines or circuits on various flexible substrates. Previous studies have reported conductive inks produced by the reduction and membrane separation method for use in flexible devices. However, it remains a challenge to synthesize conductive inks with high electrical properties at low sintering temperatures, which restricts their range of applications. Herein, we prepare inkjet-printed patterns of conductive inks consisting of Ag nanohexagonal platelets (AgNHPs) as the main component and containing graphene (GE) in different contents. It is found that GE improves the electrical conductivity of the patterns when sintering is done at relatively low temperatures. For instance, when the GE content is 0.15 mg ml(-1), the resistivity is the lowest. When sintering is done at 150 °C, the resistivity (2.7 × 10(-6) Ω · cm) of the GE-AgNHPs conductive ink (GE: 0.15 mg ml(-1)) is 14% of that of the AgNHPs conductive ink; on the other hand, after sintering at 50 °C, this ratio is 2%. It is also found that, with the increase in GE content, the resistivity of the GE-AgNHPs conductive ink increases. This study on GE-AgNHPs conductive inks sintered at low temperatures should further the development of flexible touch screens.

Cadmium sulfide nanowires for the window semiconductor layer in thin film CdS-CdTe solar cells.

Thin film CdS/CdTe heterojunction device is a leading technology for the solar cells of the next generation. We report on two novel device configurations for these cells where the traditional CdS window layer is replaced by nanowires (NW) of CdS, embedded in an aluminum oxide matrix or free-standing. An estimated 26.8% improvement in power conversion efficiency over the traditional device structure is expected, primarily because of the enhanced spectral transmission of sunlight through the NW-CdS layer and a reduction in the junction area/optical area ratio. In initial experiments, nanostructured devices of the two designs were fabricated and a power conversion efficiency value of 6.5% was achieved.

Barrier layer non-uniformity effects in anodized aluminum oxide nanopores on ITO substrates.

Nanoporous anodic aluminum oxide (AAO) has been used widely as a template for device fabrication. In many nanostructured electro-optical device designs, AAO grown on an ITO substrate is the desired configuration. However, a residual thin aluminum oxide barrier layer between ITO and the AAO pores remains and process non-uniformities during the template fabrication can cause serious problems in the quality of nanowires deposited later in these pores. It was observed that in many templates, even the pores closest to each other could have their barrier layer thicknesses differ by as much as 10-20 nm. In this paper, causes and remedies for this non-uniformity are investigated, including the effects of a thin Ti interlayer inserted between the ITO and AAO. Templates with different Ti layer thickness and annealing conditions were compared. Mechanisms for the formation of voids beneath the barrier layer were analyzed and studied experimentally. Reactive ion etch (RIE) was found to be the preferred method to mitigate process non-uniformities. Using the above methods, barrier-free AAO templates on ITO substrates were obtained; their thicknesses ranged from 200 to 1000 nm. The characteristics of CdS nanowires electrodeposited into the initial templates with non-uniform barrier layer thicknesses and into the processed, barrier-free templates were compared.