Detection of toxigenic M1UK lineage group A Streptococcus clones in Taiwan.

BACKGROUND: A new sublineage of emm1 group A Streptococcus (GAS), M1UK, has emerged in Europe, North America, and Australia. Notably, a significant portion of emm1 isolates in Asia, particularly in Hong Kong and mainland China, acquired scarlet fever-associated prophages following the 2011 Hong Kong scarlet fever outbreak. However, the presence of the M1UK sublineage has not yet been detected in Asia. METHODS: This study included 181 GAS isolates (2011-2021). The emm type of these isolates were determined, and 21 emm1 isolates from blood or pleural fluid (2011-2021) and 10 emm1 isolates from throat swabs (2016-2018) underwent analysis. The presence of the scarlet fever-associated prophages and the specific single nucleotide polymorphisms of the M1UK clone were determined by polymerase chain reaction and the genome sequencing. RESULTS: The M1UK lineage strains from throat swab and blood samples were identified. One of the M1UK strain in Taiwan carried the scarlet fever-associated prophage and therefore acquired the ssa, speC, and spd1 toxin repertoire. Nonetheless, the increase of M1UK was not observed until 2021, and there was a reduction in the diversity of emm types in 2020-2021, possibly due to the COVID-19 pandemic restriction policies in Taiwan. CONCLUSIONS: Our results suggested that the M1UK lineage clone has introduced in Taiwan. In Taiwan, the COVID-19 restrictions were officially released in March 2023; therefore, it would be crucial to continuously monitor the M1UK expansion and its related diseases in the post COVID-19 era.

BiFuse++: Self-Supervised and Efficient Bi-Projection Fusion for 360° Depth Estimation.

Due to the rise of spherical cameras, monocular 360 ° depth estimation becomes an important technique for many applications (e.g., autonomous systems). Thus, state-of-the-art frameworks for monocular 360 ° depth estimation such as bi-projection fusion in BiFuse are proposed. To train such a framework, a large number of panoramas along with the corresponding depth ground truths captured by laser sensors are required, which highly increases the cost of data collection. Moreover, since such a data collection procedure is time-consuming, the scalability of extending these methods to different scenes becomes a challenge. To this end, self-training a network for monocular depth estimation from 360 ° videos is one way to alleviate this issue. However, there are no existing frameworks that incorporate bi-projection fusion into the self-training scheme, which highly limits the self-supervised performance since bi-projection fusion can leverage information from different projection types. In this paper, we propose BiFuse++ to explore the combination of bi-projection fusion and the self-training scenario. To be specific, we propose a new fusion module and Contrast-Aware Photometric Loss to improve the performance of BiFuse and increase the stability of self-training on real-world videos. We conduct both supervised and self-supervised experiments on benchmark datasets and achieve state-of-the-art performance.

A molecular toolkit for heterologous protein secretion across Bacteroides species.

Bacteroides species are abundant and prevalent stably colonizing members of the human gut microbiota, making them a promising chassis for developing long-term interventions for chronic diseases. Engineering these bacteria as on-site production and delivery vehicles for biologic drugs or diagnostics, however, requires efficient heterologous protein secretion tools, which are currently lacking. To address this limitation, we systematically investigated methods to enable heterologous protein secretion in Bacteroides using both endogenous and exogenous secretion systems. Here, we report a collection of secretion carriers that can export functional proteins across multiple Bacteroides species at high titers. To understand the mechanistic drivers of Bacteroides secretion, we characterized signal peptide sequence features as well as post-secretion extracellular fate and cargo size limit of protein cargo. To increase titers and enable flexible control of protein secretion, we developed a strong, self-contained, inducible expression circuit. Finally, we validated the functionality of our secretion carriers in vivo in a mouse model. This toolkit should enable expanded development of long-term living therapeutic interventions for chronic gastrointestinal disease.

Rapid Polyp Classification in Colonoscopy Using Textural and Convolutional Features.

Colorectal cancer is the leading cause of cancer-associated morbidity and mortality worldwide. One of the causes of developing colorectal cancer is untreated colon adenomatous polyps. Clinically, polyps are detected in colonoscopy and the malignancies are determined according to the biopsy. To provide a quick and objective assessment to gastroenterologists, this study proposed a quantitative polyp classification via various image features in colonoscopy. The collected image database was composed of 1991 images including 1053 hyperplastic polyps and 938 adenomatous polyps and adenocarcinomas. From each image, textural features were extracted and combined in machine learning classifiers and machine-generated features were automatically selected in deep convolutional neural networks (DCNN). The DCNNs included AlexNet, Inception-V3, ResNet-101, and DenseNet-201. AlexNet trained from scratch achieved the best performance of 96.4% accuracy which is better than transfer learning and textural features. Using the prediction models, the malignancy level of polyps can be evaluated during a colonoscopy to provide a rapid treatment plan.

Fluoroquinolones Suppress TGF-ß and PMA-Induced MMP-9 Production in Cancer Cells: Implications in Repurposing Quinolone Antibiotics for Cancer Treatment.

BACKGROUND: Fluoroquinolones (FQs) are potent antimicrobials with multiple effects on host cells and tissues. Although FQs can attenuate cancer invasion and metastasis, the underlying molecular mechanisms remain unclear. Matrix metalloproteinase-9 (MMP-9) has functional roles in tumor angiogenesis, invasion, and metastasis, and is associated with cancer progression and poor prognosis, suggesting that inhibitors of MMP-9 activity and transcription are prime candidates for cancer therapy. Despite numerous preclinical data supporting the use of MMP-9 inhibitors as anticancer drugs, the few available examples are not therapeutically useful due to low specificity and off-target effects. We examined the effects of FQs on MMP-9 production in cancer cells following transforming growth factor beta (TGF-ß) and phorbol 12-myristate 13-acetate (PMA) stimulation. EXPERIMENTAL APPROACHES: Using confluent cultures of HepG2 and A549 cells, the effects of FQs (ciprofloxacin, levofloxacin, clinafloxacin, gatifloxacin, and enrofloxacin) on TGF-ß and PMA-induced MMP-9 mRNA expression and production were studied in RNA extracts and culture supernatants, respectively. FQs specifically abrogated TGF-ß and PMA-induced MMP-9 levels and activity in a concentration and time-dependent manner, without affecting other MMPs or proteins involved in epithelial-mesenchymal transition. Additionally, FQs inhibited TGF-ß and PMA-induced cell migration via p38 and cyclic AMP signaling pathways. CONCLUSIONS AND IMPLICATIONS: Overall, we demonstrated that FQs inhibit cancer cell migration and invasion by downregulating MMP-9 expression and revealed the cellular mechanisms underlying their potential value in cancer treatment.

Putative markers for the detection of early-stage bladder cancer selected by urine metabolomics.

BACKGROUND: Early detection of bladder cancer remains challenging because patients with early-stage bladder cancer usually have no incentive to take cytology or cystoscopy tests if they are asymptomatic. Our goal is to find non-invasive marker candidates that may help us gain insight into the metabolism of early-stage bladder cancer and be examined in routine health checks. RESULTS: We acquired urine samples from 124 patients diagnosed with early-stage bladder cancer or hernia (63 cancer patients and 61 controls). In which 100 samples were included in our marker discovery cohort, and the remaining 24 samples were included in our independent test cohort. We obtained metabolic profiles of 922 compounds of the samples by gas chromatography-mass spectrometry. Based on the metabolic profiles of the marker discovery cohort, we selected marker candidates using Wilcoxon rank-sum test with Bonferroni correction and leave-one-out cross-validation; we further excluded compounds detected in less than 60% of the bladder cancer samples. We finally selected eight putative markers. The abundance of all the eight markers in bladder cancer samples was high but extremely low in hernia samples. Moreover, the up-regulation of these markers might be in association with sugars and polyols metabolism. CONCLUSIONS: In the present study, comparative urine metabolomics selected putative metabolite markers for the detection of early-stage bladder cancer. The suggested relations between early-stage bladder cancer and sugars and polyols metabolism may create opportunities for improving the detection of bladder cancer.

Stabilizing resistive random access memory by constructing an oxygen reservoir with analyzed state distribution.

In this paper, the instability mechanism of resistive random access memory (RRAM) was investigated, and a technique was developed to stabilize the distribution of high resistance states (HRS) and better concentrate the set voltage. Due to the accumulation of oxygen, an interface-type switching characteristic was observed on the I-V curves beneath the filament-type switching behavior. In this work, the interface-type switching characteristic is used to fit the natural distribution of HRS as an analysis of the instability mechanism. According to the results, the HRS distribution is attributed to the accumulation of excess oxygen ions left from the lower oxygen content and oxygen vacancy recombination during the reset process. The proposed solution with simple plasma treatment, can create an excess oxygen reservoir by changing the surface topography of the electrode to store the surplus oxygen ions from the reset process, eliminating the oxygen accumulation effect and further improving the device stability.

Epithelial-mesenchymal transition (EMT) beyond EGFR mutations per se is a common mechanism for acquired resistance to EGFR TKI.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is a major advance in treating NSCLC with EGFR-activating mutations. However, acquired resistance, due partially to secondary mutations limits their use. Here we report that NSCLC cells with acquired resistance to gefitinib or osimertinib (AZD9291) exhibit EMT features, with a decrease in E-cadherin, and increases in vimentin and stemness, without possessing any EGFR secondary mutations. Knockdown of E-cadherin in parental cells increased gefitinib resistance and stemness, while knockdown of vimentin in resistant cells resulted in opposite effects. Src activation and Hakai upregulation were found in gefitinib-resistant cells. Knockdown of Hakai elevated E-cadherin expression, attenuated stemness, and resensitized the cells to gefitinib. Clinical cancer specimens with acquired gefitinib resistance also showed a decrease in E-cadherin and an increase in Hakai expression. The dual HDAC and HMGR inhibitor JMF3086 inhibited the Src/Hakai and Hakai/E-cadherin interaction to reverse E-cadherin expression, and attenuated vimentin and stemness to restore gefitinib sensitivity. The EMT features of AZD9291-resistant H1975 cells were related to the upregulation of Zeb1. Both gefitinib and AZD9291 sensitivity was restored by JMF3086 through reversing EMT. Our study not only revealed a common mechanism of EMT in both gefitinib and AZD9291 resistance beyond EGFR mutations per se, but also provides a new strategy to overcome it.

Mutation load estimation model as a predictor of the response to cancer immunotherapy.

The determination of the mutation load, a total number of nonsynonymous point mutations, by whole-exome sequencing was shown to be useful in predicting the treatment responses to cancer immunotherapy. However, this technique is expensive and time-consuming, which hampers its application in clinical practice. Therefore, the objective of this study was to construct a mutation load estimation model for lung adenocarcinoma, using a small set of genes, as a predictor of the immunotherapy treatment response. Using the somatic mutation data downloaded from The Cancer Genome Atlas (TCGA) database, a computational framework was developed. The estimation model consisted of only 24 genes, used to estimate the mutation load in the independent validation cohort precisely (R2 = 0.7626). Additionally, the estimated mutation load can be used to identify the patients with durable clinical benefits, with 85% sensitivity, 93% specificity, and 89% accuracy, indicating that the model can serve as a predictive biomarker for cancer immunotherapy treatment response. Furthermore, our analyses demonstrated the necessity of the cancer-specific models by the constructed melanoma and colorectal models. Since most genes in the lung adenocarcinoma model are not currently included in the sequencing panels, a customized targeted sequencing panel can be designed with the selected model genes to assess the mutation load, instead of whole-exome sequencing or the currently used panel-based methods. Consequently, the cost and time required for the assessment of mutation load may be considerably decreased, which indicates that the presented model is a more cost-effective approach to cancer immunotherapy response prediction in clinical practice.

Surfactant-assisted dispersive liquid-liquid microextraction combined with field-amplified sample stacking in capillary electrophoresis for the determination of mexiletine and lidocaine.

A sensitive method for the determination of mexiletine and lidocaine using surfactant-assisted dispersive liquid-liquid microextraction coupled with capillary electrophoresis was developed. Triton X-100 and dichloromethane were used as the dispersive agent and extraction solvent, respectively. After the extraction, mexiletine and lidocaine were analyzed using capillary electrophoresis with ultraviolet detection. The detection sensitivity was further enhanced through the use of field-amplified sample stacking. Under optimal extraction and stacking conditions, the calibration curves were linear over a concentration range of 0.05-1.00 µM for mexiletine and 0.03-1.00 µM for lidocaine. The limits of detection (signal-to-noise ratio of 3) were 0.01 and 0.01 µM for mexiletine and lidocaine, respectively. An approximately 1141- to 1250-fold improvement in sensitivity was observed for the two analytes compared with the injection of a standard solution without the surfactant-assisted dispersive liquid-liquid microextraction and field-amplified sample stacking procedures. This developed method was successfully applied to the determination of mexiletine and lidocaine in human urine and serum samples. Both precision and accuracy for urine and serum samples were less than 8.7 and 6.7%, respectively. The recoveries of the two analytes from urine and serum samples were 54.7-64.9% and 16.1-56.5%, respectively.

The fabrication and properties of Ag/Ni nanocomposite fluid.

In this article, an arc-submerged nanofluid synthesis system is proposed and developed for Ag/Ni nanocomposite fluid fabrication. In the fabrication process, the positive electrode uses an Ag rod and the negative electrode uses a Ni rod, with the two electrodes processed in the dielectric liquid. The nanocomposite fluid generated by the synthesis system is analyzed by morphological analysis, heat transfer analysis, magnetic analysis and the UV-Vis spectrophotometer optical property analysis. Experimental results show that the Ag/Ni nanocomposite fluid has a very high Zeta potential of 45 mV, so that without dispersant it can remain stabile longer than five months. Testing the Ag/Ni nancomposite fluid magnetism by SQUID, shows that paramagnetism appears in the nanocomposite fluid. Moreover, the Ag/Ni nanocomposite fluid preserves both the nickel's magnetic characteristic and silver's absorption capability to visible light.

Polymorphisms in metabolic GSTP1 and DNA-repair XRCC1 genes with an increased risk of DNA damage in pesticide-exposed fruit growers.

Pesticide exposure is associated with various neoplastic diseases and congenital malformations. Previous studies have indicated that pesticides may be metabolized by cytochrome P450 3A5 or glutathione S-transferases. DNA-repair genes, including X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD), may also be implicated in the process of pesticide-related carcinogenesis. Thus, we investigated whether various metabolic and DNA-repair genotypes increase the risk of DNA damage in pesticide-exposed fruit growers. Using the comet assay, the extent of DNA damage was evaluated in the peripheral blood of 135 pesticide-exposed fruit growers and 106 unexposed controls. The metabolic genotypes CYP3A5 (A(-44)G) and GSTP1 (Ile105Val) and DNA-repair genotypes XRCC1 (Arg399Gln, Arg194Trp, T(-77)C) and XPD (Asp312Asn, Lys751Gln) were identified by polymerase chain reaction. Our multiple regression model for DNA tail moment showed that age, high pesticide exposure, low pesticide exposure, GSTP1 Ile-Ile, and XRCC1 399 Arg-Arg genotype were associated with increased DNA tail moment (DNA damage). Further analysis of interaction between GSTP1 and XRCC1 genes that increase susceptibility revealed a significant difference in DNA tail moment for high pesticide-exposed subjects carrying both GSTP1 Ile-Ile with XRCC1 399 Arg-Arg genotypes (2.49+/-0.09 microm/cell; P=0.004), compared to those carrying GSTP1 Ile-Val/Val-Val with XRCC1 399 Arg-Gln/Gln-Gln genotypes (1.98+/-0.15 microm/cell). These results suggest that individuals with susceptible metabolic GSTP1 and DNA-repair XRCC1 genotypes may be at increased risk of DNA damage due to pesticide exposure.